NCBI Conserved Domain Search

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271010 [Multi-domain] Cd Length: 255 Bit Score: 525.24 E-value: 4.26e-171

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd14108     1 TDYYDIHKEIGRGAFSYLRRVKEKSSDLSFAAKFIPVRAKKKTSARRELALLAELDHKSIVRFHDAFEKRRVVIIVTELC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGagGEEQVRICDFGNAQELTPGEPQYCQ 1027
Cdd:cd14108    81 HEELLERITKRPTVCESEVRSYMRQLLEGIEYLHQNDVLHLDLKPENLLMADQ--KTDQVRICDFGNAQELTPNEPQYCK 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLV 1107
Cdd:cd14108   159 YGTPEFVAPEIVNQSPVSKVTDIWPVGVIAYLCLTGISPFVGENDRTTLMNIRNYNVAFEESMFKDLCREAKGFIIKVLV 238

                         250
                  ....*....|....*..
gi 564369110 1108 QDRLRPTAEETLEHPWF 1124
Cdd:cd14108   239 SDRLRPDAEETLEHPWF 255

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271013 [Multi-domain] Cd Length: 257 Bit Score: 510.52 E-value: 7.38e-166

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd14111     1 PQKPYTFLDEKARGRFGVIRRCRENATGKNFPAKIVPYQAEEKQGVLQEYEILKSLHHERIMALHEAYITPRYLVLIAEF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHR 2378
Cdd:cd14111    81 CSGKELLHSLIDRFRYSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQSFNPLSLRQLGRR 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFLRKVLSV 2458
Cdd:cd14111   161 TGTLEYMAPEMVKGEPVGPPADIWSIGVLTYIMLSGRSPFEDQDPQETEAKILVAKFDAFKLYPNVSQSASLFLKKVLSS 240

                         250
                  ....*....|....*..
gi 564369110 2459 HPWSRPSLQDCLAHPWL 2475
Cdd:cd14111   241 YPWSRPTTKDCFAHAWL 257

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270908 [Multi-domain] Cd Length: 247 Bit Score: 381.23 E-value: 1.04e-120

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT-EELLERM 955
Cdd:cd14006     1 LGRGRFGVVKRCIEKATGREFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSgGELLDRL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  956 ARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggEEQVRICDFGNAQELTPGEPQYCQFGTPEFVA 1035
Cdd:cd14006    81 AERGSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLADRP--SPQIKIIDFGLARKLNPGEELKEIFGTPEFVA 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1036 PEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQD-RLRPT 1114
Cdd:cd14006   159 PEIVNGEPVSLATDMWSIGVLTYVLLSGLSPFLGEDDQETLANISACRVDFSEEYFSSVSQEAKDFIRKLLVKEpRKRPT 238


                  ....*....
gi 564369110 1115 AEETLEHPW 1123
Cdd:cd14006   239 AQEALQHPW 247

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270908 [Multi-domain] Cd Length: 247 Bit Score: 375.45 E-value: 1.25e-118

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLS 2309
Cdd:cd14006     2 GRGRFGVVKRCIEKATGREFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSGGELLDRLA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA--ADNALKIVDFGSAQPYNPQalKPLGHRTGTLEFMAP 2387
Cdd:cd14006    82 ERGSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLAdrPSPQIKIIDFGLARKLNPG--EELKEIFGTPEFVAP 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2388 EMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPN-TSQSATLFLRKVLSVHPWSRPSL 2466
Cdd:cd14006   160 EIVNGEPVSLATDMWSIGVLTYVLLSGLSPFLGEDDQETLANISACRVDFSEEYFSsVSQEAKDFIRKLLVKEPRKRPTA 239


                  ....*...
gi 564369110 2467 QDCLAHPW 2474
Cdd:cd14006   240 QEALQHPW 247

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271009 [Multi-domain] Cd Length: 257 Bit Score: 294.10 E-value: 3.69e-90

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT- 948
Cdd:cd14107     3 VYEVKEEIGRGTFGFVKRVTHKGNGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILELCSs 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggEEQVRICDFGNAQELTPGEPQYCQF 1028
Cdd:cd14107    83 EELLDRLFLKGVVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILMVSPT--REDIKICDFGFAQEITPSEHQFSKY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQ 1108
Cdd:cd14107   161 GSPEFVAPEIVHQEPVSAATDIWALGVIAYLSLTCHSPFAGENDRATLLNVAEGVVSWDTPEITHLSEDAKDFIKRVLQP 240

                         250
                  ....*....|....*..
gi 564369110 1109 D-RLRPTAEETLEHPWF 1124
Cdd:cd14107   241 DpEKRPSASECLSHEWF 257

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271012 [Multi-domain] Cd Length: 257 Bit Score: 264.09 E-value: 1.23e-79

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2221 KPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd14110     3 KTYAFQTEINRGRFSVVRQCEEKRSGQMLAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEELCS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTG 2380
Cdd:cd14110    83 GPELLYNLAERNSYSEAEVTDYLWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPFNQGKVLMTDKKGD 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFLRKVLSVHP 2460
Cdd:cd14110   163 YVETMAPELLEGQGAGPQTDIWAIGVTAFIMLSADYPVSSDLNWERDRNIRKGKVQLSRCYAGLSGGAVNFLKSTLCAKP 242

                         250
                  ....*....|....*
gi 564369110 2461 WSRPSLQDCLAHPWL 2475
Cdd:cd14110   243 WGRPTASECLQNPWL 257

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271005 [Multi-domain] Cd Length: 250 Bit Score: 242.13 E-value: 3.51e-72

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQ-AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT-EELLER 954
Cdd:cd14103     1 LGRGKFGTVYRCVEKATGKELAAKFIKCRkAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAgGELFER 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  955 M-ARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeEQVRICDFGNAQELTPGEPQYCQFGTPEF 1033
Cdd:cd14103    81 VvDDDFELTERDCILFMRQICEGVQYMHKQGILHLDLKPENILCVSRTG--NQIKIIDFGLARKYDPDKKLKVLFGTPEF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1034 VAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQD-RLR 1112
Cdd:cd14103   159 VAPEVVNYEPISYATDMWSVGVICYVLLSGLSPFMGDNDAETLANVTRAKWDFDDEAFDDISDEAKDFISKLLVKDpRKR 238

                         250
                  ....*....|.
gi 564369110 1113 PTAEETLEHPW 1123
Cdd:cd14103   239 MSAAQCLQHPW 249

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.

Pssm-ID: 214567 [Multi-domain] Cd Length: 254 Bit Score: 227.41 E-value: 6.20e-67

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIP--SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC- 947
Cdd:smart00220    1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKkkKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCe 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    948 TEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQ 1027
Cdd:smart00220   81 GGDLFDLLKKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILL-DEDG---HVKLADFGLARQLDPGEKLTTF 156

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   1028 FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMN-IRNYNVAFEEtTFLSLSREARGFLIKVL 1106
Cdd:smart00220  157 VGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKkIGKPKPPFPP-PEWDISPEAKDLIRKLL 235

                           250
                    ....*....|....*....
gi 564369110   1107 VQD-RLRPTAEETLEHPWF 1124
Cdd:smart00220  236 VKDpEKRLTAEEALQHPFF 254

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.

Pssm-ID: 214567 [Multi-domain] Cd Length: 254 Bit Score: 226.64 E-value: 1.15e-66

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK--RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:smart00220    1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKKdrERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCE 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALkpLGHRTG 2380
Cdd:smart00220   81 GGDLFDLLKKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDPGEK--LTTFVG 158

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   2381 TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVG-GRFDAFQLYPNTSQSATLFLRKVLSVH 2459
Cdd:smart00220  159 TPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGkPKPPFPPPEWDISPEAKDLIRKLLVKD 238

                           250
                    ....*....|....*.
gi 564369110   2460 PWSRPSLQDCLAHPWL 2475
Cdd:smart00220  239 PEKRLTAEEALQHPFF 254

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270687 [Multi-domain] Cd Length: 258 Bit Score: 225.43 E-value: 3.33e-66

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIP-SQAKPKA--SARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd05117     2 YELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIDkKKLKSEDeeMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVMELC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEEQVRICDFGNAQELTPGEPQYC 1026
Cdd:cd05117    82 TGgELFDRIVKKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILL-ASKDPDSPIKIIDFGLAKIFEEGEKLKT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 QFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVL 1106
Cdd:cd05117   161 VCGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGETEQELFEKILKGKYSFDSPEWKNVSEEAKDLIKRLL 240

                         250
                  ....*....|....*...
gi 564369110 1107 VQD-RLRPTAEETLEHPW 1123
Cdd:cd05117   241 VVDpKKRLTAAEALNHPW 258

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271016 [Multi-domain] Cd Length: 259 Bit Score: 224.77 E-value: 5.82e-66

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIP-SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE-L 946
Cdd:cd14114     2 DHYDILEELGTGAFGVVHRCTERATGNNFAAKFIMtPHESDKETVRKEIQIMNQLHHPKLINLHDAFEDDNEMVLILEfL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTEELLERMARKPTV-CESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEeqVRICDFGNAQELTPGEPQY 1025
Cdd:cd14114    82 SGGELFERIAAEHYKmSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCTTKRSNE--VKLIDFGLATHLDPKESVK 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKV 1105
Cdd:cd14114   160 VTTGTAEFAAPEIVEREPVGFYTDMWAVGVLSYVLLSGLSPFAGENDDETLRNVKSCDWNFDDSAFSGISEEAKDFIRKL 239

                         250       260
                  ....*....|....*....|
gi 564369110 1106 LVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14114   240 LLADpNKRMTIHQALEHPWL 259

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271007 [Multi-domain] Cd Length: 269 Bit Score: 220.05 E-value: 4.31e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQaKPKASAR--------REARLLARLQHDCVLYFHEAFERRRGL 940
Cdd:cd14105     5 DFYDIGEELGSGQFAVVKKCREKSTGLEYAAKFIKKR-RSKASRRgvsredieREVSILRQVLHPNIITLHDVFENKTDV 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELT 1019
Cdd:cd14105    84 VLILELVAGgELFDFLAEKESLSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDKNVPIPRIKLIDFGLAHKIE 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREAR 1099
Cdd:cd14105   164 DGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVNYDFDDEYFSNTSELAK 243

                         250       260
                  ....*....|....*....|....*
gi 564369110 1100 GFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14105   244 DFIRQLLVKDpRKRMTIQESLRHPW 268

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271005 [Multi-domain] Cd Length: 250 Bit Score: 218.63 E-value: 5.42e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVP-YAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLcgls 2309
Cdd:cd14103     3 RGKFGTVYRCVEKATGKELAAKFIKcRKAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAGGELF---- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DR-----FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA--ADNALKIVDFGSAQPYNPQalKPLGHRTGTL 2382
Cdd:cd14103    79 ERvvdddFELTERDCILFMRQICEGVQYMHKQGILHLDLKPENILCVsrTGNQIKIIDFGLARKYDPD--KKLKVLFGTP 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD----AFQlypNTSQSATLFLRKVLSV 2458
Cdd:cd14103   157 EFVAPEVVNYEPISYATDMWSVGVICYVLLSGLSPFMGDNDAETLANVTRAKWDfddeAFD---DISDEAKDFISKLLVK 233

                         250
                  ....*....|....*..
gi 564369110 2459 HPWSRPSLQDCLAHPWL 2475
Cdd:cd14103   234 DPRKRMSAAQCLQHPWL 250

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271008 [Multi-domain] Cd Length: 268 Bit Score: 219.14 E-value: 6.87e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  863 RGRRLSDYYDI-HQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKaSARRE-----ARLLARLQHDCVLYFHEAFER 936
Cdd:cd14106     1 STENINEVYTVeSTPLGRGKFAVVRKCIHKETGKEYAAKFLRKRRRGQ-DCRNEilheiAVLELCKDCPRVVNLHEVYET 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  937 RRGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEEQVRICDFGNA 1015
Cdd:cd14106    80 RSELILILELAAGgELQTLLDEEECLTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILL-TSEFPLGDIKLCDFGIS 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1016 QELTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLS 1095
Cdd:cd14106   159 RVIGEGEEIREILGTPDYVAPEILSYEPISLATDMWSIGVLTYVLLTGHSPFGGDDKQETFLNISQCNLDFPEELFKDVS 238

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1096 REARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14106   239 PLAIDFIKRLLVKDpEKRLTAKECLEHPWL 268

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271098 [Multi-domain] Cd Length: 269 Bit Score: 218.67 E-value: 1.10e-63

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIP---SQAKPKASAR----REARLLARLQHDCVLYFHEAFERR 937
Cdd:cd14196     1 QKVEDFYDIGEELGSGQFAIVKKCREKSTGLEYAAKFIKkrqSRASRRGVSReeieREVSILRQVLHPNIITLHDVYENR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  938 RGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQ 1016
Cdd:cd14196    81 TDVVLILELVSGgELFDFLAQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPIPHIKLIDFGLAH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSR 1096
Cdd:cd14196   161 EIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDFDEEFFSHTSE 240

                         250       260
                  ....*....|....*....|....*...
gi 564369110 1097 EARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14196   241 LAKDFIRKLLVKEtRKRLTIQEALRHPW 268

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271096 [Multi-domain] Cd Length: 269 Bit Score: 217.19 E-value: 3.80e-63

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQaKPKASAR--------REARLLARLQHDCVLYFHEAFERRR 938
Cdd:cd14194     3 VDDYYDTGEELGSGQFAVVKKCREKSTGLQYAAKFIKKR-RTKSSRRgvsredieREVSILKEIQHPNVITLHEVYENKT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  939 GLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQE 1017
Cdd:cd14194    82 DVILILELVAGgELFDFLAEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVPKPRIKIIDFGLAHK 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1018 LTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSRE 1097
Cdd:cd14194   162 IDFGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVSAVNYEFEDEYFSNTSAL 241

                         250       260
                  ....*....|....*....|....*..
gi 564369110 1098 ARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14194   242 AKDFIRRLLVKDpKKRMTIQDSLQHPW 268

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270687 [Multi-domain] Cd Length: 258 Bit Score: 215.42 E-value: 9.09e-63

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV---PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd05117     2 YELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIdkkKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVMELC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA---LKIVDFGSAQPYNPQalKPLG 2376
Cdd:cd05117    82 TGGELFDRIVKKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPdspIKIIDFGLAKIFEEG--EKLK 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 HRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLYPNTSQSATLFLRKV 2455
Cdd:cd05117   160 TVCGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGETEQELFEKILKGKYSfDSPEWKNVSEEAKDLIKRL 239

                         250
                  ....*....|....*....
gi 564369110 2456 LSVHPWSRPSLQDCLAHPW 2474
Cdd:cd05117   240 LVVDPKKRLTAAEALNHPW 258

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271097 [Multi-domain] Cd Length: 271 Bit Score: 210.63 E-value: 6.65e-61

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIpsQAKPKASARR---------EARLLARLQHDCVLYFHEAFERR 937
Cdd:cd14195     3 VEDHYEMGEELGSGQFAIVRKCREKGTGKEYAAKFI--KKRRLSSSRRgvsreeierEVNILREIQHPNIITLHDIFENK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  938 RGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQ 1016
Cdd:cd14195    81 TDVVLILELVSGgELFDFLAEKESLTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVPNPRIKLIDFGIAH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSR 1096
Cdd:cd14195   161 KIEAGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYFSNTSE 240

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1097 EARGFLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd14195   241 LAKDFIRRLLVKDpKKRMTIAQSLEHSWIK 270

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271006 [Multi-domain] Cd Length: 277 Bit Score: 209.72 E-value: 2.03e-60

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT-E 949
Cdd:cd14104     2 YMIAEELGRGQFGIVHRCVETSSKKTYMAKFVKVKGADQVLVKKEISILNIARHRNILRLHESFESHEELVMIFEFISgV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMA-RKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeEQVRICDFGNAQELTPGEPQYCQF 1028
Cdd:cd14104    82 DIFERITtARFELNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIIYCTRRG--SYIKIIEFGQSRQLKPGDKFRLQY 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQ 1108
Cdd:cd14104   160 TSAEFYAPEVHQHESVSTATDMWSLGCLVYVLLSGINPFEAETNQQTIENIRNAEYAFDDEAFKNISIEALDFVDRLLVK 239

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 564369110 1109 DR-LRPTAEETLEHPWFKTeaKGAEVSTDHLKLFLSRR 1145
Cdd:cd14104   240 ERkSRMTAQEALNHPWLKQ--GMETVSSKDIKTTRHRR 275

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271095 [Multi-domain] Cd Length: 261 Bit Score: 204.76 E-value: 6.86e-59

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQE--IGRGAFSYLRRVVERSSGLEFAAKFIPSQA-KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14193     1 NSYYNVNKEeiLGGGRFGQVHKCEEKSSGLKLAAKIIKARSqKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKP-TVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeEQVRICDFGNAQELTPGE 1022
Cdd:cd14193    81 EYVDGgELFDRIIDENyNLTELDTILFIKQICEGIQYMHQMYILHLDLKPENILCVSREA--NQVKIIDFGLARRYKPRE 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFL 1102
Cdd:cd14193   159 KLRVNFGTPEFLAPEVVNYEFVSFPTDMWSLGVIAYMLLSGLSPFLGEDDNETLNNILACQWDFEDEEFADISEEAKDFI 238

                         250       260
                  ....*....|....*....|..
gi 564369110 1103 IKVLVQDR-LRPTAEETLEHPW 1123
Cdd:cd14193   239 SKLLIKEKsWRMSASEALKHPW 260

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271008 [Multi-domain] Cd Length: 268 Bit Score: 198.73 E-value: 1.05e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2227 EEKARGRFGVVRSCRENATGRTFVAKIVPyaaegKRR--------VLQEYEVLR-TLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd14106    14 TPLGRGKFAVVRKCIHKETGKEYAAKFLR-----KRRrgqdcrneILHEIAVLElCKDCPRVVNLHEVYETRSELILILE 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA---LKIVDFGSAQPYNPQAlkP 2374
Cdd:cd14106    89 LAAGGELQTLLDEEECLTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILLTSEFPlgdIKLCDFGISRVIGEGE--E 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDaF--QLYPNTSQSATLFL 2452
Cdd:cd14106   167 IREILGTPDYVAPEILSYEPISLATDMWSIGVLTYVLLTGHSPFGGDDKQETFLNISQCNLD-FpeELFKDVSPLAIDFI 245

                         250       260
                  ....*....|....*....|...
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14106   246 KRLLVKDPEKRLTAKECLEHPWL 268

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270909 [Multi-domain] Cd Length: 253 Bit Score: 196.54 E-value: 3.59e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYA----AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd14007    10 KGKFGNVYLAREKKSGFIVALKVISKSqlqkSGLEHQLRREIEIQSHLRHPNILRLYGYFEDKKRIYLILEYAPNGELYK 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAqpYNPQalKPLGHRTGTLEFM 2385
Cdd:cd14007    90 ELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGwSV--HAPS--NRRKTFCGTLDYL 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2386 APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqlYPNT-SQSATLFLRKVLSVHPWSRP 2464
Cdd:cd14007   166 PPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIK----FPSSvSPEAKDLISKLLQKDPSKRL 241

                         250
                  ....*....|..
gi 564369110 2465 SLQDCLAHPWLQ 2476
Cdd:cd14007   242 SLEQVLNHPWIK 253

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271094 [Multi-domain] Cd Length: 261 Bit Score: 195.95 E-value: 7.56e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDI--HQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQ-AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14192     1 NSYYAVcpHEVLGGGRFGQVHKCTELSTGLTLAAKIIKVKgAKEREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 E-LCTEELLERMA-RKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeEQVRICDFGNAQELTPGE 1022
Cdd:cd14192    81 EyVDGGELFDRITdESYQLTELDAILFTRQICEGVHYLHQHYILHLDLKPENILCVNSTG--NQIKIIDFGLARRYKPRE 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFL 1102
Cdd:cd14192   159 KLKVNFGTPEFLAPEVVNYDFVSFPTDMWSVGVITYMLLSGLSPFLGETDAETMNNIVNCKWDFDAEAFENLSEEAKDFI 238

                         250       260
                  ....*....|....*....|...
gi 564369110 1103 IKVLVQDR-LRPTAEETLEHPWF 1124
Cdd:cd14192   239 SRLLVKEKsCRMSATQCLKHEWL 261

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271092 [Multi-domain] Cd Length: 261 Bit Score: 195.91 E-value: 8.49e-56

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQE--IGRGAFSYLRRVVERSSGLEFAAKFIPSQ-AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14190     1 SSTFSIHSKevLGGGKFGKVHTCTEKRTGLKLAAKVINKQnSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPT-VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeEQVRICDFGNAQELTPGE 1022
Cdd:cd14190    81 EYVEGgELFERIVDEDYhLTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCVNRTG--HQVKIIDFGLARRYNPRE 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFL 1102
Cdd:cd14190   159 KLKVNFGTPEFLSPEVVNYDQVSFPTDMWSMGVITYMLLSGLSPFLGDDDTETLNNVLMGNWYFDEETFEHVSDEAKDFV 238

                         250       260
                  ....*....|....*....|...
gi 564369110 1103 IKVLVQDR-LRPTAEETLEHPWF 1124
Cdd:cd14190   239 SNLIIKERsARMSATQCLKHPWL 261

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271093 [Multi-domain] Cd Length: 259 Bit Score: 191.76 E-value: 1.76e-54

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPS-QAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd14191     1 SDFYDIEERLGSGKFGQVFRLVEKKTKKVWAGKFFKAySAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTE-ELLERMARKP-TVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeEQVRICDFGNAQELTPGEPQ 1024
Cdd:cd14191    81 VSGgELFERIIDEDfELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTG--TKIKLIDFGLARRLENAGSL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIK 1104
Cdd:cd14191   159 KVLFGTPEFVAPEVINYEPIGYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDFDDEAFDEISDDAKDFISN 238

                         250       260
                  ....*....|....*....|.
gi 564369110 1105 VLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14191   239 LLKKDmKARLTCTQCLQHPWL 259

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 184.98 E-value: 2.26e-54

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 218
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80

                          90
                  ....*....|.
gi 564369110  219 GARQCEARLEV 229
Cdd:cd20975    81 GARQCEARLEV 91

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271016 [Multi-domain] Cd Length: 259 Bit Score: 190.49 E-value: 5.60e-54

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV--PYAAEgKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd14114     4 YDILEELGTGAFGVVHRCTERATGNNFAAKFImtPHESD-KETVRKEIQIMNQLHHPKLINLHDAFEDDNEMVLILEFLS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDR-FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAA--DNALKIVDFGSAQPYNPQALKPLgh 2377
Cdd:cd14114    83 GGELFERIAAEhYKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCTTkrSNEVKLIDFGLATHLDPKESVKV-- 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLYPNTSQSATLFLRKVL 2456
Cdd:cd14114   161 TTGTAEFAAPEIVEREPVGFYTDMWAVGVLSYVLLSGLSPFAGENDDETLRNVKSCDWNfDDSAFSGISEEAKDFIRKLL 240

                         250
                  ....*....|....*....
gi 564369110 2457 SVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14114   241 LADPNKRMTIHQALEHPWL 259

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271007 [Multi-domain] Cd Length: 269 Bit Score: 190.39 E-value: 6.70e-54

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAK-IVPYAAEGKRR------VLQEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd14105     7 YDIGEELGSGQFAVVKKCREKSTGLEYAAKfIKKRRSKASRRgvsredIEREVSILRQVLHPNIITLHDVFENKTDVVLI 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA----LKIVDFGSAQPYNP-Q 2370
Cdd:cd14105    87 LELVAGGELFDFLAEKESLSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDKNVpiprIKLIDFGLAHKIEDgN 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 ALKPLghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDaF--QLYPNTSQSA 2448
Cdd:cd14105   167 EFKNI---FGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVNYD-FddEYFSNTSELA 242

                         250       260
                  ....*....|....*....|....*..
gi 564369110 2449 TLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14105   243 KDFIRQLLVKDPRKRMTIQESLRHPWI 269

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271100 [Multi-domain] Cd Length: 270 Bit Score: 188.98 E-value: 2.28e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDI-HQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKP---KASARREARLLaRLQHDC--VLYFHEAFERRRGL 940
Cdd:cd14198     5 FNNFYILtSKELGRGKFAVVRQCISKSTGQEYAAKFLKKRRRGqdcRAEILHEIAVL-ELAKSNprVVNLHEVYETTSEI 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTE---------LCTEELLERMArkptvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEEQVRICD 1011
Cdd:cd14198    84 ILILEyaaggeifnLCVPDLAEMVS------ENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILL-SSIYPLGDIKIVD 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1012 FGNAQELTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTF 1091
Cdd:cd14198   157 FGMSRKIGHACELREIMGTPEYLAPEILNYDPITTATDMWNIGVIAYMLLTHESPFVGEDNQETFLNISQVNVDYSEETF 236

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 1092 LSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14198   237 SSVSQLATDFIQKLLVKNpEKRPTAEICLSHSWL 270

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271009 [Multi-domain] Cd Length: 257 Bit Score: 185.86 E-value: 2.26e-52

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14107     4 YEVKEEIGRGTFGFVKRVTHKGNGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILELCSSE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA--ADNALKIVDFGSAQPYNPqaLKPLGHRTG 2380
Cdd:cd14107    84 ELLDRLFLKGVVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILMVspTREDIKICDFGFAQEITP--SEHQFSKYG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLYPNTSQSATLFLRKVLSVH 2459
Cdd:cd14107   162 SPEFVAPEIVHQEPVSAATDIWALGVIAYLSLTCHSPFAGENDRATLLNVAEGVVSwDTPEITHLSEDAKDFIKRVLQPD 241

                         250
                  ....*....|....*.
gi 564369110 2460 PWSRPSLQDCLAHPWL 2475
Cdd:cd14107   242 PEKRPSASECLSHEWF 257

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271100 [Multi-domain] Cd Length: 270 Bit Score: 182.81 E-value: 3.15e-51

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2227 EEKARGRFGVVRSCRENATGRTFVAKIVPYAAEG---KRRVLQEYEVLR-TLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14198    14 KELGRGKFAVVRQCISKSTGQEYAAKFLKKRRRGqdcRAEILHEIAVLElAKSNPRVVNLHEVYETTSEIILILEYAAGG 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 EL--LCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNAL---KIVDFGSAqpynpqalKPLGH 2377
Cdd:cd14198    94 EIfnLCVPDLAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSIYPLgdiKIVDFGMS--------RKIGH 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RT------GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLYPNTSQSATL 2450
Cdd:cd14198   166 ACelreimGTPEYLAPEILNYDPITTATDMWNIGVIAYMLLTHESPFVGEDNQETFLNISQVNVDySEETFSSVSQLATD 245

                         250       260
                  ....*....|....*....|....*
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14198   246 FIQKLLVKNPEKRPTAEICLSHSWL 270

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271099 [Multi-domain] Cd Length: 271 Bit Score: 181.67 E-value: 9.17e-51

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  863 RGRRLSDYYDIH--QEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQ--HDC--VLYFHEAFER 936
Cdd:cd14197     1 RSEPFQERYSLSpgRELGRGKFAVVRKCVEKDSGKEFAAKFMRKRRKGQDCRMEIIHEIAVLElaQANpwVINLHEVYET 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  937 RRGLVIVTELCTE-ELLERMA--RKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGAGGEeqVRICDF 1012
Cdd:cd14197    81 ASEMILVLEYAAGgEIFNQCVadREEAFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNiLLTSESPLGD--IKIVDF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1013 GNAQELTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFL 1092
Cdd:cd14197   159 GLSRILKNSEELREIMGTPEYVAPEILSYEPISTATDMWSIGVLAYVMLTGISPFLGDDKQETFLNISQMNVSYSEEEFE 238

                         250       260       270
                  ....*....|....*....|....*....|...
gi 564369110 1093 SLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14197   239 HLSESAIDFIKTLLIKKpENRATAEDCLKHPWL 271

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270905 [Multi-domain] Cd Length: 252 Bit Score: 180.41 E-value: 1.22e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2222 PYTFLEEKARGRFGVVRSCRENATGRTFVAKIVP---YAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd14003     1 NYELGKTLGEGSFGKVKLARHKLTGEKVAIKIIDkskLKEEIEEKIKREIEIMKLLNHPNIIKLYEVIETENKIYLVMEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQalKPLGHR 2378
Cdd:cd14003    81 ASGGELFDYIVNNGRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGG--SLLKTF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqLYPNTSQSATLFLRKVLS 2457
Cdd:cd14003   159 CGTPAYAAPEVLLGRKyDGPKADVWSLGVILYAMLTGYLPFDDDNDSKLFRKILKGKYP---IPSHLSPDARDLIRRMLV 235

                         250
                  ....*....|....*..
gi 564369110 2458 VHPWSRPSLQDCLAHPW 2474
Cdd:cd14003   236 VDPSKRITIEEILNHPW 252

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271017 [Multi-domain] Cd Length: 248 Bit Score: 179.00 E-value: 4.09e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-ELLERM 955
Cdd:cd14115     1 IGRGRFSIVKKCLHKATRKDVAVKFVSKKMKKKEQAAHEAALLQHLQHPQYITLHDTYESPTSYILVLELMDDgRLLDYL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  956 ARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEEQVRICDFGNAQELTPGEPQYCQFGTPEFVA 1035
Cdd:cd14115    81 MNHDELMEEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLI-DLRIPVPRVKLIDLEDAVQISGHRHVHHLLGNPEFAA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1036 PEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQD-RLRPT 1114
Cdd:cd14115   160 PEVIQGTPVSLATDIWSIGVLTYVMLSGVSPFLDESKEETCINVCRVDFSFPDEYFGDVSQAARDFINVILQEDpRRRPT 239


                  ....*....
gi 564369110 1115 AEETLEHPW 1123
Cdd:cd14115   240 AATCLQHPW 248

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271014 [Multi-domain] Cd Length: 259 Bit Score: 178.88 E-value: 5.92e-50

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENA--TGRTFVAKIVPYAAEGKRrVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIA 2296
Cdd:cd14112     1 PTGRFSFGSEIFRGRFSVIVKAVDSTteTDAHCAVKIFEVSDEASE-AVREFESLRTLQHENVQRLIAAFKPSNFAYLVM 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCgNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA--LKIVDFGSAQPYNPQALKP 2374
Cdd:cd14112    80 EKL-QEDVFTRFSSNDYYSEEQVATTVRQILDALHYLHFKGIAHLDVQPDNIMFQSVRSwqVKLVDFGRAQKVSKLGKVP 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 lghRTGTLEFMAPEMVRGD-PIGSATDIWGAGVLTYIMLSGYSPFY--EPDPQETEARIVGGRFDAFQLYPNTSQSATLF 2451
Cdd:cd14112   159 ---VDGDTDWASPEFHNPEtPITVQSDIWGLGVLTFCLLSGFHPFTseYDDEEETKENVIFVKCRPNLIFVEATQEALRF 235

                         250       260
                  ....*....|....*....|....
gi 564369110 2452 LRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14112   236 ATWALKKSPTRRMRTDEALEHRWL 259

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271098 [Multi-domain] Cd Length: 269 Bit Score: 175.53 E-value: 1.13e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAK-IVPYAAEGKRR------VLQEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd14196     7 YDIGEELGSGQFAIVKKCREKSTGLEYAAKfIKKRQSRASRRgvsreeIEREVSILRQVLHPNIITLHDVYENRTDVVLI 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA----LKIVDFGSAQPYNPQA 2371
Cdd:cd14196    87 LELVSGGELFDFLAQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIpiphIKLIDFGLAHEIEDGV 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 lkPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARI--VGGRFDAfQLYPNTSQSAT 2449
Cdd:cd14196   167 --EFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANItaVSYDFDE-EFFSHTSELAK 243

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2450 LFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14196   244 DFIRKLLVKETRKRLTIQEALRHPWI 269

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271006 [Multi-domain] Cd Length: 277 Bit Score: 175.43 E-value: 1.47e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14104     2 YMIAEELGRGQFGIVHRCVETSSKKTYMAKFVKVKGADQVLVKKEISILNIARHRNILRLHESFESHEELVMIFEFISGV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSD-RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAA--DNALKIVDFGSAQPYNPQALKPLGHRT 2379
Cdd:cd14104    82 DIFERITTaRFELNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIIYCTrrGSYIKIIEFGQSRQLKPGDKFRLQYTS 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GtlEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGR--FDAfQLYPNTSQSATLFLRKVLS 2457
Cdd:cd14104   162 A--EFYAPEVHQHESVSTATDMWSLGCLVYVLLSGINPFEAETNQQTIENIRNAEyaFDD-EAFKNISIEALDFVDRLLV 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 564369110 2458 VHPWSRPSLQDCLAHPWLQdaylMKLRR-QTLTFTTNRLKEF 2498
Cdd:cd14104   239 KERKSRMTAQEALNHPWLK----QGMETvSSKDIKTTRHRRY 276

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271010 [Multi-domain] Cd Length: 255 Bit Score: 173.93 E-value: 2.68e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCgNR 2302
Cdd:cd14108     4 YDIHKEIGRGAFSYLRRVKEKSSDLSFAAKFIPVRAKKKTSARRELALLAELDHKSIVRFHDAFEKRRVVIIVTELC-HE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA--ADNALKIVDFGSAQPYNPQalKPLGHRTG 2380
Cdd:cd14108    83 ELLERITKRPTVCESEVRSYMRQLLEGIEYLHQNDVLHLDLKPENLLMAdqKTDQVRICDFGNAQELTPN--EPQYCKYG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFdAFQ--LYPNTSQSATLFLRKVLsV 2458
Cdd:cd14108   161 TPEFVAPEIVNQSPVSKVTDIWPVGVIAYLCLTGISPFVGENDRTTLMNIRNYNV-AFEesMFKDLCREAKGFIIKVL-V 238

                         250
                  ....*....|....*..
gi 564369110 2459 HPWSRPSLQDCLAHPWL 2475
Cdd:cd14108   239 SDRLRPDAEETLEHPWF 255

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270909 [Multi-domain] Cd Length: 253 Bit Score: 173.04 E-value: 4.69e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFS--YLRRvvERSSGLEFAAKFIP----SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14007     2 FEIGKPLGKGKFGnvYLAR--EKKSGFIVALKVISksqlQKSGLEHQLRREIEIQSHLRHPNILRLYGYFEDKKRIYLIL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEP 1023
Cdd:cd14007    80 EYAPNgELYKELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILL----GSNGELKLADFGWSVHAPSNRR 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 Q-YCqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREARGFL 1102
Cdd:cd14007   156 KtFC--GTLDYLPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIKFPS----SVSPEAKDLI 229

                         250       260
                  ....*....|....*....|....
gi 564369110 1103 IKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd14007   230 SKLLQKDpSKRLSLEQVLNHPWIK 253

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271096 [Multi-domain] Cd Length: 269 Bit Score: 173.67 E-value: 4.90e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVP-YAAEGKRR------VLQEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd14194     7 YDTGEELGSGQFAVVKKCREKSTGLQYAAKFIKkRRTKSSRRgvsredIEREVSILKEIQHPNVITLHEVYENKTDVILI 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA----LKIVDFGSAQPYNPQa 2371
Cdd:cd14194    87 LELVAGGELFDFLAEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVpkprIKIIDFGLAHKIDFG- 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 lKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARI--VGGRFDAfQLYPNTSQSAT 2449
Cdd:cd14194   166 -NEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVsaVNYEFED-EYFSNTSALAK 243

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2450 LFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14194   244 DFIRRLLVKDPKKRMTIQDSLQHPWI 269

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270905 [Multi-domain] Cd Length: 252 Bit Score: 172.32 E-value: 9.02e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASA---RREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd14003     2 YELGKTLGEGSFGKVKLARHKLTGEKVAIKIIDKSKLKEEIEekiKREIEIMKLLNHPNIIKLYEVIETENKIYLVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYC 1026
Cdd:cd14003    82 SGgELFDYIVNNGRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILL-DKNG---NLKIIDFGLSNEFRGGSLLKT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 QFGTPEFVAPEIVNQSPVSG-VTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREARGFLIKV 1105
Cdd:cd14003   158 FCGTPAYAAPEVLLGRKYDGpKADVWSLGVILYAMLTGYLPFDDDNDSKLFRKILKGKYPIPSH----LSPDARDLIRRM 233

                         250
                  ....*....|....*....
gi 564369110 1106 LVQD-RLRPTAEETLEHPW 1123
Cdd:cd14003   234 LVVDpSKRITIEEILNHPW 252

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271011 [Multi-domain] Cd Length: 255 Bit Score: 171.93 E-value: 1.34e-47

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQE-IGRGAFSYLRRVVERSSGLEFAAKFIPSqakpKASARREARLLARLQHDCVLYFHEAFE-RRRGLVIVTEL 946
Cdd:cd14109     3 ELYEIGEEdEKRAAQGAPFHVTERSTGRNFLAQLRYG----DPFLMREVDIHNSLDHPNIVQMHDAYDdEKLAVTVIDNL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CT--EELLERMARKPTVC-ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggeEQVRICDFGNAQELTPGEP 1023
Cdd:cd14109    79 AStiELVRDNLLPGKDYYtERQVAVFVRQLLLALKHMHDLGIAHLDLRPEDILLQD-----DKLKLADFGQSRRLLRGKL 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLI 1103
Cdd:cd14109   154 TTLIYGSPEFVSPEIVNSYPVTLATDMWSVGVLTYVLLGGISPFLGDNDRETLTNVRSGKWSFDSSPLGNISDDARDFIK 233

                         250       260
                  ....*....|....*....|..
gi 564369110 1104 KVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14109   234 KLLVYIpESRLTVDEALNHPWF 255

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271092 [Multi-domain] Cd Length: 261 Bit Score: 169.33 E-value: 1.42e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIV-PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSD 2310
Cdd:cd14190    15 GKFGKVHTCTEKRTGLKLAAKVInKQNSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFMEYVEGGELFERIVD 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2311 R-FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLL--AADNALKIVDFGSAQPYNPQalKPLGHRTGTLEFMAP 2387
Cdd:cd14190    95 EdYHLTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCvnRTGHQVKIIDFGLARRYNPR--EKLKVNFGTPEFLSP 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2388 EMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGR--FDAfQLYPNTSQSATLFLRKVLSVHPWSRPS 2465
Cdd:cd14190   173 EVVNYDQVSFPTDMWSMGVITYMLLSGLSPFLGDDDTETLNNVLMGNwyFDE-ETFEHVSDEAKDFVSNLIIKERSARMS 251

                         250
                  ....*....|
gi 564369110 2466 LQDCLAHPWL 2475
Cdd:cd14190   252 ATQCLKHPWL 261

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271099 [Multi-domain] Cd Length: 271 Bit Score: 168.96 E-value: 2.37e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2215 RQGPPQKPYTFL--EEKARGRFGVVRSCRENATGRTFVAKIVPYAAEG---KRRVLQEYEVLRTLH-HERLMSLHEAYIT 2288
Cdd:cd14197     1 RSEPFQERYSLSpgRELGRGKFAVVRKCVEKDSGKEFAAKFMRKRRKGqdcRMEIIHEIAVLELAQaNPWVINLHEVYET 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2289 PRYLVLIAESCGNRELL--CGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNAL---KIVDFG- 2362
Cdd:cd14197    81 ASEMILVLEYAAGGEIFnqCVADREEAFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLTSESPLgdiKIVDFGl 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2363 SAQPYNPQALKPLghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARI-------VGGRF 2435
Cdd:cd14197   161 SRILKNSEELREI---MGTPEYVAPEILSYEPISTATDMWSIGVLAYVMLTGISPFLGDDKQETFLNIsqmnvsySEEEF 237

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 564369110 2436 DAFqlypntSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14197   238 EHL------SESAIDFIKTLLIKKPENRATAEDCLKHPWL 271

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271015 [Multi-domain] Cd Length: 263 Bit Score: 168.23 E-value: 3.58e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-ELLER 954
Cdd:cd14113    14 ELGRGRFSVVKKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQgRLLDY 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  955 MARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEEQVRICDFGNAQELTPGEPQYCQFGTPEFV 1034
Cdd:cd14113    94 VVRWGNLTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILV-DQSLSKPTIKLADFGDAVQLNTTYYIHQLLGSPEFA 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1035 APEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQDRL-RP 1113
Cdd:cd14113   173 APEIILGNPVSLTSDLWSIGVLTYVLLSGVSPFLDESVEETCLNICRLDFSFPDDYFKGVSQKAKDFVCFLLQMDPAkRP 252

                         250
                  ....*....|.
gi 564369110 1114 TAEETLEHPWF 1124
Cdd:cd14113   253 SAALCLQEQWL 263

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271017 [Multi-domain] Cd Length: 248 Bit Score: 166.67 E-value: 7.16e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSD 2310
Cdd:cd14115     3 RGRFSIVKKCLHKATRKDVAVKFVSKKMKKKEQAAHEAALLQHLQHPQYITLHDTYESPTSYILVLELMDDGRLLDYLMN 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2311 RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA---LKIVDFGSaqpynpqALKPLGHR-----TGTL 2382
Cdd:cd14115    83 HDELMEEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLIDLRIPvprVKLIDLED-------AVQISGHRhvhhlLGNP 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggRFD-AF--QLYPNTSQSATLFLRKVLSVH 2459
Cdd:cd14115   156 EFAAPEVIQGTPVSLATDIWSIGVLTYVMLSGVSPFLDESKEETCINVC--RVDfSFpdEYFGDVSQAARDFINVILQED 233

                         250
                  ....*....|....*
gi 564369110 2460 PWSRPSLQDCLAHPW 2474
Cdd:cd14115   234 PRRRPTAATCLQHPW 248

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270988 [Multi-domain] Cd Length: 292 Bit Score: 167.98 E-value: 9.10e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQakpKASAR------REARLLARLQHDCVLYFHEAFERRRGLVI 942
Cdd:cd14086     1 DEYDLKEELGKGAFSVVRRCVQKSTGQEFAAKIINTK---KLSARdhqkleREARICRLLKHPNIVRLHDSISEEGFHYL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  943 VTELCT-EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEqVRICDFGNAQELTPG 1021
Cdd:cd14086    78 VFDLVTgGELFEDIVAREFYSEADASHCIQQILESVNHCHQNGIVHRDLKPENLLLASKSKGAA-VKLADFGLAIEVQGD 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 EPQYCQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARG 1100
Cdd:cd14086   157 QQAWFGFaGTPGYLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDEDQHRLYAQIKAGAYDYPSPEWDTVTPEAKD 236

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1101 FLIKVLVQD-RLRPTAEETLEHPWFKTEAKGAEV-----STDHLKLFLSRRR 1146
Cdd:cd14086   237 LINQMLTVNpAKRITAAEALKHPWICQRDRVASMvhrqeTVDCLKKFNARRK 288

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271097 [Multi-domain] Cd Length: 271 Bit Score: 167.10 E-value: 1.05e-45

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyaaegKRR------------VLQEYEVLRTLHHERLMSLHEAYITPR 2290
Cdd:cd14195     7 YEMGEELGSGQFAIVRKCREKGTGKEYAAKFIK-----KRRlsssrrgvsreeIEREVNILREIQHPNIITLHDIFENKT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 YLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA----LKIVDFGSAqp 2366
Cdd:cd14195    82 DVVLILELVSGGELFDFLAEKESLTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVpnprIKLIDFGIA-- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2367 YNPQALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLY-PNTS 2445
Cdd:cd14195   160 HKIEAGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYfSNTS 239

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 2446 QSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd14195   240 ELAKDFIRRLLVKDPKKRMTIAQSLEHSWIK 270

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270993 [Multi-domain] Cd Length: 291 Bit Score: 163.96 E-value: 2.41e-44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIpsqAKPKASARREARLLARL-QHDCVLYFHEAFERRRGLVIVTELCT- 948
Cdd:cd14091     2 YEIKEEIGKGSYSVCKRCIHKATGKEYAVKII---DKSKRDPSEEIEILLRYgQHPNIITLRDVYDDGNSVYLVTELLRg 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQEL--------TP 1020
Cdd:cd14091    79 GELLDRILRQKFFSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNILYADESGDPESLRICDFGFAKQLraengllmTP 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 gepqyCQfgTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFV-GENDRTT--LMNIRNYNVAFEETTFLSLSRE 1097
Cdd:cd14091   159 -----CY--TANFVAPEVLKKQGYDAACDIWSLGVLLYTMLAGYTPFAsGPNDTPEviLARIGSGKIDLSGGNWDHVSDS 231

                         250       260
                  ....*....|....*....|....*....
gi 564369110 1098 ARGFLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd14091   232 AKDLVRKMLHVDpSQRPTAAQVLQHPWIR 260

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

Pssm-ID: 270622 [Multi-domain] Cd Length: 215 Bit Score: 160.13 E-value: 4.80e-44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGK--RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGL 2308
Cdd:cd00180     3 KGSFGKVYKARDKETGKKVAVKVIPKEKLKKllEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2309 SDRFRY-SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY-NPQALKPLGHRTGTLEFMA 2386
Cdd:cd00180    83 KENKGPlSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLdSDDSLLKTTGGTTPPYYAP 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2387 PEMVRGDPIGSATDIWGAGVLTYIMlsgyspfyepdpqetearivggrfdafqlypntsQSATLFLRKVLSVHPWSRPSL 2466
Cdd:cd00180   163 PELLGGRYYGPKVDIWSLGVILYEL----------------------------------EELKDLIRRMLQYDPKKRPSA 208


                  ....*..
gi 564369110 2467 QDCLAHP 2473
Cdd:cd00180   209 KELLEHL 215

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271094 [Multi-domain] Cd Length: 261 Bit Score: 161.28 E-value: 6.88e-44

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPY-AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSD 2310
Cdd:cd14192    15 GRFGQVHKCTELSTGLTLAAKIIKVkGAKEREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIMEYVDGGELFDRITD 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2311 -RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLL--AADNALKIVDFGSAQPYNPQalKPLGHRTGTLEFMAP 2387
Cdd:cd14192    95 eSYQLTELDAILFTRQICEGVHYLHQHYILHLDLKPENILCvnSTGNQIKIIDFGLARRYKPR--EKLKVNFGTPEFLAP 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2388 EMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGR--FDAfQLYPNTSQSATLFLRKVLSVHPWSRPS 2465
Cdd:cd14192   173 EVVNYDFVSFPTDMWSVGVITYMLLSGLSPFLGETDAETMNNIVNCKwdFDA-EAFENLSEEAKDFISRLLVKEKSCRMS 251

                         250
                  ....*....|
gi 564369110 2466 LQDCLAHPWL 2475
Cdd:cd14192   252 ATQCLKHEWL 261

Protein kinase domain;

Pssm-ID: 459660 [Multi-domain] Cd Length: 217 Bit Score: 159.72 E-value: 7.01e-44

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK---RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:pfam00069    1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKKEKIKKkkdKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  2300 GNRELLCGLSDRFRYSEDDVATYVVQLLQGLDylhgrhvlhldikpdnlllaadnalkivdfgSAQPYNpqalkplgHRT 2379
Cdd:pfam00069   81 EGGSLFDLLSEKGAFSEREAKFIMKQILEGLE-------------------------------SGSSLT--------TFV 121

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  2380 GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFLRKVLSVH 2459
Cdd:pfam00069  122 GTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPELPSNLSEEAKDLLKKLLKKD 201

                          250
                   ....*....|....*.
gi 564369110  2460 PWSRPSLQDCLAHPWL 2475
Cdd:pfam00069  202 PSKRLTATQALQHPWF 217

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

Pssm-ID: 271001 [Multi-domain] Cd Length: 258 Bit Score: 160.03 E-value: 1.73e-43

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQ--AKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14099     1 KRYRRGKFLGKGGFAKCYEVTDMSTGKVYAGKVVPKSslTKPKQREKlkSEIKIHRSLKHPNIVKFHDCFEDEENVYILL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTEELLERM--ARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELT-PG 1021
Cdd:cd14099    81 ELCSNGSLMELlkRRKA-LTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFL----DENMNVKIGDFGLAARLEyDG 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 EPQYCQFGTPEFVAPEIVNQSpvSGVT---DIWPVGVVAFLCLTGISPFVGENDRTTLMNIRnyNVAFEETTFLSLSREA 1098
Cdd:cd14099   156 ERKKTLCGTPNYIAPEVLEKK--KGHSfevDIWSLGVILYTLLVGKPPFETSDVKETYKRIK--KNEYSFPSHLSISDEA 231

                         250       260
                  ....*....|....*....|....*..
gi 564369110 1099 RGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14099   232 KDLIRSMLQPDpTKRPSLDEILSHPFF 258

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.

Pssm-ID: 270693 [Multi-domain] Cd Length: 250 Bit Score: 159.22 E-value: 2.51e-43

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd05123     3 KGSFGKVLLVRKKDTGKLYAMKVLRKKEIIKRKevehTLNERNILERVNHPFIVKLHYAFQTEEKLYLVLDYVPGGELFS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPynpqaLKPLGHRT----GTL 2382
Cdd:cd05123    83 HLSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKE-----LSSDGDRTytfcGTP 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggrFDAFQLYPNTSQSATLFLRKVLSVHPWS 2462
Cdd:cd05123   158 EYLAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKIL---KSPLKFPEYVSPEAKSLISGLLQKDPTK 234

                         250
                  ....*....|....*
gi 564369110 2463 R---PSLQDCLAHPW 2474
Cdd:cd05123   235 RlgsGGAEEIKAHPF 249

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271015 [Multi-domain] Cd Length: 263 Bit Score: 159.76 E-value: 3.03e-43

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14113     9 YSEVAELGRGRFSVVKKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQG 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLL---AADNALKIVDFGSA-----QPYNPQALkp 2374
Cdd:cd14113    89 RLLDYVVRWGNLTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILVdqsLSKPTIKLADFGDAvqlntTYYIHQLL-- 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 lghrtGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRF----DAFQlypNTSQSATL 2450
Cdd:cd14113   167 -----GSPEFAAPEIILGNPVSLTSDLWSIGVLTYVLLSGVSPFLDESVEETCLNICRLDFsfpdDYFK---GVSQKAKD 238

                         250       260
                  ....*....|....*....|....*
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14113   239 FVCFLLQMDPAKRPSAALCLQEQWL 263

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271095 [Multi-domain] Cd Length: 261 Bit Score: 158.15 E-value: 8.34e-43

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPY-AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSD 2310
Cdd:cd14193    15 GRFGQVHKCEEKSSGLKLAAKIIKArSQKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVMEYVDGGELFDRIID 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2311 R-FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA--LKIVDFGSAQPYNPQalKPLGHRTGTLEFMAP 2387
Cdd:cd14193    95 EnYNLTELDTILFIKQICEGIQYMHQMYILHLDLKPENILCVSREAnqVKIIDFGLARRYKPR--EKLRVNFGTPEFLAP 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2388 EMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLYPNTSQSATLFLRKVLSVHPWSRPSL 2466
Cdd:cd14193   173 EVVNYEFVSFPTDMWSLGVIAYMLLSGLSPFLGEDDNETLNNILACQWDfEDEEFADISEEAKDFISKLLIKEKSWRMSA 252


                  ....*....
gi 564369110 2467 QDCLAHPWL 2475
Cdd:cd14193   253 SEALKHPWL 261

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271013 [Multi-domain] Cd Length: 257 Bit Score: 157.68 E-value: 1.36e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT-E 949
Cdd:cd14111     5 YTFLDEKARGRFGVIRRCRENATGKNFPAKIVPYQAEEKQGVLQEYEILKSLHHERIMALHEAYITPRYLVLIAEFCSgK 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQYC--Q 1027
Cdd:cd14111    85 ELLHSLIDRFRYSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMV----TNLNAIKIVDFGSAQSFNPLSLRQLgrR 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIrnYNVAFEETT-FLSLSREARGFLIKVL 1106
Cdd:cd14111   161 TGTLEYMAPEMVKGEPVGPPADIWSIGVLTYIMLSGRSPFEDQDPQETEAKI--LVAKFDAFKlYPNVSQSASLFLKKVL 238

                         250
                  ....*....|....*...
gi 564369110 1107 -VQDRLRPTAEETLEHPW 1123
Cdd:cd14111   239 sSYPWSRPTTKDCFAHAW 256

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270997 [Multi-domain] Cd Length: 258 Bit Score: 156.72 E-value: 2.63e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIV-PYAAEGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLS 2309
Cdd:cd14095    11 GNFAVVKECRDKATDKEYALKIIdKAKCKGKEHMIEnEVAILRRVKHPNIVQLIEEYDTDTELYLVMELVKGGDLFDAIT 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADN----ALKIVDFGSAQpynpQALKPLGHRTGTLEFM 2385
Cdd:cd14095    91 SSTKFTERDASRMVTDLAQALKYLHSLSIVHRDIKPENLLVVEHEdgskSLKLADFGLAT----EVKEPLFTVCGTPTYV 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2386 APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETE--ARIVGGRFDAFQLY-PNTSQSATLFLRKVLSVHPWS 2462
Cdd:cd14095   167 APEILAETGYGLKVDIWAAGVITYILLCGFPPFRSPDRDQEElfDLILAGEFEFLSPYwDNISDSAKDLISRMLVVDPEK 246

                         250
                  ....*....|..
gi 564369110 2463 RPSLQDCLAHPW 2474
Cdd:cd14095   247 RYSAGQVLDHPW 258

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270916 [Multi-domain] Cd Length: 260 Bit Score: 156.21 E-value: 4.54e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQ--AKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd14014     2 YRLVRLLGRGGMGEVYRARDTLLGRPVAIKVLRPElaEDEEFRERflREARALARLSHPNIVRVYDVGEDDGRPYIVMEY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CT-EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQEL--TPGEP 1023
Cdd:cd14014    82 VEgGSLADLLRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILL----TEDGRVKLTDFGIARALgdSGLTQ 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLI 1103
Cdd:cd14014   158 TGSVLGTPAYMAPEQARGGPVDPRSDIYSLGVVLYELLTGRPPFDGDSPAAVLAKHLQEAPPPPSPLNPDVPPALDAIIL 237

                         250
                  ....*....|....*..
gi 564369110 1104 KVLVQDR-LRPTAEETL 1119
Cdd:cd14014   238 RALAKDPeERPQSAAEL 254

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271012 [Multi-domain] Cd Length: 257 Bit Score: 155.85 E-value: 5.27e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT-E 949
Cdd:cd14110     5 YAFQTEINRGRFSVVRQCEEKRSGQMLAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEELCSgP 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGE--PQYCQ 1027
Cdd:cd14110    85 ELLYNLAERNSYSEAEVTDYLWQILSAVDYLHSRRILHLDLRSENMII----TEKNLLKIVDLGNAQPFNQGKvlMTDKK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEtTFLSLSREARGFLIKVL- 1106
Cdd:cd14110   161 GDYVETMAPELLEGQGAGPQTDIWAIGVTAFIMLSADYPVSSDLNWERDRNIRKGKVQLSR-CYAGLSGGAVNFLKSTLc 239

                         250
                  ....*....|....*..
gi 564369110 1107 VQDRLRPTAEETLEHPW 1123
Cdd:cd14110   240 AKPWGRPTASECLQNPW 256

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270692 [Multi-domain] Cd Length: 254 Bit Score: 155.44 E-value: 6.24e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPY-AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd05122     2 FEILEKIGKGGFGVVYKARHKKTGQIVAIKKINLeSKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCSG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 ---RELLCGLSDRFrySEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQpynPQALKPLGH 2377
Cdd:cd05122    82 gslKDLLKNTNKTL--TEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGlSAQ---LSDGKTRNT 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFLRKVLS 2457
Cdd:cd05122   157 FVGTPYWMAPEVIQGKPYGFKADIWSLGITAIEMAEGKPPYSELPPMKALFLIATNGPPGLRNPKKWSKEFKDFLKKCLQ 236

                         250
                  ....*....|....*...
gi 564369110 2458 VHPWSRPSLQDCLAHPWL 2475
Cdd:cd05122   237 KDPEKRPTAEQLLKHPFI 254

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270988 [Multi-domain] Cd Length: 292 Bit Score: 156.43 E-value: 7.92e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV---PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd14086     3 YDLKEELGKGAFSVVRRCVQKSTGQEFAAKIIntkKLSARDHQKLEREARICRLLKHPNIVRLHDSISEEGFHYLVFDLV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAA---DNALKIVDFGSAQPYNPQALKPLG 2376
Cdd:cd14086    83 TGGELFEDIVAREFYSEADASHCIQQILESVNHCHQNGIVHRDLKPENLLLASkskGAAVKLADFGLAIEVQGDQQAWFG 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 HrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqlYPN-----TSQSATLF 2451
Cdd:cd14086   163 F-AGTPGYLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDEDQHRLYAQIKAGAYD----YPSpewdtVTPEAKDL 237

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 564369110 2452 LRKVLSVHPWSRPSLQDCLAHPWL--QDAYLMKLRRQTltfTTNRLKEF 2498
Cdd:cd14086   238 INQMLTVNPAKRITAAEALKHPWIcqRDRVASMVHRQE---TVDCLKKF 283

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271011 [Multi-domain] Cd Length: 255 Bit Score: 154.98 E-value: 8.79e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2227 EEKARGRFGVVRSCRENATGRTFVAKIVPyaaeGKRRVLQEYEVLRTLHHERLMSLHEAYIT-PRYLVLIAESCGNRELL 2305
Cdd:cd14109    10 EDEKRAAQGAPFHVTERSTGRNFLAQLRY----GDPFLMREVDIHNSLDHPNIVQMHDAYDDeKLAVTVIDNLASTIELV 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 --CGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNaLKIVDFGSAQPYNPQALKPLGHrtGTLE 2383
Cdd:cd14109    86 rdNLLPGKDYYTERQVAVFVRQLLLALKHMHDLGIAHLDLRPEDILLQDDK-LKLADFGQSRRLLRGKLTTLIY--GSPE 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2384 FMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDaFQLYP--NTSQSATLFLRKVLSVHPW 2461
Cdd:cd14109   163 FVSPEIVNSYPVTLATDMWSVGVLTYVLLGGISPFLGDNDRETLTNVRSGKWS-FDSSPlgNISDDARDFIKKLLVYIPE 241

                         250
                  ....*....|....
gi 564369110 2462 SRPSLQDCLAHPWL 2475
Cdd:cd14109   242 SRLTVDEALNHPWF 255

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270910 [Multi-domain] Cd Length: 267 Bit Score: 155.40 E-value: 9.90e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR---------------VLQEYEVLRTLHHERLMSLHEAYITPR----Y 2291
Cdd:cd14008     3 RGSFGKVKLALDTETGQLYAIKIFNKSRLRKRRegkndrgkiknalddVRREIAIMKKLDHPNIVRLYEVIDDPEsdklY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2292 LVLiaESCGNREL--LCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP 2369
Cdd:cd14008    83 LVL--EYCEGGPVmeLDSGDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEMFED 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLGhRTGTLEFMAPEMVRGDP---IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGrFDAFQLYPNTSQ 2446
Cdd:cd14008   161 GNDTLQK-TAGTPAFLAPELCDGDSktySGKAADIWALGVTLYCLVFGRLPFNGDNILELYEAIQNQ-NDEFPIPPELSP 238

                         250       260
                  ....*....|....*....|....*....
gi 564369110 2447 SATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14008   239 ELKDLLRRMLEKDPEKRITLKEIKEHPWV 267

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270995 [Multi-domain] Cd Length: 272 Bit Score: 155.20 E-value: 1.25e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--------PSQAKP-KASARREARLLARLQ-HDCVLYFHEAFERRRGL 940
Cdd:cd14093     5 YEPKEILGRGVSSTVRRCIEKETGQEFAVKIIditgekssENEAEElREATRREIEILRQVSgHPNIIELHDVFESPTFI 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELT 1019
Cdd:cd14093    85 FLVFELCRKgELFDYLTEVVTLSEKKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLDD----NLNVKISDFGFATRLD 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCQFGTPEFVAPEIVNQSPVSGV------TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLS 1093
Cdd:cd14093   161 EGEKLRELCGTPGYLAPEVLKCSMYDNApgygkeVDMWACGVIMYTLLAGCPPFWHRKQMVMLRNIMEGKYEFGSPEWDD 240

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 1094 LSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14093   241 ISDTAKDLISKLLVVDpKKRLTAEEALEHPFF 272

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270989 [Multi-domain] Cd Length: 259 Bit Score: 154.23 E-value: 2.08e-41

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE- 949
Cdd:cd14087     3 YDIKALIGRGSFSRVVRVEHRVTRQPYAIKMIETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGg 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgAGGEEQVRICDFG--NAQELTPGEPQYCQ 1027
Cdd:cd14087    83 ELFDRIIAKGSFTERDATRVLQMVLDGVKYLHGLGITHRDLKPENLLYYH-PGPDSKIMITDFGlaSTRKKGPNCLMKTT 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLV 1107
Cdd:cd14087   162 CGTPEYIAPEILLRKPYTQSVDMWAVGVIAYILLSGTMPFDDDNRTRLYRQILRAKYSYSGEPWPSVSNLAKDFIDRLLT 241

                         250
                  ....*....|....*..
gi 564369110 1108 QDRL-RPTAEETLEHPW 1123
Cdd:cd14087   242 VNPGeRLSATQALKHPW 258

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270916 [Multi-domain] Cd Length: 260 Bit Score: 149.66 E-value: 8.96e-40

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2222 PYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYA----AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd14014     1 RYRLVRLLGRGGMGEVYRARDTLLGRPVAIKVLRPElaedEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVME 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGH 2377
Cdd:cd14014    81 YVEGGSLADLLRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAF-QLYPNTSQSATLFLRKVL 2456
Cdd:cd14014   161 VLGTPAYMAPEQARGGPVDPRSDIYSLGVVLYELLTGRPPFDGDSPAAVLAKHLQEAPPPPsPLNPDVPPALDAIILRAL 240


                  ....*....
gi 564369110 2457 SVHPWSRPS 2465
Cdd:cd14014   241 AKDPEERPQ 249

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271069 [Multi-domain] Cd Length: 263 Bit Score: 149.41 E-value: 1.03e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA--KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14167     1 IRDIYDFREVLGTGAFSEVVLAEEKRTQKLVAIKCIAKKAleGKETSIENEIAVLHKIKHPNIVALDDIYESGGHLYLIM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgAGGEEQVRICDFGNAQELTPGEP 1023
Cdd:cd14167    81 QLVSGgELFDRIVEKGFYTERDASKLIFQILDAVKYLHDMGIVHRDLKPENLLYYS-LDEDSKIMISDFGLSKIEGSGSV 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLI 1103
Cdd:cd14167   160 MSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDAKLFEQILKAEYEFDSPYWDDISDSAKDFIQ 239

                         250       260
                  ....*....|....*....|.
gi 564369110 1104 KVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14167   240 HLMEKDpEKRFTCEQALQHPW 260

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270985 [Multi-domain] Cd Length: 259 Bit Score: 149.44 E-value: 1.05e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA--KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14083     1 IRDKYEFKEVLGTGAFSEVVLAEDKATGKLVAIKCIDKKAlkGKEDSLENEIAVLRKIKHPNIVQLLDIYESKSHLYLVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgEEQVRICDFGnaqeLTPGEP 1023
Cdd:cd14083    81 ELVTGgELFDRIVEKGSYTEKDASHLIRQVLEAVDYLHSLGIVHRDLKPENLLYYSPDE-DSKIMISDFG----LSKMED 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 Q-----YCqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREA 1098
Cdd:cd14083   156 SgvmstAC--GTPGYVAPEVLAQKPYGKAVDCWSIGVISYILLCGYPPFYDENDSKLFAQILKAEYEFDSPYWDDISDSA 233

                         250       260
                  ....*....|....*....|....*.
gi 564369110 1099 RGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14083   234 KDFIRHLMEKDpNKRYTCEQALEHPW 259

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270986 [Multi-domain] Cd Length: 275 Bit Score: 149.85 E-value: 1.06e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI---------PSQAKPKASARREARLLARLQHDCVLYFHEAFE 935
Cdd:cd14084     2 KELRKKYIMSRTLGSGACGEVKLAYDKSTCKKVAIKIInkrkftigsRREINKPRNIETEIEILKKLSHPCIIKIEDFFD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  936 RRRGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgAGGEEQ--VRICDF 1012
Cdd:cd14084    82 AEDDYYIVLELMEGgELFDRVVSNKRLKEAICKLYFYQMLLAVKYLHSNGIIHRDLKPENVLL---SSQEEEclIKITDF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1013 GNAQELTPGEPQYCQFGTPEFVAPEIVN---QSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMN-IRNYNVAFEE 1088
Cdd:cd14084   159 GLSKILGETSLMKTLCGTPTYLAPEVLRsfgTEGYTRAVDCWSLGVILFICLSGYPPFSEEYTQMSLKEqILSGKYTFIP 238

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 1089 TTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14084   239 KAWKNVSEEAKDLVKKMLVVDpSRRPSIEEALEHPW 274

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270985 [Multi-domain] Cd Length: 259 Bit Score: 149.06 E-value: 1.08e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2221 KPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVP-YAAEGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd14083     3 DKYEFKEVLGTGAFSEVVLAEDKATGKLVAIKCIDkKALKGKEDSLEnEIAVLRKIKHPNIVQLLDIYESKSHLYLVMEL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLL---LAADNALKIVDFGSAQPYNPQAlkpL 2375
Cdd:cd14083    83 VTGGELFDRIVEKGSYTEKDASHLIRQVLEAVDYLHSLGIVHRDLKPENLLyysPDEDSKIMISDFGLSKMEDSGV---M 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGG--RFDAfQLYPNTSQSATLFLR 2453
Cdd:cd14083   160 STACGTPGYVAPEVLAQKPYGKAVDCWSIGVISYILLCGYPPFYDENDSKLFAQILKAeyEFDS-PYWDDISDSAKDFIR 238

                         250       260
                  ....*....|....*....|.
gi 564369110 2454 KVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd14083   239 HLMEKDPNKRYTCEQALEHPW 259

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

Pssm-ID: 270622 [Multi-domain] Cd Length: 215 Bit Score: 147.03 E-value: 1.50e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQA--KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT----EE 950
Cdd:cd00180     1 LGKGSFGKVYKARDKETGKKVAVKVIPKEKlkKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEggslKD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  951 LLERmaRKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEPQYCQFGT 1030
Cdd:cd00180    81 LLKE--NKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDS----DGTVKLADFGLAKDLDSDDSLLKTTGG 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1031 PEFV---APEIVNQSPVSGVTDIWPVGVVaFLCLtgispfvgendrttlmnirnynvafeettflslsREARGFLIKVLV 1107
Cdd:cd00180   155 TTPPyyaPPELLGGRYYGPKVDIWSLGVI-LYEL----------------------------------EELKDLIRRMLQ 199

                         250
                  ....*....|....*.
gi 564369110 1108 QD-RLRPTAEETLEHP 1122
Cdd:cd00180   200 YDpKKRPSAKELLEHL 215

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271071 [Multi-domain] Cd Length: 277 Bit Score: 148.89 E-value: 2.63e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAA-EGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd14169     5 YELKEKLGEGAFSEVVLAQERGSQRLVALKCIPKKAlRGKEAMVEnEIAVLRRINHENIVSLEDIYESPTHLYLAMELVT 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAA---DNALKIVDFGSAQpynPQALKPLGH 2377
Cdd:cd14169    85 GGELFDRIIERGSYTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLLYATpfeDSKIMISDFGLSK---IEAQGMLST 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGG--RFDAfQLYPNTSQSATLFLRKV 2455
Cdd:cd14169   162 ACGTPGYVAPELLEQKPYGKAVDVWAIGVISYILLCGYPPFYDENDSELFNQILKAeyEFDS-PYWDDISESAKDFIRHL 240

                         250       260
                  ....*....|....*....|
gi 564369110 2456 LSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14169   241 LERDPEKRFTCEQALQHPWI 260

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270996 [Multi-domain] Cd Length: 300 Bit Score: 149.23 E-value: 3.90e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYA------AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIA 2296
Cdd:cd14094     5 YELCEVIGKGPFSVVRRCIHRETGQQFAVKIVDVAkftsspGLSTEDLKREASICHMLKHPHIVELLETYSSDGMLYMVF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLCGLSDR----FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAA-DNA--LKIVDFGSAQPYNP 2369
Cdd:cd14094    85 EFMDGADLCFEIVKRadagFVYSEAVASHYMRQILEALRYCHDNNIIHRDVKPHCVLLASkENSapVKLGGFGVAIQLGE 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLGhRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEaRIVGGR--FDAFQlYPNTSQS 2447
Cdd:cd14094   165 SGLVAGG-RVGTPHFMAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFE-GIIKGKykMNPRQ-WSHISES 241

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2448 ATLFLRKVLSVHPWSRPSLQDCLAHPWLQDAYLMkLRRQTLTFTTNRLKEF 2498
Cdd:cd14094   242 AKDLVRRMLMLDPAERITVYEALNHPWIKERDRY-AYRIHLPETVEQLRKF 291

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270783 [Multi-domain] Cd Length: 258 Bit Score: 147.28 E-value: 5.20e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAK---IVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE--SCGNrelL 2305
Cdd:cd06606    10 KGSFGSVYLALNLDTGELMAVKeveLSGDSEEELEALEREIRILSSLKHPNIVRYLGTERTENTLNIFLEyvPGGS---L 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRF-RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA-QPYNPQALKPLGHRTGTLE 2383
Cdd:cd06606    87 ASLLKKFgKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAkRLAEIATGEGTKSLRGTPY 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2384 FMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFLRKVLSVHPWSR 2463
Cdd:cd06606   167 WMAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPWSELGNPVAALFKIGSSGEPPPIPEHLSEEAKDFLRKCLQRDPKKR 246

                         250
                  ....*....|..
gi 564369110 2464 PSLQDCLAHPWL 2475
Cdd:cd06606   247 PTADELLQHPFL 258

Serine/threonine protein kinase [Signal transduction mechanisms];

Pssm-ID: 440281 [Multi-domain] Cd Length: 482 Bit Score: 153.63 E-value: 5.40e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR----REARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:COG0515     9 YRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAADPEARerfrREARALARLNHPNIVRVYDVGEEDGRPYLVMEY 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CT-EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGE--P 1023
Cdd:COG0515    89 VEgESLADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILL----TPDGRVKLIDFGIARALGGATltQ 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLI 1103
Cdd:COG0515   165 TGTVVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPPPSELRPDLPPALDAIVL 244

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1104 KVLVQDRLR--PTAEE---TLEHPWFKTEAKGAEVSTDHLKLFLSRRRWQRSQISYKCHLVLRPIPELLRAPPERVWVAM 1178
Cdd:COG0515   245 RALAKDPEEryQSAAElaaALRAVLRSLAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAPA 324

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1179 PRRQPPSGGLSSSSDSEEEELEELPSVPRPLQPEFSGSRVSLTDIPTEDEALGTPEAGAATPMDWQEQGRAPSKDQEAPS 1258
Cdd:COG0515   325 AAAAAAAAAAALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAALAAAA 404

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 1259 PEALPSPGQESPDGPSPRRPELRRGSSAESALPRVGSREPGRSLHKAASVELPQRRSPSPGATRLTRGGLGEGEYAQR 1336
Cdd:COG0515   405 AAAAAAAAAAAAAAALAAAAAAAAAAAAAAAAAAAAAARLLAAAAAAAAAAAAAPLLAALLAAAALAAAAAAAALALA 482

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271093 [Multi-domain] Cd Length: 259 Bit Score: 146.69 E-value: 9.19e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV-PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd14191     4 YDIEERLGSGKFGQVFRLVEKKTKKVWAGKFFkAYSAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMVSG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDR-FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA--ADNALKIVDFGSAQPY-NPQALKPLgh 2377
Cdd:cd14191    84 GELFERIIDEdFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVnkTGTKIKLIDFGLARRLeNAGSLKVL-- 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 rTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLYPNTSQSATLFLRKVL 2456
Cdd:cd14191   162 -FGTPEFVAPEVINYEPIGYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDfDDEAFDEISDDAKDFISNLL 240

                         250
                  ....*....|....*....
gi 564369110 2457 SVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14191   241 KKDMKARLTCTQCLQHPWL 259

Serine/threonine protein kinase [Signal transduction mechanisms];

Pssm-ID: 440281 [Multi-domain] Cd Length: 482 Bit Score: 152.86 E-value: 9.63e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2222 PYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYA----AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:COG0515     8 RYRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPElaadPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYLVME 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGH 2377
Cdd:COG0515    88 YVEGESLADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGT 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRF-DAFQLYPNTSQSATLFLRKVL 2456
Cdd:COG0515   168 VVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPpPPSELRPDLPPALDAIVLRAL 247


                  ....*....
gi 564369110 2457 SVHPWSRPS 2465
Cdd:COG0515   248 AKDPEERYQ 256

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270993 [Multi-domain] Cd Length: 291 Bit Score: 147.01 E-value: 1.60e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVpyaAEGKRRVLQEYEVL-RTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd14091     2 YEIKEEIGKGSYSVCKRCIHKATGKEYAVKII---DKSKRDPSEEIEILlRYGQHPNIITLRDVYDDGNSVYLVTELLRG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAAD----NALKIVDFGSAqpynpqalKPLGH 2377
Cdd:cd14091    79 GELLDRILRQKFFSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNILYADEsgdpESLRICDFGFA--------KQLRA 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTG-------TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF-YEPD--PQETEARIVGGRFDAFQLYPNT-SQ 2446
Cdd:cd14091   151 ENGllmtpcyTANFVAPEVLKKQGYDAACDIWSLGVLLYTMLAGYTPFaSGPNdtPEVILARIGSGKIDLSGGNWDHvSD 230

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 2447 SATLFLRKVLSVHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd14091   231 SAKDLVRKMLHVDPSQRPTAAQVLQHPWIRN 261

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270987 [Multi-domain] Cd Length: 294 Bit Score: 146.89 E-value: 1.95e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKAsARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd14085     1 LEDFFEIESELGRGATSVVYRCRQKGTQKPYAVKKLKKTVDKKI-VRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLEL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgAGGEEQVRICDFGNAQELTPGEPQY 1025
Cdd:cd14085    80 VTGgELFDRIVEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYAT-PAPDAPLKIADFGLSKIVDQQVTMK 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEN-DRTTLMNIRNYNVAFEETTFLSLSREARGFLIK 1104
Cdd:cd14085   159 TVCGTPGYCAPEILRGCAYGPEVDMWSVGVITYILLCGFEPFYDERgDQYMFKRILNCDYDFVSPWWDDVSLNAKDLVKK 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 564369110 1105 VLVQD-RLRPTAEETLEHPWFKTEAKGA---EVSTDHLKLFLSRRR 1146
Cdd:cd14085   239 LIVLDpKKRLTTQQALQHPWVTGKAANFahmDTAQKKLQEFNARRK 284

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271070 [Multi-domain] Cd Length: 301 Bit Score: 146.73 E-value: 2.48e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA--KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14168     8 IKKIFEFKEVLGTGAFSEVVLAEERATGKLFAVKCIPKKAlkGKESSIENEIAVLRKIKHENIVALEDIYESPNHLYLVM 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgAGGEEQVRICDFGNAQELTPGEP 1023
Cdd:cd14168    88 QLVSGgELFDRIVEKGFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLYFS-QDEESKIMISDFGLSKMEGKGDV 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLI 1103
Cdd:cd14168   167 MSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDSKLFEQILKADYEFDSPYWDDISDSAKDFIR 246

                         250       260
                  ....*....|....*....|.
gi 564369110 1104 KVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14168   247 NLMEKDpNKRYTCEQALRHPW 267

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271068 [Multi-domain] Cd Length: 285 Bit Score: 145.91 E-value: 3.47e-38

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIP-SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE 949
Cdd:cd14166     5 FIFMEVLGSGAFSEVYLVKQRSTGKLYALKCIKkSPLSRDSSLENEIAVLKRIKHENIVTLEDIYESTTHYYLVMQLVSG 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 -ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgAGGEEQVRICDFGNAQELTPG-EPQYCq 1027
Cdd:cd14166    85 gELFDRILERGVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLYLT-PDENSKIMITDFGLSKMEQNGiMSTAC- 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 fGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLV 1107
Cdd:cd14166   163 -GTPGYVAPEVLAQKPYSKAVDCWSIGVITYILLCGYPPFYEETESRLFEKIKEGYYEFESPFWDDISESAKDFIRHLLE 241

                         250
                  ....*....|....*..
gi 564369110 1108 QD-RLRPTAEETLEHPW 1123
Cdd:cd14166   242 KNpSKRYTCEKALSHPW 258

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270987 [Multi-domain] Cd Length: 294 Bit Score: 143.43 E-value: 2.79e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEgKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14085     5 FEIESELGRGATSVVYRCRQKGTQKPYAVKKLKKTVD-KKIVRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLELVTGG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAA---DNALKIVDFGSAQPYNPQALkpLGHRT 2379
Cdd:cd14085    84 ELFDRIVEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYATpapDAPLKIADFGLSKIVDQQVT--MKTVC 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFY-EPDPQETEARIVGGRFDAFQ-LYPNTSQSATLFLRKVLS 2457
Cdd:cd14085   162 GTPGYCAPEILRGCAYGPEVDMWSVGVITYILLCGFEPFYdERGDQYMFKRILNCDYDFVSpWWDDVSLNAKDLVKKLIV 241

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 564369110 2458 VHPWSRPSLQDCLAHPWLQDAylmKLRRQTLTFTTNRLKEF 2498
Cdd:cd14085   242 LDPKKRLTTQQALQHPWVTGK---AANFAHMDTAQKKLQEF 279

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270783 [Multi-domain] Cd Length: 258 Bit Score: 142.27 E-value: 3.05e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSylrRVVE---RSSGLEFAAK--FIPSQAKPKASA-RREARLLARLQHD-CVLYFHEAFERRrGLVIVTELCTE 949
Cdd:cd06606     8 LGKGSFG---SVYLalnLDTGELMAVKevELSGDSEEELEAlEREIRILSSLKHPnIVRYLGTERTEN-TLNIFLEYVPG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 -ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNA---QELTPGEPQY 1025
Cdd:cd06606    84 gSLASLLKKFGKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANILV-DSDG---VVKLADFGCAkrlAEIATGEGTK 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMnirnYNVAF-EETTFL--SLSREARGFL 1102
Cdd:cd06606   160 SLRGTPYWMAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPWSELGNPVAAL----FKIGSsGEPPPIpeHLSEEAKDFL 235

                         250       260
                  ....*....|....*....|...
gi 564369110 1103 IKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd06606   236 RKCLQRDpKKRPTADELLQHPFL 258

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

Pssm-ID: 271001 [Multi-domain] Cd Length: 258 Bit Score: 141.92 E-value: 3.41e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQ----EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd14099    11 KGGFAKCYEVTDMSTGKVYAGKVVPKSSLTKPKQREklksEIKIHRSLKHPNIVKFHDCFEDEENVYILLELCSNGSLME 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQpynpqaLKPLGHRT----GT 2381
Cdd:cd14099    91 LLKRRKALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGlAAR------LEYDGERKktlcGT 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2382 LEFMAPEMVRGDpIGSAT--DIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFdAFQLYPNTSQSATLFLRKVLSVH 2459
Cdd:cd14099   165 PNYIAPEVLEKK-KGHSFevDIWSLGVILYTLLVGKPPFETSDVKETYKRIKKNEY-SFPSHLSISDEAKDLIRSMLQPD 242

                         250
                  ....*....|....*.
gi 564369110 2460 PWSRPSLQDCLAHPWL 2475
Cdd:cd14099   243 PTKRPSLDEILSHPFF 258

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271079 [Multi-domain] Cd Length: 295 Bit Score: 143.23 E-value: 3.75e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  866 RLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPsqaKPKASARREARLLARL-QHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14177     1 QFTDVYELKEDIGVGSYSVCKRCIHRATNMEFAVKIID---KSKRDPSEEIEILMRYgQHPNIITLKDVYDDGRYVYLVT 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELTpGE- 1022
Cdd:cd14177    78 ELMKGgELLDRILRQKFFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNILYMDDSANADSIRICDFGFAKQLR-GEn 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 -----PQYcqfgTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFV-GEND--RTTLMNIRNYNVAFEETTFLSL 1094
Cdd:cd14177   157 gllltPCY----TANFVAPEVLMRQGYDAACDIWSLGVLLYTMLAGYTPFAnGPNDtpEEILLRIGSGKFSLSGGNWDTV 232

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1095 SREARGFLIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14177   233 SDAAKDLLSHMLhVDPHQRYTAEQVLKHSW 262

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270692 [Multi-domain] Cd Length: 254 Bit Score: 141.57 E-value: 3.90e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIP-SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT 948
Cdd:cd05122     1 LFEILEKIGKGGFGVVYKARHKKTGQIVAIKKINlESKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 ----EELLErmARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPQ 1024
Cdd:cd05122    81 ggslKDLLK--NTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDG----EVKLIDFGLSAQLSDGKTR 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFvGENDRTTLMNIRNYNVA--FEETTFLSLsrEARGFL 1102
Cdd:cd05122   155 NTFVGTPYWMAPEVIQGKPYGFKADIWSLGITAIEMAEGKPPY-SELPPMKALFLIATNGPpgLRNPKKWSK--EFKDFL 231

                         250       260
                  ....*....|....*....|...
gi 564369110 1103 IKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd05122   232 KKCLQKDpEKRPTAEQLLKHPFI 254

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271133 [Multi-domain] Cd Length: 256 Bit Score: 141.77 E-value: 4.42e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVpyaaeGKRRVLQ---------EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14663    11 GTFAKVKFARNTKTGESVAIKII-----DKEQVARegmveqikrEIAIMKLLRHPNIVELHEVMATKTKIFFVMELVTGG 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPLGHRTGT 2381
Cdd:cd14663    86 ELFSKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGlSALSEQFRQDGLLHTTCGT 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2382 LEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqlYPN-TSQSATLFLRKVLSVH 2459
Cdd:cd14663   166 PNYVAPEVLARRGyDGAKADIWSCGVILFVLLAGYLPFDDENLMALYRKIMKGEFE----YPRwFSPGAKSLIKRILDPN 241

                         250
                  ....*....|....*
gi 564369110 2460 PWSRPSLQDCLAHPW 2474
Cdd:cd14663   242 PSTRITVEQIMASPW 256

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271087 [Multi-domain] Cd Length: 258 Bit Score: 141.24 E-value: 7.06e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAA-EGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLS 2309
Cdd:cd14185    11 GNFAVVKECRHWNENQEYAMKIIDKSKlKGKEDMIEsEILIIKSLSHPNIVKLFEVYETEKEIYLILEYVRGGDLFDAII 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAAD----NALKIVDFGSAQpynpQALKPLGHRTGTLEFM 2385
Cdd:cd14185    91 ESVKFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENLLVQHNpdksTTLKLADFGLAK----YVTGPIFTVCGTPTYV 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2386 APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETE--ARIVGGRFDAFQLY-PNTSQSATLFLRKVLSVHPWS 2462
Cdd:cd14185   167 APEILSEKGYGLEVDMWAAGVILYILLCGFPPFRSPERDQEElfQIIQLGHYEFLPPYwDNISEAAKDLISRLLVVDPEK 246

                         250
                  ....*....|..
gi 564369110 2463 RPSLQDCLAHPW 2474
Cdd:cd14185   247 RYTAKQVLQHPW 258

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271086 [Multi-domain] Cd Length: 259 Bit Score: 141.32 E-value: 7.18e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYA-AEGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLS 2309
Cdd:cd14184    12 GNFAVVKECVERSTGKEFALKIIDKAkCCGKEHLIEnEVSILRRVKHPNIIMLIEEMDTPAELYLVMELVKGGDLFDAIT 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA----ADNALKIVDFGSAQPYNpqalKPLGHRTGTLEFM 2385
Cdd:cd14184    92 SSTKYTERDASAMVYNLASALKYLHGLCIVHRDIKPENLLVCeypdGTKSLKLGDFGLATVVE----GPLYTVCGTPTYV 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2386 APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF-YEPDPQETE-ARIVGGRFDAFQLY-PNTSQSATLFLRKVLSVHPWS 2462
Cdd:cd14184   168 APEIIAETGYGLKVDIWAAGVITYILLCGFPPFrSENNLQEDLfDQILLGKLEFPSPYwDNITDSAKELISHMLQVNVEA 247

                         250
                  ....*....|..
gi 564369110 2463 RPSLQDCLAHPW 2474
Cdd:cd14184   248 RYTAEQILSHPW 259

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270855 [Multi-domain] Cd Length: 258 Bit Score: 140.68 E-value: 8.77e-37

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYA---AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd08215     2 YEKIRVIGKGSFGSAYLVRRKSDGKLYVLKEIDLSnmsEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 --GNrellcgLSDRFR--------YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynp 2369
Cdd:cd08215    82 dgGD------LAQKIKkqkkkgqpFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGIS----- 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 qalKPLGHRT-------GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFqlyP 2442
Cdd:cd08215   151 ---KVLESTTdlaktvvGTPYYLSPELCENKPYNYKSDIWALGCVLYELCTLKHPFEANNLPALVYKIVKGQYPPI---P 224

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 2443 NT-SQSATLFLRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd08215   225 SQySSELRDLVNSMLQKDPEKRPSANEILSSP 256

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271000 [Multi-domain] Cd Length: 265 Bit Score: 140.30 E-value: 1.65e-36

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVpyaaeGKRRVL----------QEYEVLRTLHHERLMSLHEAYITPRYL 2292
Cdd:cd14098     2 YQIIDRLGSGTFAEVKKAVEVETGKMRAIKQI-----VKRKVAgndknlqlfqREINILKSLEHPGIVRLIDWYEDDQHI 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA--LKIVDFGSAQPYNPQ 2370
Cdd:cd14098    77 YLVMEYVEGGDLMDFIMAWGAIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQDDPviVKISDFGLAKVIHTG 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 ALkpLGHRTGTLEFMAPEMVRG----DPIG--SATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYP-N 2443
Cdd:cd14098   157 TF--LVTFCGTMAYLAPEILMSkeqnLQGGysNLVDMWSVGCLVYVMLTGALPFDGSSQLPVEKRIRKGRYTQPPLVDfN 234

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 2444 TSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd14098   235 ISEEAIDFILRLLDVDPEKRMTAAQALDHPW 265

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271080 [Multi-domain] Cd Length: 293 Bit Score: 139.38 E-value: 6.63e-36

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPsqaKPKASARREARLLARL-QHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14178     1 FTDGYEIKEDIGIGSYSVCKRCVHKATSTEYAVKIID---KSKRDPSEEIEILLRYgQHPNIITLKDVYDDGKFVYLVME 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELTPGE-- 1022
Cdd:cd14178    78 LMRGgELLDRILRQKCFSEREASAVLCTITKTVEYLHSQGVVHRDLKPSNILYMDESGNPESIRICDFGFAKQLRAENgl 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 ---PQYcqfgTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRT---TLMNIRNYNVAFEETTFLSLSR 1096
Cdd:cd14178   158 lmtPCY----TANFVAPEVLKRQGYDAACDIWSLGILLYTMLAGFTPFANGPDDTpeeILARIGSGKYALSGGNWDSISD 233

                         250       260
                  ....*....|....*....|....*...
gi 564369110 1097 EARGFLIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14178   234 AAKDIVSKMLhVDPHQRLTAPQVLRHPW 261

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270983 [Multi-domain] Cd Length: 255 Bit Score: 138.16 E-value: 6.89e-36

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYE----VLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd14081    11 KGQTGLVKLAKHCVTGQKVAIKIVNKEKLSKESVLMKVEreiaIMKLIEHPNVLKLYDVYENKKYLYLVLEYVSGGELFD 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpqALKPLGHR----TGTL 2382
Cdd:cd14081    91 YLVKKGRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMA------SLQPEGSLletsCGSP 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMVRGDPI-GSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvggRFDAFQLYPNTSQSATLFLRKVLSVHPW 2461
Cdd:cd14081   165 HYACPEVIKGEKYdGRKADIWSCGVILYALLVGALPFDDDNLRQLLEKV---KRGVFHIPHFISPDAQDLLRRMLEVNPE 241

                         250
                  ....*....|....
gi 564369110 2462 SRPSLQDCLAHPWL 2475
Cdd:cd14081   242 KRITIEEIKKHPWF 255

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271083 [Multi-domain] Cd Length: 279 Bit Score: 138.95 E-value: 7.68e-36

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--------PSQAKP-KASARREARLLARLQ-HDCVLYFHEAFERRRGL 940
Cdd:cd14181    12 YDPKEVIGRGVSSVVRRCVHRHTGQEFAVKIIevtaerlsPEQLEEvRSSTLKEIHILRQVSgHPSIITLIDSYESSTFI 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELT 1019
Cdd:cd14181    92 FLVFDLMRRgELFDYLTEKVTLSEKETRSIMRSLLEAVSYLHANNIVHRDLKPENILLDD----QLHIKLSDFGFSCHLE 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCQFGTPEFVAPEIVNQS-----PVSGV-TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLS 1093
Cdd:cd14181   168 PGEKLRELCGTPGYLAPEILKCSmdethPGYGKeVDLWACGVILFTLLAGSPPFWHRRQMLMLRMIMEGRYQFSSPEWDD 247

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 1094 LSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14181   248 RSSTVKDLISRLLVVDpEIRLTAEQALQHPFF 279

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270732 [Multi-domain] Cd Length: 290 Bit Score: 138.87 E-value: 9.73e-36

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd05580     3 FEFLKTLGTGSFGRVRLVKHKDSGKYYALKILKKAKIIKLKqvehVLNEKRILSEVRHPFIVNLLGSFQDDRNLYMVMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpqalKPLGHR 2378
Cdd:cd05580    83 VPGGELFSLLRRSGRFPNDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFA--------KRVKDR 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 T----GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqlYPNT-SQSATLFLR 2453
Cdd:cd05580   155 TytlcGTPEYLAPEIILSKGHGKAVDWWALGILIYEMLAGYPPFFDENPMKIYEKILEGKIR----FPSFfDPDAKDLIK 230

                         250       260
                  ....*....|....*....|....*....
gi 564369110 2454 KVLSVHPWSR-----PSLQDCLAHPWLQD 2477
Cdd:cd05580   231 RLLVVDLTKRlgnlkNGVEDIKNHPWFAG 259

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271078 [Multi-domain] Cd Length: 339 Bit Score: 140.16 E-value: 1.10e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  862 HRGR-RLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPsqaKPKASARREARLLARL-QHDCVLYFHEAFERRRG 939
Cdd:cd14176    11 HRNSiQFTDGYEVKEDIGVGSYSVCKRCIHKATNMEFAVKIID---KSKRDPTEEIEILLRYgQHPNIITLKDVYDDGKY 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  940 LVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQEL 1018
Cdd:cd14176    88 VYVVTELMKGgELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYVDESGNPESIRICDFGFAKQL 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1019 TPGE-----PQYcqfgTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRT---TLMNIRNYNVAFEETT 1090
Cdd:cd14176   168 RAENgllmtPCY----TANFVAPEVLERQGYDAACDIWSLGVLLYTMLTGYTPFANGPDDTpeeILARIGSGKFSLSGGY 243

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 1091 FLSLSREARGFLIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14176   244 WNSVSDTAKDLVSKMLhVDPHQRLTAALVLRHPW 277

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270996 [Multi-domain] Cd Length: 300 Bit Score: 138.83 E-value: 1.20e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFA------AKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGL 940
Cdd:cd14094     1 FEDVYELCEVIGKGPFSVVRRCIHRETGQQFAvkivdvAKFTSSPGLSTEDLKREASICHMLKHPHIVELLETYSSDGML 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTE------LCTEeLLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgAGGEEQ--VRICDF 1012
Cdd:cd14094    81 YMVFEfmdgadLCFE-IVKRADAGFVYSEAVASHYMRQILEALRYCHDNNIIHRDVKPHCVLL---ASKENSapVKLGGF 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1013 GNAQELTPGEPQYC-QFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNyNVAFEETTF 1091
Cdd:cd14094   157 GVAIQLGESGLVAGgRVGTPHFMAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKG-KYKMNPRQW 235

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1092 LSLSREARGFLIKVLVQD-RLRPTAEETLEHPWFKTEAKGAEV-----STDHLKLFLSRRR 1146
Cdd:cd14094   236 SHISESAKDLVRRMLMLDpAERITVYEALNHPWIKERDRYAYRihlpeTVEQLRKFNARRK 296

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271071 [Multi-domain] Cd Length: 277 Bit Score: 138.10 E-value: 1.41e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA--KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT 948
Cdd:cd14169     5 YELKEKLGEGAFSEVVLAQERGSQRLVALKCIPKKAlrGKEAMVENEIAVLRRINHENIVSLEDIYESPTHLYLAMELVT 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 E-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLvWDGAGGEEQVRICDFGnAQELTPGEPQYCQ 1027
Cdd:cd14169    85 GgELFDRIIERGSYTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLL-YATPFEDSKIMISDFG-LSKIEAQGMLSTA 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLV 1107
Cdd:cd14169   163 CGTPGYVAPELLEQKPYGKAVDVWAIGVISYILLCGYPPFYDENDSELFNQILKAEYEFDSPYWDDISESAKDFIRHLLE 242

                         250
                  ....*....|....*..
gi 564369110 1108 QD-RLRPTAEETLEHPW 1123
Cdd:cd14169   243 RDpEKRFTCEQALQHPW 259

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270797 [Multi-domain] Cd Length: 254 Bit Score: 136.97 E-value: 1.56e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPK---ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd06627     2 YQLGDLIGRGAFGSVYKGLNLNTGEFVAIKQISLEKIPKsdlKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE----ELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEP 1023
Cdd:cd06627    82 ENgslaSIIKKFGKFP---ESLVAVYIYQVLEGLAYLHEQGVIHRDIKGANILT----TKDGLVKLADFGVATKLNEVEK 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQ-FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIrnynVAFEETTF-LSLSREARGF 1101
Cdd:cd06627   155 DENSvVGTPYWMAPEVIEMSGVTTASDIWSVGCTVIELLTGNPPYYDLQPMAALFRI----VQDDHPPLpENISPELRDF 230

                         250       260
                  ....*....|....*....|....
gi 564369110 1102 LIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd06627   231 LLQCFQKDpTLRPSAKELLKHPWL 254

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270986 [Multi-domain] Cd Length: 275 Bit Score: 137.52 E-value: 1.65e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2221 KPYTFLEEKARGRFGVVRSCRENATGRTFVAKIV---------PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRY 2291
Cdd:cd14084     6 KKYIMSRTLGSGACGEVKLAYDKSTCKKVAIKIInkrkftigsRREINKPRNIETEIEILKKLSHPCIIKIEDFFDAEDD 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2292 LVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA---LKIVDFGSAqpyn 2368
Cdd:cd14084    86 YYIVLELMEGGELFDRVVSNKRLKEAICKLYFYQMLLAVKYLHSNGIIHRDLKPENVLLSSQEEeclIKITDFGLS---- 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2369 pqalKPLGHRT------GTLEFMAPEMVR---GDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEA-RIVGGR--FD 2436
Cdd:cd14084   162 ----KILGETSlmktlcGTPTYLAPEVLRsfgTEGYTRAVDCWSLGVILFICLSGYPPFSEEYTQMSLKeQILSGKytFI 237

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 564369110 2437 AfQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14084   238 P-KAWKNVSEEAKDLVKKMLVVDPSRRPSIEEALEHPWL 275

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271068 [Multi-domain] Cd Length: 285 Bit Score: 137.82 E-value: 2.01e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2220 QKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd14166     2 RETFIFMEVLGSGAFSEVYLVKQRSTGKLYALKCIKKSPLSRDSSLEnEIAVLKRIKHENIVTLEDIYESTTHYYLVMQL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLL-LAADNALKIV--DFGSAQPYNPQALKPl 2375
Cdd:cd14166    82 VSGGELFDRILERGVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLyLTPDENSKIMitDFGLSKMEQNGIMST- 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 ghRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEpdpqETEAR----IVGGRFdAFQ--LYPNTSQSAT 2449
Cdd:cd14166   161 --ACGTPGYVAPEVLAQKPYSKAVDCWSIGVITYILLCGYPPFYE----ETESRlfekIKEGYY-EFEspFWDDISESAK 233

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2450 LFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14166   234 DFIRHLLEKNPSKRYTCEKALSHPWI 259

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270904 [Multi-domain] Cd Length: 253 Bit Score: 136.23 E-value: 2.70e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPK---ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14002     1 ENYHVLELIGEGSFGKVYKGRRKYTGQVVALKFIPKRGKSEkelRNLRQEIEILRKLNHPNIIEMLDSFETKKEFVVVTE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGeeQVRICDFGNAQELTpgepqy 1025
Cdd:cd14002    81 YAQGELFQILEDDGTLPEEEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILI--GKGG--VVKLCDFGFARAMS------ 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQF-------GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREA 1098
Cdd:cd14002   151 CNTlvltsikGTPLYMAPELVQEQPYDHTADLWSLGCILYELFVGQPPFYTNSIYQLVQMIVKDPVKWPSN----MSPEF 226

                         250       260
                  ....*....|....*....|....*
gi 564369110 1099 RGFLIKVLVQD-RLRPTAEETLEHP 1122
Cdd:cd14002   227 KSFLQGLLNKDpSKRLSWPDLLEHP 251

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270724 [Multi-domain] Cd Length: 262 Bit Score: 135.43 E-value: 6.43e-35

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELL 2305
Cdd:cd05572     2 GVGGFGRVELVQLKSKGRTFALKCVKKRHIVQTRqqehIFSEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLGGELW 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpqalKPL--GHRT---- 2379
Cdd:cd05572    82 TILRDRGLFDEYTARFYTACVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFA--------KKLgsGRKTwtfc 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEP--DPQETEARIVGGRFDAFqlYPN-TSQSATLFLRKVL 2456
Cdd:cd05572   154 GTPEYVAPEIILNKGYDFSVDYWSLGILLYELLTGRPPFGGDdeDPMKIYNIILKGIDKIE--FPKyIDKNAKNLIKQLL 231

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2457 SVHPWSR-----PSLQDCLAHPWLQD 2477
Cdd:cd05572   232 RRNPEERlgylkGGIRDIKKHKWFEG 257

Protein kinase domain;

Pssm-ID: 459660 [Multi-domain] Cd Length: 217 Bit Score: 133.14 E-value: 1.15e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIP-SQAKPK--ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:pfam00069    1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKkEKIKKKkdKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   948 -TEELLERMARKPTVCESETRTYMRQVLEGIgylhqshvlhldvkpenllvwdgaggEEQVRICDFgnaqeltpgepqyc 1026
Cdd:pfam00069   81 eGGSLFDLLSEKGAFSEREAKFIMKQILEGL--------------------------ESGSSLTTF-------------- 120

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  1027 qFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEtTFLSLSREARGFLIKVL 1106
Cdd:pfam00069  121 -VGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPE-LPSNLSEEAKDLLKKLL 198

                          250
                   ....*....|....*....
gi 564369110  1107 VQD-RLRPTAEETLEHPWF 1124
Cdd:pfam00069  199 KKDpSKRLTATQALQHPWF 217

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270797 [Multi-domain] Cd Length: 254 Bit Score: 133.50 E-value: 2.60e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRtFVA-KIVPYAAEGK---RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd06627     2 YQLGDLIGRGAFGSVYKGLNLNTGE-FVAiKQISLEKIPKsdlKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpyNPQALKPLGHR 2378
Cdd:cd06627    81 VENGSLASIIKKFGKFPESLVAVYIYQVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVAT--KLNEVEKDENS 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 T-GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggRFDAFQLYPNTSQSATLFLRKVLS 2457
Cdd:cd06627   159 VvGTPYWMAPEVIEMSGVTTASDIWSVGCTVIELLTGNPPYYDLQPMAALFRIV--QDDHPPLPENISPELRDFLLQCFQ 236

                         250
                  ....*....|....*...
gi 564369110 2458 VHPWSRPSLQDCLAHPWL 2475
Cdd:cd06627   237 KDPTLRPSAKELLKHPWL 254

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270994 [Multi-domain] Cd Length: 311 Bit Score: 135.12 E-value: 3.08e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVpyaaegKRRV--LQEYEVLRTLH-HERLMSLHEAYITP--RYLVLiaescgnrELLC 2306
Cdd:cd14092    17 GSFSVCRKCVHKKTGQEFAVKIV------SRRLdtSREVQLLRLCQgHPNIVKLHEVFQDElhTYLVM--------ELLR 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 G--LSDRFR----YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADN---ALKIVDFGSAQpYNPQAlKPLGH 2377
Cdd:cd14092    83 GgeLLERIRkkkrFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFTDEDddaEIKIVDFGFAR-LKPEN-QPLKT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGS----ATDIWGAGVLTYIMLSGYSPFYEPDPQETEA----RIVGGRFDaF--QLYPNTSQS 2447
Cdd:cd14092   161 PCFTLPYAAPEVLKQALSTQgydeSCDLWSLGVILYTMLSGQVPFQSPSRNESAAeimkRIKSGDFS-FdgEEWKNVSSE 239

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 2448 ATLFLRKVLSVHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd14092   240 AKSLIQGLLTVDPSKRLTMSELRNHPWLQGS 270

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270789 [Multi-domain] Cd Length: 255 Bit Score: 133.10 E-value: 4.15e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE--SCG 2300
Cdd:cd06614     2 YKNLEKIGEGASGEVYKATDRATGKEVAIKKMRLRKQNKELIINEILIMKECKHPNIVDYYDSYLVGDELWVVMEymDGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NrellcgLSD-----RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGsaqpYNPQALKPL 2375
Cdd:cd06614    82 S------LTDiitqnPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFG----FAAQLTKEK 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRT---GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFL 2452
Cdd:cd06614   152 SKRNsvvGTPYWMAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPPYLEEPPLRALFLITTKGIPPLKNPEKWSPEFKDFL 231

                         250       260
                  ....*....|....*....|....
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd06614   232 NKCLVKDPEKRPSAEELLQHPFLK 255

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270997 [Multi-domain] Cd Length: 258 Bit Score: 132.83 E-value: 4.93e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIpsqAKPKASARR-----EARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14095     2 YDIGRVIGDGNFAVVKECRDKATDKEYALKII---DKAKCKGKEhmienEVAILRRVKHPNIVQLIEEYDTDTELYLVME 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELTpgEPQ 1024
Cdd:cd14095    79 LVKGgDLFDAITSSTKFTERDASRMVTDLAQALKYLHSLSIVHRDIKPENLLVVEHEDGSKSLKLADFGLATEVK--EPL 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENdrttlmniRNYNVAFE-----ETTFLS-----L 1094
Cdd:cd14095   157 FTVCGTPTYVAPEILAETGYGLKVDIWAAGVITYILLCGFPPFRSPD--------RDQEELFDlilagEFEFLSpywdnI 228

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1095 SREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14095   229 SDSAKDLISRMLVVDpEKRYSAGQVLDHPW 258

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270980 [Multi-domain] Cd Length: 257 Bit Score: 132.51 E-value: 5.59e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2220 QKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKR--RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd14078     2 LKYYELHETIGSGGFAKVKLATHILTGEKVAIKIMDKKALGDDlpRVKTEIEALKNLSHQHICRLYHVIETDNKIFMVLE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpyNPQALKPLGH 2377
Cdd:cd14078    82 YCPGGELFDYIVAKDRLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLCA--KPKGGMDHHL 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RT--GTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAfqlyPN-TSQSATLFLR 2453
Cdd:cd14078   160 ETccGSPAYAAPELIQGKPyIGSEADVWSMGVLLYALLCGFLPFDDDNVMALYRKIQSGKYEE----PEwLSPSSKLLLD 235

                         250       260
                  ....*....|....*....|..
gi 564369110 2454 KVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14078   236 QMLQVDPKKRITVKELLNHPWV 257

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270733 [Multi-domain] Cd Length: 278 Bit Score: 133.11 E-value: 6.18e-34

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVpyaaeGKRRVLQ---------EYEVLRTLHHERLMSLHEAYITPRYLV 2293
Cdd:cd05581     3 FKFGKPLGEGSYSTVVLAKEKETGKEYAIKVL-----DKRHIIKekkvkyvtiEKEVLSRLAHPGIVKLYYTFQDESKLY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2294 LIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP---- 2369
Cdd:cd05581    78 FVLEYAPNGDLLEYIRKYGSLDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKVLGPdssp 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 --------QALKPLGHRT----GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDa 2437
Cdd:cd05581   158 estkgdadSQIAYNQARAasfvGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLEYE- 236

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 564369110 2438 fqlYP-NTSQSATLFLRKVLSVHPWSRPSLQDC------LAHPW 2474
Cdd:cd05581   237 ---FPeNFPPDAKDLIQKLLVLDPSKRLGVNENggydelKAHPF 277

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271077 [Multi-domain] Cd Length: 291 Bit Score: 132.07 E-value: 1.94e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPsqaKPKASARREARLLARL-QHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd14175     1 DGYVVKETIGVGSYSVCKRCVHKATNMEYAVKVID---KSKRDPSEEIEILLRYgQHPNIITLKDVYDDGKHVYLVTELM 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELTPGE---- 1022
Cdd:cd14175    78 RGgELLDKILRQKFFSEREASSVLHTICKTVEYLHSQGVVHRDLKPSNILYVDESGNPESLRICDFGFAKQLRAENgllm 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 -PQYcqfgTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFV---GENDRTTLMNIRNYNVAFEETTFLSLSREA 1098
Cdd:cd14175   158 tPCY----TANFVAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFAngpSDTPEEILTRIGSGKFTLSGGNWNTVSDAA 233

                         250       260
                  ....*....|....*....|....*.
gi 564369110 1099 RGFLIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14175   234 KDLVSKMLhVDPHQRLTAKQVLQHPW 259

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270971 [Multi-domain] Cd Length: 261 Bit Score: 130.91 E-value: 2.35e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2221 KPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK---RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd14069     1 EDWDLVQTLGEGAFGEVFLAVNRNTEEAVAVKFVDMKRAPGdcpENIKKEVCIQKMLSHKNVVRFYGHRREGEFQYLFLE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELL------CGLSdrfrysEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY-NPQ 2370
Cdd:cd14069    81 YASGGELFdkiepdVGMP------EDVAQFYFQQLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLATVFrYKG 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 ALKPLGHRTGTLEFMAPEMVRGDPI-GSATDIWGAGVLTYIMLSGYSPFYEPDP--QETEARIVGGRFDaFQLYPNTSQS 2447
Cdd:cd14069   155 KERLLNKMCGTLPYVAPELLAKKKYrAEPVDVWSCGIVLFAMLAGELPWDQPSDscQEYSDWKENKKTY-LTPWKKIDTA 233

                         250       260
                  ....*....|....*....|....*...
gi 564369110 2448 ATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14069   234 ALSLLRKILTENPNKRITIEDIKKHPWY 261

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271069 [Multi-domain] Cd Length: 263 Bit Score: 130.53 E-value: 3.52e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAA-EGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd14167     5 YDFREVLGTGAFSEVVLAEEKRTQKLVAIKCIAKKAlEGKETSIEnEIAVLHKIKHPNIVALDDIYESGGHLYLIMQLVS 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLL---LAADNALKIVDFGSAQPYNPQALkpLGH 2377
Cdd:cd14167    85 GGELFDRIVEKGFYTERDASKLIFQILDAVKYLHDMGIVHRDLKPENLLyysLDEDSKIMISDFGLSKIEGSGSV--MST 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLY-PNTSQSATLFLRKVL 2456
Cdd:cd14167   163 ACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDAKLFEQILKAEYEFDSPYwDDISDSAKDFIQHLM 242

                         250
                  ....*....|....*....
gi 564369110 2457 SVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14167   243 EKDPEKRFTCEQALQHPWI 261

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270994 [Multi-domain] Cd Length: 311 Bit Score: 131.65 E-value: 4.50e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDI-HQE--IGRGAFSYLRRVVERSSGLEFAAKfIPSQakpKASARREARLLARLQ-HDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd14092     5 YELdLREeaLGDGSFSVCRKCVHKKTGQEFAVK-IVSR---RLDTSREVQLLRLCQgHPNIVKLHEVFQDELHTYLVMEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CT-EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgAGGEEQVRICDFGNAQELTPGEPqy 1025
Cdd:cd14092    81 LRgGELLERIRKKKRFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFTD-EDDDAEIKIVDFGFARLKPENQP-- 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 cqFGTPEFV----APEIVNQS-PVSGVT---DIWPVGVVAFLCLTGISPFV---GENDRTTLMN-IRNYNVAFEETTFLS 1093
Cdd:cd14092   158 --LKTPCFTlpyaAPEVLKQAlSTQGYDescDLWSLGVILYTMLSGQVPFQspsRNESAAEIMKrIKSGDFSFDGEEWKN 235

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 564369110 1094 LSREARGfLIKVLV----QDRLrpTAEETLEHPWFKTEAK 1129
Cdd:cd14092   236 VSSEAKS-LIQGLLtvdpSKRL--TMSELRNHPWLQGSSS 272

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271070 [Multi-domain] Cd Length: 301 Bit Score: 130.55 E-value: 9.18e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2220 QKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAA-EGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd14168     9 KKIFEFKEVLGTGAFSEVVLAEERATGKLFAVKCIPKKAlKGKESSIEnEIAVLRKIKHENIVALEDIYESPNHLYLVMQ 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLL-LAADNALKIV--DFGSAQPYNPQALkp 2374
Cdd:cd14168    89 LVSGGELFDRIVEKGFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLyFSQDEESKIMisDFGLSKMEGKGDV-- 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGG--RFDAfQLYPNTSQSATLFL 2452
Cdd:cd14168   167 MSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDSKLFEQILKAdyEFDS-PYWDDISDSAKDFI 245

                         250       260
                  ....*....|....*....|...
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14168   246 RNLMEKDPNKRYTCEQALRHPWI 268

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271018 [Multi-domain] Cd Length: 258 Bit Score: 129.31 E-value: 9.96e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYA----AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd14116    15 KGKFGNVYLAREKQSKFILALKVLFKAqlekAGVEHQLRREVEIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGTVYR 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGsaqpYNPQAlkPLGHRT---GTLE 2383
Cdd:cd14116    95 ELQKLSKFDEQRTATYITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFG----WSVHA--PSSRRTtlcGTLD 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2384 FMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvgGRFDaFQLYPNTSQSATLFLRKVLSVHPWSR 2463
Cdd:cd14116   169 YLPPEMIEGRMHDEKVDLWSLGVLCYEFLVGKPPFEANTYQETYKRI--SRVE-FTFPDFVTEGARDLISRLLKHNPSQR 245

                         250
                  ....*....|..
gi 564369110 2464 PSLQDCLAHPWL 2475
Cdd:cd14116   246 PMLREVLEHPWI 257

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270995 [Multi-domain] Cd Length: 272 Bit Score: 129.40 E-value: 1.04e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2222 PYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEG---------KRRVLQEYEVLRTLH-HERLMSLHEAYITPRY 2291
Cdd:cd14093     4 KYEPKEILGRGVSSTVRRCIEKETGQEFAVKIIDITGEKsseneaeelREATRREIEILRQVSgHPNIIELHDVFESPTF 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2292 LVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP-Q 2370
Cdd:cd14093    84 IFLVFELCRKGELFDYLTEVVTLSEKKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFATRLDEgE 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 ALKPLghrTGTLEFMAPEMVR-----GDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGR--FDAFQlYP 2442
Cdd:cd14093   164 KLREL---CGTPGYLAPEVLKcsmydNAPgYGKEVDMWACGVIMYTLLAGCPPFWHRKQMVMLRNIMEGKyeFGSPE-WD 239

                         250       260       270
                  ....*....|....*....|....*....|...
gi 564369110 2443 NTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14093   240 DISDTAKDLISKLLVVDPKKRLTAEEALEHPFF 272

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271000 [Multi-domain] Cd Length: 265 Bit Score: 129.13 E-value: 1.12e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIpSQAKPKASAR------REARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14098     2 YQIIDRLGSGTFAEVKKAVEVETGKMRAIKQI-VKRKVAGNDKnlqlfqREINILKSLEHPGIVRLIDWYEDDQHIYLVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaGGEEQVRICDFGNAQELTPGEP 1023
Cdd:cd14098    81 EYVEGgDLMDFIMAWGAIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQ--DDPVIVKISDFGLAKVIHTGTF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPV------SGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSRE 1097
Cdd:cd14098   159 LVTFCGTMAYLAPEILMSKEQnlqggySNLVDMWSVGCLVYVMLTGALPFDGSSQLPVEKRIRKGRYTQPPLVDFNISEE 238

                         250       260
                  ....*....|....*....|....*..
gi 564369110 1098 ARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14098   239 AIDFILRLLDVDpEKRMTAAQALDHPW 265

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 122.60 E-value: 1.29e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  334 PLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNE-SENLRLRQDGGLHSLHIARVGSEDEGLYEVSATNTH 412
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPdSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 564369110  413 GQAHCSAQLYV 423
Cdd:cd05744    81 GENSFNAELVV 91

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270910 [Multi-domain] Cd Length: 267 Bit Score: 128.44 E-value: 2.13e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFI-----------PSQAKPKASA----RREARLLARLQHDCVLYFHEAFE--RRRG 939
Cdd:cd14008     1 LGRGSFGKVKLALDTETGQLYAIKIFnksrlrkrregKNDRGKIKNAlddvRREIAIMKKLDHPNIVRLYEVIDdpESDK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  940 LVIVTELCteELLERMARKPTVC-----ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGN 1014
Cdd:cd14008    81 LYLVLEYC--EGGPVMELDSGDRvpplpEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLL----TADGTVKISDFGV 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1015 AQELTPGePQYCQF--GTPEFVAPEI--VNQSPVSG-VTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEET 1089
Cdd:cd14008   155 SEMFEDG-NDTLQKtaGTPAFLAPELcdGDSKTYSGkAADIWALGVTLYCLVFGRLPFNGDNILELYEAIQNQNDEFPIP 233

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 1090 TflSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14008   234 P--ELSPELKDLLRRMLEKDpEKRITLKEIKEHPWV 267

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132954 [Multi-domain] Cd Length: 264 Bit Score: 128.09 E-value: 2.17e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYA--AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE--SCGNrellc 2306
Cdd:cd06623    11 QGSSGVVYKVRHKPTGKIYALKKIHVDgdEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEymDGGS----- 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 gLSDRFRY----SEDDVATYVVQLLQGLDYLHG-RHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQAlkplGHRT- 2379
Cdd:cd06623    86 -LADLLKKvgkiPEPVLAYIARQILKGLDYLHTkRHIIHRDIKPSNLLINSKGEVKIADFGiSKVLENTLD----QCNTf 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 -GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFY---EPDPQETEARIVGGrfDAFQLYPNT-SQSATLFLRK 2454
Cdd:cd06623   161 vGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFLppgQPSFFELMQAICDG--PPPSLPAEEfSPEFRDFISA 238

                         250       260
                  ....*....|....*....|..
gi 564369110 2455 VLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd06623   239 CLQKDPKKRPSAAELLQHPFIK 260

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270999 [Multi-domain] Cd Length: 266 Bit Score: 128.05 E-value: 3.14e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIpsqAKPKASA------RREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14097     3 YTFGRKLGQGSFGVVIEATHKETQTKWAIKKI---NREKAGSsavkllEREVDILKHVNHAHIIHLEEVFETPKRMYLVM 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEE---QVRICDFGNA-QELT 1019
Cdd:cd14097    80 ELCEDgELKELLLRKGFFSENETRHIIQSLASAVAYLHKNDIVHRDLKLENILVKSSIIDNNdklNIKVTDFGLSvQKYG 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQY---CqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSR 1096
Cdd:cd14097   160 LGEDMLqetC--GTPIYMAPEVISAHGYSQQCDIWSIGVIMYMLLCGEPPFVAKSEEKLFEEIRKGDLTFTQSVWQSVSD 237

                         250       260
                  ....*....|....*....|....*...
gi 564369110 1097 EARGFLIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14097   238 AAKNVLQQLLkVDPAHRMTASELLDNPW 265

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270731 [Multi-domain] Cd Length: 272 Bit Score: 127.72 E-value: 4.27e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFS--YLRRvvERSSGLEFAAKFIPsqakpKASARR---------EARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd05579     1 ISRGAYGrvYLAK--KKSTGDLYAIKVIK-----KRDMIRknqvdsvlaERNILSQAQNPFVVKLYYSFQGKKNLYLVME 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LC----TEELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFG-------- 1013
Cdd:cd05579    74 YLpggdLYSLLENVGALD---EDVARIYIAEIVLALEYLHSHGIIHRDLKPDNILI-DANG---HLKLTDFGlskvglvr 146

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1014 -------NAQELTPGEPQYCQ-FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVA 1085
Cdd:cd05579   147 rqiklsiQKKSNGAPEKEDRRiVGTPDYLAPEILLGQGHGKTVDWWSLGVILYEFLVGIPPFHAETPEEIFQNILNGKIE 226

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 564369110 1086 FEEttFLSLSREARGFLIKVLVQD---RLRPT-AEETLEHPWFK 1125
Cdd:cd05579   227 WPE--DPEVSDEAKDLISKLLTPDpekRLGAKgIEEIKNHPFFK 268

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271086 [Multi-domain] Cd Length: 259 Bit Score: 127.07 E-value: 5.34e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPsqaKPKASARR-----EARLLARLQHDCVLYFHEAFERRRGLVIV 943
Cdd:cd14184     1 EKYKIGKVIGDGNFAVVKECVERSTGKEFALKIID---KAKCCGKEhlienEVSILRRVKHPNIIMLIEEMDTPAELYLV 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQeLTPGe 1022
Cdd:cd14184    78 MELVKGgDLFDAITSSTKYTERDASAMVYNLASALKYLHGLCIVHRDIKPENLLVCEYPDGTKSLKLGDFGLAT-VVEG- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEND--RTTLMNIRNYNVAFEETTFLSLSREARG 1100
Cdd:cd14184   156 PLYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENNlqEDLFDQILLGKLEFPSPYWDNITDSAKE 235

                         250       260
                  ....*....|....*....|....
gi 564369110 1101 FLIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14184   236 LISHMLqVNVEARYTAEQILSHPW 259

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.

Pssm-ID: 270693 [Multi-domain] Cd Length: 250 Bit Score: 126.48 E-value: 7.00e-32

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIP----SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC-TEEL 951
Cdd:cd05123     1 LGKGSFGKVLLVRKKDTGKLYAMKVLRkkeiIKRKEVEHTLNERNILERVNHPFIVKLHYAFQTEEKLYLVLDYVpGGEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQF-GT 1030
Cdd:cd05123    81 FSHLSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILL-DSDG---HIKLTDFGLAKELSSDGDRTYTFcGT 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1031 PEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREARGFLIKVLVQD- 1109
Cdd:cd05123   157 PEYLAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKILKSPLKFPE----YVSPEAKSLISGLLQKDp 232

                         250
                  ....*....|....*...
gi 564369110 1110 --RL-RPTAEETLEHPWF 1124
Cdd:cd05123   233 tkRLgSGGAEEIKAHPFF 250

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270979 [Multi-domain] Cd Length: 267 Bit Score: 126.41 E-value: 1.10e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKR----------------RVLQEYEVLRTLHHERLMSLHEAY 2286
Cdd:cd14077     3 WEFVKTIGAGSMGKVKLAKHIRTGEKCAIKIIPRASNAGLkkerekrlekeisrdiRTIREAALSSLLNHPHICRLRDFL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2287 ITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQP 2366
Cdd:cd14077    83 RTPNHYYMLFEYVDGGQLLDYIISHGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLSNL 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2367 YNPQALkpLGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqlYPNT- 2444
Cdd:cd14077   163 YDPRRL--LRTFCGSLYFAAPELLQAQPyTGPEVDVWSFGVVLYVLVCGKVPFDDENMPALHAKIKKGKVE----YPSYl 236

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 2445 SQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14077   237 SSECKSLISRMLVVDPKKRATLEQVLNHPWM 267

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270731 [Multi-domain] Cd Length: 272 Bit Score: 126.18 E-value: 1.28e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYA-AEGKR---RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd05579     3 RGAYGRVYLAKKKSTGDLYAIKVIKKRdMIRKNqvdSVLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDLYS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 gLSDRFRYSEDDVAT-YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG--------------SAQPYNPQA 2371
Cdd:cd05579    83 -LLENVGALDEDVARiYIAEIVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGlskvglvrrqiklsIQKKSNGAP 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 LKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFdAFQLYPNTSQSATLF 2451
Cdd:cd05579   162 EKEDRRIVGTPDYLAPEILLGQGHGKTVDWWSLGVILYEFLVGIPPFHAETPEEIFQNILNGKI-EWPEDPEVSDEAKDL 240

                         250       260
                  ....*....|....*....|....*....
gi 564369110 2452 LRKVLSVHPWSRP---SLQDCLAHPWLQD 2477
Cdd:cd05579   241 ISKLLTPDPEKRLgakGIEEIKNHPFFKG 269

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270827 [Multi-domain] Cd Length: 288 Bit Score: 126.66 E-value: 1.35e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRtFVA----KIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd07833     3 YEVLGVVGEGAYGVVLKCRNKATGE-IVAikkfKESEDDEDVKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNR--ELLcglsDRFRY--SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKP 2374
Cdd:cd07833    82 VERTllELL----EASPGglPPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTARPASP 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFyeP------------------DPQETE-----ARI 2430
Cdd:cd07833   158 LTDYVATRWYRAPELLVGDTnYGKPVDVWAIGCIMAELLDGEPLF--PgdsdidqlyliqkclgplPPSHQElfssnPRF 235

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 2431 VGGRFDAF-------QLYPNTSQSATL-FLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07833   236 AGVAFPEPsqpesleRRYPGKVSSPALdFLKACLRMDPKERLTCDELLQHPYF 288

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270911 [Multi-domain] Cd Length: 251 Bit Score: 125.41 E-value: 1.37e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRV---LQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCG 2307
Cdd:cd14009     3 RGSFATVWKGRHKQTGEVVAIKEISRKKLNKKLQenlESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLSQY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 LSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA---LKIVDFGSAQPYNPQALK------PLghr 2378
Cdd:cd14009    83 IRKRGRLPEAVARHFMQQLASGLKFLRSKNIIHRDLKPQNLLLSTSGDdpvLKIADFGFARSLQPASMAetlcgsPL--- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 tgtleFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV-GGRFDAFQLYPNTSQSATLFLRKVLS 2457
Cdd:cd14009   160 -----YMAPEILQFQKYDAKADLWSVGAILFEMLVGKPPFRGSNHVQLLRNIErSDAVIPFPIAAQLSPDCKDLLRRLLR 234

                         250
                  ....*....|....*..
gi 564369110 2458 VHPWSRPSLQDCLAHPW 2474
Cdd:cd14009   235 RDPAERISFEEFFAHPF 251

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270989 [Multi-domain] Cd Length: 259 Bit Score: 125.34 E-value: 2.04e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSD 2310
Cdd:cd14087    11 RGSFSRVVRVEHRVTRQPYAIKMIETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGGELFDRIIA 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2311 RFRYSEDDvATYVVQ-LLQGLDYLHGRHVLHLDIKPDNLLLA---ADNALKIVDFG--SAQPYNPQALkpLGHRTGTLEF 2384
Cdd:cd14087    91 KGSFTERD-ATRVLQmVLDGVKYLHGLGITHRDLKPENLLYYhpgPDSKIMITDFGlaSTRKKGPNCL--MKTTCGTPEY 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2385 MAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLYPNTSQSATLFLRKVLSVHPWSR 2463
Cdd:cd14087   168 IAPEILLRKPYTQSVDMWAVGVIAYILLSGTMPFDDDNRTRLYRQILRAKYSySGEPWPSVSNLAKDFIDRLLTVNPGER 247

                         250
                  ....*....|..
gi 564369110 2464 PSLQDCLAHPWL 2475
Cdd:cd14087   248 LSATQALKHPWI 259

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271085 [Multi-domain] Cd Length: 268 Bit Score: 125.11 E-value: 2.92e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYA-AEGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLS 2309
Cdd:cd14183    17 GNFAVVKECVERSTGREYALKIINKSkCRGKEHMIQnEVSILRRVKHPNIVLLIEEMDMPTELYLVMELVKGGDLFDAIT 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLL----AADNALKIVDFGSAQPYNpqalKPLGHRTGTLEFM 2385
Cdd:cd14183    97 STNKYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVyehqDGSKSLKLGDFGLATVVD----GPLYTVCGTPTYV 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2386 APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFY-EPDPQETE-ARIVGGRFD-AFQLYPNTSQSATLFLRKVLSVHPWS 2462
Cdd:cd14183   173 APEIIAETGYGLKVDIWAAGVITYILLCGFPPFRgSGDDQEVLfDQILMGQVDfPSPYWDNVSDSAKELITMMLQVDVDQ 252

                         250
                  ....*....|....*
gi 564369110 2463 RPSLQDCLAHPWLQD 2477
Cdd:cd14183   253 RYSALQVLEHPWVND 267

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271133 [Multi-domain] Cd Length: 256 Bit Score: 124.44 E-value: 3.56e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASA----RREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd14663     2 YELGRTLGEGTFAKVKFARNTKTGESVAIKIIDKEQVAREGMveqiKREIAIMKLLRHPNIVELHEVMATKTKIFFVMEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFG---NAQELTPGE 1022
Cdd:cd14663    82 VTGgELFSKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLL-DEDG---NLKISDFGlsaLSEQFRQDG 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQFGTPEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFVGENdrttLMNI--RNYNVAFEETTFlsLSREAR 1099
Cdd:cd14663   158 LLHTTCGTPNYVAPEVLARRGYDGAkADIWSCGVILFVLLAGYLPFDDEN----LMALyrKIMKGEFEYPRW--FSPGAK 231

                         250       260
                  ....*....|....*....|....*
gi 564369110 1100 GFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14663   232 SLIKRILDPNpSTRITVEQIMASPW 256

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270975 [Multi-domain] Cd Length: 254 Bit Score: 124.42 E-value: 4.22e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPsQAKPKASA-----RREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14073     3 YELLETLGKGTYGKVKLAIERATGREVAIKSIK-KDKIEDEQdmvriRREIEIMSSLNHPHIIRIYEVFENKDKIVIVME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGE-- 1022
Cdd:cd14073    82 YASGgELYDYISERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILL-DQNG---NAKIADFGLSNLYSKDKll 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCqfGTPEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRnyNVAFEETTFLSlsrEARGf 1101
Cdd:cd14073   158 QTFC--GSPLYASPEIVNGTPYQGPeVDCWSLGVLLYTLVYGTMPFDGSDFKRLVKQIS--SGDYREPTQPS---DASG- 229

                         250       260
                  ....*....|....*....|....
gi 564369110 1102 LIKVL--VQDRLRPTAEETLEHPW 1123
Cdd:cd14073   230 LIRWMltVNPKRRATIEDIANHWW 253

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270725 [Multi-domain] Cd Length: 350 Bit Score: 127.02 E-value: 4.37e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVpyaaeGKRRVLQ---------EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd05573    10 GRGAFGEVWLVRDKDTGQVYAMKIL-----RKSDMLKreqiahvraERDILADADSPWIVRLHYAFQDEDHLYLVMEYMP 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA--------------QP 2366
Cdd:cd05573    85 GGDLMNLLIKYDVFPEETARFYIAELVLALDSLHKLGFIHRDIKPDNILLDADGHIKLADFGLCtkmnksgdresylnDS 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2367 YNPQALKPLGHRT--------------GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVG 2432
Cdd:cd05573   165 VNTLFQDNVLARRrphkqrrvraysavGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGFPPFYSDSLVETYSKIMN 244

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2433 GRFD-AFQLYPNTSQSATLFLRKVLsVHPWSR-PSLQDCLAHPWLQDAYLMKLRRQT 2487
Cdd:cd05573   245 WKESlVFPDDPDVSPEAIDLIRRLL-CDPEDRlGSAEEIKAHPFFKGIDWENLRESP 300

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270688 [Multi-domain] Cd Length: 249 Bit Score: 123.50 E-value: 7.53e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRtFVA-KIV---PYAAEGKRRVLQEYEVLRTLH-HERLMSLHEAY--ITPRYLVLI 2295
Cdd:cd05118     1 YEVLRKIGEGAFGTVWLARDKVTGE-KVAiKKIkndFRHPKAALREIKLLKHLNDVEgHPNIVKLLDVFehRGGNHLCLV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGnrELLCGLSDRF--RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADN-ALKIVDFGSAQPYNPQal 2372
Cdd:cd05118    80 FELMG--MNLYELIKDYprGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELgQLKLADFGLARSFTSP-- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2373 kPLGHRTGTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVG--GRFDAFQLypntsqsat 2449
Cdd:cd05118   156 -PYTPYVATRWYRAPEvLLGAKPYGSSIDIWSLGCILAELLTGRPLFPGDSEVDQLAKIVRllGTPEALDL--------- 225

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2450 lfLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd05118   226 --LSKMLKYDPAKRITASQALAHPYF 249

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270733 [Multi-domain] Cd Length: 278 Bit Score: 124.25 E-value: 8.00e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAK-----FIPSQAKPKaSARREARLLARLQHDCV--LYFHeaFERRRGLVIV 943
Cdd:cd05581     3 FKFGKPLGEGSYSTVVLAKEKETGKEYAIKvldkrHIIKEKKVK-YVTIEKEVLSRLAHPGIvkLYYT--FQDESKLYFV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTP-- 1020
Cdd:cd05581    80 LEYAPNgDLLEYIRKYGSLDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILL----DEDMHIKITDFGTAKVLGPds 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 ------------GEPQYCQ---F-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNV 1084
Cdd:cd05581   156 spestkgdadsqIAYNQARaasFvGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLEY 235

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 1085 AFEEttflSLSREARGFLIKVLV---QDRL----RPTAEETLEHPWF 1124
Cdd:cd05581   236 EFPE----NFPPDAKDLIQKLLVldpSKRLgvneNGGYDELKAHPFF 278

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271088 [Multi-domain] Cd Length: 256 Bit Score: 123.43 E-value: 8.76e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKAS----ARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd14186     3 FKVLNLLGKGSFACVYRARSLHTGLEVAIKMIDKKAMQKAGmvqrVRNEVEIHCQLKHPSILELYNYFEDSNYVYLVLEM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTEELLERMA--RKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELT-PGEP 1023
Cdd:cd14186    83 CHNGEMSRYLknRKKPFTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLL----TRNMNIKIADFGLATQLKmPHEK 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFvgenDRTTLMNIRNYNVAFEETTFLSLSREARGFLI 1103
Cdd:cd14186   159 HFTMCGTPNYISPEIATRSAHGLESDVWSLGCMFYTLLVGRPPF----DTDTVKNTLNKVVLADYEMPAFLSREAQDLIH 234

                         250       260
                  ....*....|....*....|.
gi 564369110 1104 KVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14186   235 QLLRKNpADRLSLSSVLDHPF 255

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270857 [Multi-domain] Cd Length: 265 Bit Score: 123.42 E-value: 1.10e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAA--EGKRRVL-QEYEVLRTLHHERLMSLHEAYITPR----YLVLi 2295
Cdd:cd08217     2 YEVLETIGKGSFGTVRKVRRKSDGKILVWKEIDYGKmsEKEKQQLvSEVNILRELKHPNIVRYYDRIVDRAnttlYIVM- 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 aESCGNREL-----LCgLSDRFRYSEDDVATYVVQLLQGLDYLHGRH-----VLHLDIKPDNLLLAADNALKIVDFGSAq 2365
Cdd:cd08217    81 -EYCEGGDLaqlikKC-KKENQYIPEEFIWKIFTQLLLALYECHNRSvgggkILHRDLKPANIFLDSDNNVKLGDFGLA- 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2366 pynpqalKPLGHRT-------GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAF 2438
Cdd:cd08217   158 -------RVLSHDSsfaktyvGTPYYMSPELLNEQSYDEKSDIWSLGCLIYELCALHPPFQAANQLELAKKIKEGKFPRI 230

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 2439 qlyPNT-SQSATLFLRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd08217   231 ---PSRySSELNEVIKSMLNVDPDKRPSVEELLQLP 263

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270976 [Multi-domain] Cd Length: 258 Bit Score: 122.52 E-value: 1.97e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV---PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAEsc 2299
Cdd:cd14074     5 YDLEETLGRGHFAVVKLARHVFTGEKVAVKVIdktKLDDVSKAHLFQEVRCMKLVQHPNVVRLYEVIDTQTKLYLILE-- 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 gnrelLCGLSDRFRY--------SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNAL-KIVDFGSAQPYNPQ 2370
Cdd:cd14074    83 -----LGDGGDMYDYimkhenglNEDLARKYFRQIVSAISYCHKLHVVHRDLKPENVVFFEKQGLvKLTDFGFSNKFQPG 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 alKPLGHRTGTLEFMAPEMVRGDPI-GSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqLYPNTSQSAT 2449
Cdd:cd14074   158 --EKLETSCGSLAYSAPEILLGDEYdAPAVDIWSLGVILYMLVCGQPPFQEANDSETLTMIMDCKYT---VPAHVSPECK 232

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2450 LFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14074   233 DLIRRMLIRDPKKRASLEEIENHPWL 258

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270730 [Multi-domain] Cd Length: 257 Bit Score: 121.98 E-value: 2.85e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAY--ITPRYLVLiaescgnrEL 2304
Cdd:cd05578    10 KGSFGKVCIVQKKDTKKMFAMKYMNKQKCIEKDsvrnVLNELEILQELEHPFLVNLWYSFqdEEDMYMVV--------DL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 LCG------LSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALkpLGHR 2378
Cdd:cd05578    82 LLGgdlryhLQQKVKFSEETVKFYICEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKLTDGTL--ATST 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEArIVGGRFDAFQLYPNT-SQSATLFLRKVLS 2457
Cdd:cd05578   160 SGTKPYMAPEVFMRAGYSFAVDWWSLGVTAYEMLRGKRPYEIHSRTSIEE-IRAKFETASVLYPAGwSEEAIDLINKLLE 238

                         250
                  ....*....|....*....
gi 564369110 2458 VHPWSRPS-LQDCLAHPWL 2475
Cdd:cd05578   239 RDPQKRLGdLSDLKNHPYF 257

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270971 [Multi-domain] Cd Length: 261 Bit Score: 121.67 E-value: 4.52e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd14069     3 WDLVQTLGEGAFGEVFLAVNRNTEEAVAVKFVDMKRAPGDCPENikkEVCIQKMLSHKNVVRFYGHRREGEFQYLFLEYA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNA---------QE 1017
Cdd:cd14069    83 SGgELFDKIEPDVGMPEDVAQFYFQQLMAGLKYLHSCGITHRDIKPENLLL----DENDNLKISDFGLAtvfrykgkeRL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1018 LTPgepqycQFGTPEFVAPEIVNQSPVSG-VTDIWPVGVVAFLCLTGISPFVGENDRTTL-MNIRNyNVAFEETTFLSLS 1095
Cdd:cd14069   159 LNK------MCGTLPYVAPELLAKKKYRAePVDVWSCGIVLFAMLAGELPWDQPSDSCQEySDWKE-NKKTYLTPWKKID 231

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1096 REARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14069   232 TAALSLLRKILTENpNKRITIEDIKKHPWY 261

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270904 [Multi-domain] Cd Length: 253 Bit Score: 121.20 E-value: 5.24e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVL---QEYEVLRTLHHERLMSLHEAYITPRYLVLIAESc 2299
Cdd:cd14002     3 YHVLELIGEGSFGKVYKGRRKYTGQVVALKFIPKRGKSEKELRnlrQEIEILRKLNHPNIIEMLDSFETKKEFVVVTEY- 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ--PYNPQALKPLgh 2377
Cdd:cd14002    82 AQGELFQILEDDGTLPEEEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARamSCNTLVLTSI-- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 rTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGgrfDAFQLYPNTSQSATLFLRKVLS 2457
Cdd:cd14002   160 -KGTPLYMAPELVQEQPYDHTADLWSLGCILYELFVGQPPFYTNSIYQLVQMIVK---DPVKWPSNMSPEFKSFLQGLLN 235

                         250
                  ....*....|....*...
gi 564369110 2458 VHPWSRPSLQDCLAHPWL 2475
Cdd:cd14002   236 KDPSKRLSWPDLLEHPFV 253

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271078 [Multi-domain] Cd Length: 339 Bit Score: 123.21 E-value: 8.16e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyaaEGKRRVLQEYEVL-RTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd14176    21 YEVKEDIGVGSYSVCKRCIHKATNMEFAVKIID---KSKRDPTEEIEILlRYGQHPNIITLKDVYDDGKYVYVVTELMKG 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADN----ALKIVDFGSAQPY---NPQALKP 2374
Cdd:cd14176    98 GELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYVDESgnpeSIRICDFGFAKQLraeNGLLMTP 177

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 lghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFY---EPDPQETEARIVGGRFDAFQLYPNT-SQSATL 2450
Cdd:cd14176   178 ----CYTANFVAPEVLERQGYDAACDIWSLGVLLYTMLTGYTPFAngpDDTPEEILARIGSGKFSLSGGYWNSvSDTAKD 253

                         250       260
                  ....*....|....*....|....*
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14176   254 LVSKMLHVDPHQRLTAALVLRHPWI 278

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271085 [Multi-domain] Cd Length: 268 Bit Score: 120.87 E-value: 9.03e-30

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI-PSQAKPKASA-RREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14183     4 ISERYKVGRTIGDGNFAVVKECVERSTGREYALKIInKSKCRGKEHMiQNEVSILRRVKHPNIVLLIEEMDMPTELYLVM 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQeLTPGeP 1023
Cdd:cd14183    84 ELVKGgDLFDAITSTNKYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVYEHQDGSKSLKLGDFGLAT-VVDG-P 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLM--NIRNYNVAFEETTFLSLSREARGF 1101
Cdd:cd14183   162 LYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRGSGDDQEVLfdQILMGQVDFPSPYWDNVSDSAKEL 241

                         250       260
                  ....*....|....*....|...
gi 564369110 1102 LIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14183   242 ITMMLQVDvDQRYSALQVLEHPW 264

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270998 [Multi-domain] Cd Length: 295 Bit Score: 121.39 E-value: 1.00e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVV-ERSSGLEFAAKFIP--------SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLV 941
Cdd:cd14096     3 YRLINKIGEGAFSNVYKAVpLRNTGKPVAIKVVRkadlssdnLKGSSRANILKEVQIMKRLSHPNIVKLLDFQESDEYYY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWD--------------------- 999
Cdd:cd14096    83 IVLELADGgEIFHQIVRLTYFSEDLSRHVITQVASAVKYLHEIGVVHRDIKPENLLFEPipfipsivklrkadddetkvd 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1000 --------GAGGEEQVRICDFGNAQELTPGEPQY-CqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGE 1070
Cdd:cd14096   163 egefipgvGGGGIGIVKLADFGLSKQVWDSNTKTpC--GTVGYTAPEVVKDERYSKKVDMWALGCVLYTLLCGFPPFYDE 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1071 NDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14096   241 SIETLTEKISRGDYTFLSPWWDEISKSAKDLISHLLtVDPAKRYDIDEFLAHPW 294

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270999 [Multi-domain] Cd Length: 266 Bit Score: 120.73 E-value: 1.05e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2221 KPYTFLEEKARGRFGVVRSCRENATGRTFVAKIV--PYAAEGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd14097     1 KIYTFGRKLGQGSFGVVIEATHKETQTKWAIKKInrEKAGSSAVKLLErEVDILKHVNHAHIIHLEEVFETPKRMYLVME 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAA---DNA----LKIVDFGSAQPYNPQ 2370
Cdd:cd14097    81 LCEDGELKELLLRKGFFSENETRHIIQSLASAVAYLHKNDIVHRDLKLENILVKSsiiDNNdklnIKVTDFGLSVQKYGL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 ALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNT-SQSAT 2449
Cdd:cd14097   161 GEDMLQETCGTPIYMAPEVISAHGYSQQCDIWSIGVIMYMLLCGEPPFVAKSEEKLFEEIRKGDLTFTQSVWQSvSDAAK 240

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2450 LFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14097   241 NVLQQLLKVDPAHRMTASELLDNPWI 266

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271019 [Multi-domain] Cd Length: 270 Bit Score: 120.74 E-value: 1.15e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCREN------ATGRTFVAKIVPYAAEGKRRvlQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNREL 2304
Cdd:cd14117    16 KGKFGNVYLAREKqskfivALKVLFKSQIEKEGVEHQLR--REIEIQSHLRHPNILRLYNYFHDRKRIYLILEYAPRGEL 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 LCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpYNPQalkpLGHRT--GTL 2382
Cdd:cd14117    94 YKELQKHGRFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGWSV-HAPS----LRRRTmcGTL 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggRFDaFQLYPNTSQSATLFLRKVLSVHPWS 2462
Cdd:cd14117   169 DYLPPEMIEGRTHDEKVDLWCIGVLCYELLVGMPPFESASHTETYRRIV--KVD-LKFPPFLSDGSRDLISKLLRYHPSE 245

                         250
                  ....*....|....
gi 564369110 2463 RPSLQDCLAHPWLQ 2476
Cdd:cd14117   246 RLPLKGVMEHPWVK 259

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270869 [Multi-domain] Cd Length: 256 Bit Score: 120.19 E-value: 1.27e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYA----AEgKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd08530    10 KGSYGSVYKVKRLSDNQVYALKEVNLGslsqKE-REDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVMEYAPFGDLSK 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFR----YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPlghRTGTL 2382
Cdd:cd08530    89 LISKRKKkrrlFPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGISKVLKKNLAKT---QIGTP 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAfqLYPNTSQSATLFLRKVLSVHPWS 2462
Cdd:cd08530   166 LYAAPEVWKGRPYDYKSDIWSLGCLLYEMATFRPPFEARTMQELRYKVCRGKFPP--IPPVYSQDLQQIIRSLLQVNPKK 243

                         250
                  ....*....|.
gi 564369110 2463 RPSLQDCLAHP 2473
Cdd:cd08530   244 RPSCDKLLQSP 254

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271021 [Multi-domain] Cd Length: 255 Bit Score: 119.67 E-value: 1.80e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYA-----AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPR----YLVLiaESCGnr 2302
Cdd:cd14119     4 GSYGKVKEVLDTETLCRRAVKILKKRklrriPNGEANVKREIQILRRLNHRNVIKLVDVLYNEEkqklYMVM--EYCV-- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ellCGLSDRFRYSED------DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLG 2376
Cdd:cd14119    80 ---GGLQEMLDSAPDkrlpiwQAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGVAEALDLFAEDDTC 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 HRT-GTLEFMAPEMVRGDPI--GSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRfdaFQLYPNTSQSATLFLR 2453
Cdd:cd14119   157 TTSqGSPAFQPPEIANGQDSfsGFKVDIWSAGVTLYNMTTGKYPFEGDNIYKLFENIGKGE---YTIPDDVDPDLQDLLR 233

                         250       260
                  ....*....|....*....|..
gi 564369110 2454 KVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14119   234 GMLEKDPEKRFTIEQIRQHPWF 255

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270982 [Multi-domain] Cd Length: 262 Bit Score: 119.60 E-value: 2.15e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLE--FAAKFIpsqAKPKASAR-------REARLLARLQHDCVLYFHEAFERRRGLV 941
Cdd:cd14080     2 YRLGKTIGEGSYSKVKLAEYTKSGLKekVACKII---DKKKAPKDflekflpRELEILRKLRHPNIIQVYSIFERGSKVF 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTP 1020
Cdd:cd14080    79 IFMEYAEHgDLLEYIQKRGALSESQARIWFRQLALAVQYLHSLDIAHRDLKCENILL----DSNNNVKLSDFGFARLCPD 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQ-----YCqfGTPEFVAPEIVNQSPVSG-VTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFeETTFLSL 1094
Cdd:cd14080   155 DDGDvlsktFC--GSAAYAAPEILQGIPYDPkKYDIWSLGVILYIMLCGSMPFDDSNIKKMLKDQQNRKVRF-PSSVKKL 231

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 1095 SREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14080   232 SPECKDLIDQLLEPDpTKRATIEEILNHPWL 262

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271087 [Multi-domain] Cd Length: 258 Bit Score: 119.28 E-value: 2.40e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI-PSQAKPKAS-ARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd14185     1 HYEIGRTIGDGNFAVVKECRHWNENQEYAMKIIdKSKLKGKEDmIESEILIIKSLSHPNIVKLFEVYETEKEIYLILEYV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELTpgEPQYC 1026
Cdd:cd14185    81 RGgDLFDAIIESVKFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENLLVQHNPDKSTTLKLADFGLAKYVT--GPIFT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 QFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVG-ENDRTTLMNIrnynVAFEETTFLS-----LSREARG 1100
Cdd:cd14185   159 VCGTPTYVAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFRSpERDQEELFQI----IQLGHYEFLPpywdnISEAAKD 234

                         250       260
                  ....*....|....*....|....
gi 564369110 1101 FLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14185   235 LISRLLVVDpEKRYTAKQVLQHPW 258

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271084 [Multi-domain] Cd Length: 276 Bit Score: 119.63 E-value: 2.71e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR----------REARLLARLQ-HDCVLYFHEAFERRRG 939
Cdd:cd14182     5 YEPKEILGRGVSSVVRRCIHKPTRQEYAVKIIDITGGGSFSPEevqelreatlKEIDILRKVSgHPNIIQLKDTYETNTF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  940 LVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQEL 1018
Cdd:cd14182    85 FFLVFDLMKKgELFDYLTEKVTLSEKETRKIMRALLEVICALHKLNIVHRDLKPENILLDD----DMNIKLTDFGFSCQL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1019 TPGEPQYCQFGTPEFVAPEIV------NQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFL 1092
Cdd:cd14182   161 DPGEKLREVCGTPGYLAPEIIecsmddNHPGYGKEVDMWSTGVIMYTLLAGSPPFWHRKQMLMLRMIMSGNYQFGSPEWD 240

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 1093 SLSREARGFLIKVL-VQDRLRPTAEETLEHPWFK 1125
Cdd:cd14182   241 DRSDTVKDLISRFLvVQPQKRYTAEEALAHPFFQ 274

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270823 [Multi-domain] Cd Length: 282 Bit Score: 119.51 E-value: 3.65e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVP--YAAEGkrrV----LQEYEVLRTLHHERLMSLHEAYITPRYLVLIA 2296
Cdd:cd07829     1 YEKLEKLGEGTYGVVYKAKDKKTGEIVALKKIRldNEEEG---IpstaLREISLLKELKHPNIVKLLDVIHTENKLYLVF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGN--RELLCGLSDRFrySEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPqALKP 2374
Cdd:cd07829    78 EYCDQdlKKYLDKRPGPL--PPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAFGI-PLRT 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHRTGTLEFMAPEMVRGDPI-GSATDIWGAGVLTYIMLSGySPFYepdPQETEA-------RIVG-------------- 2432
Cdd:cd07829   155 YTHEVVTLWYRAPEILLGSKHySTAVDIWSVGCIFAELITG-KPLF---PGDSEIdqlfkifQILGtpteeswpgvtklp 230

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2433 ---GRFDAF------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07829   231 dykPTFPKWpkndleKVLPRLDPEGIDLLSKMLQYNPAKRISAKEALKHPYF 282

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270855 [Multi-domain] Cd Length: 258 Bit Score: 118.72 E-value: 3.76e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFS--YLrrVVERSSGLEFAAKFIP---SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd08215     2 YEKIRVIGKGSFGsaYL--VRRKSDGKLYVLKEIDlsnMSEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVME 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LC-----TEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGaggeeQVRICDFGNAQELT 1019
Cdd:cd08215    80 YAdggdlAQKIKKQKKKGQPFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNiFLTKDG-----VVKLGDFGISKVLE 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAF-LClTGISPFVGENDRTTLMNIRNYNVAFEETTFlslSRE 1097
Cdd:cd08215   155 STTDLAKTVvGTPYYLSPELCENKPYNYKSDIWALGCVLYeLC-TLKHPFEANNLPALVYKIVKGQYPPIPSQY---SSE 230

                         250       260
                  ....*....|....*....|....*.
gi 564369110 1098 ARGFLIKVLVQD-RLRPTAEETLEHP 1122
Cdd:cd08215   231 LRDLVNSMLQKDpEKRPSANEILSSP 256

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132954 [Multi-domain] Cd Length: 264 Bit Score: 118.46 E-value: 5.01e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFSYLRRVVERSSGLEFAAKFI--PSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL----CTE 949
Cdd:cd06623     8 VLGQGSSGVVYKVRHKPTGKIYALKKIhvDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYmdggSLA 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLermARKPTVCESETRTYMRQVLEGIGYLHQ-SHVLHLDVKPENLLVwdGAGGEeqVRICDFGNAQELTPGEPQYCQF 1028
Cdd:cd06623    88 DLL---KKVGKIPEPVLAYIARQILKGLDYLHTkRHIIHRDIKPSNLLI--NSKGE--VKIADFGISKVLENTLDQCNTF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 -GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF--VGENDRTTLMnirnYNVAFEETTFLS---LSREARGFL 1102
Cdd:cd06623   161 vGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFlpPGQPSFFELM----QAICDGPPPSLPaeeFSPEFRDFI 236

                         250       260
                  ....*....|....*....|....
gi 564369110 1103 IKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd06623   237 SACLQKDpKKRPSAAELLQHPFIK 260

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 112.35 E-value: 5.26e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   755 PRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLAG 834
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 564369110   835 EVSCKAELSV 844
Cdd:pfam07679   81 EAEASAELTV 90

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271079 [Multi-domain] Cd Length: 295 Bit Score: 119.35 E-value: 6.24e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyaaEGKRRVLQEYEVL-RTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd14177     6 YELKEDIGVGSYSVCKRCIHRATNMEFAVKIID---KSKRDPSEEIEILmRYGQHPNIITLKDVYDDGRYVYLVTELMKG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA----LKIVDFGSAQPY---NPQALKP 2374
Cdd:cd14177    83 GELLDRILRQKFFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNILYMDDSAnadsIRICDFGFAKQLrgeNGLLLTP 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 lghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYE-PD--PQETEARIVGGRFD-AFQLYPNTSQSATL 2450
Cdd:cd14177   163 ----CYTANFVAPEVLMRQGYDAACDIWSLGVLLYTMLAGYTPFANgPNdtPEEILLRIGSGKFSlSGGNWDTVSDAAKD 238

                         250       260
                  ....*....|....*....|....*
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14177   239 LLSHMLHVDPHQRYTAEQVLKHSWI 263

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271014 [Multi-domain] Cd Length: 259 Bit Score: 117.63 E-value: 8.94e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQEIGRGAFSYLRRVVERSS--GLEFAAK-FIPSQAKPKASarREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14112     2 TGRFSFGSEIFRGRFSVIVKAVDSTTetDAHCAVKiFEVSDEASEAV--REFESLRTLQHENVQRLIAAFKPSNFAYLVM 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGEEQVRICDFGNAQELTPGEPQ 1024
Cdd:cd14112    80 EKLQEDVFTRFSSNDYYSEEQVATTVRQILDALHYLHFKGIAHLDVQPDNIMF--QSVRSWQVKLVDFGRAQKVSKLGKV 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQFGTpEFVAPEIVN-QSPVSGVTDIWPVGVVAFLCLTGISPFVGENDR--TTLMNIRNYNVAFeETTFLSLSREARGF 1101
Cdd:cd14112   158 PVDGDT-DWASPEFHNpETPITVQSDIWGLGVLTFCLLSGFHPFTSEYDDeeETKENVIFVKCRP-NLIFVEATQEALRF 235

                         250       260
                  ....*....|....*....|...
gi 564369110 1102 LIKVLVQDRL-RPTAEETLEHPW 1123
Cdd:cd14112   236 ATWALKKSPTrRMRTDEALEHRW 258

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271080 [Multi-domain] Cd Length: 293 Bit Score: 118.58 E-value: 9.59e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyaaEGKRRVLQEYEVL-RTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd14178     5 YEIKEDIGIGSYSVCKRCVHKATSTEYAVKIID---KSKRDPSEEIEILlRYGQHPNIITLKDVYDDGKFVYLVMELMRG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADN----ALKIVDFGSAQPY---NPQALKP 2374
Cdd:cd14178    82 GELLDRILRQKCFSEREASAVLCTITKTVEYLHSQGVVHRDLKPSNILYMDESgnpeSIRICDFGFAKQLraeNGLLMTP 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 lghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYE-PD--PQETEARIVGGRFD-AFQLYPNTSQSATL 2450
Cdd:cd14178   162 ----CYTANFVAPEVLKRQGYDAACDIWSLGILLYTMLAGFTPFANgPDdtPEEILARIGSGKYAlSGGNWDSISDAAKD 237

                         250       260
                  ....*....|....*....|....*
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14178   238 IVSKMLHVDPHQRLTAPQVLRHPWI 262

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271091 [Multi-domain] Cd Length: 255 Bit Score: 117.34 E-value: 1.08e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQ--AKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd14189     9 LGKGGFARCYEMTDLATNKTYAVKVIPHSrvAKPHQREKivNEIELHRDLHHKHVVKFSHHFEDAENIYIFLELCSRKSL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMAR-KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPQ---YCqf 1028
Cdd:cd14189    89 AHIWKaRHTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENM----ELKVGDFGLAARLEPPEQRkktIC-- 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRnyNVAFEETTFLSLSreARGFLIKVLVQ 1108
Cdd:cd14189   163 GTPNYLAPEVLLRQGHGPESDVWSLGCVMYTLLCGNPPFETLDLKETYRCIK--QVKYTLPASLSLP--ARHLLAGILKR 238

                         250
                  ....*....|....*..
gi 564369110 1109 D-RLRPTAEETLEHPWF 1124
Cdd:cd14189   239 NpGDRLTLDQILEHEFF 255

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270983 [Multi-domain] Cd Length: 255 Bit Score: 117.35 E-value: 1.12e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIP----SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd14081     3 YRLGKTLGKGQTGLVKLAKHCVTGQKVAIKIVNkeklSKESVLMKVEREIAIMKLIEHPNVLKLYDVYENKKYLYLVLEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGE--P 1023
Cdd:cd14081    83 VSGgELFDYLVKKGRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDE----KNNIKIADFGMASLQPEGSllE 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCqfGTPEFVAPEIVNQSPVSGVT-DIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYnvAFEETTFlsLSREARGFL 1102
Cdd:cd14081   159 TSC--GSPHYACPEVIKGEKYDGRKaDIWSCGVILYALLVGALPFDDDNLRQLLEKVKRG--VFHIPHF--ISPDAQDLL 232

                         250       260
                  ....*....|....*....|...
gi 564369110 1103 IKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14081   233 RRMLEVNpEKRITIEEIKKHPWF 255

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271077 [Multi-domain] Cd Length: 291 Bit Score: 118.21 E-value: 1.21e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyaaEGKRRVLQEYEVL-RTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd14175     3 YVVKETIGVGSYSVCKRCVHKATNMEYAVKVID---KSKRDPSEEIEILlRYGQHPNIITLKDVYDDGKHVYLVTELMRG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADN----ALKIVDFGSAQPY---NPQALKP 2374
Cdd:cd14175    80 GELLDKILRQKFFSEREASSVLHTICKTVEYLHSQGVVHRDLKPSNILYVDESgnpeSLRICDFGFAKQLraeNGLLMTP 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 lghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFY---EPDPQETEARIVGGRFDAFQLYPNT-SQSATL 2450
Cdd:cd14175   160 ----CYTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFAngpSDTPEEILTRIGSGKFTLSGGNWNTvSDAAKD 235

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWL-------------QDAYLMK 2482
Cdd:cd14175   236 LVSKMLHVDPHQRLTAKQVLQHPWItqkdklpqsqlnhQDVQLVK 280

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271090 [Multi-domain] Cd Length: 255 Bit Score: 117.04 E-value: 1.39e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEGK----RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELL 2305
Cdd:cd14188    10 GKGGFAKCYEMTDLTTNKVYAAKIIPHSRVSKphqrEKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSMA 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpQALKPLGHR----TGT 2381
Cdd:cd14188    90 HILKARKVLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLA-----ARLEPLEHRrrtiCGT 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2382 LEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRfdaFQLYPNTSQSATLFLRKVLSVHPW 2461
Cdd:cd14188   165 PNYLSPEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNLKETYRCIREAR---YSLPSSLLAPAKHLIASMLSKNPE 241

                         250
                  ....*....|.
gi 564369110 2462 SRPSLQDCLAH 2472
Cdd:cd14188   242 DRPSLDEIIRH 252

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271135 [Multi-domain] Cd Length: 257 Bit Score: 117.01 E-value: 1.47e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14665     2 YELVKDIGSGNFGVARLMRDKQTKELVAVKYIERGEKIDENVQREIINHRSLRHPNIVRFKEVILTPTHLAIVMEYAAGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA--LKIVDFGsaqpYNPQAL---KPlGH 2377
Cdd:cd14665    82 ELFERICNAGRFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAprLKICDFG----YSKSSVlhsQP-KS 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDP----QETEARIVGGRFdAFQLYPNTSQSATLFL 2452
Cdd:cd14665   157 TVGTPAYIAPEvLLKKEYDGKIADVWSCGVTLYVMLVGAYPFEDPEEprnfRKTIQRILSVQY-SIPDYVHISPECRHLI 235

                         250       260
                  ....*....|....*....|..
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd14665   236 SRIFVADPATRITIPEIRNHEW 257

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270796 [Multi-domain] Cd Length: 265 Bit Score: 117.02 E-value: 1.83e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAaEGKRRVLQ----EYEVLRTLHHERLMSLHEAYITPRYLVLIAESC--GNRELL 2305
Cdd:cd06626    11 GTFGKVYTAVNLDTGELMAMKEIRFQ-DNDPKTIKeiadEMKVLEGLDHPNLVRYYGVEVHREEVYIFMEYCqeGTLEEL 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CglsdRFRYSEDDVAT--YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLG----HRT 2379
Cdd:cd06626    90 L----RHGRILDEAVIrvYTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAVKLKNNTTTMAPgevnSLV 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDP---IGSATDIWGAGVLTYIMLSGYSPFYEPDPQ-ETEARIVGGRFDAFqlyPNTSQSATL---FL 2452
Cdd:cd06626   166 GTPAYMAPEVITGNKgegHGRAADIWSLGCVVLEMATGKRPWSELDNEwAIMYHVGMGHKPPI---PDSLQLSPEgkdFL 242

                         250       260
                  ....*....|....*....|...
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06626   243 SRCLESDPKKRPTASELLDHPFI 265

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270688 [Multi-domain] Cd Length: 249 Bit Score: 115.79 E-value: 2.67e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARL----QHDCVLYFHEAFERRRG--LVIVT 944
Cdd:cd05118     1 YEVLRKIGEGAFGTVWLARDKVTGEKVAIKKIKNDFRHPKAALREIKLLKHLndveGHPNIVKLLDVFEHRGGnhLCLVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTEELLErMARKPTVC--ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgAGGEEQVRICDFGNAQELTPGE 1022
Cdd:cd05118    81 ELMGMNLYE-LIKDYPRGlpLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILI---NLELGQLKLADFGLARSFTSPP 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PqYCQFGTPEFVAPEIVNQSPVSGVT-DIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNynvafeettfLSLSREARGF 1101
Cdd:cd05118   157 Y-TPYVATRWYRAPEVLLGAKPYGSSiDIWSLGCILAELLTGRPLFPGDSEVDQLAKIVR----------LLGTPEALDL 225

                         250       260
                  ....*....|....*....|....
gi 564369110 1102 LIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd05118   226 LSKMLKYDpAKRITASQALAHPYF 249

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270796 [Multi-domain] Cd Length: 265 Bit Score: 116.25 E-value: 3.06e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQ-AKPKA--SARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLE 953
Cdd:cd06626     8 IGEGTFGKVYTAVNLDTGELMAMKEIRFQdNDPKTikEIADEMKVLEGLDHPNLVRYYGVEVHREEVYIFMEYCQEGTLE 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  954 RMARKpTVCESE--TRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPG------EPQY 1025
Cdd:cd06626    88 ELLRH-GRILDEavIRVYTLQLLEGLAYLHENGIVHRDIKPANIFL-DSNG---LIKLGDFGSAVKLKNNtttmapGEVN 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQFGTPEFVAPEIVNQSPVSG---VTDIWPVGVVAFLCLTGISPFVGENDRTTLMnirnYNVAFEET----TFLSLSREA 1098
Cdd:cd06626   163 SLVGTPAYMAPEVITGNKGEGhgrAADIWSLGCVVLEMATGKRPWSELDNEWAIM----YHVGMGHKppipDSLQLSPEG 238

                         250       260
                  ....*....|....*....|....*.
gi 564369110 1099 RGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd06626   239 KDFLSRCLESDpKKRPTASELLDHPF 264

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173686 [Multi-domain] Cd Length: 323 Bit Score: 117.80 E-value: 3.52e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKI----VPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd05595     5 KGTFGKVILVREKATGRYYAMKIlrkeVIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGELFF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQP--YNPQALKPLghrTGTLEF 2384
Cdd:cd05595    85 HLSRERVFTEDRARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEgiTDGATMKTF---CGTPEY 161

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 564369110 2385 MAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPD 2422
Cdd:cd05595   162 LAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQD 199

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271089 [Multi-domain] Cd Length: 265 Bit Score: 116.19 E-value: 3.69e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQ--AKP--KASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEE-L 951
Cdd:cd14187    15 LGKGGFAKCYEITDADTKEVFAGKIVPKSllLKPhqKEKMSMEIAIHRSLAHQHVVGFHGFFEDNDFVYVVLELCRRRsL 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELT-PGEPQYCQFGT 1030
Cdd:cd14187    95 LELHKRRKALTEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLND----DMEVKIGDFGLATKVEyDGERKKTLCGT 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1031 PEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYnvafEETTFLSLSREARGFLIKVLVQD- 1109
Cdd:cd14187   171 PNYIAPEVLSKKGHSFEVDIWSIGCIMYTLLVGKPPFETSCLKETYLRIKKN----EYSIPKHINPVAASLIQKMLQTDp 246

                         250
                  ....*....|....*..
gi 564369110 1110 RLRPTAEETLEHPWFKT 1126
Cdd:cd14187   247 TARPTINELLNDEFFTS 263

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270730 [Multi-domain] Cd Length: 257 Bit Score: 115.82 E-value: 3.81e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPK----ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd05578     2 FQILRVIGKGSFGKVCIVQKKDTKKMFAMKYMNKQKCIEkdsvRNVLNELEILQELEHPFLVNLWYSFQDEEDMYMVVDL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQY 1025
Cdd:cd05578    82 LLGgDLRYHLQQKVKFSEETVKFYICEIVLALDYLHSKNIIHRDIKPDNILL-DEQG---HVHITDFNIATKLTDGTLAT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGeNDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKV 1105
Cdd:cd05578   158 STSGTKPYMAPEVFMRAGYSFAVDWWSLGVTAYEMLRGKRPYEI-HSRTSIEEIRAKFETASVLYPAGWSEEAIDLINKL 236

                         250       260
                  ....*....|....*....|..
gi 564369110 1106 LVQD---RLRpTAEETLEHPWF 1124
Cdd:cd05578   237 LERDpqkRLG-DLSDLKNHPYF 257

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270973 [Multi-domain] Cd Length: 253 Bit Score: 115.18 E-value: 5.07e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATgRTFVA-KIVPYA---AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd14071    10 KGNFAVVKLARHRIT-KTEVAiKIIDKSqldEENLKKIYREVQIMKMLNHPHIIKLYQVMETKDMLYLVTEYASNGEIFD 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQalKPLGHRTGTLEFMA 2386
Cdd:cd14071    89 YLAQHGRMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFSNFFKPG--ELLKTWCGSPPYAA 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2387 PEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLypntSQSATLFLRKVLSVHPWSRP 2464
Cdd:cd14071   167 PEVFEGKEyEGPQLDIWSLGVVLYVLVCGALPFDGSTLQTLRDRVLSGRFRiPFFM----STDCEHLIRRMLVLDPSKRL 242

                         250
                  ....*....|.
gi 564369110 2465 SLQDCLAHPWL 2475
Cdd:cd14071   243 TIEQIKKHKWM 253

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271063 [Multi-domain] Cd Length: 255 Bit Score: 115.05 E-value: 6.35e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVL---QEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd14161     5 YEFLETLGKGTYGRVKKARDSSGRLVAIKSIRKDRIKDEQDLLhirREIEIMSSLNHPHIISVYEVFENSSKIVIVMEYA 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALkpLGHRT 2379
Cdd:cd14161    85 SRGDLYDYISERQRLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQDKF--LQTYC 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAfqlyPNTSQSATLFLRKVLSV 2458
Cdd:cd14161   163 GSPLYASPEIVNGRPyIGPEVDSWSLGVLLYILVHGTMPFDGHDYKILVKQISSGAYRE----PTKPSDACGLIRWLLMV 238

                         250
                  ....*....|....*..
gi 564369110 2459 HPWSRPSLQDCLAHPWL 2475
Cdd:cd14161   239 NPERRATLEDVASHWWV 255

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270762 [Multi-domain] Cd Length: 263 Bit Score: 115.27 E-value: 6.45e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFS--YLRRvvERSSGLEFAAKFIPSQ---AKPKASARREARLLARLQHD----CVLYFheAFERRRGLVIVTE 945
Cdd:cd05611     2 KPISKGAFGsvYLAK--KRSTGDYFAIKVLKKSdmiAKNQVTNVKAERAIMMIQGEspyvAKLYY--SFQSKDYLYLVME 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCT----EELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPG 1021
Cdd:cd05611    78 YLNggdcASLIKTLGGLP---EDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLI-DQTG---HLKLTDFGLSRNGLEK 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 EPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGF 1101
Cdd:cd05611   151 RHNKKFVGTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEEVKEFCSPEAVDL 230

                         250       260
                  ....*....|....*....|....*....
gi 564369110 1102 LIKVLVQD---RLRPT-AEETLEHPWFKT 1126
Cdd:cd05611   231 INRLLCMDpakRLGANgYQEIKSHPFFKS 259

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271090 [Multi-domain] Cd Length: 255 Bit Score: 115.11 E-value: 6.59e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQ--AKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd14188     9 LGKGGFAKCYEMTDLTTNKVYAAKIIPHSrvSKPHQREKidKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSM 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERM--ARKpTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPQYCQF-G 1029
Cdd:cd14188    89 AHIlkARK-VLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINENM----ELKVGDFGLAARLEPLEHRRRTIcG 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1030 TPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREARGFLIKVLVQD 1109
Cdd:cd14188   164 TPNYLSPEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNLKETYRCIREARYSLPS----SLLAPAKHLIASMLSKN 239

                         250
                  ....*....|....*.
gi 564369110 1110 -RLRPTAEETLEHPWF 1124
Cdd:cd14188   240 pEDRPSLDEIIRHDFF 255

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270975 [Multi-domain] Cd Length: 254 Bit Score: 114.79 E-value: 8.40e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAA----EGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd14073     3 YELLETLGKGTYGKVKLAIERATGREVAIKSIKKDKiedeQDMVRIRREIEIMSSLNHPHIIRIYEVFENKDKIVIVMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALkpLGHR 2378
Cdd:cd14073    83 ASGGELYDYISERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKDKL--LQTF 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFdafqLYPNTSQSATLFLRKVLS 2457
Cdd:cd14073   161 CGSPLYASPEIVNGTPyQGPEVDCWSLGVLLYTLVYGTMPFDGSDFKRLVKQISSGDY----REPTQPSDASGLIRWMLT 236

                         250
                  ....*....|....*...
gi 564369110 2458 VHPWSRPSLQDCLAHPWL 2475
Cdd:cd14073   237 VNPKRRATIEDIANHWWV 254

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271135 [Multi-domain] Cd Length: 257 Bit Score: 114.70 E-value: 9.13e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE- 949
Cdd:cd14665     2 YELVKDIGSGNFGVARLMRDKQTKELVAVKYIERGEKIDENVQREIINHRSLRHPNIVRFKEVILTPTHLAIVMEYAAGg 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGeEQVRICDFGNAQE-LTPGEPQyCQF 1028
Cdd:cd14665    82 ELFERICNAGRFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLL-DGSPA-PRLKICDFGYSKSsVLHSQPK-STV 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSG-VTDIWPVGVVAFLCLTGISPFVGEND----RTTLMNIrnYNVAFEETTFLSLSREARGFLI 1103
Cdd:cd14665   159 GTPAYIAPEVLLKKEYDGkIADVWSCGVTLYVMLVGAYPFEDPEEprnfRKTIQRI--LSVQYSIPDYVHISPECRHLIS 236

                         250       260
                  ....*....|....*....|.
gi 564369110 1104 KVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14665   237 RIFVADpATRITIPEIRNHEW 257

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271064 [Multi-domain] Cd Length: 259 Bit Score: 114.70 E-value: 9.92e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  896 EFAAKFIPsqakpkasarREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVL 974
Cdd:cd14162    41 DYLQKFLP----------REIEVIKGLKHPNLICFYEAIETTSRVYIIMELAENgDLLDYIRKNGALPEPQARRWFRQLV 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  975 EGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQ---ELTPGEPQ----YCqfGTPEFVAPEIVNQSPVSGV 1047
Cdd:cd14162   111 AGVEYCHSKGVVHRDLKCENLLL----DKNNNLKITDFGFARgvmKTKDGKPKlsetYC--GSYAYASPEILRGIPYDPF 184

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 1048 -TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNyNVAFEETTflSLSREARGFLIKVLVQDRLRPTAEETLEHPWF 1124
Cdd:cd14162   185 lSDIWSMGVVLYTMVYGRLPFDDSNLKVLLKQVQR-RVVFPKNP--TVSEECKDLILRMLSPVKKRITIEEIKRDPWF 259

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271021 [Multi-domain] Cd Length: 255 Bit Score: 114.28 E-value: 1.06e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPK-----ASARREARLLARLQHDCVLYFHEAF--ERRRGLVIVTELC-- 947
Cdd:cd14119     1 LGEGSYGKVKEVLDTETLCRRAVKILKKRKLRRipngeANVKREIQILRRLNHRNVIKLVDVLynEEKQKLYMVMEYCvg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 -TEELLERMARK--PTvceSETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQ 1024
Cdd:cd14119    81 gLQEMLDSAPDKrlPI---WQAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLL----TTDGTLKISDFGVAEALDLFAED 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 Y-CQ--FGTPEFVAPEIVN-QSPVSGV-TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREAR 1099
Cdd:cd14119   154 DtCTtsQGSPAFQPPEIANgQDSFSGFkVDIWSAGVTLYNMTTGKYPFEGDNIYKLFENIGKGEYTIPD----DVDPDLQ 229

                         250       260
                  ....*....|....*....|....*.
gi 564369110 1100 GFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14119   230 DLLRGMLEKDpEKRFTIEQIRQHPWF 255

protein kinase A catalytic subunit; Provisional

Pssm-ID: 140289 [Multi-domain] Cd Length: 329 Bit Score: 116.46 E-value: 1.23e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVpyaaegKRR----------VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:PTZ00263   29 GSFGRVRIAKHKGTGEYYAIKCL------KKReilkmkqvqhVAQEKSILMELSHPFIVNMMCSFQDENRVYFLLEFVVG 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpqalKPLGHRT-- 2379
Cdd:PTZ00263  103 GELFTHLRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFA--------KKVPDRTft 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 --GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFdafqLYPNTSQS-ATLFLRKVL 2456
Cdd:PTZ00263  175 lcGTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDDTPFRIYEKILAGRL----KFPNWFDGrARDLVKGLL 250

                         250       260
                  ....*....|....*....|....*..
gi 564369110 2457 SVHPWSR-----PSLQDCLAHPWLQDA 2478
Cdd:PTZ00263  251 QTDHTKRlgtlkGGVADVKNHPYFHGA 277

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270911 [Multi-domain] Cd Length: 251 Bit Score: 113.86 E-value: 1.32e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPS---QAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT----E 949
Cdd:cd14009     1 IGRGSFATVWKGRHKQTGEVVAIKEISRkklNKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAggdlS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEEQVRICDFGNAQELTPGE--PQYCq 1027
Cdd:cd14009    81 QYIRKRGRLP---EAVARHFMQQLASGLKFLRSKNIIHRDLKPQNLLL-STSGDDPVLKIADFGFARSLQPASmaETLC- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 fGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLV 1107
Cdd:cd14009   156 -GSPLYMAPEILQFQKYDAKADLWSVGAILFEMLVGKPPFRGSNHVQLLRNIERSDAVIPFPIAAQLSPDCKDLLRRLLR 234

                         250
                  ....*....|....*..
gi 564369110 1108 QD-RLRPTAEETLEHPW 1123
Cdd:cd14009   235 RDpAERISFEEFFAHPF 251

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270837 [Multi-domain] Cd Length: 286 Bit Score: 115.16 E-value: 1.42e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAK-FIPSQAKP--KASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd07847     1 EKYEKLSKIGEGSYGVVFKCRNRETGQIVAIKkFVESEDDPviKKIALREIRMLKQLKHPNLVNLIEVFRRKRKLHLVFE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPT-VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQ 1024
Cdd:cd07847    81 YCDHTVLNELEKNPRgVPEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILI----TKQGQIKLCDFGFARILTGPGDD 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQF-GTPEFVAPE-IVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEND-------RTTL-------MNIRNYNVAFE- 1087
Cdd:cd07847   157 YTDYvATRWYRAPElLVGDTQYGPPVDVWAIGCVFAELLTGQPLWPGKSDvdqlyliRKTLgdliprhQQIFSTNQFFKg 236

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 1088 ------------ETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07847   237 lsipepetreplESKFPNISSPALSFLKGCLQMDpTERLSCEELLEHPYF 286

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270789 [Multi-domain] Cd Length: 255 Bit Score: 113.84 E-value: 1.43e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL--- 946
Cdd:cd06614     1 LYKNLEKIGEGASGEVYKATDRATGKEVAIKKMRLRKQNKELIINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYmdg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 -CTEELLERMARKPTvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGEeqVRICDFGNAQELTPGEPQY 1025
Cdd:cd06614    81 gSLTDIITQNPVRMN--ESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILL--SKDGS--VKLADFGFAAQLTKEKSKR 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 -CQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNV-AFEETTflSLSREARGFLI 1103
Cdd:cd06614   155 nSVVGTPYWMAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPPYLEEPPLRALFLITTKGIpPLKNPE--KWSPEFKDFLN 232

                         250       260
                  ....*....|....*....|...
gi 564369110 1104 KVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd06614   233 KCLVKDpEKRPSAEELLQHPFLK 255

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270976 [Multi-domain] Cd Length: 258 Bit Score: 114.05 E-value: 1.57e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR---REARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd14074     5 YDLEETLGRGHFAVVKLARHVFTGEKVAVKVIDKTKLDDVSKAhlfQEVRCMKLVQHPNVVRLYEVIDTQTKLYLILELG 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE-ELLERMARKPT-VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeeQVRICDFGNAQELTPGEPQY 1025
Cdd:cd14074    85 DGgDMYDYIMKHENgLNEDLARKYFRQIVSAISYCHKLHVVHRDLKPENVVFFEKQG---LVKLTDFGFSNKFQPGEKLE 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQFGTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRN--YNVAFEettflsLSREARGFL 1102
Cdd:cd14074   162 TSCGSLAYSAPEIlLGDEYDAPAVDIWSLGVILYMLVCGQPPFQEANDSETLTMIMDckYTVPAH------VSPECKDLI 235

                         250       260
                  ....*....|....*....|..
gi 564369110 1103 IKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14074   236 RRMLIRDpKKRASLEEIENHPW 257

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.

Pssm-ID: 270723 [Multi-domain] Cd Length: 322 Bit Score: 115.53 E-value: 1.90e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKI----VPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd05571     5 KGTFGKVILCREKATGELYAIKIlkkeVIIAKDEVAHTLTENRVLQNTRHPFLTSLKYSFQTNDRLCFVMEYVNGGELFF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ---PYnpqalkplGHRT---- 2379
Cdd:cd05571    85 HLSRERVFSEDRTRFYGAEIVLALGYLHSQGIVYRDLKLENLLLDKDGHIKITDFGLCKeeiSY--------GATTktfc 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGG--RFDafqlyPNTSQSATLFLRKVLS 2457
Cdd:cd05571   157 GTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNRDHEVLFELILMEevRFP-----STLSPEAKSLLAGLLK 231

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 2458 VHPWSR----PS-LQDCLAHPWL-----QDAYLMKL 2483
Cdd:cd05571   232 KDPKKRlgggPRdAKEIMEHPFFasinwDDLYQKKI 267

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270998 [Multi-domain] Cd Length: 295 Bit Score: 114.84 E-value: 2.13e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFG-VVRSCRENATGRTFVAKIVP------YAAEGKRR--VLQEYEVLRTLHHERLMSLHEAYITPRYLV 2293
Cdd:cd14096     3 YRLINKIGEGAFSnVYKAVPLRNTGKPVAIKVVRkadlssDNLKGSSRanILKEVQIMKRLSHPNIVKLLDFQESDEYYY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2294 LIAESCGNRELLCGLSdRFRYSEDDVATYVV-QLLQGLDYLHGRHVLHLDIKPDNLLLA--------------------A 2352
Cdd:cd14096    83 IVLELADGGEIFHQIV-RLTYFSEDLSRHVItQVASAVKYLHEIGVVHRDIKPENLLFEpipfipsivklrkadddetkV 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2353 DNA-------------LKIVDFG-SAQPYNPQALKPlghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd14096   162 DEGefipgvggggigiVKLADFGlSKQVWDSNTKTP----CGTVGYTAPEVVKDERYSKKVDMWALGCVLYTLLCGFPPF 237

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2419 YEPDPQETEARIVGGRFdAFqLYP---NTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14096   238 YDESIETLTEKISRGDY-TF-LSPwwdEISKSAKDLISHLLTVDPAKRYDIDEFLAHPWI 295

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271081 [Multi-domain] Cd Length: 310 Bit Score: 114.37 E-value: 3.71e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEGKRRvlQEYEVLRTLH-HERLMSLHEAYITPRYLVLIAESCGNRELLCGLSD 2310
Cdd:cd14179    18 GSFSICRKCLHKKTNQEYAVKIVSKRMEANTQ--REIAALKLCEgHPNIVKLHEVYHDQLHTFLVMELLKGGELLERIKK 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2311 RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA--ADNA-LKIVDFGSAQpYNPQALKPLGHRTGTLEFMAP 2387
Cdd:cd14179    96 KQHFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFTdeSDNSeIKIIDFGFAR-LKPPDNQPLKTPCFTLHYAAP 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2388 EMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPD-------PQETEARIVGGRFD-AFQLYPNTSQSATLFLRKVLSVH 2459
Cdd:cd14179   175 ELLNYNGYDESCDLWSLGVILYTMLSGQVPFQCHDksltctsAEEIMKKIKQGDFSfEGEAWKNVSQEAKDLIQGLLTVD 254

                         250
                  ....*....|....*...
gi 564369110 2460 PWSRPSLQDCLAHPWLQD 2477
Cdd:cd14179   255 PNKRIKMSGLRYNEWLQD 272

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271082 [Multi-domain] Cd Length: 309 Bit Score: 114.58 E-value: 3.79e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2226 LEEKA--RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRvlQEYEVLRTLH-HERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14180     9 LEEPAlgEGSFSVCRKCRHRQSGQEYAVKIISRRMEANTQ--REVAALRLCQsHPNIVALHEVLHDQYHTYLVMELLRGG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA--ADNA-LKIVDFGSAQpYNPQALKPLGHRT 2379
Cdd:cd14180    87 ELLDRIKKKARFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYAdeSDGAvLKVIDFGFAR-LRPQGSRPLQTPC 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEAR-------IVGGRFD-AFQLYPNTSQSATLF 2451
Cdd:cd14180   166 FTLQYAAPELFSNQGYDESCDLWSLGVILYTMLSGQVPFQSKRGKMFHNHaadimhkIKEGDFSlEGEAWKGVSEEAKDL 245

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2452 LRKVLSVHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd14180   246 VRGLLTVDPAKRLKLSELRESDWLQG 271

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270896 [Multi-domain] Cd Length: 265 Bit Score: 113.17 E-value: 3.90e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSC--RENATGRTFVAKIV--PYAAEGKR----RVLQEYEVLRTLHHERLMSLHEAYITP-RYLVLIAESCG 2300
Cdd:cd13994     2 GKGATSVVRIVtkKNPRSGVLYAVKEYrrRDDESKRKdyvkRLTSEYIISSKLHHPNIVKVLDLCQDLhGKWCLVMEYCP 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ----PYNPQALKPLG 2376
Cdd:cd13994    82 GGDLFTLIEKADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAEvfgmPAEKESPMSAG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 HRtGTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQET--EARIVGGRF--DAFQLYPNTSQS-ATL 2450
Cdd:cd13994   162 LC-GSEPYMAPEvFTSGSYDGRAVDVWSCGIVLFALFTGRFPWRSAKKSDSayKAYEKSGDFtnGPYEPIENLLPSeCRR 240

                         250       260
                  ....*....|....*....|....*
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd13994   241 LIYRMLHPDPEKRITIDEALNDPWV 265

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271132 [Multi-domain] Cd Length: 257 Bit Score: 112.56 E-value: 4.89e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE- 949
Cdd:cd14662     2 YELVKDIGSGNFGVARLMRNKETKELVAVKYIERGLKIDENVQREIINHRSLRHPNIIRFKEVVLTPTHLAIVMEYAAGg 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGeEQVRICDFGNAQE-LTPGEPQyCQF 1028
Cdd:cd14662    82 ELFERICNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLL-DGSPA-PRLKICDFGYSKSsVLHSQPK-STV 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSG-VTDIWPVGVVAFLCLTGISPFVGEND----RTTLMNIRNYNVAFEEttFLSLSREARGFLI 1103
Cdd:cd14662   159 GTPAYIAPEVLSRKEYDGkVADVWSCGVTLYVMLVGAYPFEDPDDpknfRKTIQRIMSVQYKIPD--YVRVSQDCRHLLS 236

                         250       260
                  ....*....|....*....|.
gi 564369110 1104 KVLVQDRL-RPTAEETLEHPW 1123
Cdd:cd14662   237 RIFVANPAkRITIPEIKNHPW 257

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270984 [Multi-domain] Cd Length: 260 Bit Score: 112.51 E-value: 5.18e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQE--IGRGAFSYLRRVVERSSGLEFAAKFIPS---QAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14082     3 YQIFPDevLGSGQFGIVYGGKHRKTGRDVAIKVIDKlrfPTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVME 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPT--VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgAGGEEQVRICDFGNAQELtpGEP 1023
Cdd:cd14082    83 KLHGDMLEMILSSEKgrLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLAS-AEPFPQVKLCDFGFARII--GEK 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQ--FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTlmNIRNYNVAFEETTFLSLSREARGF 1101
Cdd:cd14082   160 SFRRsvVGTPAYLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNEDEDIND--QIQNAAFMYPPNPWKEISPDAIDL 237

                         250       260
                  ....*....|....*....|...
gi 564369110 1102 LIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14082   238 INNLLqVKMRKRYSVDKSLSHPW 260

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270826 [Multi-domain] Cd Length: 287 Bit Score: 112.81 E-value: 9.18e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAK----PKaSARREARLLARLQ-HDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd07832     2 YKILGRIGEGAHGIVFKAKDRETGETVALKKVALRKLeggiPN-QALREIKALQACQgHPYVVKLRDVFPHGTGFVLVFE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERM--ARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEP 1023
Cdd:cd07832    81 YMLSSLSEVLrdEERP-LTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLI----SSTGVLKIADFGLARLFSEEDP 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 Q--YCQFGTPEFVAPEIVNQSPV--SGVtDIWPVGVVAFLCLTGISPFVGEND--------RTT----------LMNIRN 1081
Cdd:cd07832   156 RlySHQVATRWYRAPELLYGSRKydEGV-DLWAVGCIFAELLNGSPLFPGENDieqlaivlRTLgtpnektwpeLTSLPD 234

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1082 YN-VAFE-------ETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07832   235 YNkITFPeskgirlEEIFPDCSPEAIDLLKGLLVYNpKKRLSAEEALRHPYF 286

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271132 [Multi-domain] Cd Length: 257 Bit Score: 111.78 E-value: 9.72e-27

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14662     2 YELVKDIGSGNFGVARLMRNKETKELVAVKYIERGLKIDENVQREIINHRSLRHPNIIRFKEVVLTPTHLAIVMEYAAGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA--LKIVDFGsaqpYNPQAL---KPlGH 2377
Cdd:cd14662    82 ELFERICNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAprLKICDFG----YSKSSVlhsQP-KS 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPEMV-RGDPIGSATDIWGAGVLTYIMLSGYSPFYEP-DPQ---ETEARIVGGRFdAFQLYPNTSQSATLFL 2452
Cdd:cd14662   157 TVGTPAYIAPEVLsRKEYDGKVADVWSCGVTLYVMLVGAYPFEDPdDPKnfrKTIQRIMSVQY-KIPDYVRVSQDCRHLL 235

                         250       260
                  ....*....|....*....|..
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd14662   236 SRIFVANPAKRITIPEIKNHPW 257

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271063 [Multi-domain] Cd Length: 255 Bit Score: 111.58 E-value: 1.00e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSsGLEFAAKFIPSQ----AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVI 942
Cdd:cd14161     1 LKHRYEFLETLGKGTYGRVKKARDSS-GRLVAIKSIRKDrikdEQDLLHIRREIEIMSSLNHPHIISVYEVFENSSKIVI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  943 VTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPG 1021
Cdd:cd14161    80 VMEYASRgDLYDYISERQRLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILL-DANG---NIKIADFGLSNLYNQD 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 E--PQYCqfGTPEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYnvAFEETTFLSlsrEA 1098
Cdd:cd14161   156 KflQTYC--GSPLYASPEIVNGRPYIGPeVDSWSLGVLLYILVHGTMPFDGHDYKILVKQISSG--AYREPTKPS---DA 228

                         250       260
                  ....*....|....*....|....*..
gi 564369110 1099 RGfLIK--VLVQDRLRPTAEETLEHPW 1123
Cdd:cd14161   229 CG-LIRwlLMVNPERRATLEDVASHWW 254

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 105.42 E-value: 1.22e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   334 PLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDGGLHSLHIARVGSEDEGLYEVSATNTHG 413
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 564369110   414 QAHCSAQLYV 423
Cdd:pfam07679   81 EAEASAELTV 90

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270826 [Multi-domain] Cd Length: 287 Bit Score: 112.04 E-value: 1.39e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyaaeGKRR-------VLQEYEVLRTL-HHERLMSLHEAYITPRYLVL 2294
Cdd:cd07832     2 YKILGRIGEGAHGIVFKAKDRETGETVALKKVA----LRKLeggipnqALREIKALQACqGHPYVVKLRDVFPHGTGFVL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2295 IAEScgnreLLCGLSDRFRYSED-----DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP 2369
Cdd:cd07832    78 VFEY-----MLSSLSEVLRDEERplteaQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSE 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGySPFYepdPQETEA-------RIVGG-------- 2433
Cdd:cd07832   153 EDPRLYSHQVATRWYRAPELLYGSRkYDEGVDLWAVGCIFAELLNG-SPLF---PGENDIeqlaivlRTLGTpnektwpe 228

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2434 ----------RFDAF------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07832   229 ltslpdynkiTFPESkgirleEIFPDCSPEAIDLLKGLLVYNPKKRLSAEEALRHPYF 286

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270980 [Multi-domain] Cd Length: 257 Bit Score: 111.32 E-value: 1.52e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAK----PKAsaRREARLLARL--QHDCVLYfhEAFERRRGL 940
Cdd:cd14078     1 LLKYYELHETIGSGGFAKVKLATHILTGEKVAIKIMDKKALgddlPRV--KTEIEALKNLshQHICRLY--HVIETDNKI 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFG---NAQ 1016
Cdd:cd14078    77 FMVLEYCPGgELFDYIVAKDRLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDE----DQNLKLIDFGlcaKPK 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPGEPQYCqFGTPEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFvgENDRTTLMNIRNYNVAFEETTFLSLS 1095
Cdd:cd14078   153 GGMDHHLETC-CGSPAYAAPELIQGKPYIGSeADVWSMGVLLYALLCGFLPF--DDDNVMALYRKIQSGKYEEPEWLSPS 229

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1096 REargFLIKVLVQ--DRLRPTAEETLEHPW 1123
Cdd:cd14078   230 SK---LLLDQMLQvdPKKRITVKELLNHPW 256

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270990 [Multi-domain] Cd Length: 265 Bit Score: 111.27 E-value: 1.68e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSG-LEFAAKFIPSQA-KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd14088     1 DRYDLGQVIKTEEFCEIFRAKDKTTGkLYTCKKFLKRDGrKVRKAAKNEINILKMVKHPNILQLVDVFETRKEYFIFLEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CT-EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVrICDFGNAQELTPGEPQY 1025
Cdd:cd14088    81 ATgREVFDWILDQGYYSERDTSNVIRQVLEAVAYLHSLKIVHRNLKLENLVYYNRLKNSKIV-ISDFHLAKLENGLIKEP 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGE--------NDRTTLMNIRNYNVAFEETTFLSLSRE 1097
Cdd:cd14088   160 C--GTPEYLAPEVVGRQRYGRPVDCWAIGVIMYILLSGNPPFYDEaeeddyenHDKNLFRKILAGDYEFDSPYWDDISQA 237

                         250       260
                  ....*....|....*....|....*..
gi 564369110 1098 ARGFLIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14088   238 AKDLVTRLMeVEQDQRITAEEAISHEW 264

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270745 [Multi-domain] Cd Length: 348 Bit Score: 113.25 E-value: 1.92e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2211 STTLRQGPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKI----VPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAY 2286
Cdd:cd05593     5 STTHHKRKTMNDFDYLKLLGKGTFGKVILVREKASGKYYAMKIlkkeVIIAKDEVAHTLTESRVLKNTRHPFLTSLKYSF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2287 ITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQP 2366
Cdd:cd05593    85 QTKDRLCFVMEYVNGGELFFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKE 164

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2367 YNPQAlKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQE 2425
Cdd:cd05593   165 GITDA-ATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEK 222

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270896 [Multi-domain] Cd Length: 265 Bit Score: 110.86 E-value: 2.03e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRV--VERSSGLEFAAKFIPSQAKP------KASARREARLLARLQHDCVLyfhEAFE----RRRGLVIVT 944
Cdd:cd13994     1 IGKGATSVVRIVtkKNPRSGVLYAVKEYRRRDDEskrkdyVKRLTSEYIISSKLHHPNIV---KVLDlcqdLHGKWCLVM 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQEL-TPGE 1022
Cdd:cd13994    78 EYCPGgDLFTLIEKADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILL-DEDG---VLKLTDFGTAEVFgMPAE 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQF----GTPEFVAPEIVNQSPVSG-VTDIWPVGVVAFLCLTGISPF----VGENDRTTLMNIRNYNVAFEETTFLS 1093
Cdd:cd13994   154 KESPMSaglcGSEPYMAPEVFTSGSYDGrAVDVWSCGIVLFALFTGRFPWrsakKSDSAYKAYEKSGDFTNGPYEPIENL 233

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 1094 LSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd13994   234 LPSECRRLIYRMLHPDpEKRITIDEALNDPWV 265

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271081 [Multi-domain] Cd Length: 310 Bit Score: 112.06 E-value: 2.16e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKpkASARREARLLARLQ-HDCVLYFHEAFERRRGLVIVTELCTE-ELLER 954
Cdd:cd14179    15 LGEGSFSICRKCLHKKTNQEYAVKIVSKRME--ANTQREIAALKLCEgHPNIVKLHEVYHDQLHTFLVMELLKGgELLER 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  955 MARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEqVRICDFGNAQeLTPGEPQYCQfgTP--- 1031
Cdd:cd14179    93 IKKKQHFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFTDESDNSE-IKIIDFGFAR-LKPPDNQPLK--TPcft 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1032 -EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTT-------LMNIRNYNVAFEETTFLSLSREARGFLI 1103
Cdd:cd14179   169 lHYAAPELLNYNGYDESCDLWSLGVILYTMLSGQVPFQCHDKSLTctsaeeiMKKIKQGDFSFEGEAWKNVSQEAKDLIQ 248


                  ....*.
gi 564369110 1104 KVLVQD 1109
Cdd:cd14179   249 GLLTVD 254

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270992 [Multi-domain] Cd Length: 289 Bit Score: 111.35 E-value: 2.75e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEGKR-RVLQEYEvlrTLH----HERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd14090    13 GAYASVQTCINLYTGKEYAVKIIEKHPGHSRsRVFREVE---TLHqcqgHPNILQLIEYFEDDERFYLVFEKMRGGPLLS 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA---LKIVDF--GSAQPYNPQALKP-----LG 2376
Cdd:cd14090    90 HIEKRVHFTEQEASLVVRDIASALDFLHDKGIAHRDLKPENILCESMDKvspVKICDFdlGSGIKLSSTSMTPvttpeLL 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 HRTGTLEFMAPEMVRGDpIGSAT------DIWGAGVLTYIMLSGYSPFYE--------------PDPQETE-ARIVGGRF 2435
Cdd:cd14090   170 TPVGSAEYMAPEVVDAF-VGEALsydkrcDLWSLGVILYIMLCGYPPFYGrcgedcgwdrgeacQDCQELLfHSIQEGEY 248

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 564369110 2436 DafqlYPN-----TSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd14090   249 E----FPEkewshISAEAKDLISHLLVRDASQRYTAEQVLQHPW 288

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270982 [Multi-domain] Cd Length: 262 Bit Score: 110.35 E-value: 2.85e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2267 EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPD 2346
Cdd:cd14080    52 ELEILRKLRHPNIIQVYSIFERGSKVFIFMEYAEHGDLLEYIQKRGALSESQARIWFRQLALAVQYLHSLDIAHRDLKCE 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2347 NLLLAADNALKIVDFGSAQPYNPQALKPLGhRT--GTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDP 2423
Cdd:cd14080   132 NILLDSNNNVKLSDFGFARLCPDDDGDVLS-KTfcGSAAYAAPEILQGIPyDPKKYDIWSLGVILYIMLCGSMPFDDSNI 210

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2424 QETEARIVGGRFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14080   211 KKMLKDQQNRKVRFPSSVKKLSPECKDLIDQLLEPDPTKRATIEEILNHPWL 262

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270833 [Multi-domain] Cd Length: 298 Bit Score: 111.51 E-value: 3.03e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTfVA--KI----VPYAAEG-KRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd07841     2 YEKGKKLGEGTYAVVYKARDKETGRI-VAikKIklgeRKEAKDGiNFTALREIKLLQELKHPNIIGLLDVFGHKSNINLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESC-GNRELLcgLSDRF-RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYnPQALK 2373
Cdd:cd07841    81 FEFMeTDLEKV--IKDKSiVLTPADIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLARSF-GSPNR 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2374 PLGHRTGTLEFMAPEMVRGDPI-GSATDIWGAG-VLTYIMLSgySPFYepdPQETEARIVGGRFDAF------------- 2438
Cdd:cd07841   158 KMTHQVVTRWYRAPELLFGARHyGVGVDMWSVGcIFAELLLR--VPFL---PGDSDIDQLGKIFEALgtpteenwpgvts 232

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2439 ----------------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd07841   233 lpdyvefkpfpptplkQIFPAASDDALDLLQRLLTLNPNKRITARQALEHPY 284

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270785 [Multi-domain] Cd Length: 275 Bit Score: 110.47 E-value: 3.39e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2218 PPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTL-HHERLMSLHEAYITPRYLV--- 2293
Cdd:cd06608     3 DPAGIFELVEVIGEGTYGKVYKARHKKTGQLAAIKIMDIIEDEEEEIKLEINILRKFsNHPNIATFYGAFIKKDPPGgdd 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2294 ---LIAESCGN---RELLCGLSDRFRYSEDDVATYVVQ-LLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQ 2365
Cdd:cd06608    83 qlwLVMEYCGGgsvTDLVKGLRKKGKRLKEEWIAYILReTLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGvSAQ 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2366 pynpqaLK-PLGHR---TGTLEFMAPEMVRGDPIGSAT-----DIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggRFD 2436
Cdd:cd06608   163 ------LDsTLGRRntfIGTPYWMAPEVIACDQQPDASydarcDVWSLGITAIELADGKPPLCDMHPMRALFKIP--RNP 234

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 564369110 2437 AFQLYPNTSQSATL--FLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06608   235 PPTLKSPEKWSKEFndFISECLIKNYEQRPFTEELLEHPFI 275

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270763 [Multi-domain] Cd Length: 292 Bit Score: 110.60 E-value: 5.16e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKI--VPYAAEGKR--RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCG 2307
Cdd:cd05612    12 GTFGRVHLVRDRISEHYYALKVmaIPEVIRLKQeqHVHNEKRVLKEVSHPFIIRLFWTEHDQRFLYMLMEYVPGGELFSY 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 LSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpqalKPLGHRT----GTLE 2383
Cdd:cd05612    92 LRNSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFA--------KKLRDRTwtlcGTPE 163

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 2384 FMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD 2436
Cdd:cd05612   164 YLAPEVIQSKGHNKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILAGKLE 216

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270978 [Multi-domain] Cd Length: 270 Bit Score: 109.88 E-value: 5.70e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2222 PYTFLEEKARGRFGVVR-----SCRENATGRTFVAKIVPYAAEGKR----RVLQEYEVLRTLHHERLMSLHEAYITPRYL 2292
Cdd:cd14076     2 PYILGRTLGEGEFGKVKlgwplPKANHRSGVQVAIKLIRRDTQQENcqtsKIMREINILKGLTHPNIVRLLDVLKTKKYI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLIAESCGNRELLCGLSDRfRYSEDDVATYV-VQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQA 2371
Cdd:cd14076    82 GIVLEFVSGGELFDYILAR-RRLKDSVACRLfAQLISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANTFDHFN 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 LKPLGHRTGTLEFMAPEMVRGDPI--GSATDIWGAGVLTYIMLSGYSPFyEPDPQETEARivggrfDAFQLYPNTSQSAT 2449
Cdd:cd14076   161 GDLMSTSCGSPCYAAPELVVSDSMyaGRKADIWSCGVILYAMLAGYLPF-DDDPHNPNGD------NVPRLYRYICNTPL 233

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 564369110 2450 LF-----------LRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14076   234 IFpeyvtpkardlLRRILVPNPRKRIRLSAIMRHAWL 270

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270984 [Multi-domain] Cd Length: 260 Bit Score: 109.42 E-value: 6.68e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVP---YAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGL 2308
Cdd:cd14082    14 GQFGIVYGGKHRKTGRDVAIKVIDklrFPTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVMEKLHGDMLEMIL 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2309 S-DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNAL---KIVDFGSAQPYNPQALKplghRT--GTL 2382
Cdd:cd14082    94 SsEKGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLASAEPFpqvKLCDFGFARIIGEKSFR----RSvvGTP 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEpdPQETEARIVGGRFdafqLYPNT-----SQSATLFLRKVLS 2457
Cdd:cd14082   170 AYLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNE--DEDINDQIQNAAF----MYPPNpwkeiSPDAIDLINNLLQ 243

                         250
                  ....*....|....*..
gi 564369110 2458 VHPWSRPSLQDCLAHPW 2474
Cdd:cd14082   244 VKMRKRYSVDKSLSHPW 260

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270795 [Multi-domain] Cd Length: 260 Bit Score: 109.37 E-value: 6.88e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKR-----RVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAEscgnreL 2304
Cdd:cd06625    10 QGAFGQVYLCYDADTGRELAVKQVEIDPINTEaskevKALEcEIQLLKNLQHERIVQYYGCLQDEKSLSIFME------Y 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 LCGLS--DRFR----YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP----QALKP 2374
Cdd:cd06625    84 MPGGSvkDEIKaygaLTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRLQTicssTGMKS 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRfDAFQLYPNTSQSATLFLRK 2454
Cdd:cd06625   164 V---TGTPYWMSPEVINGEGYGRKADIWSVGCTVVEMLTTKPPWAEFEPMAAIFKIATQP-TNPQLPPHVSEDARDFLSL 239

                         250       260
                  ....*....|....*....|
gi 564369110 2455 VLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd06625   240 IFVRNKKQRPSAEELLSHSF 259

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270821 [Multi-domain] Cd Length: 297 Bit Score: 110.46 E-value: 7.65e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKAR---GRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVL-QEYEVLRTLHHERLMSLHEAYITPRYLVL 2294
Cdd:cd06659    16 QGDPRQLLENYVKigeGSTGVVCIAREKHSGRQVAVKMMDLRKQQRRELLfNEVVIMRDYQHPNVVEMYKSYLVGEELWV 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2295 IAESCGNRELlCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGsaqpYNPQALKP 2374
Cdd:cd06659    96 LMEYLQGGAL-TDIVSQTRLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFG----FCAQISKD 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHR---TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLF 2451
Cdd:cd06659   171 VPKRkslVGTPYWMAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKRLRDSPPPKLKNSHKASPVLRDF 250

                         250       260
                  ....*....|....*....|....
gi 564369110 2452 LRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06659   251 LERMLVRDPQERATAQELLDHPFL 274

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270906 [Multi-domain] Cd Length: 256 Bit Score: 109.01 E-value: 8.31e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIpsqAKPKASA------RR------EARLLARLQ---HDCVLYFHEAF 934
Cdd:cd14004     1 DYTILKEMGEGAYGQVNLAIYKSKGKEVVIKFI---FKERILVdtwvrdRKlgtvplEIHILDTLNkrsHPNIVKLLDFF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  935 ERRRGLVIVTELCTE--ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDF 1012
Cdd:cd14004    78 EDDEFYYLVMEKHGSgmDLFDFIERKPNMDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVIL-DGNG---TIKLIDF 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1013 GNAQELTPGePQYCQFGTPEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFVgENDRTTLMNIRNYNvafeettf 1091
Cdd:cd14004   154 GSAAYIKSG-PFDTFVGTIDYAAPEVLRGNPYGGKeQDIWALGVLLYTLVFKENPFY-NIEEILEADLRIPY-------- 223

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 1092 lSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14004   224 -AVSEDLIDLISRMLNRDvGDRPTIEELLTDPWL 256

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270827 [Multi-domain] Cd Length: 288 Bit Score: 109.71 E-value: 8.89e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAK-F--IPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd07833     3 YEVLGVVGEGAYGVVLKCRNKATGEIVAIKkFkeSEDDEDVKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TEELLERMARKPT-VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELT-PGEPQY 1025
Cdd:cd07833    83 ERTLLELLEASPGgLPPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPENILV-SESG---VLKLCDFGFARALTaRPASPL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQF-GTPEFVAPEIVNQSPVSG-VTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRN--------------YNVAFEET 1089
Cdd:cd07833   159 TDYvATRWYRAPELLVGDTNYGkPVDVWAIGCIMAELLDGEPLFPGDSDIDQLYLIQKclgplppshqelfsSNPRFAGV 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 1090 TFLSL----SREAR----------GFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07833   239 AFPEPsqpeSLERRypgkvsspalDFLKACLRMDpKERLTCDELLQHPYF 288

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270973 [Multi-domain] Cd Length: 253 Bit Score: 108.63 E-value: 9.51e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR---REARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd14071     1 FYDIERTIGKGNFAVVKLARHRITKTEVAIKIIDKSQLDEENLKkiyREVQIMKMLNHPHIIKLYQVMETKDMLYLVTEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEP-- 1023
Cdd:cd14071    81 ASNgEIFDYLAQHGRMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLL-DANM---NIKIADFGFSNFFKPGELlk 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCqfGTPEFVAPEIVNQSPVSG-VTDIWPVGVVAFLCLTGISPFvgenDRTTLMNIRNYNVA--FEETTFlsLSREARG 1100
Cdd:cd14071   157 TWC--GSPPYAAPEVFEGKEYEGpQLDIWSLGVVLYVLVCGALPF----DGSTLQTLRDRVLSgrFRIPFF--MSTDCEH 228

                         250       260
                  ....*....|....*....|....*
gi 564369110 1101 FLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14071   229 LIRRMLVLDpSKRLTIEQIKKHKWM 253

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271035 [Multi-domain] Cd Length: 262 Bit Score: 108.89 E-value: 9.64e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARL-QHDC-----VLYFHEAFERRRGLVIVT 944
Cdd:cd14133     1 YEVLEVLGKGTFGQVVKCYDLLTGEEVALKIIKNNKDYLDQSLDEIRLLELLnKKDKadkyhIVRLKDVFYFKNHLCIVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTEELLE--RMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaGGEEQVRICDFGNAQELTPGE 1022
Cdd:cd14133    81 ELLSQNLYEflKQNKFQYLSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILLAS--YSRCQIKIIDFGSSCFLTQRL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQfgTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIrnynvafeETTFLSLSRE--ARG 1100
Cdd:cd14133   159 YSYIQ--SRYYRAPEVILGLPYDEKIDMWSLGCILAELYTGEPLFPGASEVDQLARI--------IGTIGIPPAHmlDQG 228

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 1101 ---------FLIKVLVQDRL-RPTAEETLEHPWF 1124
Cdd:cd14133   229 kaddelfvdFLKKLLEIDPKeRPTASQALSHPWL 262

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 102.34 E-value: 1.41e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110     1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQASCASSLA 80
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89


                   .
gi 564369110    81 V 81
Cdd:pfam07679   90 V 90

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270887 [Multi-domain] Cd Length: 272 Bit Score: 108.58 E-value: 1.60e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2222 PYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK-RRVLQEYEVLRTL-HHERLMSLHEA---YITPRYLVLIA 2296
Cdd:cd13985     1 RYQVTKQLGEGGFSYVYLAHDVNTGRRYALKRMYFNDEEQlRVAIKEIEIMKRLcGHPNIVQYYDSailSSEGRKEVLLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 -ESCGNrELLCGLSDRF--RYSEDDVATYVVQLLQGLDYLH--GRHVLHLDIKPDNLLLAADNALKIVDFGSA----QPY 2367
Cdd:cd13985    81 mEYCPG-SLVDILEKSPpsPLSEEEVLRIFYQICQAVGHLHsqSPPIIHRDIKIENILFSNTGRFKLCDFGSAttehYPL 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2368 NPQ-----ALKPLGHRTgTLEFMAPEMV---RGDPIGSATDIWGAGVLTYIMLSGYSPFYEpdpqETEARIVGGRFDaFQ 2439
Cdd:cd13985   160 ERAeevniIEEEIQKNT-TPMYRAPEMIdlySKKPIGEKADIWALGCLLYKLCFFKLPFDE----SSKLAIVAGKYS-IP 233

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2440 LYPNTSQSATLFLRKVLSVHPWSRPS 2465
Cdd:cd13985   234 EQPRYSPELHDLIRHMLTPDPAERPD 259

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270977 [Multi-domain] Cd Length: 255 Bit Score: 107.81 E-value: 1.77e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2262 RRVL-QEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLH 2340
Cdd:cd14075    45 QRLLsREISSMEKLHHPNIIRLYEVVETLSKLHLVMEYASGGELYTKISTEGKLSESEAKPLFAQIVSAVKHMHENNIIH 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2341 LDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPLghrTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd14075   125 RDLKAENVFYASNNCVKVGDFGfSTHAKRGETLNTF---CGSPPYAAPELFKDEHyIGIYVDIWALGVLLYFMVTGVMPF 201

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2419 YEPDPQETEARIVGGRfdaFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14075   202 RAETVAKLKKCILEGT---YTIPSYVSEPCQELIRGILQPVPSDRYSIDEIKNSEWL 255

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270912 [Multi-domain] Cd Length: 269 Bit Score: 108.15 E-value: 2.09e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFS--YLRRvveRSSGLEFAAkfIPSQAKPK-ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd14010     2 YVLYDEIGRGKHSvvYKGR---RKGTIEFVA--IKCVDKSKrPEVLNEVRLTHELKHPNVLKFYEWYETSNHLWLVVEYC 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 T----EELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELT---- 1019
Cdd:cd14010    77 TggdlETLLRQDGNLP---ESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILL-DGNG---TLKLSDFGLARREGeilk 149

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1020 -------------PGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENdRTTLMN 1078
Cdd:cd14010   150 elfgqfsdegnvnKVSKKQAKRGTPYYMAPELFQGGVHSFASDLWALGCVLYEMFTGKPPFVAES-FTELVE 220

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270734 [Multi-domain] Cd Length: 317 Bit Score: 109.03 E-value: 2.79e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFG---VVRSCRENATGRTFVAKIVPYAAEGKR---RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNREL 2304
Cdd:cd05582     5 QGSFGkvfLVRKITGPDAGTLYAMKVLKKATLKVRdrvRTKMERDILADVNHPFIVKLHYAFQTEGKLYLILDFLRGGDL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 LCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHrTGTLEF 2384
Cdd:cd05582    85 FTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKESIDHEKKAYSF-CGTVEY 163

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2385 MAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQlypNTSQSATLFLRKVLSVHPWSR 2463
Cdd:cd05582   164 MAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKETMTMILKAKLGMPQ---FLSPEAQSLLRALFKRNPANR 239

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271083 [Multi-domain] Cd Length: 279 Bit Score: 108.13 E-value: 2.96e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEG---------KRRVLQEYEVLRTLH-HERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd14181    20 RGVSSVVRRCVHRHTGQEFAVKIIEVTAERlspeqleevRSSTLKEIHILRQVSgHPSIITLIDSYESSTFIFLVFDLMR 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP-QALKPLghrT 2379
Cdd:cd14181   100 RGELFDYLTEKVTLSEKETRSIMRSLLEAVSYLHANNIVHRDLKPENILLDDQLHIKLSDFGFSCHLEPgEKLREL---C 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVR------GDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLYPNTSQSATLFL 2452
Cdd:cd14181   177 GTPGYLAPEILKcsmdetHPGYGKEVDLWACGVILFTLLAGSPPFWHRRQMLMLRMIMEGRYQfSSPEWDDRSSTVKDLI 256

                         250       260
                  ....*....|....*....|...
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14181   257 SRLLVVDPEIRLTAEQALQHPFF 279

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270726 [Multi-domain] Cd Length: 316 Bit Score: 108.86 E-value: 3.31e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKR----RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd05574    11 KGDVGRVYLVRLKGTGKLFAMKVLDKEEMIKRnkvkRVLTEREILATLDHPFLPTLYASFQTSTHLCFVMDYCPGGELFR 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDR--FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDF----------------------- 2361
Cdd:cd05574    91 LLQKQpgKRLPEEVARFYAAEVLLALEYLHLLGFVYRDLKPENILLHESGHIMLTDFdlskqssvtpppvrkslrkgsrr 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2362 -GSAQPYNPQALKPLGHRT----GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD 2436
Cdd:cd05574   171 sSVKSIEKETFVAEPSARSnsfvGTEEYIAPEVIKGDGHGSAVDWWTLGILLYEMLYGTTPFKGSNRDETFSNILKKELT 250

                         250       260
                  ....*....|....*....|....*..
gi 564369110 2437 aFQLYPNTSQSATLFLRKVLSVHPWSR 2463
Cdd:cd05574   251 -FPESPPVSSEAKDLIRKLLVKDPSKR 276

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270814 [Multi-domain] Cd Length: 261 Bit Score: 107.32 E-value: 3.76e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2217 GPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR-VLQEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd06647     3 GDPKKKYTRFEKIGQGASGTVYTAIDVATGQEVAIKQMNLQQQPKKElIINEILVMRENKNPNIVNYLDSYLVGDELWVV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKpl 2375
Cdd:cd06647    83 MEYLAGGSLTDVVTET-CMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSK-- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 ghRT---GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFL 2452
Cdd:cd06647   160 --RStmvGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSAIFRDFL 237

                         250       260
                  ....*....|....*....|....
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd06647   238 NRCLEMDVEKRGSAKELLQHPFLK 261

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270735 [Multi-domain] Cd Length: 268 Bit Score: 107.09 E-value: 4.44e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPyaaegKRRVLQEYEVLRTLHHER-----------LMSLHEAYITPRYLVLIAES 2298
Cdd:cd05583     6 AYGKVFLVRKVGGHDAGKLYAMKVLK-----KATIVQKAKTAEHTMTERqvleavrqspfLVTLHYAFQTDAKLHLILDY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPqalkPLGHR 2378
Cdd:cd05583    81 VNGGELFTHLYQREHFTESEVRIYIGEIVLALEHLHKLGIIYRDIKLENILLDSEGHVVLTDFGLSKEFLP----GENDR 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 T----GTLEFMAPEMVRGDPIG--SATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNT-SQSATLF 2451
Cdd:cd05583   157 AysfcGTIEYMAPEVVRGGSDGhdKAVDWWSLGVLTYELLTGASPFTVDGERNSQSEISKRILKSHPPIPKTfSAEAKDF 236

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 2452 LRKVLSVHPWSR-----PSLQDCLAHPWLQ 2476
Cdd:cd05583   237 ILKLLEKDPKKRlgagpRGAHEIKEHPFFK 266

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271111 [Multi-domain] Cd Length: 290 Bit Score: 107.87 E-value: 4.72e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCG 2307
Cdd:cd14209    12 GSFGRVMLVRHKETGNYYAMKILDKQKVVKLKqvehTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVMEYVPGGEMFSH 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 LSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpqalKPLGHRT----GTLE 2383
Cdd:cd14209    92 LRRIGRFSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFGFA--------KRVKGRTwtlcGTPE 163

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2384 FMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRF 2435
Cdd:cd14209   164 YLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKV 215

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270992 [Multi-domain] Cd Length: 289 Bit Score: 107.50 E-value: 6.27e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEI-GRGAFSYLRRVVERSSGLEFAAKFIPSQ-AKPKASARREARLLARLQ-HDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14090     1 DLYKLTGELlGEGAYASVQTCINLYTGKEYAVKIIEKHpGHSRSRVFREVETLHQCQgHPNILQLIEYFEDDERFYLVFE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 -LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEEQVRICDFG-------NAQE 1017
Cdd:cd14090    81 kMRGGPLLSHIEKRVHFTEQEASLVVRDIASALDFLHDKGIAHRDLKPENILC-ESMDKVSPVKICDFDlgsgiklSSTS 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1018 LTPgePQYCQFGTP----EFVAPEIVNQSPVSGVT-----DIWPVGVVAFLCLTGISPFV-----------GENDRTT-- 1075
Cdd:cd14090   160 MTP--VTTPELLTPvgsaEYMAPEVVDAFVGEALSydkrcDLWSLGVILYIMLCGYPPFYgrcgedcgwdrGEACQDCqe 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1076 --LMNIRNYNVAFEETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14090   238 llFHSIQEGEYEFPEKEWSHISAEAKDLISHLLVRDaSQRYTAEQVLQHPW 288

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270898 [Multi-domain] Cd Length: 273 Bit Score: 106.61 E-value: 6.89e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  863 RGRRLSDYYDIhQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHEAFERRRGL 940
Cdd:cd13996     1 NSRYLNDFEEI-ELLGSGGFGSVYKVRNKVDGVTYAIKKIRLTEKSSASEKvlREVKALAKLNHPNIVRYYTAWVEEPPL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTEELLERMARKPTVCESETRT----YMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeeQVRICDFG--- 1013
Cdd:cd13996    80 YIQMELCEGGTLRDWIDRRNSSSKNDRKlaleLFKQILKGVSYIHSKGIVHRDLKPSNIFLDNDDL---QVKIGDFGlat 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1014 -----------NAQELTPGEPQYCQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAF--LCltgisPFVGENDR-TTLMN 1078
Cdd:cd13996   157 signqkrelnnLNNNNNGNTSNNSVGiGTPLYASPEQLDGENYNEKADIYSLGIILFemLH-----PFKTAMERsTILTD 231

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 564369110 1079 IRNYNVAFEettFLSLSREARGFLIKVLVQD-RLRPTAEETLE 1120
Cdd:cd13996   232 LRNGILPES---FKAKHPKEADLIQSLLSKNpEERPSAEQLLR 271

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271088 [Multi-domain] Cd Length: 256 Bit Score: 106.10 E-value: 7.66e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGK----RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd14186    11 KGSFACVYRARSLHTGLEVAIKMIDKKAMQKagmvQRVRNEVEIHCQLKHPSILELYNYFEDSNYVYLVLEMCHNGEMSR 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFR-YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKplgHRT--GTLE 2383
Cdd:cd14186    91 YLKNRKKpFTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQLKMPHEK---HFTmcGTPN 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2384 FMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRfdaFQLYPNTSQSATLFLRKVLSVHPWSR 2463
Cdd:cd14186   168 YISPEIATRSAHGLESDVWSLGCMFYTLLVGRPPFDTDTVKNTLNKVVLAD---YEMPAFLSREAQDLIHQLLRKNPADR 244

                         250
                  ....*....|..
gi 564369110 2464 PSLQDCLAHPWL 2475
Cdd:cd14186   245 LSLSSVLDHPFM 256

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270722 [Multi-domain] Cd Length: 318 Bit Score: 107.69 E-value: 9.66e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPyaaegKRRVLQEYEVLRTLHHER----------LMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd05570     5 KGSFGKVMLAERKKTDELYAIKVLK-----KEVIIEDDDVECTMTEKRvlalanrhpfLTGLHACFQTEDRLYFVMEYVN 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpynpQALKPlGHRT- 2379
Cdd:cd05570    80 GGDLMFHIQRARRFTEERARFYAAEICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCK----EGIWG-GNTTs 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 ---GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETearivggrFDAFQ----LYPNT-SQSATLF 2451
Cdd:cd05570   155 tfcGTPDYIAPEILREQDYGFSVDWWALGVLLYEMLAGQSPFEGDDEDEL--------FEAILndevLYPRWlSREAVSI 226

                         250       260
                  ....*....|....*....|....*..
gi 564369110 2452 LRKVLSVHPWSR----PS-LQDCLAHP 2473
Cdd:cd05570   227 LKGLLTKDPARRlgcgPKgEADIKAHP 253

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270981 [Multi-domain] Cd Length: 256 Bit Score: 105.43 E-value: 1.42e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIpSQAKPKAS-----ARREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14079     4 YILGKTLGVGSFGKVKLAEHELTGHKVAVKIL-NRQKIKSLdmeekIRREIQILKLFRHPHIIRLYEVIETPTDIFMVME 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCT-EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQ 1024
Cdd:cd14079    83 YVSgGELFDYIVQKGRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLL----DSNMNVKIADFGLSNIMRDGEFL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQFGTPEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREARGFLI 1103
Cdd:cd14079   159 KTSCGSPNYAAPEVISGKLYAGPeVDVWSCGVILYALLCGSLPFDDEHIPNLFKKIKSGIYTIPS----HLSPGARDLIK 234

                         250       260
                  ....*....|....*....|..
gi 564369110 1104 KVLVQDRL-RPTAEETLEHPWF 1124
Cdd:cd14079   235 RMLVVDPLkRITIPEIRQHPWF 256

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270795 [Multi-domain] Cd Length: 260 Bit Score: 105.52 E-value: 1.61e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIP-----SQAKPKASA-RREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE- 949
Cdd:cd06625     8 LGQGAFGQVYLCYDADTGRELAVKQVEidpinTEASKEVKAlECEIQLLKNLQHERIVQYYGCLQDEKSLSIFMEYMPGg 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQEL-TPGEPQYCQ- 1027
Cdd:cd06625    88 SVKDEIKAYGALTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILR-DSNG---NVKLGDFGASKRLqTICSSTGMKs 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 -FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFvgeNDRTTLMNIrnYNVAFEETTF---LSLSREARGFLI 1103
Cdd:cd06625   164 vTGTPYWMSPEVINGEGYGRKADIWSVGCTVVEMLTTKPPW---AEFEPMAAI--FKIATQPTNPqlpPHVSEDARDFLS 238

                         250       260
                  ....*....|....*....|..
gi 564369110 1104 KVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd06625   239 LIFVRNkKQRPSAEELLSHSFV 260

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270832 [Multi-domain] Cd Length: 291 Bit Score: 106.11 E-value: 1.66e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2265 LQEYEVLRTLHHERLMSLHEAYITPR--------YLVLiaESCGNRelLCGLSDR--FRYSEDDVATYVVQLLQGLDYLH 2334
Cdd:cd07840    46 IREIKLLQKLDHPNVVRLKEIVTSKGsakykgsiYMVF--EYMDHD--LTGLLDNpeVKFTESQIKCYMKQLLEGLQYLH 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2335 GRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEFMAPEMVRGDPI-GSATDIWGAGVLTYIMLS 2413
Cdd:cd07840   122 SNGILHRDIKGSNILINNDGVLKLADFGLARPYTKENNADYTNRVITLWYRPPELLLGATRyGPEVDMWSVGCILAELFT 201

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2414 G----------------YS----------------PFYE-PDPQETEARIVGGRFDAFQlypntSQSATLFLRKVLSVHP 2460
Cdd:cd07840   202 GkpifqgkteleqlekiFElcgspteenwpgvsdlPWFEnLKPKKPYKRRLREVFKNVI-----DPSALDLLDKLLTLDP 276

                         250
                  ....*....|....
gi 564369110 2461 WSRPSLQDCLAHPW 2474
Cdd:cd07840   277 KKRISADQALQHEY 290

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271023 [Multi-domain] Cd Length: 252 Bit Score: 105.06 E-value: 1.75e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2265 LQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIK 2344
Cdd:cd14121    43 LTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGDLSRFIRSRRTLPESTVRRFLQQLASALQFLREHNISHMDLK 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2345 PDNLLLAA--DNALKIVDFGSAQpynpqALKPLGHRT---GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFY 2419
Cdd:cd14121   123 PQNLLLSSryNPVLKLADFGFAQ-----HLKPNDEAHslrGSPLYMAPEMILKKKYDARVDLWSVGVILYECLFGRAPFA 197

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 2420 EPDPQETEARIVGGRFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd14121   198 SRSFEELEEKIRSSKPIEIPTRPELSADCRDLLLRLLQRDPDRRISFEEFFAHPF 252

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270764 [Multi-domain] Cd Length: 290 Bit Score: 105.85 E-value: 2.01e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYA-----AEGKRRVLQEYEVLRTLHHER-LMSLHEAYITPRYLVLIAESCGNRE 2303
Cdd:cd05613    12 AYGKVFLVRKVSGHDAGKLYAMKVLKKAtivqkAKTAEHTRTERQVLEHIRQSPfLVTLHYAFQTDTKLHLILDYINGGE 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2304 LLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLE 2383
Cdd:cd05613    92 LFTHLSQRERFTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKEFLLDENERAYSFCGTIE 171

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 564369110 2384 FMAPEMVRGDPIG--SATDIWGAGVLTYIMLSGYSPFYEPDPQETEARI 2430
Cdd:cd05613   172 YMAPEIVRGGDSGhdKAVDWWSLGVLMYELLTGASPFTVDGEKNSQAEI 220

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270732 [Multi-domain] Cd Length: 290 Bit Score: 105.74 E-value: 2.10e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA----KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd05580     3 FEFLKTLGTGSFGRVRLVKHKDSGKYYALKILKKAKiiklKQVEHVLNEKRILSEVRHPFIVNLLGSFQDDRNLYMVMEY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CT--E--ELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGE 1022
Cdd:cd05580    83 VPggElfSLLRRSGRFP---NDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLL-DSDG---HIKITDFGFAKRVKDRT 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREARGFL 1102
Cdd:cd05580   156 YTLC--GTPEYLAPEIILSKGHGKAVDWWALGILIYEMLAGYPPFFDENPMKIYEKILEGKIRFPSF----FDPDAKDLI 229

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1103 IKVLVQDR------LRPTAEETLEHPWFKT 1126
Cdd:cd05580   230 KRLLVVDLtkrlgnLKNGVEDIKNHPWFAG 259

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 98.87 E-value: 2.50e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   139 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQrRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 218
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSD-RFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 564369110   219 GARQCEARLEV 229
Cdd:pfam07679   80 GEAEASAELTV 90

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270869 [Multi-domain] Cd Length: 256 Bit Score: 104.78 E-value: 2.54e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--PSQA-KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE-- 945
Cdd:cd08530     2 FKVLKKLGKGSYGSVYKVKRLSDNQVYALKEVnlGSLSqKEREDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVMEya 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 ----LCTEELLERMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGaggeEQVRICDFGNAQELTpG 1021
Cdd:cd08530    82 pfgdLSKLISKRKKKRRL-FPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSAG----DLVKIGDLGISKVLK-K 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 EPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENdrttlMNIRNYNVAFEETTFLS--LSREAR 1099
Cdd:cd08530   156 NLAKTQIGTPLYAAPEVWKGRPYDYKSDIWSLGCLLYEMATFRPPFEART-----MQELRYKVCRGKFPPIPpvYSQDLQ 230

                         250       260
                  ....*....|....*....|....
gi 564369110 1100 GFLIKVLVQD-RLRPTAEETLEHP 1122
Cdd:cd08530   231 QIIRSLLQVNpKKRPSCDKLLQSP 254

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270823 [Multi-domain] Cd Length: 282 Bit Score: 105.26 E-value: 2.58e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  902 IPSqakpkaSARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEEL---LERMARKPTvcESETRTYMRQVLEGIG 978
Cdd:cd07829    41 IPS------TALREISLLKELKHPNIVKLLDVIHTENKLYLVFEYCDQDLkkyLDKRPGPLP--PNLIKSIMYQLLRGLA 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  979 YLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQYcqfgTPEFV-----APEIVNQSPV--SGVtDIW 1051
Cdd:cd07829   113 YCHSHRILHRDLKPQNLLI----NRDGVLKLADFGLARAFGIPLRTY----THEVVtlwyrAPEILLGSKHysTAV-DIW 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1052 PVGVVAFLCLTGISPFVGENDRTTLMNI------------------RNYNVAFE-------ETTFLSLSREARGFLIKVL 1106
Cdd:cd07829   184 SVGCIFAELITGKPLFPGDSEIDQLFKIfqilgtpteeswpgvtklPDYKPTFPkwpkndlEKVLPRLDPEGIDLLSKML 263

                         250
                  ....*....|....*....
gi 564369110 1107 VQD-RLRPTAEETLEHPWF 1124
Cdd:cd07829   264 QYNpAKRISAKEALKHPYF 282

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270815 [Multi-domain] Cd Length: 261 Bit Score: 104.45 E-value: 2.91e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2216 QGPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVL-QEYEVLRTLHHERLMSLHEAYITPRYLVL 2294
Cdd:cd06648     2 PGDPRSDLDNFVKIGEGSTGIVCIATDKSTGRQVAVKKMDLRKQQRRELLfNEVVIMRDYQHPNIVEMYSSYLVGDELWV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2295 IAEscgnreLLCG--LSD---RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGsaqpYNP 2369
Cdd:cd06648    82 VME------FLEGgaLTDivtHTRMNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFG----FCA 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLGHR---TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQ 2446
Cdd:cd06648   152 QVSKEVPRRkslVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRIRDNEPPKLKNLHKVSP 231

                         250       260
                  ....*....|....*....|....*....
gi 564369110 2447 SATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06648   232 RLRSFLDRMLVRDPAQRATAAELLNHPFL 260

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270868 [Multi-domain] Cd Length: 256 Bit Score: 104.42 E-value: 2.94e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAK---IVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd08529     2 FEILNKLGKGSFGVVYKVVRKVDGRVYALKqidISRMSRKMREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GN---RELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALkpLG 2376
Cdd:cd08529    82 ENgdlHSLIKSQRGR-PLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKILSDTTN--FA 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 HR-TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFyepDPQETEA---RIVGGRFDAF-QLYpntSQSATLF 2451
Cdd:cd08529   159 QTiVGTPYYLSPELCEDKPYNEKSDVWALGCVLYELCTGKHPF---EAQNQGAlilKIVRGKYPPIsASY---SQDLSQL 232

                         250       260
                  ....*....|....*....|....
gi 564369110 2452 LRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd08529   233 IDSCLTKDYRQRPDTTELLRNPSL 256

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271075 [Multi-domain] Cd Length: 288 Bit Score: 105.49 E-value: 3.12e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEI-GRGAFSYLRRVVERSSGLEFAAKFIPSQ-AKPKASARREARLLARLQ-HDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14173     1 DVYQLQEEVlGEGAYARVQTCINLITNKEYAVKIIEKRpGHSRSRVFREVEMLYQCQgHRNVLELIEFFEEEDKFYLVFE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 -LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEEQVRICDF--GNAQEL---- 1018
Cdd:cd14173    81 kMRGGSILSHIHRRRHFNELEASVVVQDIASALDFLHNKGIAHRDLKPENILC-EHPNQVSPVKICDFdlGSGIKLnsdc 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1019 ----TPGEPQYCqfGTPEFVAPEIV-----NQSPVSGVTDIWPVGVVAFLCLTGISPFVGEN------DR---------T 1074
Cdd:cd14173   160 spisTPELLTPC--GSAEYMAPEVVeafneEASIYDKRCDLWSLGVILYIMLSGYPPFVGRCgsdcgwDRgeacpacqnM 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 1075 TLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14173   238 LFESIQEGKYEFPEKDWAHISCAAKDLISKLLVRDaKQRLSAAQVLQHPW 287

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271064 [Multi-domain] Cd Length: 259 Bit Score: 104.30 E-value: 3.26e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVpyaaeGKRRVLQEY---------EVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14162    11 GSYAVVKKAYSTKHKCKVAIKIV-----SKKKAPEDYlqkflpreiEVIKGLKHPNLICFYEAIETTSRVYIIMELAENG 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA--QPYNPQALKPLGHR-T 2379
Cdd:cd14162    86 DLLDYIRKNGALPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFArgVMKTKDGKPKLSETyC 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDPI-GSATDIWGAGVLTYIMLSGYSPFYEPDP----QETEARIVggrfdaFQLYPNTSQSATLFLRK 2454
Cdd:cd14162   166 GSYAYASPEILRGIPYdPFLSDIWSMGVVLYTMVYGRLPFDDSNLkvllKQVQRRVV------FPKNPTVSEECKDLILR 239

                         250       260
                  ....*....|....*....|.
gi 564369110 2455 VLSVHPwSRPSLQDCLAHPWL 2475
Cdd:cd14162   240 MLSPVK-KRITIEEIKRDPWF 259

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270750 [Multi-domain] Cd Length: 324 Bit Score: 106.16 E-value: 3.26e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAK-FIPSQAKPK---ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-EL 951
Cdd:cd05599     9 IGRGAFGEVRLVRKKDTGHVYAMKkLRKSEMLEKeqvAHVRAERDILAEADNPWVVKLYYSFQDEENLYLIMEFLPGgDM 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQFGTP 1031
Cdd:cd05599    89 MTLLMKKDTLTEEETRFYIAETVLAIESIHKLGYIHRDIKPDNLLL-DARG---HIKLSDFGLCTGLKKSHLAYSTVGTP 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1032 EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVL--VQD 1109
Cdd:cd05599   165 DYIAPEVFLQKGYGKECDWWSLGVIMYEMLIGYPPFCSDDPQETCRKIMNWRETLVFPPEVPISPEAKDLIERLLcdAEH 244

                         250
                  ....*....|....*..
gi 564369110 1110 RL-RPTAEETLEHPWFK 1125
Cdd:cd05599   245 RLgANGVEEIKSHPFFK 261

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270972 [Multi-domain] Cd Length: 262 Bit Score: 104.51 E-value: 3.61e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKAS-----ARREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14070     4 YLIGRKLGEGSFAKVREGLHAVTGEKVAIKVIDKKKAKKDSyvtknLRREGRIQQMIRHPNITQLLDILETENSYYLVME 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFG---NAQELTPG 1021
Cdd:cd14070    84 LCPGgNLMHRIYDKKRLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDE----NDNIKLIDFGlsnCAGILGYS 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 564369110 1022 EPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGE 1070
Cdd:cd14070   160 DPFSTQCGSPAYAAPELLARKKYGPKVDVWSIGVNMYAMLTGTLPFTVE 208

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271084 [Multi-domain] Cd Length: 276 Bit Score: 104.61 E-value: 4.11e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----------VLQEYEVLRTLH-HERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd14182    13 RGVSSVVRRCIHKPTRQEYAVKIIDITGGGSFSpeevqelreaTLKEIDILRKVSgHPNIIQLKDTYETNTFFFLVFDLM 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPLghr 2378
Cdd:cd14182    93 KKGELFDYLTEKVTLSEKETRKIMRALLEVICALHKLNIVHRDLKPENILLDDDMNIKLTDFGfSCQLDPGEKLREV--- 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRG--DP----IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLYPNTSQSATLF 2451
Cdd:cd14182   170 CGTPGYLAPEIIECsmDDnhpgYGKEVDMWSTGVIMYTLLAGSPPFWHRKQMLMLRMIMSGNYQfGSPEWDDRSDTVKDL 249

                         250       260
                  ....*....|....*....|....*
gi 564369110 2452 LRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd14182   250 ISRFLVVQPQKRYTAEEALAHPFFQ 274

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270981 [Multi-domain] Cd Length: 256 Bit Score: 103.89 E-value: 4.20e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2222 PYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPY----AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd14079     3 NYILGKTLGVGSFGKVKLAEHELTGHKVAVKILNRqkikSLDMEEKIRREIQILKLFRHPHIIRLYEVIETPTDIFMVME 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGsaqpynpqaLKPL-- 2375
Cdd:cd14079    83 YVSGGELFDYIVQKGRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFG---------LSNImr 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 -GH--RT--GTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGrfdAFQLYPNTSQSAT 2449
Cdd:cd14079   154 dGEflKTscGSPNYAAPEVISGKLyAGPEVDVWSCGVILYALLCGSLPFDDEHIPNLFKKIKSG---IYTIPSHLSPGAR 230

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2450 LFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14079   231 DLIKRMLVVDPLKRITIPEIRQHPWF 256

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132943 [Multi-domain] Cd Length: 256 Bit Score: 103.50 E-value: 5.77e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKaSARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd06612     2 EEVFDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVEEDLQ-EIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYC 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 T----EELLERMARkpTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEP 1023
Cdd:cd06612    81 GagsvSDIMKITNK--TLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNE----EGQAKLADFGVSGQLTDTMA 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEND-RTTLMNIRNYNVAFEETTflSLSREARGF 1101
Cdd:cd06612   155 KRNTViGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPmRAIFMIPNKPPPTLSDPE--KWSPEFNDF 232

                         250       260
                  ....*....|....*....|....
gi 564369110 1102 LIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd06612   233 VKKCLVKDpEERPSAIQLLQHPFI 256

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270974 [Multi-domain] Cd Length: 253 Bit Score: 103.37 E-value: 7.33e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI-PSQAKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd14072     2 YRLLKTIGKGNFAKVKLARHVLTGREVAIKIIdKTQLNPSSLQKlfREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEP--Q 1024
Cdd:cd14072    82 SGgEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLL----DADMNIKIADFGFSNEFTPGNKldT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCqfGTPEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFVGENdrttLMNIR------NYNVAFeettflSLSRE 1097
Cdd:cd14072   158 FC--GSPPYAAPELFQGKKYDGPeVDVWSLGVILYTLVSGSLPFDGQN----LKELRervlrgKYRIPF------YMSTD 225

                         250       260
                  ....*....|....*....|...
gi 564369110 1098 ARGFLIKVLVqdrLRPTAEETLE 1120
Cdd:cd14072   226 CENLLKKFLV---LNPSKRGTLE 245

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270724 [Multi-domain] Cd Length: 262 Bit Score: 103.46 E-value: 7.62e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIP----SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT-EEL 951
Cdd:cd05572     1 LGVGGFGRVELVQLKSKGRTFALKCVKkrhiVQTRQQEHIFSEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLgGEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQFGTP 1031
Cdd:cd05572    81 WTILRDRGLFDEYTARFYTACVVLAFEYLHSRGIIYRDLKPENLLL-DSNG---YVKLVDFGFAKKLGSGRKTWTFCGTP 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1032 EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTtlmnIRNYNVAFEETTFLS----LSREARGfLIKVLV 1107
Cdd:cd05572   157 EYVAPEIILNKGYDFSVDYWSLGILLYELLTGRPPFGGDDEDP----MKIYNIILKGIDKIEfpkyIDKNAKN-LIKQLL 231

                         250       260
                  ....*....|....*....|....
gi 564369110 1108 QD----RL---RPTAEETLEHPWF 1124
Cdd:cd05572   232 RRnpeeRLgylKGGIRDIKKHKWF 255

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270868 [Multi-domain] Cd Length: 256 Bit Score: 103.26 E-value: 7.70e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQ---AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd08529     2 FEILNKLGKGSFGVVYKVVRKVDGRVYALKQIDISrmsRKMREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE----ELLERMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGaggeEQVRICDFGNAQELTP-GE 1022
Cdd:cd08529    82 ENgdlhSLIKSQRGRP-LPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKG----DNVKIGDLGVAKILSDtTN 156

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 564369110 1023 PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEN 1071
Cdd:cd08529   157 FAQTIVGTPYYLSPELCEDKPYNEKSDVWALGCVLYELCTGKHPFEAQN 205

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270798 [Multi-domain] Cd Length: 267 Bit Score: 103.38 E-value: 8.17e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEG------KRRVLQ----EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd06628    11 GSFGSVYLGMNASSGELMAVKQVELPSVSaenkdrKKSMLDalqrEIALLRELQHENIVQYLGSSSDANHLNIFLEYVPG 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAL--KPLGHR- 2378
Cdd:cd06628    91 GSVATLLNNYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEANSLstKNNGARp 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 --TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFyePDPQETEARIVGGRFDAFQLYPNTSQSATLFLRKVL 2456
Cdd:cd06628   171 slQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLTGTHPF--PDCTQMQAIFKIGENASPTIPSNISSEARDFLEKTF 248

                         250
                  ....*....|....*....
gi 564369110 2457 SVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06628   249 EIDHNKRPTADELLKHPFL 267

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271091 [Multi-domain] Cd Length: 255 Bit Score: 102.70 E-value: 1.04e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2224 TFLEEKARGRFGVVRsCREN---ATGRTFVAKIVPYAAEGK----RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIA 2296
Cdd:cd14189     2 SYCKGRLLGKGGFAR-CYEMtdlATNKTYAVKVIPHSRVAKphqrEKIVNEIELHRDLHHKHVVKFSHHFEDAENIYIFL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP--QALKP 2374
Cdd:cd14189    81 ELCSRKSLAHIWKARHTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEPpeQRKKT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvggRFDAFQLYPNTSQSATLFLRK 2454
Cdd:cd14189   161 I---CGTPNYLAPEVLLRQGHGPESDVWSLGCVMYTLLCGNPPFETLDLKETYRCI---KQVKYTLPASLSLPARHLLAG 234

                         250
                  ....*....|....*...
gi 564369110 2455 VLSVHPWSRPSLQDCLAH 2472
Cdd:cd14189   235 ILKRNPGDRLTLDQILEH 252

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271018 [Multi-domain] Cd Length: 258 Bit Score: 102.73 E-value: 1.15e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFS--YLRRvvERSSGLEFAAKFIPSQAKPKASA----RREARLLARLQHDCVL----YFHEAferRR 938
Cdd:cd14116     5 EDFEIGRPLGKGKFGnvYLAR--EKQSKFILALKVLFKAQLEKAGVehqlRREVEIQSHLRHPNILrlygYFHDA---TR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  939 GLVIVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGEeqVRICDFGNAQEl 1018
Cdd:cd14116    80 VYLILEYAPLGTVYRELQKLSKFDEQRTATYITELANALSYCHSKRVIHRDIKPENLLL--GSAGE--LKIADFGWSVH- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1019 TPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRnyNVAFEETTFlsLSREA 1098
Cdd:cd14116   155 APSSRRTTLCGTLDYLPPEMIEGRMHDEKVDLWSLGVLCYEFLVGKPPFEANTYQETYKRIS--RVEFTFPDF--VTEGA 230

                         250       260
                  ....*....|....*....|....*.
gi 564369110 1099 RGFLIKVLVQDRL-RPTAEETLEHPW 1123
Cdd:cd14116   231 RDLISRLLKHNPSqRPMLREVLEHPW 256

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270974 [Multi-domain] Cd Length: 253 Bit Score: 102.60 E-value: 1.19e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV---PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd14072     2 YRLLKTIGKGNFAKVKLARHVLTGREVAIKIIdktQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQalKPLGHRT 2379
Cdd:cd14072    82 SGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTPG--NKLDTFC 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDPI-GSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFdAFQLYPNTSQSAtlFLRKVLSV 2458
Cdd:cd14072   160 GSPPYAAPELFQGKKYdGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKY-RIPFYMSTDCEN--LLKKFLVL 236

                         250
                  ....*....|....*..
gi 564369110 2459 HPWSRPSLQDCLAHPWL 2475
Cdd:cd14072   237 NPSKRGTLEQIMKDRWM 253

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270906 [Multi-domain] Cd Length: 256 Bit Score: 102.46 E-value: 1.26e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyaaegKRRVLQ--------------EYEVLRTLH---HERLMSLHEA 2285
Cdd:cd14004     2 YTILKEMGEGAYGQVNLAIYKSKGKEVVIKFIF-----KERILVdtwvrdrklgtvplEIHILDTLNkrsHPNIVKLLDF 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2286 YITPRYLVLIAESCGN-RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA 2364
Cdd:cd14004    77 FEDDEFYYLVMEKHGSgMDLFDFIERKPNMDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSA 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2365 QPYNPqalKPLGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDpqETEARivggrfdAFQLYPN 2443
Cdd:cd14004   157 AYIKS---GPFDTFVGTIDYAAPEVLRGNPyGGKEQDIWALGVLLYTLVFKENPFYNIE--EILEA-------DLRIPYA 224

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 2444 TSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14004   225 VSEDLIDLISRMLNRDVGDRPTIEELLTDPWL 256

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270746 [Multi-domain] Cd Length: 356 Bit Score: 104.73 E-value: 1.66e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKI----VPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd05594    27 FEYLKLLGKGTFGKVILVKEKATGRYYAMKIlkkeVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEY 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHG-RHVLHLDIKPDNLLLAADNALKIVDFGSAQpynpQALK---P 2374
Cdd:cd05594   107 ANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSeKNVVYRDLKLENLMLDKDGHIKITDFGLCK----EGIKdgaT 182

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2375 LGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQE 2425
Cdd:cd05594   183 MKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEK 233

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270736 [Multi-domain] Cd Length: 323 Bit Score: 103.64 E-value: 2.11e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  878 GRGAFSYLRRVVERSSGLEFAAKF-----IPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE-LCTEEL 951
Cdd:cd05584     8 GYGKVFQVRKTTGSDKGKIFAMKVlkkasIVRNQKDTAHTKAERNILEAVKHPFIVDLHYAFQTGGKLYLILEyLSGGEL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE-LTPGEPQYCQFGT 1030
Cdd:cd05584    88 FMHLEREGIFMEDTACFYLAEITLALGHLHSLGIIYRDLKPENILL-DAQG---HVKLTDFGLCKEsIHDGTVTHTFCGT 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1031 PEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTL-------MNIRNYnvafeettflsLSREARGFLI 1103
Cdd:cd05584   164 IEYMAPEILTRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIdkilkgkLNLPPY-----------LTNEARDLLK 232

                         250       260
                  ....*....|....*....|....*....
gi 564369110 1104 KVL---VQDRLRPT---AEETLEHPWFKT 1126
Cdd:cd05584   233 KLLkrnVSSRLGSGpgdAEEIKAHPFFRH 261

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271082 [Multi-domain] Cd Length: 309 Bit Score: 103.41 E-value: 2.25e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKpkASARREARLLARLQ-HDCVLYFHEAFERRRGLVIVTELCTE-ELLER 954
Cdd:cd14180    14 LGEGSFSVCRKCRHRQSGQEYAVKIISRRME--ANTQREVAALRLCQsHPNIVALHEVLHDQYHTYLVMELLRGgELLDR 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  955 MARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgAGGEEQVRICDFGNAQELTPG-EPQYCQFGTPEF 1033
Cdd:cd14180    92 IKKKARFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYAD-ESDGAVLKVIDFGFARLRPQGsRPLQTPCFTLQY 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1034 VAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTT-------LMNIRNYNVAFEETTFLSLSREA----RGFL 1102
Cdd:cd14180   171 AAPELFSNQGYDESCDLWSLGVILYTMLSGQVPFQSKRGKMFhnhaadiMHKIKEGDFSLEGEAWKGVSEEAkdlvRGLL 250


                  .
gi 564369110 1103 I 1103
Cdd:cd14180   251 T 251

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270762 [Multi-domain] Cd Length: 263 Bit Score: 102.17 E-value: 2.45e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2226 LEEKARGRFGVVRSCRENATGRTFVAKIVPYAA-EGKRRVLQEYEVLRTLHHER----LMSLHEAYITPRYLVLIAE--- 2297
Cdd:cd05611     1 LKPISKGAFGSVYLAKKRSTGDYFAIKVLKKSDmIAKNQVTNVKAERAIMMIQGespyVAKLYYSFQSKDYLYLVMEyln 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 --SCGNR-ELLCGLSdrfrysEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALK 2373
Cdd:cd05611    81 ggDCASLiKTLGGLP------EDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGlSRNGLEKRHNK 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2374 PLghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFD-AFQLYPNTSQSATLFL 2452
Cdd:cd05611   155 KF---VGTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINwPEEVKEFCSPEAVDLI 231

                         250       260
                  ....*....|....*....|....*...
gi 564369110 2453 RKVLSVHPWSR---PSLQDCLAHPWLQD 2477
Cdd:cd05611   232 NRLLCMDPAKRlgaNGYQEIKSHPFFKS 259

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132989 [Multi-domain] Cd Length: 292 Bit Score: 102.81 E-value: 2.50e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2217 GPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVL-QEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd06658    18 GDPREYLDSFIKIGEGSTGIVCIATEKHTGKQVAVKKMDLRKQQRRELLfNEVVIMRDYHHENVVDMYNSYLVGDELWVV 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELlCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGsaqpYNPQALKPL 2375
Cdd:cd06658    98 MEFLEGGAL-TDIVTHTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFG----FCAQVSKEV 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHR---TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFL 2452
Cdd:cd06658   173 PKRkslVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRDNLPPRVKDSHKVSSVLRGFL 252

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd06658   253 DLMLVREPSQRATAQELLQHPFLKLA 278

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270990 [Multi-domain] Cd Length: 265 Bit Score: 102.03 E-value: 2.70e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2241 RENATGRTFVAKivPYAAEGKRRVLQ----EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSE 2316
Cdd:cd14088    21 KDKTTGKLYTCK--KFLKRDGRKVRKaaknEINILKMVKHPNILQLVDVFETRKEYFIFLELATGREVFDWILDQGYYSE 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2317 DDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAadNALK-----IVDFGSAQPYNPQALKPlghrTGTLEFMAPEMVR 2391
Cdd:cd14088    99 RDTSNVIRQVLEAVAYLHSLKIVHRNLKLENLVYY--NRLKnskivISDFHLAKLENGLIKEP----CGTPEYLAPEVVG 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2392 GDPIGSATDIWGAGVLTYIMLSGYSPFY-EPDPQETEA-------RIVGG--RFDAfQLYPNTSQSATLFLRKVLSVHPW 2461
Cdd:cd14088   173 RQRYGRPVDCWAIGVIMYILLSGNPPFYdEAEEDDYENhdknlfrKILAGdyEFDS-PYWDDISQAAKDLVTRLMEVEQD 251

                         250
                  ....*....|....
gi 564369110 2462 SRPSLQDCLAHPWL 2475
Cdd:cd14088   252 QRITAEEAISHEWI 265

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270738 [Multi-domain] Cd Length: 330 Bit Score: 103.42 E-value: 2.94e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVpyaaeGKRRVLQEYEVLRTLHhER-------------LMSLHEAYITPRYLVLIAE 2297
Cdd:cd05586     3 KGTFGQVYQVRKKDTRRIYAMKVL-----SKKVIVAKKEVAHTIG-ERnilvrtaldespfIVGLKFSFQTPTDLYLVTD 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPyNPQALKPLGH 2377
Cdd:cd05586    77 YMSGGELFWHLQKEGRFSEDRAKFYIAELVLALEHLHKNDIVYRDLKPENILLDANGHIALCDFGLSKA-DLTDNKTTNT 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqlYPNT--SQSATLFLRK 2454
Cdd:cd05586   156 FCGTTEYLAPEVLLDEKgYTKMVDFWSLGVLVFEMCCGWSPFYAEDTQQMYRNIAFGKVR----FPKDvlSDEGRSFVKG 231

                         250       260
                  ....*....|....*....|....*..
gi 564369110 2455 VLSVHPWSRPSLQD----CLAHPWLQD 2477
Cdd:cd05586   232 LLNRNPKHRLGAHDdaveLKEHPFFAD 258

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.

Pssm-ID: 132987 [Multi-domain] Cd Length: 297 Bit Score: 102.49 E-value: 3.88e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2217 GPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR-VLQEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd06656    15 GDPKKKYTRFEKIGQGASGTVYTAIDIATGQEVAIKQMNLQQQPKKElIINEILVMRENKNPNIVNYLDSYLVGDELWVV 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRFrYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPl 2375
Cdd:cd06656    95 MEYLAGGSLTDVVTETC-MDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKR- 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFLRKV 2455
Cdd:cd06656   173 STMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPERLSAVFRDFLNRC 252

                         250       260
                  ....*....|....*....|...
gi 564369110 2456 LSVHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd06656   253 LEMDVDRRGSAKELLQHPFLKLA 275

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270952 [Multi-domain] Cd Length: 249 Bit Score: 100.85 E-value: 3.95e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAK-PKASAR--REARLLARL-QHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd14050     3 FTILSKLGEGSFGEVFKVRSREDGKLYAVKRSRSRFRgEKDRKRklEEVERHEKLgEHPNCVRFIKAWEEKGILYIQTEL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQYC 1026
Cdd:cd14050    83 CDTSLQQYCEETHSLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFL----SKDGVCKLGDFGLVVELDKEDIHDA 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 QFGTPEFVAPEIVNQSPvSGVTDIWPVGVVAFLCLTGIS-PFVGendrTTLMNIRNYNVAFEETTflSLSREARGFLIKV 1105
Cdd:cd14050   159 QEGDPRYMAPELLQGSF-TKAADIFSLGITILELACNLElPSGG----DGWHQLRQGYLPEEFTA--GLSPELRSIIKLM 231

                         250
                  ....*....|....*...
gi 564369110 1106 LVQD-RLRPTAEETLEHP 1122
Cdd:cd14050   232 MDPDpERRPTAEDLLALP 249

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271020 [Multi-domain] Cd Length: 275 Bit Score: 101.67 E-value: 4.11e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2263 RVLQEYEVLRTLHHERLMSLHEAYITPR--YLVLIAESCGNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRHVLH 2340
Cdd:cd14118    60 RVYREIAILKKLDHPNVVKLVEVLDDPNedNLYMVFELVDKGAVMEVPTDN-PLSEETARSYFRDIVLGIEYLHYQKIIH 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2341 LDIKPDNLLLAADNALKIVDFGSAQPYN-PQALkpLGHRTGTLEFMAPEMVRGDPI---GSATDIWGAGVLTYIMLSGYS 2416
Cdd:cd14118   139 RDIKPSNLLLGDDGHVKIADFGVSNEFEgDDAL--LSSTAGTPAFMAPEALSESRKkfsGKALDIWAMGVTLYCFVFGRC 216

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2417 PFYEPDPQETEARIvggRFDAFQLYPNTSQSATL--FLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd14118   217 PFEDDHILGLHEKI---KTDPVVFPDDPVVSEQLkdLILRMLDKNPSERITLPEIKEHPW 273

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271035 [Multi-domain] Cd Length: 262 Bit Score: 101.19 E-value: 4.64e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLH------HERLMSLHEAYITPRYLVLIA 2296
Cdd:cd14133     1 YEVLEVLGKGTFGQVVKCYDLLTGEEVALKIIKNNKDYLDQSLDEIRLLELLNkkdkadKYHIVRLKDVFYFKNHLCIVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLCGLSDRFRY-SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA--ADNALKIVDFGSAQpYNPQAlk 2373
Cdd:cd14133    81 ELLSQNLYEFLKQNKFQYlSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILLAsySRCQIKIIDFGSSC-FLTQR-- 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2374 pLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVG--GRFDAFQLY--PNTSQSAT 2449
Cdd:cd14133   158 -LYSYIQSRYYRAPEVILGLPYDEKIDMWSLGCILAELYTGEPLFPGASEVDQLARIIGtiGIPPAHMLDqgKADDELFV 236

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2450 LFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14133   237 DFLKKLLEIDPKERPTASQALSHPWL 262

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271089 [Multi-domain] Cd Length: 265 Bit Score: 101.16 E-value: 4.68e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRF---GVVRSCRENA---TGRTFVAKIVPYA----AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd14187    11 RGRFlgkGGFAKCYEITdadTKEVFAGKIVPKSlllkPHQKEKMSMEIAIHRSLAHQHVVGFHGFFEDNDFVYVVLELCR 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQP--YNPQALKPLghr 2378
Cdd:cd14187    91 RRSLLELHKRRKALTEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKveYDGERKKTL--- 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvggRFDAFQLYPNTSQSATLFLRKVLSV 2458
Cdd:cd14187   168 CGTPNYIAPEVLSKKGHSFEVDIWSIGCIMYTLLVGKPPFETSCLKETYLRI---KKNEYSIPKHINPVAASLIQKMLQT 244

                         250       260
                  ....*....|....*....|.
gi 564369110 2459 HPWSRPSLQDCLAHPWLQDAY 2479
Cdd:cd14187   245 DPTARPTINELLNDEFFTSGY 265

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270887 [Multi-domain] Cd Length: 272 Bit Score: 101.26 E-value: 5.51e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA-SARREARLLARL-QHD--CVLYFHEAFER--RRGLVIVT 944
Cdd:cd13985     2 YQVTKQLGEGGFSYVYLAHDVNTGRRYALKRMYFNDEEQLrVAIKEIEIMKRLcGHPniVQYYDSAILSSegRKEVLLLM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTEELLERMARKPT--VCESETRTYMRQVLEGIGYLHQSH--VLHLDVKPENLLVWDgaggEEQVRICDFGNA-QELT 1019
Cdd:cd13985    82 EYCPGSLVDILEKSPPspLSEEEVLRIFYQICQAVGHLHSQSppIIHRDIKIENILFSN----TGRFKLCDFGSAtTEHY 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQyCQFG----------TPEFVAPEIVN---QSPVSGVTDIWPVGVVAFLCLTGISPFvgenDRTTLMNIRNYNVAF 1086
Cdd:cd13985   158 PLERA-EEVNiieeeiqkntTPMYRAPEMIDlysKKPIGEKADIWALGCLLYKLCFFKLPF----DESSKLAIVAGKYSI 232

                         250       260
                  ....*....|....*....|...
gi 564369110 1087 EETTflSLSREARGFLIKVLVQD 1109
Cdd:cd13985   233 PEQP--RYSPELHDLIRHMLTPD 253

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270794 [Multi-domain] Cd Length: 268 Bit Score: 100.95 E-value: 5.59e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVL-RTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLS 2309
Cdd:cd06624    18 KGTFGVVYAARDLSTQVRIAIKEIPERDSREVQPLHEEIALhSRLSHKNIVQYLGSVSEDGFFKIFMEQVPGGSLSALLR 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRF---RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAA-DNALKIVDFGSAQPY---NPQAlkplGHRTGTL 2382
Cdd:cd06624    98 SKWgplKDNENTIGYYTKQILEGLKYLHDNKIVHRDIKGDNVLVNTySGVVKISDFGTSKRLagiNPCT----ETFTGTL 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMV----RGdpIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGgrfdAFQLYPNT----SQSATLFLRK 2454
Cdd:cd06624   174 QYMAPEVIdkgqRG--YGPPADIWSLGCTIIEMATGKPPFIELGEPQAAMFKVG----MFKIHPEIpeslSEEAKSFILR 247

                         250       260
                  ....*....|....*....|.
gi 564369110 2455 VLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06624   248 CFEPDPDKRATASDLLQDPFL 268

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271066 [Multi-domain] Cd Length: 256 Bit Score: 100.70 E-value: 6.48e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLR-------------RVVERSSG-LEFAAKFIPsqakpkasarREARLLARLQHDCVLYFHEAFER 936
Cdd:cd14164     2 YTLGTTIGEGSFSKVKlatsqkycckvaiKIVDRRRAsPDFVQKFLP----------RELSILRRVNHPNIVQMFECIEV 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  937 RRGLV-IVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgAGGEEQVRICDFGNA 1015
Cdd:cd14164    72 ANGRLyIVMEAAATDLLQKIQEVHHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILL---SADDRKIKIADFGFA 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1016 QELTpGEPQ----YCqfGTPEFVAPEIVNQSPVSGVT-DIWPVGVVAFLCLTGISPFVGENDRTtlmnIRNYNVAFEETT 1090
Cdd:cd14164   149 RFVE-DYPElsttFC--GSRAYTPPEVILGTPYDPKKyDVWSLGVVLYVMVTGTMPFDETNVRR----LRLQQRGVLYPS 221

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 1091 FLSLSREARGFLIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14164   222 GVALEEPCRALIRTLLqFNPSTRPSIQQVAGNSW 255

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270991 [Multi-domain] Cd Length: 263 Bit Score: 100.44 E-value: 7.74e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKpkasARREARLLARL-QHDCVLYFHEAFE----RRRGLVIV 943
Cdd:cd14089     1 DYTISKQVLGLGINGKVLECFHKKTGEKFALKVLRDNPK----ARREVELHWRAsGCPHIVRIIDVYEntyqGRKCLLVV 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TElCTE--ELLERMARKPT--VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLvWDGAGGEEQVRICDFGNAQELT 1019
Cdd:cd14089    77 ME-CMEggELFSRIQERADsaFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLL-YSSKGPNAILKLTDFGFAKETT 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGE----PQYcqfgTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFV---------GENDRttlmnIRNYNVAF 1086
Cdd:cd14089   155 TKKslqtPCY----TPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYsnhglaispGMKKR-----IRNGQYEF 225

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 564369110 1087 EETTFLSLSREA----RGfLIKVLVQDRLrpTAEETLEHPW 1123
Cdd:cd14089   226 PNPEWSNVSEEAkdliRG-LLKTDPSERL--TIEEVMNHPW 263

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270885 [Multi-domain] Cd Length: 258 Bit Score: 100.38 E-value: 8.26e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIhqEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQHDCVLYFHEAFE--RRRGLVIVTE 945
Cdd:cd13983     5 FNE--VLGRGSFKTVYRAFDTEEGIEVAWNEIKLRKLPKAERQRfkqEIEILKSLKHPNIIKFYDSWEskSKKEVIFITE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHqSH---VLHLDVKPENLLVwDGAGGEeqVRICDFGNAQELTPG 1021
Cdd:cd13983    83 LMTSgTLKQYLKRFKRLKLKVIKSWCRQILEGLNYLH-TRdppIIHRDLKCDNIFI-NGNTGE--VKIGDLGLATLLRQS 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 EPQYCqFGTPEFVAPEIVNQSPVSGVtDIWpvgvvAF-LCL----TGISPF-----VGENDRTTLMNIRNYnvafeettf 1091
Cdd:cd13983   159 FAKSV-IGTPEFMAPEMYEEHYDEKV-DIY-----AFgMCLlemaTGEYPYsectnAAQIYKKVTSGIKPE--------- 222

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 564369110 1092 lSLSR----EARGFLIKVLVQDRLRPTAEETLEHPWF 1124
Cdd:cd13983   223 -SLSKvkdpELKDFIEKCLKPPDERPSARELLEHPFF 258

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270912 [Multi-domain] Cd Length: 269 Bit Score: 100.45 E-value: 8.79e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRtFVAkiVPYAAEGKR-RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd14010     2 YVLYDEIGRGKHSVVYKGRRKGTIE-FVA--IKCVDKSKRpEVLNEVRLTHELKHPNVLKFYEWYETSNHLWLVVEYCTG 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG----------------SAQ 2365
Cdd:cd14010    79 GDLETLLRQDGNLPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGlarregeilkelfgqfSDE 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 2366 PYNPQALKPLGHRtGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd14010   159 GNVNKVSKKQAKR-GTPYYMAPELFQGGVHSFASDLWALGCVLYEMFTGKPPF 210

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132942 [Multi-domain] Cd Length: 280 Bit Score: 100.59 E-value: 1.01e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR-EARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd06611     5 DIWEIIGELGDGAFGKVYKAQHKETGLFAAAKIIQIESEEELEDFMvEIDILSECKHPNIVGLYEAYFYENKLWILIEFC 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 T----EELLERMARKPTvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGaggeeQVRICDFGNAQELTPGE 1022
Cdd:cd06611    85 DggalDSIMLELERGLT--EPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNiLLTLDG-----DVKLADFGVSAKNKSTL 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQF-GTPEFVAPEIVN-----QSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYnvafEETTFLS--- 1093
Cdd:cd06611   158 QKRDTFiGTPYWMAPEVVAcetfkDNPYDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKILKS----EPPTLDQpsk 233

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 1094 LSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd06611   234 WSSSFNDFLKSCLVKDpDDRPTAAELLKHPFV 265

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270899 [Multi-domain] Cd Length: 252 Bit Score: 99.77 E-value: 1.20e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFIPSQ---AKPKASARREARLLARL-QHDCVLYFHEAFERRRGLVIVTELCT-- 948
Cdd:cd13997     6 EQIGSGSFSEVFKVRSKVDGCLYAVKKSKKPfrgPKERARALREVEAHAALgQHPNIVRYYSSWEEGGHLYIQMELCEng 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 --EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQyc 1026
Cdd:cd13997    86 slQDALEELSPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFI----SNKGTCKIGDFGLATRLETSGDV-- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 QFGTPEFVAPEIVNQSPV-SGVTDIWPVGvVAFLCLTGISPFvgENDRTTLMNIRNYNVAFEETtfLSLSREARGFLIKV 1105
Cdd:cd13997   160 EEGDSRYLAPELLNENYThLPKADIFSLG-VTVYEAATGEPL--PRNGQQWQQLRQGKLPLPPG--LVLSQELTRLLKVM 234

                         250
                  ....*....|....*...
gi 564369110 1106 LVQD-RLRPTAEETLEHP 1122
Cdd:cd13997   235 LDPDpTRRPTADQLLAHD 252

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173686 [Multi-domain] Cd Length: 323 Bit Score: 101.24 E-value: 1.37e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQ---AKPK-ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-EL 951
Cdd:cd05595     3 LGKGTFGKVILVREKATGRYYAMKILRKEviiAKDEvAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGgEL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE-LTPGEPQYCQFGT 1030
Cdd:cd05595    83 FFHLSRERVFTEDRARFYGAEIVSALEYLHSRDVVYRDIKLENLML-DKDG---HIKITDFGLCKEgITDGATMKTFCGT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1031 PEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEnDRTTLMNIrnynVAFEETTF-LSLSREARGFLIKVLVQD 1109
Cdd:cd05595   159 PEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQ-DHERLFEL----ILMEEIRFpRTLSPEAKSLLAGLLKKD 233

                         250       260
                  ....*....|....*....|.
gi 564369110 1110 ---RL--RPT-AEETLEHPWF 1124
Cdd:cd05595   234 pkqRLggGPSdAKEVMEHRFF 254

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270961 [Multi-domain] Cd Length: 237 Bit Score: 98.72 E-value: 1.61e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2261 KRRVLQEYEV--LRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHV 2338
Cdd:cd14059    23 KVRDEKETDIkhLRKLNHPNIIKFKGVCTQAPCYCILMEYCPYGQLYEVLRAGREITPSLLVDWSKQIASGMNYLHLHKI 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2339 LHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPlgHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd14059   103 IHRDLKSPNVLVTYNDVLKISDFGTSKELSEKSTKM--SFAGTVAWMAPEVIRNEPCSEKVDIWSFGVVLWELLTGEIPY 180

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 2419 YEPDpqeTEARIVGGRFDAFQL-YPNTSQSA-TLFLRKVLSVHPWSRPSLQDCLAH 2472
Cdd:cd14059   181 KDVD---SSAIIWGVGSNSLQLpVPSTCPDGfKLLMKQCWNSKPRNRPSFRQILMH 233

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270819 [Multi-domain] Cd Length: 264 Bit Score: 99.33 E-value: 1.82e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPY---AAEGKRRVLQ---EYEVLRTLHHERLMSLHEAYITP--RYLVLIAESCGNR 2302
Cdd:cd06653    12 RGAFGEVYLCYDADTGRELAVKQVPFdpdSQETSKEVNAlecEIQLLKNLRHDRIVQYYGCLRDPeeKKLSIFVEYMPGG 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHR--TG 2380
Cdd:cd06653    92 SVKDQLKAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRIQTICMSGTGIKsvTG 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAfQLYPNTSQSATLFLRKVLsVHP 2460
Cdd:cd06653   172 TPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPWAEYEAMAAIFKIATQPTKP-QLPDGVSDACRDFLRQIF-VEE 249

                         250
                  ....*....|....
gi 564369110 2461 WSRPSLQDCLAHPW 2474
Cdd:cd06653   250 KRRPTAEFLLRHPF 263

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132986 [Multi-domain] Cd Length: 296 Bit Score: 100.18 E-value: 1.88e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2212 TTLRQGPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR-VLQEYEVLRTLHHERLMSLHEAYITPR 2290
Cdd:cd06655    10 TIVSIGDPKKKYTRYEKIGQGASGTVFTAIDVATGQEVAIKQINLQKQPKKElIINEILVMKELKNPNIVNFLDSFLVGD 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 YLVLIAESCGNRELLCGLSDRFrYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQ 2370
Cdd:cd06655    90 ELFVVMEYLAGGSLTDVVTETC-MDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPE 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 ALKPlGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATL 2450
Cdd:cd06655   169 QSKR-STMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSPIFRD 247

                         250       260
                  ....*....|....*....|....*...
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd06655   248 FLNRCLEMDVEKRGSAKELLQHPFLKLA 275

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271076 [Multi-domain] Cd Length: 289 Bit Score: 99.33 E-value: 3.42e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEI-GRGAFSYLRRVVERSSGLEFAAKFIPSQA-KPKASARREARLLARLQ-HDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14174     1 DLYRLTDELlGEGAYAKVQGCVSLQNGKEYAVKIIEKNAgHSRSRVFREVETLYQCQgNKNILELIEFFEDDTRFYLVFE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 -LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEEQVRICDF--GNAQEL---- 1018
Cdd:cd14174    81 kLRGGSILAHIQKRKHFNEREASRVVRDIASALDFLHTKGIAHRDLKPENILC-ESPDKVSPVKICDFdlGSGVKLnsac 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1019 ----TPGEPQYCqfGTPEFVAPEIV-----NQSPVSGVTDIWPVGVVAFLCLTGISPFVGEN------DR---------T 1074
Cdd:cd14174   160 tpitTPELTTPC--GSAEYMAPEVVevftdEATFYDKRCDLWSLGVILYIMLSGYPPFVGHCgtdcgwDRgevcrvcqnK 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1075 TLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd14174   238 LFESIQEGKYEFPDKDWSHISSEAKDLISKLLVRDaKERLSAAQVLQHPWVQ 289

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271074 [Multi-domain] Cd Length: 267 Bit Score: 98.91 E-value: 3.48e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2235 GVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHE-AYITPRYLVLIAESCGNRELLCGLSDRF- 2312
Cdd:cd14172    18 GKVLECFHRRTGQKCALKLLYDSPKARREVEHHWRASGGPHIVHILDVYEnMHHGKRCLLIIMECMEGGELFSRIQERGd 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2313 -RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAA---DNALKIVDFGSAQPYNPQalKPLGHRTGTLEFMAPE 2388
Cdd:cd14172    98 qAFTEREASEIMRDIGTAIQYLHSMNIAHRDVKPENLLYTSkekDAVLKLTDFGFAKETTVQ--NALQTPCYTPYYVAPE 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2389 MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQE----TEARIVGGRFDafqlYPN-----TSQSATLFLRKVLSVH 2459
Cdd:cd14172   176 VLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSNTGQAispgMKRRIRMGQYG----FPNpewaeVSEEAKQLIRHLLKTD 251

                         250
                  ....*....|....*.
gi 564369110 2460 PWSRPSLQDCLAHPWL 2475
Cdd:cd14172   252 PTERMTITQFMNHPWI 267

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270736 [Multi-domain] Cd Length: 323 Bit Score: 100.17 E-value: 3.54e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2267 EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPD 2346
Cdd:cd05584    50 ERNILEAVKHPFIVDLHYAFQTGGKLYLILEYLSGGELFMHLEREGIFMEDTACFYLAEITLALGHLHSLGIIYRDLKPE 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2347 NLLLAADNALKIVDFG----SAQpynpqalkpLGHRT----GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd05584   130 NILLDAQGHVKLTDFGlckeSIH---------DGTVThtfcGTIEYMAPEILTRSGHGKAVDWWSLGALMYDMLTGAPPF 200

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2419 YEPDPQETEARIVGGRFDafqLYPNTSQSATLFLRKVLSVHPWSR----PS-LQDCLAHPWLQD 2477
Cdd:cd05584   201 TAENRKKTIDKILKGKLN---LPPYLTNEARDLLKKLLKRNVSSRlgsgPGdAEEIKAHPFFRH 261

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271066 [Multi-domain] Cd Length: 256 Bit Score: 98.39 E-value: 3.95e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVpyaaeGKRR---------VLQEYEVLRTLHHERLMSLHEAYITPRYLV 2293
Cdd:cd14164     2 YTLGTTIGEGSFSKVKLATSQKYCCKVAIKIV-----DRRRaspdfvqkfLPRELSILRRVNHPNIVQMFECIEVANGRL 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2294 LIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADN-ALKIVDFG-SAQPYNPQA 2371
Cdd:cd14164    77 YIVMEAAATDLLQKIQEVHHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLSADDrKIKIADFGfARFVEDYPE 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 LKPLghRTGTLEFMAPEMVRGDPIGSAT-DIWGAGVLTYIMLSGYSPFyepdpQETEARIVGGRFDAFqLYPN---TSQS 2447
Cdd:cd14164   157 LSTT--FCGSRAYTPPEVILGTPYDPKKyDVWSLGVVLYVMVTGTMPF-----DETNVRRLRLQQRGV-LYPSgvaLEEP 228

                         250       260
                  ....*....|....*....|....*...
gi 564369110 2448 ATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14164   229 CRALIRTLLQFNPSTRPSIQQVAGNSWL 256

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173765 [Multi-domain] Cd Length: 257 Bit Score: 98.49 E-value: 3.95e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAK---FIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd08225     2 YEIIKKIGEGSFGKIYLAKAKSDSEHCVIKeidLTKMPVKEKEASKKEVILLAKMKHPNIVTFFASFQENGRLFIVMEYC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE-ELLERMARKPTVCESETR--TYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgAGGEEQVRICDFGNAQELTPG-EP 1023
Cdd:cd08225    82 DGgDLMKRINRQRGVLFSEDQilSWFVQISLGLKHIHDRKILHRDIKSQNIFL---SKNGMVAKLGDFGIARQLNDSmEL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFlslSREARGFLI 1103
Cdd:cd08225   159 AYTCVGTPYYLSPEICQNRPYNNKTDIWSLGCVLYELCTLKHPFEGNNLHQLVLKICQGYFAPISPNF---SRDLRSLIS 235

                         250       260
                  ....*....|....*....|..
gi 564369110 1104 KVL-VQDRLRPTAEETLEHPWF 1124
Cdd:cd08225   236 QLFkVSPRDRPSITSILKRPFL 257

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270725 [Multi-domain] Cd Length: 350 Bit Score: 100.44 E-value: 4.08e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQ---AKPKASARREAR-LLARLQHDCVLYFHEAFERRRGLVIVTE- 945
Cdd:cd05573     3 FEVIKVIGRGAFGEVWLVRDKDTGQVYAMKILRKSdmlKREQIAHVRAERdILADADSPWIVRLHYAFQDEDHLYLVMEy 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFG------------ 1013
Cdd:cd05573    83 MPGGDLMNLLIKYDVFPEETARFYIAELVLALDSLHKLGFIHRDIKPDNILL-DADG---HIKLADFGlctkmnksgdre 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1014 -------------NAQELTPGEPQYCQF-----GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTT 1075
Cdd:cd05573   159 sylndsvntlfqdNVLARRRPHKQRRVRaysavGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGFPPFYSDSLVET 238

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1076 LMNIRNYNVAFEETTFLSLSREARGFLIKVLV--QDRLRpTAEETLEHPWFK 1125
Cdd:cd05573   239 YSKIMNWKESLVFPDDPDVSPEAIDLIRRLLCdpEDRLG-SAEEIKAHPFFK 289

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173759 [Multi-domain] Cd Length: 255 Bit Score: 98.12 E-value: 4.31e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--PSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT 948
Cdd:cd08219     2 YNVLRVVGEGSFGRALLVQHVNSDQKYAMKEIrlPKSSSAVEDSRKEAVLLAKMKHPNIVAFKESFEADGHLYIVMEYCD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 E-ELLERMA--RKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPQY 1025
Cdd:cd08219    82 GgDLMQKIKlqRGKLFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNG----KVKLGDFGSARLLTSPGAYA 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 564369110 1026 CQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd08219   158 CTYvGTPYYVPPEIWENMPYNNKSDIWSLGCILYELCTLKHPF 200

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271019 [Multi-domain] Cd Length: 270 Bit Score: 98.40 E-value: 5.08e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLS-DYYDIHQEIGRGAFS--YLRRvvERSSGLEFAAKFI-PSQAKPKA---SARREARLLARLQHDCVLYFHEAFERR 937
Cdd:cd14117     1 RKFTiDDFDIGRPLGKGKFGnvYLAR--EKQSKFIVALKVLfKSQIEKEGvehQLRREIEIQSHLRHPNILRLYNYFHDR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  938 RGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGEeqVRICDFGNAQ 1016
Cdd:cd14117    79 KRIYLILEYAPRgELYKELQKHGRFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLM--GYKGE--LKIADFGWSV 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ElTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEettfLSLSR 1096
Cdd:cd14117   155 H-APSLRRRTMCGTLDYLPPEMIEGRTHDEKVDLWCIGVLCYELLVGMPPFESASHTETYRRIVKVDLKFP----PFLSD 229

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 1097 EARGFLIKVL-VQDRLRPTAEETLEHPWFKTEAK 1129
Cdd:cd14117   230 GSRDLISKLLrYHPSERLPLKGVMEHPWVKANSR 263

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270991 [Multi-domain] Cd Length: 263 Bit Score: 98.13 E-value: 5.22e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2235 GVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHE-AYITPRYLVLIAESCGNRELLCGLSDRFR 2313
Cdd:cd14089    15 GKVLECFHKKTGEKFALKVLRDNPKARREVELHWRASGCPHIVRIIDVYEnTYQGRKCLLVVMECMEGGELFSRIQERAD 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2314 --YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA---ADNALKIVDFGSAQpyNPQALKPLGHRTGTLEFMAPE 2388
Cdd:cd14089    95 saFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSskgPNAILKLTDFGFAK--ETTTKKSLQTPCYTPYYVAPE 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2389 MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYE----PDPQETEARIVGGRFDafqlYPNT-----SQSATLFLRKVLSVH 2459
Cdd:cd14089   173 VLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSnhglAISPGMKKRIRNGQYE----FPNPewsnvSEEAKDLIRGLLKTD 248

                         250
                  ....*....|....*
gi 564369110 2460 PWSRPSLQDCLAHPW 2474
Cdd:cd14089   249 PSERLTIEEVMNHPW 263

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270802 [Multi-domain] Cd Length: 259 Bit Score: 97.86 E-value: 5.34e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR------REARLLARLQH-DCVLYFHEAFERRRgLVIVTELC 947
Cdd:cd06632     6 QLLGSGSFGSVYEGFNGDTGDFFAVKEVSLVDDDKKSREsvkqleQEIALLSKLRHpNIVQYYGTEREEDN-LYIFLEYV 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQEL-TPGEPQY 1025
Cdd:cd06632    85 PGgSIHKLLQRYGAFEEPVIRLYTRQILSGLAYLHSRNTVHRDIKGANILV-DTNG---VVKLADFGMAKHVeAFSFAKS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQfGTPEFVAPEIVNQ--SPVSGVTDIWPVGVVAFLCLTGISPFvGENDRTTLMnirnYNVAFEETTFL---SLSREARG 1100
Cdd:cd06632   161 FK-GSPYWMAPEVIMQknSGYGLAVDIWSLGCTVLEMATGKPPW-SQYEGVAAI----FKIGNSGELPPipdHLSPDAKD 234

                         250       260
                  ....*....|....*....|...
gi 564369110 1101 FLIKVLVQD-RLRPTAEETLEHP 1122
Cdd:cd06632   235 FIRLCLQRDpEDRPTASQLLEHP 257

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132975 [Multi-domain] Cd Length: 292 Bit Score: 98.95 E-value: 5.75e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK-RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd06644    10 PNEVWEIIGELGDGAFGKVYKAKNKETGALAAAKVIETKSEEElEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIE 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SC--GNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQpyNPQALKP 2374
Cdd:cd06644    90 FCpgGAVDAIMLELDR-GLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGvSAK--NVKTLQR 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHRTGTLEFMAPEMV-----RGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSAT 2449
Cdd:cd06644   167 RDSFIGTPYWMAPEVVmcetmKDTPYDYKADIWSLGITLIEMAQIEPPHHELNPMRVLLKIAKSEPPTLSQPSKWSMEFR 246

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 2450 LFLRKVLSVHPWSRPSLQDCLAHPWLQdaylmklrrqtlTFTTNR-LKEFLGE 2501
Cdd:cd06644   247 DFLKTALDKHPETRPSAAQLLEHPFVS------------SVTSNRpLRELVAE 287

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270786 [Multi-domain] Cd Length: 274 Bit Score: 98.09 E-value: 5.89e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV--PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd06609     3 FTLLERIGKGSFGEVYKGIDKRTNQVVAIKVIdlEEAEDEIEDIQQEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEYCG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLcGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQpynpqalkpLGHRT 2379
Cdd:cd06609    83 GGSVL-DLLKPGPLDETYIAFILREVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGvSGQ---------LTSTM 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 -------GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPD--------PQETEARIVGGRFdafqlypnt 2444
Cdd:cd06609   153 skrntfvGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLHpmrvlfliPKNNPPSLEGNKF--------- 223

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 2445 SQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd06609   224 SKPFKDFVELCLNKDPKERPSAKELLKHKFIKKA 257

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 5 (MAPKAP5 or MK5) is also called PRAK (p38-regulated/activated protein kinase). It contains a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271073 [Multi-domain] Cd Length: 289 Bit Score: 98.69 E-value: 5.92e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDI--HQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKpkasARREARLLARLQ-HD-----------CVLYFHEAF 934
Cdd:cd14171     4 EEYEVnwTQKLGTGISGPVRVCVKKSTGERFALKILLDRPK----ARTEVRLHMMCSgHPnivqiydvyanSVQFPGESS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  935 ERRRGLVIVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAgGEEQVRICDFGN 1014
Cdd:cd14171    80 PRARLLIVMELMEGGELFDRISQHRHFTEKQAAQYTKQIALAVQHCHSLNIAHRDLKPENLLLKDNS-EDAPIKLCDFGF 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1015 AQeLTPGEPQYCQFgTPEFVAPEIV-----NQSPVSGVT------------DIWPVGVVAFLCLTGISPFVGENDRTTLM 1077
Cdd:cd14171   159 AK-VDQGDLMTPQF-TPYYVAPQVLeaqrrHRKERSGIPtsptpytydkscDMWSLGVIIYIMLCGYPPFYSEHPSRTIT 236

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1078 N-----IRNYNVAFEETTFLSLSREARGFLIKVL-VQDRLRPTAEETLEHPW 1123
Cdd:cd14171   237 KdmkrkIMTGSYEFPEEEWSQISEMAKDIVRKLLcVDPEERMTIEEVLHHPW 288

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270752 [Multi-domain] Cd Length: 328 Bit Score: 99.69 E-value: 6.12e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKI----VPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLc 2306
Cdd:cd05601    11 RGHFGEVQVVKEKATGDIYAMKVlkksETLAQEEVSFFEEERDIMAKANSPWITKLQYAFQDSENLYLVMEYHPGGDLL- 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRF--RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEF 2384
Cdd:cd05601    90 SLLSRYddIFEESMARFYLAELVLAIHSLHSMGYVHRDIKPENILIDRTGHIKLADFGSAAKLSSDKTVTSKMPVGTPDY 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2385 MAPEM------VRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVG-GRFDAFQLYPNTSQSATLFLRKVLS 2457
Cdd:cd05601   170 IAPEVltsmngGSKGTYGVECDWWSLGIVAYEMLYGKTPFTEDTVIKTYSNIMNfKKFLKFPEDPKVSESAVDLIKGLLT 249

                         250       260
                  ....*....|....*....|....*....
gi 564369110 2458 vHPWSRPSLQDCLAHPWLQDAYLMKLRRQ 2486
Cdd:cd05601   250 -DAKERLGYEGLCCHPFFSGIDWNNLRQT 277

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270819 [Multi-domain] Cd Length: 264 Bit Score: 97.79 E-value: 6.18e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIP----SQ--AKPKASARREARLLARLQHDCVLYFHEAF---ERRRGLVIVTELC 947
Cdd:cd06653    10 LGRGAFGEVYLCYDADTGRELAVKQVPfdpdSQetSKEVNALECEIQLLKNLRHDRIVQYYGCLrdpEEKKLSIFVEYMP 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELT----PGEP 1023
Cdd:cd06653    90 GGSVKDQLKAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILR-DSAG---NVKLGDFGASKRIQticmSGTG 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLmnirnYNVAFEETTFL---SLSREARG 1100
Cdd:cd06653   166 IKSVTGTPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPWAEYEAMAAI-----FKIATQPTKPQlpdGVSDACRD 240

                         250       260
                  ....*....|....*....|...
gi 564369110 1101 FLIKVLVQDRLRPTAEETLEHPW 1123
Cdd:cd06653   241 FLRQIFVEEKRRPTAEFLLRHPF 263

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270786 [Multi-domain] Cd Length: 274 Bit Score: 98.09 E-value: 6.23e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--PSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT 948
Cdd:cd06609     3 FTLLERIGKGSFGEVYKGIDKRTNQVVAIKVIdlEEAEDEIEDIQQEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEYCG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 ----EELLeRMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEPQ 1024
Cdd:cd06609    83 ggsvLDLL-KPGPLD---ETYIAFILREVLLGLEYLHSEGKIHRDIKAANILLSE----EGDVKLADFGVSGQLTSTMSK 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI-RNYNVAFEETTFlslSREARGFL 1102
Cdd:cd06609   155 RNTFvGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLHPMRVLFLIpKNNPPSLEGNKF---SKPFKDFV 231

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 564369110 1103 IKVLVQD-RLRPTAEETLEHPWFKTEAKgaevsTDHLKLFLSRR-RWQ 1148
Cdd:cd06609   232 ELCLNKDpKERPSAKELLKHKFIKKAKK-----TSYLTLLIERIkKWK 274

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270745 [Multi-domain] Cd Length: 348 Bit Score: 99.77 E-value: 7.00e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  862 HRGRRLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQ---AKPK-ASARREARLLARLQHDCVLYFHEAFERR 937
Cdd:cd05593     8 HHKRKTMNDFDYLKLLGKGTFGKVILVREKASGKYYAMKILKKEviiAKDEvAHTLTESRVLKNTRHPFLTSLKYSFQTK 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  938 RGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQ 1016
Cdd:cd05593    88 DRLCFVMEYVNGgELFFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLML-DKDG---HIKITDFGLCK 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 E-LTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLS 1095
Cdd:cd05593   164 EgITDAATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEDIKFPRT----LS 239

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 564369110 1096 REARGFLIKVLVQD---RL---RPTAEETLEHPWF 1124
Cdd:cd05593   240 ADAKSLLSGLLIKDpnkRLgggPDDAKEIMRHSFF 274

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270820 [Multi-domain] Cd Length: 296 Bit Score: 98.64 E-value: 7.52e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2217 GPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR-VLQEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd06654    16 GDPKKKYTRFEKIGQGASGTVYTAMDVATGQEVAIRQMNLQQQPKKElIINEILVMRENKNPNIVNYLDSYLVGDELWVV 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRFrYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPl 2375
Cdd:cd06654    96 MEYLAGGSLTDVVTETC-MDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKR- 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFLRKV 2455
Cdd:cd06654   174 STMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLIATNGTPELQNPEKLSAIFRDFLNRC 253

                         250       260
                  ....*....|....*....|...
gi 564369110 2456 LSVHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd06654   254 LEMDVEKRGSAKELLQHQFLKIA 276

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271065 [Multi-domain] Cd Length: 257 Bit Score: 96.98 E-value: 1.22e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR----REARLLARLQHDCVLYFHEAFERRRG-LVIVTE 945
Cdd:cd14163     2 YQLGKTIGEGTYSKVKEAFSKKHQRKVAIKIIDKSGGPEEFIQrflpRELQIVERLDHKNIIHVYEMLESADGkIYLVME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggeEQVRICDFGNAQELTPGEPQ 1024
Cdd:cd14163    82 LAEDgDVFDCVLHGGPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKCENALLQG-----FTLKLTDFGFAKQLPKGGRE 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQF--GTPEFVAPEIVNQSPV-SGVTDIWPVGVVAFLCLTGISPFvGENDRTTLMNIRNYNVAFeeTTFLSLSREARGF 1101
Cdd:cd14163   157 LSQTfcGSTAYAAPEVLQGVPHdSRKGDIWSMGVVLYVMLCAQLPF-DDTDIPKMLCQQQKGVSL--PGHLGVSRTCQDL 233

                         250       260
                  ....*....|....*....|....
gi 564369110 1102 LIKVLVQDR-LRPTAEETLEHPWF 1124
Cdd:cd14163   234 LKRLLEPDMvLRPSIEEVSWHPWL 257

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271101 [Multi-domain] Cd Length: 286 Bit Score: 97.73 E-value: 1.26e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2263 RVLQEYEVLRTLHHERLMSLHEAYITPR--YLVLIAESCGNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRHVLH 2340
Cdd:cd14199    71 RVYQEIAILKKLDHPNVVKLVEVLDDPSedHLYMVFELVKQGPVMEVPTLK-PLSEDQARFYFQDLIKGIEYLHYQKIIH 149

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2341 LDIKPDNLLLAADNALKIVDFGSAQPYN-PQALkpLGHRTGTLEFMAPEMV---RGDPIGSATDIWGAGVLTYIMLSGYS 2416
Cdd:cd14199   150 RDVKPSNLLVGEDGHIKIADFGVSNEFEgSDAL--LTNTVGTPAFMAPETLsetRKIFSGKALDVWAMGVTLYCFVFGQC 227

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2417 PFYEPDPQETEARIVGGRFDaFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd14199   228 PFMDERILSLHSKIKTQPLE-FPDQPDISDDLKDLLFRMLDKNPESRISVPEIKLHPWVT 286

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270802 [Multi-domain] Cd Length: 259 Bit Score: 96.70 E-value: 1.32e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR------VLQEYEVLRTLHHERL-------MSLHEAYItprYLVLIae 2297
Cdd:cd06632    10 SGSFGSVYEGFNGDTGDFFAVKEVSLVDDDKKSresvkqLEQEIALLSKLRHPNIvqyygteREEDNLYI---FLEYV-- 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEddVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALkPLGH 2377
Cdd:cd06632    85 PGGSIHKLLQRYGAFEEPV--IRLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHVEAFSF-AKSF 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RtGTLEFMAPEMVR--GDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvgGRFDAFQLYPNT-SQSATLFLRK 2454
Cdd:cd06632   162 K-GSPYWMAPEVIMqkNSGYGLAVDIWSLGCTVLEMATGKPPWSQYEGVAAIFKI--GNSGELPPIPDHlSPDAKDFIRL 238

                         250       260
                  ....*....|....*....|.
gi 564369110 2455 VLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06632   239 CLQRDPEDRPTASQLLEHPFV 259

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270765 [Multi-domain] Cd Length: 332 Bit Score: 98.07 E-value: 1.86e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEvlRT----LHHER----LMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd05614    12 AYGKVFLVRKVSGHDANKLYAMKVLRKAALVQKAKTVEHT--RTernvLEHVRqspfLVTLHYAFQTDAKLHLILDYVSG 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGT 2381
Cdd:cd05614    90 GELFTHLYQRDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSKEFLTEEKERTYSFCGT 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2382 LEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPN-TSQSATLFLRKVLSVH 2459
Cdd:cd05614   170 IEYMAPEIIRGKSgHGKAVDWWSLGILMFELLTGASPFTLEGEKNTQSEVSRRILKCDPPFPSfIGPVARDLLQKLLCKD 249

                         250       260
                  ....*....|....*....|...
gi 564369110 2460 PWSR-----PSLQDCLAHPWLQD 2477
Cdd:cd05614   250 PKKRlgagpQGAQEIKEHPFFKG 272

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270836 [Multi-domain] Cd Length: 286 Bit Score: 97.11 E-value: 1.90e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAK-FIPS--QAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd07846     3 YENLGLVGEGSYGMVMKCRHKETGQIVAIKkFLESedDKMVKKIAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TEELLERMARKPTVCESET-RTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQEL-TPGEPQY 1025
Cdd:cd07846    83 DHTVLDDLEKYPNGLDESRvRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSG----VVKLCDFGFARTLaAPGEVYT 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQFGTPEFVAPEIVNQSPVSG-VTDIWPVGVVAFLCLTGISPFVGENDRTTL--------------MNIRNYNVAFE--- 1087
Cdd:cd07846   159 DYVATRWYRAPELLVGDTKYGkAVDVWAVGCLVTEMLTGEPLFPGDSDIDQLyhiikclgnliprhQELFQKNPLFAgvr 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 564369110 1088 ----------ETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07846   239 lpevkeveplERRYPKLSGVVIDLAKKCLHIDpDKRPSCSELLHHEFF 286

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 5 (MAPKAP5 or MK5) is also called PRAK (p38-regulated/activated protein kinase). It contains a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271073 [Multi-domain] Cd Length: 289 Bit Score: 97.15 E-value: 2.02e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2235 GVVRSCRENATGRTFVAKIV---PYA---------AEGKRRVLQEYEVLRTlhheRLMSLHEAYITPRyLVLIAESCGNR 2302
Cdd:cd14171    20 GPVRVCVKKSTGERFALKILldrPKArtevrlhmmCSGHPNIVQIYDVYAN----SVQFPGESSPRAR-LLIVMELMEGG 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLL---AADNALKIVDFGSAQPYNPQALKPlghrT 2379
Cdd:cd14171    95 ELFDRISQHRHFTEKQAAQYTKQIALAVQHCHSLNIAHRDLKPENLLLkdnSEDAPIKLCDFGFAKVDQGDLMTP----Q 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMV---------RGDPIGSAT--------DIWGAGVLTYIMLSGYSPFYEPDPQET-----EARIVGGRFDa 2437
Cdd:cd14171   171 FTPYYVAPQVLeaqrrhrkeRSGIPTSPTpytydkscDMWSLGVIIYIMLCGYPPFYSEHPSRTitkdmKRKIMTGSYE- 249

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 564369110 2438 fqlYPN-----TSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14171   250 ---FPEeewsqISEMAKDIVRKLLCVDPEERMTIEEVLHHPWL 289

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270800 [Multi-domain] Cd Length: 268 Bit Score: 96.34 E-value: 2.10e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFI-------PSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL--- 946
Cdd:cd06630     8 LGTGAFSSCYQARDVKTGTLMAVKQVsfcrnssSEQEEVVEAIREEIRMMARLNHPNIVRMLGATQHKSHFNIFVEWmag 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 -CTEELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeEQVRICDFGNAQELTP----- 1020
Cdd:cd06630    88 gSVASLLSKYGAFS---ENVIINYTLQILRGLAYLHDNQIIHRDLKGANLLV-DSTG--QRLRIADFGAAARLASkgtga 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIrnYNVAFEETT---FLSLSRE 1097
Cdd:cd06630   162 GEFQGQLLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKISNHLALI--FKIASATTPppiPEHLSPG 239

                         250       260
                  ....*....|....*....|....*....
gi 564369110 1098 ARGFLIKVLVQDR-LRPTAEETLEHPWFK 1125
Cdd:cd06630   240 LRDVTLRCLELQPeDRPPARELLKHPVFT 268

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270867 [Multi-domain] Cd Length: 270 Bit Score: 96.42 E-value: 2.29e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVA-KIVPY--AAEGK---------RRVLQEYEVLR-TLHHERLMSLHEAYITP 2289
Cdd:cd08528     2 YAVLELLGSGAFGCVYKVRKKSNGQTLLAlKEINMtnPAFGRteqerdksvGDIISEVNIIKeQLRHPNIVRYYKTFLEN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2290 R--YLVL-IAESCGNRELLCGLSDR-FRYSEDDVATYVVQLLQGLDYLHG-RHVLHLDIKPDNLLLAADNALKIVDFGSA 2364
Cdd:cd08528    82 DrlYIVMeLIEGAPLGEHFSSLKEKnEHFTEDRIWNIFVQMVLALRYLHKeKQIVHRDLKPNNIMLGEDDKVTITDFGLA 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2365 QPYNPQALKpLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQ--LYp 2442
Cdd:cd08528   162 KQKGPESSK-MTSVVGTILYSCPEIVQNEPYGEKADIWALGCILYQMCTLQPPFYSTNMLTLATKIVEAEYEPLPegMY- 239

                         250       260
                  ....*....|....*....|..
gi 564369110 2443 ntSQSATLFLRKVLSVHPWSRP 2464
Cdd:cd08528   240 --SDDITFVIRSCLTPDPEARP 259

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270881 [Multi-domain] Cd Length: 265 Bit Score: 96.30 E-value: 2.55e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2225 FLEEKARGRFGVVRScrenAT--GRTFVAKIV---PYAAEGKRRVLQEYEVLRtLHHE---RLMSLHEAYITPRYLVLIA 2296
Cdd:cd13979     7 LQEPLGSGGFGSVYK----ATykGETVAVKIVrrrRKNRASRQSFWAELNAAR-LRHEnivRVLAAETGTDFASLGLIIM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNREL---------LCGLSDRFRYSEDDVAtyvvqllqGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY 2367
Cdd:cd13979    82 EYCGNGTLqqliyegsePLPLAHRILISLDIAR--------ALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKL 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 2368 NP--QALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd13979   154 GEgnEVGTPRSHIGGTYTYRAPELLKGERVTPKADIYSFGITLWQMLTRELPY 206

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270752 [Multi-domain] Cd Length: 328 Bit Score: 97.77 E-value: 2.73e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI-----PSQAKpKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd05601     3 FEVKNVIGRGHFGEVQVVKEKATGDIYAMKVLkksetLAQEE-VSFFEEERDIMAKANSPWITKLQYAFQDSENLYLVME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 -LCTEELLERMARKPTVC-ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGE- 1022
Cdd:cd05601    82 yHPGGDLLSLLSRYDDIFeESMARFYLAELVLAIHSLHSMGYVHRDIKPENILI-DRTG---HIKLADFGSAAKLSSDKt 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 -----PqycqFGTPEFVAPEI---VNQSPVS--GVT-DIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNY--NVAFEET 1089
Cdd:cd05601   158 vtskmP----VGTPDYIAPEVltsMNGGSKGtyGVEcDWWSLGIVAYEMLYGKTPFTEDTVIKTYSNIMNFkkFLKFPED 233

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 1090 tfLSLSREARGFLIKVLVQDRLRPTAEETLEHPWFK 1125
Cdd:cd05601   234 --PKVSESAVDLIKGLLTDAKERLGYEGLCCHPFFS 267

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270907 [Multi-domain] Cd Length: 255 Bit Score: 95.38 E-value: 3.37e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIP-SQAKPKASARREARLLA---------RLQHDCVLYFHEAFERRRGL 940
Cdd:cd14005     2 YEVGDLLGKGGFGTVYSGVRIRDGLPVAVKFVPkSRVTEWAMINGPVPVPLeialllkasKPGVPGVIRLLDWYERPDGF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTE--LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEeqVRICDFGNAQEL 1018
Cdd:cd14005    82 LLIMErpEPCQDLFDFITERGALSENLARIIFRQVVEAVRHCHQRGVLHRDIKDENLLI-NLRTGE--VKLIDFGCGALL 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1019 TpgEPQYCQF-GTPEFVAPEIVNQSPVSG--VTdIWPVGVVAFLCLTGISPFvgENDrttLMNIRNyNVAFEEttflSLS 1095
Cdd:cd14005   159 K--DSVYTDFdGTRVYSPPEWIRHGRYHGrpAT-VWSLGILLYDMLCGDIPF--END---EQILRG-NVLFRP----RLS 225

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1096 REARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14005   226 KECCDLISRCLQFDpSKRPSLEQILSHPWF 255

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271039 [Multi-domain] Cd Length: 293 Bit Score: 96.42 E-value: 4.07e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKasaRREARLLARLQHDCVLYFHEAFERRRG------LVIVT 944
Cdd:cd14137     6 YTIEKVIGSGSFGVVYQAKLLETGEVVAIKKVLQDKRYK---NRELQIMRRLKHPNIVKLKYFFYSSGEkkdevyLNLVM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ElCTEELLERMAR-----KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEeqVRICDFGNAQELT 1019
Cdd:cd14137    83 E-YMPETLYRVIRhysknKQTIPIIYVKLYSYQLFRGLAYLHSLGICHRDIKPQNLLV-DPETGV--LKLCDFGSAKRLV 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCQFGTPEFVAPEIVNQSPVSGVT-DIWPVG-VVAFLcLTGISPFVGEND------------RTTLMNIRNYNVA 1085
Cdd:cd14137   159 PGEPNVSYICSRYYRAPELIFGATDYTTAiDIWSAGcVLAEL-LLGQPLFPGESSvdqlveiikvlgTPTREQIKAMNPN 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1086 FEETTFLSLSR-------------EARGFLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd14137   238 YTEFKFPQIKPhpwekvfpkrtppDAIDLLSKILVYNpSKRLTALEALAHPFFD 291

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270793 [Multi-domain] Cd Length: 287 Bit Score: 95.95 E-value: 4.11e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAA--EGKRRVLQEYEVLRTLHHErlmslheaYITPRYLVLIAESCGNRELL---C 2306
Cdd:cd06621    12 GAGGSVTKCRLRNTKTIFALKTITTDPnpDVQKQILRELEINKSCASP--------YIVKYYGAFLDEQDSSIGIAmeyC 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 G-----------LSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQAlkp 2374
Cdd:cd06621    84 EggsldsiykkvKKKGGRIGEKVLGKIAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGvSGELVNSLA--- 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 lGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFyEPD------PQETEARIVggRFDAFQLYPNT---- 2444
Cdd:cd06621   161 -GTFTGTSYYMAPERIQGGPYSITSDVWSLGLTLLEVAQNRFPF-PPEgepplgPIELLSYIV--NMPNPELKDEPengi 236

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 564369110 2445 --SQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd06621   237 kwSESFKDFIEKCLEKDGTRRPGPWQMLAHPWIKA 271

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270754 [Multi-domain] Cd Length: 321 Bit Score: 96.96 E-value: 4.11e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVL-RTLHHERLMSLHEAYITPRYLVLIAESCGNRELL 2305
Cdd:cd05603     5 KGSFGKVLLAKRKCDGKFYAVKVLQKKTILKKKeqnhIMAERNVLlKNLKHPFLVGLHYSFQTSEKLYFVLDYVNGGELF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpynpQALKPLGHRT---GTL 2382
Cdd:cd05603    85 FHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGLCK----EGMEPEETTStfcGTP 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2383 EFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggrFDAFQLYPNTSQSATLFLRKVL 2456
Cdd:cd05603   161 EYLAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPFYSRDVSQMYDNIL---HKPLHLPGGKTVAACDLLQGLL 231

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271104 [Multi-domain] Cd Length: 267 Bit Score: 95.46 E-value: 4.77e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSS-GLEFAAKFIPSQ--AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-ELL 952
Cdd:cd14202    10 IGHGAFAVVFKGRHKEKhDLEVAVKCINKKnlAKSQTLLGKEIKILKELKHENIVALYDFQEIANSVYLVMEYCNGgDLA 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEE-----QVRICDFGNAQELTPGEPQYCQ 1027
Cdd:cd14202    90 DYLHTMRTLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLSYSGGRKSnpnniRIKIADFGFARYLQNNMMAATL 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFvgenDRTTLMNIRNYnvaFEETTFL--SLSREARGFLIKV 1105
Cdd:cd14202   170 CGSPMYMAPEVIMSQHYDAKADLWSIGTIIYQCLTGKAPF----QASSPQDLRLF---YEKNKSLspNIPRETSSHLRQL 242

                         250       260
                  ....*....|....*....|....
gi 564369110 1106 LV-----QDRLRPTAEETLEHPWF 1124
Cdd:cd14202   243 LLgllqrNQKDRMDFDEFFHHPFL 266

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270824 [Multi-domain] Cd Length: 283 Bit Score: 95.68 E-value: 4.78e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGlEFAAkfIPSQAKPKASAR-----REARLLARLQ-HDCVLYFHEAFERRRGLVIVT 944
Cdd:cd07830     1 YKVIKQLGDGTFGSVYLARNKETG-ELVA--IKKMKKKFYSWEecmnlREVKSLRKLNeHPNIVKLKEVFRENDELYFVF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTEELLERM-ARKPTV-CESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGE 1022
Cdd:cd07830    78 EYMEGNLYQLMkDRKGKPfSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLV----SGPEVVKIADFGLAREIRSRP 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PqYCQF-GTPEFVAPEIVNQSPV-SGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI-------------------RN 1081
Cdd:cd07830   154 P-YTDYvSTRWYRAPEILLRSTSySSPVDIWALGCIMAELYTLRPLFPGSSEIDQLYKIcsvlgtptkqdwpegyklaSK 232

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1082 YNVAFEETTFLSL-------SREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07830   233 LGFRFPQFAPTSLhqlipnaSPEAIDLIKDMLRWDpKKRPTASQALQHPYF 283

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132942 [Multi-domain] Cd Length: 280 Bit Score: 95.58 E-value: 5.18e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEGK-RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN-------RE 2303
Cdd:cd06611    16 GAFGKVYKAQHKETGLFAAAKIIQIESEEElEDFMVEIDILSECKHPNIVGLYEAYFYENKLWILIEFCDGgaldsimLE 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2304 LLCGLSdrfrysEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQpyNPQALKPLGHRTGTL 2382
Cdd:cd06611    96 LERGLT------EPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGvSAK--NKSTLQKRDTFIGTP 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMV-----RGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLFLRKVLS 2457
Cdd:cd06611   168 YWMAPEVVacetfKDNPYDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKILKSEPPTLDQPSKWSSSFNDFLKSCLV 247

                         250       260
                  ....*....|....*....|.
gi 564369110 2458 VHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd06611   248 KDPDDRPTAAELLKHPFVSDQ 268

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270895 [Multi-domain] Cd Length: 267 Bit Score: 95.11 E-value: 5.55e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV-------PYAAEGKRRV-LQEYEVLRTLH-HERLMSLHEAYITPRYLV 2293
Cdd:cd13993     2 YQLISPIGEGAYGVVYLAVDLRTGRKYAIKCLyksgpnsKDGNDFQKLPqLREIDLHRRVSrHPNIITLHDVFETEVAIY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2294 LIAESCGNRELLCGLSDRFRY--SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAAD-NALKIVDFGSA--QPYN 2368
Cdd:cd13993    82 IVLEYCPNGDLFEAITENRIYvgKTELIKNVFLQLIDAVKHCHSLGIYHRDIKPENILLSQDeGTVKLCDFGLAttEKIS 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2369 PQAlkplghRTGTLEFMAPEMVRGDPIGSAT------DIWGAGVLTYIMLSGYSPFYEPDPQE-TEARIVGGRFDAFQLY 2441
Cdd:cd13993   162 MDF------GVGSEFYMAPECFDEVGRSLKGypcaagDIWSLGIILLNLTFGRNPWKIASESDpIFYDYYLNSPNLFDVI 235

                         250       260
                  ....*....|....*....|....*..
gi 564369110 2442 PNTSQSATLFLRKVLSVHPWSRPSLQD 2468
Cdd:cd13993   236 LPMSDDFYNLLRQIFTVNPNNRILLPE 262

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132988 [Multi-domain] Cd Length: 292 Bit Score: 95.86 E-value: 5.70e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLE---EKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVL-QEYEVLRTLHHERLMSLHEAYITPRYLVL 2294
Cdd:cd06657    15 PGDPRTYLDnfiKIGEGSTGIVCIATVKSSGKLVAVKKMDLRKQQRRELLfNEVVIMRDYQHENVVEMYNSYLVGDELWV 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2295 IAESCGNRELlCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGsaqpYNPQALKP 2374
Cdd:cd06657    95 VMEFLEGGAL-TDIVTHTRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFG----FCAQVSKE 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHR---TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATLF 2451
Cdd:cd06657   170 VPRRkslVGTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRDNLPPKLKNLHKVSPSLKGF 249

                         250       260
                  ....*....|....*....|....*..
gi 564369110 2452 LRKVLSVHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd06657   250 LDRLLVRDPAQRATAAELLKHPFLAKA 276

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270722 [Multi-domain] Cd Length: 318 Bit Score: 96.51 E-value: 5.90e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE-LTPGE--PQYCqfGTPEFVAPEIV 1039
Cdd:cd05570    95 EERARFYAAEICLALQFLHERGIIYRDLKLDNVLL-DAEG---HIKIADFGMCKEgIWGGNttSTFC--GTPDYIAPEIL 168

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1040 NQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEettfLSLSREARGFLIKVLVQD---RL--RPT 1114
Cdd:cd05570   169 REQDYGFSVDWWALGVLLYEMLAGQSPFEGDDEDELFEAILNDEVLYP----RWLSREAVSILKGLLTKDparRLgcGPK 244

                         170
                  ....*....|..
gi 564369110 1115 AEETL-EHPWFK 1125
Cdd:cd05570   245 GEADIkAHPFFR 256

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271102 [Multi-domain] Cd Length: 284 Bit Score: 95.40 E-value: 6.21e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV-------------------PYAAEGKR--------RVLQEYEVLRTLH 2275
Cdd:cd14200     2 YKLQSEIGKGSYGVVKLAYNESDDKYYAMKVLskkkllkqygfprrppprgSKAAQGEQakplapleRVYQEIAILKKLD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2276 HERLMSLHEAYITPRY--LVLIAESCGNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAAD 2353
Cdd:cd14200    82 HVNIVKLIEVLDDPAEdnLYMVFDLLRKGPVMEVPSDK-PFSEDQARLYFRDIVLGIEYLHYQKIVHRDIKPSNLLLGDD 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2354 NALKIVDFG-SAQPYNPQALkpLGHRTGTLEFMAPEMV---RGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEAR 2429
Cdd:cd14200   161 GHVKIADFGvSNQFEGNDAL--LSSTAGTPAFMAPETLsdsGQSFSGKALDVWAMGVTLYCFVYGKCPFIDEFILALHNK 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 564369110 2430 IVGGRFDaFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14200   239 IKNKPVE-FPEEPEISEELKDLILKMLDKNPETRITVPEIKVHPWV 283

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132986 [Multi-domain] Cd Length: 296 Bit Score: 95.95 E-value: 6.43e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKAS-ARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE 949
Cdd:cd06655    21 YTRYEKIGQGASGTVFTAIDVATGQEVAIKQINLQKQPKKElIINEILVMKELKNPNIVNFLDSFLVGDELFVVMEYLAG 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQYCQF- 1028
Cdd:cd06655   101 GSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLL----GMDGSVKLTDFGFCAQITPEQSKRSTMv 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNyNVAFEETTFLSLSREARGFLIKVLVQ 1108
Cdd:cd06655   177 GTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIAT-NGTPELQNPEKLSPIFRDFLNRCLEM 255

                         250
                  ....*....|....*...
gi 564369110 1109 D-RLRPTAEETLEHPWFK 1125
Cdd:cd06655   256 DvEKRGSAKELLQHPFLK 273

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270788 [Multi-domain] Cd Length: 259 Bit Score: 94.68 E-value: 6.61e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPY-AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN 2301
Cdd:cd06613     2 YELIQRIGSGTYGDVYKARNIATGELAAVKVIKLePGDDFEIIQQEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELlcglSDRFRY----SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpynpQALKPLGH 2377
Cdd:cd06613    82 GSL----QDIYQVtgplSELQIAYVCRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSA----QLTATIAK 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RT---GTLEFMAPEMV---RGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATL- 2450
Cdd:cd06613   154 RKsfiGTPYWMAPEVAaveRKGGYDGKCDIWALGITAIELAELQPPMFDLHPMRALFLIPKSNFDPPKLKDKEKWSPDFh 233

                         250       260
                  ....*....|....*....|....
gi 564369110 2451 -FLRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd06613   234 dFIKKCLTKNPKKRPTATKLLQHP 257

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.

Pssm-ID: 214568 [Multi-domain] Cd Length: 258 Bit Score: 94.54 E-value: 6.81e-21

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   2224 TFLEEKARGRFGVVRSCR---ENATGRTFVA-KIV--PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:smart00221    2 TLGKKLGEGAFGEVYKGTlkgKGDGKEVEVAvKTLkeDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVME 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   2298 SCGNRELLcglsDRFRYSED------DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQA 2371
Cdd:smart00221   82 YMPGGDLL----DYLRKNRPkelslsDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDD 157

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110   2372 LKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPFYEPDPQETEARIVGGRF 2435
Cdd:smart00221  158 YYKVKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTlGEEPYPGMSNAEVLEYLKKGYR 222

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270727 [Multi-domain] Cd Length: 323 Bit Score: 96.23 E-value: 7.16e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVL-RTLHHERLMSLHEAYITPRYLVLIAESCGNRELL 2305
Cdd:cd05575     5 KGSFGKVLLARHKAEGKLYAVKVLQKKAILKRNevkhIMAERNVLlKNVKHPFLVGLHYSFQTKDKLYFVLDYVNGGELF 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpynpQALKPLGHRT---GTL 2382
Cdd:cd05575    85 FHLQRERHFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGLCK----EGIEPSDTTStfcGTP 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2383 EFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggrFDAFQLYPNTSQSATLFLRKVL 2456
Cdd:cd05575   161 EYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRDTAEMYDNIL---HKPLRLRTNVSPSARDLLEGLL 231

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271102 [Multi-domain] Cd Length: 284 Bit Score: 95.40 E-value: 7.43e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPS------------------------QAKPKASARR---EARLLARLQ 923
Cdd:cd14200     2 YKLQSEIGKGSYGVVKLAYNESDDKYYAMKVLSKkkllkqygfprrppprgskaaqgeQAKPLAPLERvyqEIAILKKLD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  924 HDCVLYFHEAFE--RRRGLVIVTELCTE-ELLERMARKPTVcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdg 1000
Cdd:cd14200    82 HVNIVKLIEVLDdpAEDNLYMVFDLLRKgPVMEVPSDKPFS-EDQARLYFRDIVLGIEYLHYQKIVHRDIKPSNLLL--- 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1001 aGGEEQVRICDFGNAQELTPGEPQYCQF-GTPEFVAPEIVN---QSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTL 1076
Cdd:cd14200   158 -GDDGHVKIADFGVSNQFEGNDALLSSTaGTPAFMAPETLSdsgQSFSGKALDVWAMGVTLYCFVYGKCPFIDEFILALH 236

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 564369110 1077 MNIRNYNVAFEETTflSLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14200   237 NKIKNKPVEFPEEP--EISEELKDLILKMLDKNpETRITVPEIKVHPW 282

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

Pssm-ID: 270901 [Multi-domain] Cd Length: 245 Bit Score: 94.14 E-value: 8.23e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENatGRTfVA----KIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN---R 2302
Cdd:cd13999     2 GSGSFGEVYKGKWR--GTD-VAikklKVEDDNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGgslY 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLcgLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKpLGHRTGTL 2382
Cdd:cd13999    79 DLL--HKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIKNSTTEK-MTGVVGTP 155

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 564369110 2383 EFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYE 2420
Cdd:cd13999   156 RWMAPEVLRGEPYTEKADVYSFGIVLWELLTGEVPFKE 193

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271074 [Multi-domain] Cd Length: 267 Bit Score: 94.67 E-value: 9.05e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKpkasARREARLLARL---QHD-CVLYFHEAFER-RRGLVIV 943
Cdd:cd14172     4 DYKLSKQVLGLGVNGKVLECFHRRTGQKCALKLLYDSPK----ARREVEHHWRAsggPHIvHILDVYENMHHgKRCLLII 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TElCTE--ELLERMARK--PTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLvWDGAGGEEQVRICDFGNAQELT 1019
Cdd:cd14172    80 ME-CMEggELFSRIQERgdQAFTEREASEIMRDIGTAIQYLHSMNIAHRDVKPENLL-YTSKEKDAVLKLTDFGFAKETT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRT----TLMNIRNYNVAFEETTFLSLS 1095
Cdd:cd14172   158 VQNALQTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSNTGQAispgMKRRIRMGQYGFPNPEWAEVS 237

                         250       260
                  ....*....|....*....|....*....
gi 564369110 1096 REARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14172   238 EEAKQLIRHLLKTDpTERMTITQFMNHPW 266

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271072 [Multi-domain] Cd Length: 303 Bit Score: 95.49 E-value: 1.01e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIpsQAKPKAsaRREARLLARLQH-----DCVLYFHEAFERRRGLVIV 943
Cdd:cd14170     2 DYKVTSQVLGLGINGKVLQIFNKRTQEKFALKML--QDCPKA--RREVELHWRASQcphivRIVDVYENLYAGRKCLLIV 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TElCTE--ELLERMARK--PTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLvWDGAGGEEQVRICDFGNAQELT 1019
Cdd:cd14170    78 ME-CLDggELFSRIQDRgdQAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLL-YTSKRPNAILKLTDFGFAKETT 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRT----TLMNIRNYNVAFEETTFLSLS 1095
Cdd:cd14170   156 SHNSLTTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAispgMKTRIRMGQYEFPNPEWSEVS 235

                         250       260
                  ....*....|....*....|....*....
gi 564369110 1096 REARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14170   236 EEVKMLIRNLLKTEpTQRMTITEFMNHPW 264

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270787 [Multi-domain] Cd Length: 267 Bit Score: 94.35 E-value: 1.01e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA--SARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd06610     1 DDYELIEVIGSGATAVVYAAYCLPKKEKVAIKRIDLEKCQTSmdELRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTE----ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGEeqVRICDFG-NAQELTPG 1021
Cdd:cd06610    81 LSGgsllDIMKSSYPRGGLDEAIIATVLKEVLKGLEYLHSNGQIHRDVKAGNILL--GEDGS--VKIADFGvSASLATGG 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 EPQ----YCQFGTPEFVAPEIVNQspVSGVT---DIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAF--EETTFL 1092
Cdd:cd06610   157 DRTrkvrKTFVGTPCWMAPEVMEQ--VRGYDfkaDIWSFGITAIELATGAAPYSKYPPMKVLMLTLQNDPPSleTGADYK 234

                         250       260       270
                  ....*....|....*....|....*....|...
gi 564369110 1093 SLSREARGFLIKVLVQDRL-RPTAEETLEHPWF 1124
Cdd:cd06610   235 KYSKSFRKMISLCLQKDPSkRPTAEELLKHKFF 267

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270767 [Multi-domain] Cd Length: 323 Bit Score: 95.84 E-value: 1.10e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyaaegKRRVLQEYEVLRTLHHERLMSL----------HEAYITPRYL 2292
Cdd:cd05616     2 FNFLMVLGKGSFGKVMLAERKGTDELYAVKILK-----KDVVIQDDDVECTMVEKRVLALsgkppfltqlHSCFQTMDRL 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPynpQAL 2372
Cdd:cd05616    77 YFVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKE---NIW 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2373 KPLGHRT--GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggrfDAFQLYPNT-SQSAT 2449
Cdd:cd05616   154 DGVTTKTfcGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIM----EHNVAYPKSmSKEAV 229

                         250
                  ....*....|....
gi 564369110 2450 LFLRKVLSVHPWSR 2463
Cdd:cd05616   230 AICKGLMTKHPGKR 243

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270828 [Multi-domain] Cd Length: 329 Bit Score: 95.67 E-value: 1.12e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTfVA--KIVP------YAaegkRRVLQEYEVLRTLHHERLMSLHEAYITPR---- 2290
Cdd:cd07834     2 YELLKPIGSGAYGVVCSAYDKRTGRK-VAikKISNvfddliDA----KRILREIKILRHLKHENIIGLLDILRPPSpeef 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 ---YLVLiaescgnrELLcgLSD-------RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVD 2360
Cdd:cd07834    77 ndvYIVT--------ELM--ETDlhkviksPQPLTDDHIQYFLYQILRGLKYLHSAGVIHRDLKPSNILVNSNCDLKICD 146

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2361 FGSAQPYNPQALKplGHRTG---TLEFMAPE-MVRGDPIGSATDIWGAGVL--------------TYI-MLS------Gy 2415
Cdd:cd07834   147 FGLARGVDPDEDK--GFLTEyvvTRWYRAPElLLSSKKYTKAIDIWSVGCIfaelltrkplfpgrDYIdQLNlivevlG- 223

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2416 SPFYEPDPQET--EAR--IVGGRF----DAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd07834   224 TPSEEDLKFISseKARnyLKSLPKkpkkPLSEVFPGASPEAIDLLEKMLVFNPKKRITADEALAHPYLAQ 293

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270907 [Multi-domain] Cd Length: 255 Bit Score: 93.84 E-value: 1.24e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVP------YAA-EGKRRVLQEYEVLR---TLHHERLMSLHEAYITPRYL 2292
Cdd:cd14005     2 YEVGDLLGKGGFGTVYSGVRIRDGLPVAVKFVPksrvteWAMiNGPVPVPLEIALLLkasKPGVPGVIRLLDWYERPDGF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLI---AESCGNreLLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA-LKIVDFGSAQPyn 2368
Cdd:cd14005    82 LLImerPEPCQD--LFDFITERGALSENLARIIFRQVVEAVRHCHQRGVLHRDIKDENLLINLRTGeVKLIDFGCGAL-- 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2369 pqaLKPLGHRT--GTLEFMAPEMVR-----GDPigsATdIWGAGVLTYIMLSGYSPFyepdpqETEARIVGGRFdafQLY 2441
Cdd:cd14005   158 ---LKDSVYTDfdGTRVYSPPEWIRhgryhGRP---AT-VWSLGILLYDMLCGDIPF------ENDEQILRGNV---LFR 221

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 2442 PNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14005   222 PRLSKECCDLISRCLQFDPSKRPSLEQILSHPWF 255

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270735 [Multi-domain] Cd Length: 268 Bit Score: 94.00 E-value: 1.33e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFS---YLRRVVERSSGLEFAAKF-----IPSQAKPKASARREARLLARLQHDCVLY-FHEAFERRRGLVIVTE-L 946
Cdd:cd05583     2 LGTGAYGkvfLVRKVGGHDAGKLYAMKVlkkatIVQKAKTAEHTMTERQVLEAVRQSPFLVtLHYAFQTDAKLHLILDyV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQ-- 1024
Cdd:cd05583    82 NGGELFTHLYQREHFTESEVRIYIGEIVLALEHLHKLGIIYRDIKLENILL-DSEG---HVVLTDFGLSKEFLPGENDra 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 --YCqfGTPEFVAPEIVNqSPVSG---VTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREAR 1099
Cdd:cd05583   158 ysFC--GTIEYMAPEVVR-GGSDGhdkAVDWWSLGVLTYELLTGASPFTVDGERNSQSEISKRILKSHPPIPKTFSAEAK 234

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 1100 GFLIKVLVQD---RL---RPTAEETLEHPWFK 1125
Cdd:cd05583   235 DFILKLLEKDpkkRLgagPRGAHEIKEHPFFK 266

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.

Pssm-ID: 197581 [Multi-domain] Cd Length: 257 Bit Score: 93.75 E-value: 1.36e-20

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   2224 TFLEEKARGRFGVVRSCR---ENATGRTFVA-KIV--PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:smart00219    2 TLGKKLGEGAFGEVYKGKlkgKGGKKKVEVAvKTLkeDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVME 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   2298 SCGNRELLcglsDRFRYSEDDVAT-----YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAL 2372
Cdd:smart00219   82 YMEGGDLL----SYLRKNRPKLSLsdllsFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDY 157

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110   2373 KPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPFYEPDPQETEARIVGGRF 2435
Cdd:smart00219  158 YRKRGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTlGEQPYPGMSNEEVLEYLKNGYR 221

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270843 [Multi-domain] Cd Length: 328 Bit Score: 95.72 E-value: 1.36e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTF-VAKIV-PYAAEG-KRRVLQEYEVLRTLHHERLMSLHEAYITPR---YLVlia 2296
Cdd:cd07856    12 YSDLQPVGMGAFGLVCSARDQLTGQNVaVKKIMkPFSTPVlAKRTYRELKLLKHLRHENIISLSDIFISPLediYFV--- 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 escgnRELLCGLSDRF---RYSEDDVATYVV-QLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQal 2372
Cdd:cd07856    89 -----TELLGTDLHRLltsRPLEKQFIQYFLyQILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLARIQDPQ-- 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2373 kpLGHRTGTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPD---------------PQETEARIVGGRFD 2436
Cdd:cd07856   162 --MTGYVSTRYYRAPEiMLTWQKYDVEVDIWSAGCIFAEMLEGKPLFPGKDhvnqfsiitellgtpPDDVINTICSENTL 239

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2437 AF-------------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07856   240 RFvqslpkrervpfsEKFKNADPDAIDLLEKMLVFDPKKRISAAEALAHPYL 291

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270782 [Multi-domain] Cd Length: 265 Bit Score: 93.95 E-value: 1.36e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2225 FLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK--RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGnr 2302
Cdd:cd06605     5 YLGELGEGNGGVVSKVRHRPSGQIMAVKVIRLEIDEAlqKQILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEYMD-- 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ellCGLSDRFRYS-----EDDVATYVVQLLQGLDYLH-GRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQAlkpl 2375
Cdd:cd06605    83 ---GGSLDKILKEvgripERILGKIAVAVVKGLIYLHeKHKIIHRDVKPSNILVNSRGQVKLCDFGvSGQLVDSLA---- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDP--------------QETEARIVGGRFdafqly 2441
Cdd:cd06605   156 KTFVGTRSYMAPERISGGKYTVKSDIWSLGLSLVELATGRFPYPPPNAkpsmmifellsyivDEPPPLLPSGKF------ 229

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 564369110 2442 pntSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd06605   230 ---SPDFQDFVSQCLQKDPTERPSYKELMEHPFIK 261

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271067 [Multi-domain] Cd Length: 263 Bit Score: 94.08 E-value: 1.39e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR----REARLLARLQHDCVLYFHEAFERRRGLV-IVTE 945
Cdd:cd14165     3 YILGINLGEGSYAKVKSAYSERLKCNVAIKIIDKKKAPDDFVEkflpRELEILARLNHKSIIKTYEIFETSDGKVyIVME 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGE-- 1022
Cdd:cd14165    83 LGVQgDLLEFIKLRGALPEDVARKMFHQLSSAIKYCHELDIVHRDLKCENLLL----DKDFNIKLTDFGFSKRCLRDEng 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 -----PQYCqfGTPEFVAPEIVNQSPVS-GVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTflSLSR 1096
Cdd:cd14165   159 rivlsKTFC--GSAAYAAPEVLQGIPYDpRIYDIWSLGVILYIMVCGSMPYDDSNVKKMLKIQKEHRVRFPRSK--NLTS 234

                         250       260
                  ....*....|....*....|....*....
gi 564369110 1097 EARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14165   235 ECKDLIYRLLQPDvSQRLCIDEVLSHPWL 263

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270814 [Multi-domain] Cd Length: 261 Bit Score: 93.84 E-value: 1.46e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKAS-ARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE 949
Cdd:cd06647     9 YTRFEKIGQGASGTVYTAIDVATGQEVAIKQMNLQQQPKKElIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAG 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQYCQF- 1028
Cdd:cd06647    89 GSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILL----GMDGSVKLTDFGFCAQITPEQSKRSTMv 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLmnirnYNVAFEETTFL----SLSREARGFLIK 1104
Cdd:cd06647   165 GTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRAL-----YLIATNGTPELqnpeKLSAIFRDFLNR 239

                         250       260
                  ....*....|....*....|..
gi 564369110 1105 VL-VQDRLRPTAEETLEHPWFK 1125
Cdd:cd06647   240 CLeMDVEKRGSAKELLQHPFLK 261

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270785 [Multi-domain] Cd Length: 275 Bit Score: 94.29 E-value: 1.48e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARL-QHDCVLYFHEAFERRRGLV----- 941
Cdd:cd06608     5 AGIFELVEVIGEGTYGKVYKARHKKTGQLAAIKIMDIIEDEEEEIKLEINILRKFsNHPNIATFYGAFIKKDPPGgddql 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 -IVTELCT----EELLERMARKPTVCESETRTY-MRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeeqVRICDFGNA 1015
Cdd:cd06608    85 wLVMEYCGggsvTDLVKGLRKKGKRLKEEWIAYiLRETLRGLAYLHENKVIHRDIKGQNILLTEEAE----VKLVDFGVS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1016 QEL--TPGEPQYCqFGTPEFVAPEIV--NQSPVSGVT---DIWPVGVVAFLCLTGISPF-----------VGENDRTTLM 1077
Cdd:cd06608   161 AQLdsTLGRRNTF-IGTPYWMAPEVIacDQQPDASYDarcDVWSLGITAIELADGKPPLcdmhpmralfkIPRNPPPTLK 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 1078 NIRNYnvafeettflslSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd06608   240 SPEKW------------SKEFNDFISECLIKNyEQRPFTEELLEHPF 274

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132943 [Multi-domain] Cd Length: 256 Bit Score: 93.48 E-value: 1.51e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRrVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd06612     1 PEEVFDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVEEDLQE-IIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEY 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGN---RELLCGLSDRFrySEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKp 2374
Cdd:cd06612    80 CGAgsvSDIMKITNKTL--TEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGvSGQLTDTMAKR- 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 lGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPqetearivggrFDAFQLYPNT---------- 2444
Cdd:cd06612   157 -NTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHP-----------MRAIFMIPNKppptlsdpek 224

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 2445 -SQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06612   225 wSPEFNDFVKKCLVKDPEERPSAIQLLQHPFI 256

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270839 [Multi-domain] Cd Length: 336 Bit Score: 95.45 E-value: 1.58e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATG-RTFVAKIVP-----YAaegkRRVLQEYEVLRTLHHERLMSLHEAyITPR------ 2290
Cdd:cd07849     7 YQNLSYIGEGAYGMVCSAVHKPTGqKVAIKKISPfehqtYC----LRTLREIKILLRFKHENIIGILDI-QRPPtfesfk 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 --YLVliaescgnREL----LCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA 2364
Cdd:cd07849    82 dvYIV--------QELmetdLYKLIKTQHLSNDHIQYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGLA 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2365 QPYNPQAlKPLGHRT---GTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPD---------------PQE 2425
Cdd:cd07849   154 RIADPEH-DHTGFLTeyvATRWYRAPEiMLNSKGYTKAIDIWSVGCILAEMLSNRPLFPGKDylhqlnlilgilgtpSQE 232

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2426 TEARIVGGRFDAF-------------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQDAY 2479
Cdd:cd07849   233 DLNCIISLKARNYikslpfkpkvpwnKLFPNADPKALDLLDKMLTFNPHKRITVEEALAHPYLEQYH 299

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270753 [Multi-domain] Cd Length: 339 Bit Score: 95.47 E-value: 1.64e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2218 PPQKP--YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVL-RTLHHERLMSLHEAYITPR 2290
Cdd:cd05602     2 PHAKPsdFHFLKVIGKGSFGKVLLARHKSDEKFYAVKVLQKKAILKKKeekhIMSERNVLlKNVKHPFLVGLHFSFQTTD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 YLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpynpQ 2370
Cdd:cd05602    82 KLYFVLDYINGGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCK----E 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 ALKPLGHRT---GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGgrfDAFQLYPNTSQS 2447
Cdd:cd05602   158 NIEPNGTTStfcGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILN---KPLQLKPNITNS 234


                  ....*....
gi 564369110 2448 ATLFLRKVL 2456
Cdd:cd05602   235 ARHLLEGLL 243

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270847 [Multi-domain] Cd Length: 302 Bit Score: 94.48 E-value: 2.03e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKR---RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd07864     9 FDIIGIIGEGTYGQVYKAKDKDTGELVALKKVRLDNEKEGfpiTAIREIKILRQLNHRSVVNLKEIVTDKQDALDFKKDK 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNREL--------LCGL--SDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP 2369
Cdd:cd07864    89 GAFYLvfeymdhdLMGLleSGLVHFSEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGLARLYNS 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSgYSPFYEPDPQ----ETEARIVGGRFDA------- 2437
Cdd:cd07864   169 EESRPYTNKVITLWYRPPELLLGEErYGPAIDVWSCGCILGELFT-KKPIFQANQElaqlELISRLCGSPCPAvwpdvik 247

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2438 --------------------FQLYPntsQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07864   248 lpyfntmkpkkqyrrrlreeFSFIP---TPALDLLDHMLTLDPSKRCTAEQALNSPWL 302

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.

Pssm-ID: 270723 [Multi-domain] Cd Length: 322 Bit Score: 94.73 E-value: 2.06e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQ---AKPK-ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-EL 951
Cdd:cd05571     3 LGKGTFGKVILCREKATGELYAIKILKKEviiAKDEvAHTLTENRVLQNTRHPFLTSLKYSFQTNDRLCFVMEYVNGgEL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE-LTPGEPQ--YCqf 1028
Cdd:cd05571    83 FFHLSRERVFSEDRTRFYGAEIVLALGYLHSQGIVYRDLKLENLLL-DKDG---HIKITDFGLCKEeISYGATTktFC-- 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFvgendrttlmNIRNYNVAFE-----ETTFLS-LSREARGFL 1102
Cdd:cd05571   157 GTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPF----------YNRDHEVLFElilmeEVRFPStLSPEAKSLL 226

                         250       260
                  ....*....|....*....|....*...
gi 564369110 1103 IKVLVQD---RL---RPTAEETLEHPWF 1124
Cdd:cd05571   227 AGLLKKDpkkRLgggPRDAKEIMEHPFF 254

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270921 [Multi-domain] Cd Length: 252 Bit Score: 93.06 E-value: 2.07e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFS--YL-----RRVVERSSGLEFAAKFIPSQAKPKASARrEARLLARLQ-HDCVLYFHEAFERRRGL 940
Cdd:cd14019     1 NKYRIIEKIGEGTFSsvYKaedklHDLYDRNKGRLVALKHIYPTSSPSRILN-ELECLERLGgSNNVSGLITAFRNEDQV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTEELLERMARKPTVceSETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLvWDGAGGeeQVRICDFGNAQELTP 1020
Cdd:cd14019    80 VAVLPYIEHDDFRDFYRKMSL--TDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFL-YNRETG--KGVLVDFGLAQREED 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYC-QFGTPEFVAPEIVNQSPVSGVT-DIWPVGVVaFLC-LTGI-SPFVGENDRTTL---MNIRNYNVAFEettfls 1093
Cdd:cd14019   155 RPEQRApRAGTRGFRAPEVLFKCPHQTTAiDIWSAGVI-LLSiLSGRfPFFFSSDDIDALaeiATIFGSDEAYD------ 227

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 1094 lsreargFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14019   228 -------LLDKLLELDpSKRITAEEALKHPFF 252

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270898 [Multi-domain] Cd Length: 273 Bit Score: 93.51 E-value: 2.11e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPY--AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNREL--LC 2306
Cdd:cd13996    16 SGGFGSVYKVRNKVDGVTYAIKKIRLteKSSASEKVLREVKALAKLNHPNIVRYYTAWVEEPPLYIQMELCEGGTLrdWI 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVAT-YVVQLLQGLDYLHGRHVLHLDIKPDNLLLA-ADNALKIVDFG---------------SAQPYNP 2369
Cdd:cd13996    96 DRRNSSSKNDRKLALeLFKQILKGVSYIHSKGIVHRDLKPSNIFLDnDDLQVKIGDFGlatsignqkrelnnlNNNNNGN 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLGhrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEAR--IVGGRFDafQLYPNTSQs 2447
Cdd:cd13996   176 TSNNSVG--IGTPLYASPEQLDGENYNEKADIYSLGIILFEMLHPFKTAMERSTILTDLRngILPESFK--AKHPKEAD- 250

                         250       260
                  ....*....|....*....|...
gi 564369110 2448 atlFLRKVLSVHPWSRPSLQDCL 2470
Cdd:cd13996   251 ---LIQSLLSKNPEERPSAEQLL 270

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270838 [Multi-domain] Cd Length: 287 Bit Score: 93.91 E-value: 2.25e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGlEFAA--KFIPSQAKP--KASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd07848     9 VGEGAYGVVLKCRHKETK-EIVAikKFKDSEENEevKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNML 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARKPT-VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPG-EPQYCQF-G 1029
Cdd:cd07848    88 ELLEEMPNgVPPEKVRSYIYQLIKAIHWCHKNDIVHRDIKPENLLI----SHNDVLKLCDFGFARNLSEGsNANYTEYvA 163

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1030 TPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIR 1080
Cdd:cd07848   164 TRWYRSPELLLGAPYGKAVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQ 214

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270838 [Multi-domain] Cd Length: 287 Bit Score: 93.52 E-value: 2.77e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEG---KRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR--ELLC 2306
Cdd:cd07848    12 GAYGVVLKCRHKETKEIVAIKKFKDSEENeevKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNmlELLE 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRfrYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEFMA 2386
Cdd:cd07848    92 EMPNG--VPPEKVRSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGSNANYTEYVATRWYRS 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2387 PEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF---YEPDPQETEARIVG-------------GRFDAFQlYPNTSQSATL 2450
Cdd:cd07848   170 PELLLGAPYGKAVDMWSVGCILGELSDGQPLFpgeSEIDQLFTIQKVLGplpaeqmklfysnPRFHGLR-FPAVNHPQSL 248

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 564369110 2451 --------------FLRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd07848   249 errylgilsgvlldLMKNLLKLNPTDRYLTEQCLNHP 285

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270863 [Multi-domain] Cd Length: 262 Bit Score: 93.10 E-value: 2.90e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVP----YAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE--SCGNrel 2304
Cdd:cd08224    10 KGQFSVVYRARCLLDGRLVALKKVQifemMDAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLElaDAGD--- 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 LCGLSDRFR-----YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKplGHRT 2379
Cdd:cd08224    87 LSRLIKHFKkqkrlIPERTIWKYFVQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFSSKTTA--AHSL 164

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 564369110 2380 -GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFY 2419
Cdd:cd08224   165 vGTPYYMSPERIREQGYDFKSDIWSLGCLLYEMAALQSPFY 205

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270782 [Multi-domain] Cd Length: 265 Bit Score: 92.79 E-value: 3.17e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLVIVTELCT----E 949
Cdd:cd06605     8 ELGEGNGGVVSKVRHRPSGQIMAVKVIRLEIDEALQKQilRELDVLHKCNSPYIVGFYGAFYSEGDISICMEYMDggslD 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPtvcESETRTYMRQVLEGIGYLHQSH-VLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQyCQF 1028
Cdd:cd06605    88 KILKEVGRIP---ERILGKIAVAVVKGLIYLHEKHkIIHRDVKPSNILV-NSRG---QVKLCDFGVSGQLVDSLAK-TFV 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYN-VAFEETTFLS---LSREARGFLIK 1104
Cdd:cd06605   160 GTRSYMAPERISGGKYTVKSDIWSLGLSLVELATGRFPYPPPNAKPSMMIFELLSyIVDEPPPLLPsgkFSPDFQDFVSQ 239

                         250       260
                  ....*....|....*....|..
gi 564369110 1105 VLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd06605   240 CLQKDpTERPSYKELMEHPFIK 261

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270837 [Multi-domain] Cd Length: 286 Bit Score: 93.59 E-value: 3.29e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEG---KRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd07847     3 YEKLSKIGEGSYGVVFKCRNRETGQIVAIKKFVESEDDpviKKIALREIRMLKQLKHPNLVNLIEVFRRKRKLHLVFEYC 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 gNRELLCGLSDRFR-YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPqalkPLGHR 2378
Cdd:cd07847    83 -DHTVLNELEKNPRgVPEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARILTG----PGDDY 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 T---GTLEFMAPEMVRGD-PIGSATDIWGAGVLTYIMLSG------------------------------------YSPF 2418
Cdd:cd07847   158 TdyvATRWYRAPELLVGDtQYGPPVDVWAIGCVFAELLTGqplwpgksdvdqlylirktlgdliprhqqifstnqfFKGL 237

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 2419 YEPDPQETEarivggrfDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd07847   238 SIPEPETRE--------PLESKFPNISSPALSFLKGCLQMDPTERLSCEELLEHPY 285

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270842 [Multi-domain] Cd Length: 336 Bit Score: 94.35 E-value: 4.13e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAE---GKRRVLQEYEVLRTLHHERLMSLHEAYITPR--------Y 2291
Cdd:cd07855     7 YEPIETIGSGAYGVVCSAIDTKSGQKVAIKKIPNAFDvvtTAKRTLRELKILRHFKHDNIIAIRDILRPKVpyadfkdvY 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2292 LVL-IAESCGNRELLCGLSdrfrYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYnpq 2370
Cdd:cd07855    87 VVLdLMESDLHHIIHSDQP----LTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFGMARGL--- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 ALKPLGHRT------GTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLS------GYSPFYE----------PDPQ--- 2424
Cdd:cd07855   160 CTSPEEHKYfmteyvATRWYRAPElMLSLPEYTQAIDMWSVGCIFAEMLGrrqlfpGKNYVHQlqliltvlgtPSQAvin 239

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2425 ETEARIVGGRFDAF---------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd07855   240 AIGADRVRRYIQNLpnkqpvpweTLYPKADQQALDLLSQMLRFDPSERITVAEALQHPFLA 300

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270818 [Multi-domain] Cd Length: 264 Bit Score: 92.80 E-value: 4.13e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFI------PSQAKPKASARREARLLARLQHDCVLYFHEAFE--RRRGLVIVTELCT 948
Cdd:cd06652    10 LGQGAFGRVYLCYDADTGRELAVKQVqfdpesPETSKEVNALECEIQLLKNLLHERIVQYYGCLRdpQERTLSIFMEYMP 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 E-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELT----PGEP 1023
Cdd:cd06652    90 GgSIKDQLKSYGALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILR-DSVG---NVKLGDFGASKRLQticlSGTG 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLmnirnYNVAFEETTFL---SLSREARG 1100
Cdd:cd06652   166 MKSVTGTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPWAEFEAMAAI-----FKIATQPTNPQlpaHVSDHCRD 240

                         250       260
                  ....*....|....*....|.
gi 564369110 1101 FLIKVLVQDRLRPTAEETLEH 1121
Cdd:cd06652   241 FLKRIFVEAKLRPSADELLRH 261

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270750 [Multi-domain] Cd Length: 324 Bit Score: 93.83 E-value: 4.51e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKR----RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd05599    11 RGAFGEVRLVRKKDTGHVYAMKKLRKSEMLEKeqvaHVRAERDILAEADNPWVVKLYYSFQDEENLYLIMEFLPGGDMMT 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQalkPLGHRT-GTLEFM 2385
Cdd:cd05599    91 LLMKKDTLTEEETRFYIAETVLAIESIHKLGYIHRDIKPDNLLLDARGHIKLSDFGLCTGLKKS---HLAYSTvGTPDYI 167

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 564369110 2386 APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV 2431
Cdd:cd05599   168 APEVFLQKGYGKECDWWSLGVIMYEMLIGYPPFCSDDPQETCRKIM 213

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143341 [Multi-domain] Cd Length: 284 Bit Score: 92.93 E-value: 4.79e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAE--GKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd07836     2 FKQLEKLGEGTYATVYKGRNRTTGEIVALKEIHLDAEegTPSTAIREISLMKELKHENIVRLHDVIHTENKLMLVFEYMD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NrellcglsDRFRYSE----------DDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYN-P 2369
Cdd:cd07836    82 K--------DLKKYMDthgvrgaldpNTVKSFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLARAFGiP 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 qaLKPLGHRTGTLEFMAPEMVRGDPIGSAT-DIWGAGVLTYIMLSGY--------------------------------S 2416
Cdd:cd07836   154 --VNTFSNEVVTLWYRAPDVLLGSRTYSTSiDIWSVGCIMAEMITGRplfpgtnnedqllkifrimgtptestwpgisqL 231

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2417 PFYEPDPQETEARivggrfDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd07836   232 PEYKPTFPRYPPQ------DLQQLFPHADPLGIDLLHRLLQLNPELRISAHDALQHPW 283

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271072 [Multi-domain] Cd Length: 303 Bit Score: 93.18 E-value: 5.31e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2245 TGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHE-AYITPRYLVLIAESCGNRELLCGLSDRF--RYSEDDVAT 2321
Cdd:cd14170    26 TQEKFALKMLQDCPKARREVELHWRASQCPHIVRIVDVYEnLYAGRKCLLIVMECLDGGELFSRIQDRGdqAFTEREASE 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2322 YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAA---DNALKIVDFGSAQPYNPQalKPLGHRTGTLEFMAPEMVRGDPIGSA 2398
Cdd:cd14170   106 IMKSIGEAIQYLHSINIAHRDVKPENLLYTSkrpNAILKLTDFGFAKETTSH--NSLTTPCYTPYYVAPEVLGPEKYDKS 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2399 TDIWGAGVLTYIMLSGYSPFYEPD----PQETEARIVGGRFDafqlYPNT-----SQSATLFLRKVLSVHPWSRPSLQDC 2469
Cdd:cd14170   184 CDMWSLGVIMYILLCGYPPFYSNHglaiSPGMKTRIRMGQYE----FPNPewsevSEEVKMLIRNLLKTEPTQRMTITEF 259

                         250       260
                  ....*....|....*....|....*...
gi 564369110 2470 LAHPWLQDAYLMKlrrQTLTFTTNRLKE 2497
Cdd:cd14170   260 MNHPWIMQSTKVP---QTPLHTSRVLKE 284

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270979 [Multi-domain] Cd Length: 267 Bit Score: 92.51 E-value: 5.37e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIP----------SQAKPKASARREAR--------LLARLQHDCVL---- 928
Cdd:cd14077     3 WEFVKTIGAGSMGKVKLAKHIRTGEKCAIKIIPrasnaglkkeREKRLEKEISRDIRtireaalsSLLNHPHICRLrdfl 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  929 ----YFHEAFERRRGlvivtelctEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggE 1004
Cdd:cd14077    83 rtpnHYYMLFEYVDG---------GQLLDYIISHGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISK----S 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1005 EQVRICDFGNAQELTPGE--PQYCqfGTPEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRN 1081
Cdd:cd14077   150 GNIKIIDFGLSNLYDPRRllRTFC--GSLYFAAPELLQAQPYTGPeVDVWSFGVVLYVLVCGKVPFDDENMPALHAKIKK 227

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 564369110 1082 YNVAFEETtflsLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14077   228 GKVEYPSY----LSSECKSLISRMLVVDpKKRATLEQVLNHPW 266

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270729 [Multi-domain] Cd Length: 278 Bit Score: 92.59 E-value: 5.59e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd05577     3 RGGFGEVCACQVKATGKMYACKKLDKKRIKKKKgetmALNEKIILEKVSSPFIVSLAYAFETKDKLCLVLTLMNGGDLKY 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLS--DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQalKPLGHRTGTLEF 2384
Cdd:cd05577    83 HIYnvGTRGFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLAVEFKGG--KKIKGRVGTHGY 160

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 564369110 2385 MAPEMVRGD-PIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd05577   161 MAPEVLQKEvAYDFSVDWFALGCMLYEMIAGRSPF 195

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270799 [Multi-domain] Cd Length: 270 Bit Score: 92.44 E-value: 5.97e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIV---PYAAE----GKRRVL----QEYEVLRTLHHERLMslheAYI----TPRYLVLI 2295
Cdd:cd06629    11 KGTYGRVYLAMNATTGEMLAVKQVelpKTSSDradsRQKTVVdalkSEIDTLKDLDHPNIV----QYLgfeeTEDYFSIF 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG----SAQPYNPQA 2371
Cdd:cd06629    87 LEYVPGGSIGSCLRKYGKFEEDLVRFFTRQILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGiskkSDDIYGNNG 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 LKPLghrTGTLEFMAPEMVRGDPIG-SA-TDIWGAGVLTYIMLSGYSPfYEPDPQETEARIVGGRFDAFQLYPNT--SQS 2447
Cdd:cd06629   167 ATSM---QGSVFWMAPEVIHSQGQGySAkVDIWSLGCVVLEMLAGRRP-WSDDEAIAAMFKLGNKRSAPPVPEDVnlSPE 242

                         250       260
                  ....*....|....*....|....*...
gi 564369110 2448 ATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06629   243 ALDFLNACFAIDPRDRPTAAELLSHPFL 270

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270800 [Multi-domain] Cd Length: 268 Bit Score: 92.11 E-value: 6.21e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2314 YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLL-AADNALKIVDFGSAQPYNPQALKP---LGHRTGTLEFMAPEM 2389
Cdd:cd06630   100 FSENVIINYTLQILRGLAYLHDNQIIHRDLKGANLLVdSTGQRLRIADFGAAARLASKGTGAgefQGQLLGTIAFMAPEV 179

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2390 VRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggRFDAFQLYPNTSQSATLFLRKV----LSVHPWSRPS 2465
Cdd:cd06630   180 LRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKISNHLALIF--KIASATTPPPIPEHLSPGLRDVtlrcLELQPEDRPP 257


                  ....*...
gi 564369110 2466 LQDCLAHP 2473
Cdd:cd06630   258 ARELLKHP 265

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271023 [Multi-domain] Cd Length: 252 Bit Score: 91.58 E-value: 6.23e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  915 EARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMAR-KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPE 993
Cdd:cd14121    45 EIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGDLSRFIRsRRTLPESTVRRFLQQLASALQFLREHNISHMDLKPQ 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  994 NLLVwdGAGGEEQVRICDFGNAQELTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDR 1073
Cdd:cd14121   125 NLLL--SSRYNPVLKLADFGFAQHLKPNDEAHSLRGSPLYMAPEMILKKKYDARVDLWSVGVILYECLFGRAPFASRSFE 202

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1074 TTLMNIRNyNVAFEETTFLSLSREARGFLIKVLVQDRL-RPTAEETLEHPW 1123
Cdd:cd14121   203 ELEEKIRS-SKPIEIPTRPELSADCRDLLLRLLQRDPDrRISFEEFFAHPF 252

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271020 [Multi-domain] Cd Length: 275 Bit Score: 92.04 E-value: 7.14e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMA--RKPT---VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEPQ 1024
Cdd:cd14118    96 ELVDKGAvmEVPTdnpLSEETARSYFRDIVLGIEYLHYQKIIHRDIKPSNLLLGD----DGHVKIADFGVSNEFEGDDAL 171

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQ-FGTPEFVAPEIV--NQSPVSG-VTDIWPVGVVAFLCLTGISPFVGENdRTTLMN-IRNYNVAFEETTflSLSREAR 1099
Cdd:cd14118   172 LSStAGTPAFMAPEALseSRKKFSGkALDIWAMGVTLYCFVFGRCPFEDDH-ILGLHEkIKTDPVVFPDDP--VVSEQLK 248

                         170       180
                  ....*....|....*....|....*
gi 564369110 1100 GFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14118   249 DLILRMLDKNpSERITLPEIKEHPW 273

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270972 [Multi-domain] Cd Length: 262 Bit Score: 91.80 E-value: 7.31e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIV--------PYAAEGKRRvlqEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14070    12 EGSFAKVREGLHAVTGEKVAIKVIdkkkakkdSYVTKNLRR---EGRIQQMIRHPNITQLLDILETENSYYLVMELCPGG 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAL-KPLGHRTGT 2381
Cdd:cd14070    89 NLMHRIYDKKRLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLSNCAGILGYsDPFSTQCGS 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2382 LEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF-YEP-DPQETEARIVGGRFDAfqLYPNTSQSATLFLRKVLSVH 2459
Cdd:cd14070   169 PAYAAPELLARKKYGPKVDVWSIGVNMYAMLTGTLPFtVEPfSLRALHQKMVDKEMNP--LPTDLSPGAISFLRSLLEPD 246

                         250
                  ....*....|....*.
gi 564369110 2460 PWSRPSLQDCLAHPWL 2475
Cdd:cd14070   247 PLKRPNIKQALANRWL 262

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR2 (also called STK38-like) plays a role in proper centrosome duplication. In addition, it is involved in regulating neuronal growth and differentiation, as well as in facilitating neurite outgrowth. NDR2 is also implicated in fear conditioning as it contributes to the coupling of neuronal morphological changes with fear-memory consolidation. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270776 [Multi-domain] Cd Length: 366 Bit Score: 93.97 E-value: 7.58e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPS----QAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd05627     2 DDFESLKVIGRGAFGEVRLVQKKDTGHIYAMKILRKadmlEKEQVAHIRAERDILVEADGAWVVKMFYSFQDKRNLYLIM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 E-LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNA-------- 1015
Cdd:cd05627    82 EfLPGGDMMTLLMKKDTLSEEATQFYIAETVLAIDAIHQLGFIHRDIKPDNLLL-DAKG---HVKLSDFGLCtglkkahr 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1016 ----QELTPGEPQ------------------------YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd05627   158 tefyRNLTHNPPSdfsfqnmnskrkaetwkknrrqlaYSTVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPF 237

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1068 VGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQDRLR---PTAEETLEHPWFKT 1126
Cdd:cd05627   238 CSETPQETYRKVMNWKETLVFPPEVPISEKAKDLILRFCTDAENRigsNGVEEIKSHPFFEG 299

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270817 [Multi-domain] Cd Length: 271 Bit Score: 92.07 E-value: 7.79e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFI------PSQAKPKASARREARLLARLQHDCVLYFHEAFERR--RGLVIVTE-LC 947
Cdd:cd06651    15 LGQGAFGRVYLCYDVDTGRELAAKQVqfdpesPETSKEVSALECEIQLLKNLQHERIVQYYGCLRDRaeKTLTIFMEyMP 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQEL----TPGEP 1023
Cdd:cd06651    95 GGSVKDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILR-DSAG---NVKLGDFGASKRLqticMSGTG 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTflSLSREARGFLI 1103
Cdd:cd06651   171 IRSVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKIATQPTNPQLPS--HISEHARDFLG 248

                         250       260
                  ....*....|....*....|
gi 564369110 1104 KVLVQDRLRPTAEETLEHPW 1123
Cdd:cd06651   249 CIFVEARHRPSAEELLRHPF 268

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270859 [Multi-domain] Cd Length: 256 Bit Score: 91.33 E-value: 9.45e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVP---YAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCG 2307
Cdd:cd08220    10 RGAYGTVYLCRRKDDNKLVIIKQIPveqMTKEERQAALNEVKVLSMLHHPNIIEYYESFLEDKALMIVMEYAPGGTLFEY 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 LSDR--FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLL-AADNALKIVDFGSAQPYNPQALKPLghRTGTLEF 2384
Cdd:cd08220    90 IQQRkgSLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLnKKRTVVKIGDFGISKILSSKSKAYT--VVGTPCY 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2385 MAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAfqLYPNTSQSATLFLRKVLSVHPWSRP 2464
Cdd:cd08220   168 ISPELCEGKPYNQKSDIWALGCVLYELASLKRAFEAANLPALVLKIMRGTFAP--ISDRYSEELRHLILSMLHLDPNKRP 245


                  ....*....
gi 564369110 2465 SLQDCLAHP 2473
Cdd:cd08220   246 TLSEIMAQP 254

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270892 [Multi-domain] Cd Length: 279 Bit Score: 92.00 E-value: 9.59e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2262 RRVLQEYEVLRTLHHERLMSLHEAY-ITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYL--HGRHV 2338
Cdd:cd13990    49 KHALREYEIHKSLDHPRIVKLYDVFeIDTDSFCTVLEYCDGNDLDFYLKQHKSIPEREARSIIMQVVSALKYLneIKPPI 128

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2339 LHLDIKPDNLLLAADN---ALKIVDFG-SAQ----PYNPQALKPLGHRTGTLEFMAPE--MVRGDP--IGSATDIWGAGV 2406
Cdd:cd13990   129 IHYDLKPGNILLHSGNvsgEIKITDFGlSKImddeSYNSDGMELTSQGAGTYWYLPPEcfVVGKTPpkISSKVDVWSVGV 208

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2407 LTYIMLSGYSPFYEPDPQETEAR---IVGGRFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd13990   209 IFYQMLYGRKPFGHNQSQEAILEentILKATEVEFPSKPVVSSEAKDFIRRCLTYRKEDRPDVLQLANDPY 279

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270833 [Multi-domain] Cd Length: 298 Bit Score: 92.25 E-value: 9.81e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA------SARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd07841     2 YEKGKKLGEGTYAVVYKARDKETGRIVAIKKIKLGERKEAkdginfTALREIKLLQELKHPNIIGLLDVFGHKSNINLVF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCT---EELLERmaRKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGeeQVRICDFGNAQEL-TP 1020
Cdd:cd07841    82 EFMEtdlEKVIKD--KSIVLTPADIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLI--ASDG--VLKLADFGLARSFgSP 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYCQFGTPEFVAPEIVNQSPVSGVT-DIWPVGVV-AFLCLTgiSPFV-GENDRTTLMNIRN---------------- 1081
Cdd:cd07841   156 NRKMTHQVVTRWYRAPELLFGARHYGVGvDMWSVGCIfAELLLR--VPFLpGDSDIDQLGKIFEalgtpteenwpgvtsl 233

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1082 -YNVAFEETT-------FLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWFKT 1126
Cdd:cd07841   234 pDYVEFKPFPptplkqiFPAASDDALDLLQRLLTLNpNKRITARQALEHPYFSN 287

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173765 [Multi-domain] Cd Length: 257 Bit Score: 91.17 E-value: 1.04e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2233 RFGVVRSCRENATGRTFVAK--------------IVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd08225     1 RYEIIKKIGEGSFGKIYLAKaksdsehcvikeidLTKMPVKEKEASKKEVILLAKMKHPNIVTFFASFQENGRLFIVMEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDR--FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNAL-KIVDFGSAQPYNpQALKPL 2375
Cdd:cd08225    81 CDGGDLMKRINRQrgVLFSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGMVaKLGDFGIARQLN-DSMELA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAfqLYPNTSQSATLFLRKV 2455
Cdd:cd08225   160 YTCVGTPYYLSPEICQNRPYNNKTDIWSLGCVLYELCTLKHPFEGNNLHQLVLKICQGYFAP--ISPNFSRDLRSLISQL 237

                         250       260
                  ....*....|....*....|
gi 564369110 2456 LSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd08225   238 FKVSPRDRPSITSILKRPFL 257

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270763 [Multi-domain] Cd Length: 292 Bit Score: 91.73 E-value: 1.29e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKF--IPS--QAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd05612     1 DDFERIKTIGTGTFGRVHLVRDRISEHYYALKVmaIPEviRLKQEQHVHNEKRVLKEVSHPFIIRLFWTEHDQRFLYMLM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 E-LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEP 1023
Cdd:cd05612    81 EyVPGGELFSYLRNSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILL----DKEGHIKLTDFGFAKKLRDRTW 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREARGFLI 1103
Cdd:cd05612   157 TLC--GTPEYLAPEVIQSKGHNKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILAGKLEFPR----HLDLYAKDLIK 230

                         250       260
                  ....*....|....*....|....*....
gi 564369110 1104 KVLVQDRLRPT------AEETLEHPWFKT 1126
Cdd:cd05612   231 KLLVVDRTRRLgnmkngADDVKNHRWFKS 259

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 85.39 E-value: 1.40e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  1849 PVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIvSCKDGRQLLSIPRASKRHAGLYECSATNVL 1928
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKV-TYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 564369110  1929 GSITSSCTVAV 1939
Cdd:pfam07679   80 GEAEASAELTV 90

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270734 [Multi-domain] Cd Length: 317 Bit Score: 92.08 E-value: 1.54e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFS---YLRRVVERSSGLEFAAKFIpSQAKPKASAR----REARLLARLQHDCVLYFHEAFERRRGLVIVTE-LCT 948
Cdd:cd05582     3 LGQGSFGkvfLVRKITGPDAGTLYAMKVL-KKATLKVRDRvrtkMERDILADVNHPFIVKLHYAFQTEGKLYLILDfLRG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQF 1028
Cdd:cd05582    82 GDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILL-DEDG---HIKLTDFGLSKESIDHEKKAYSF 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 -GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREARGF---LIK 1104
Cdd:cd05582   158 cGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKETMTMILKAKLGMPQ----FLSPEAQSLlraLFK 233

                         250       260
                  ....*....|....*....|....*
gi 564369110 1105 VLVQDRL---RPTAEETLEHPWFKT 1126
Cdd:cd05582   234 RNPANRLgagPDGVEEIKRHPFFAT 258

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270824 [Multi-domain] Cd Length: 283 Bit Score: 91.06 E-value: 1.73e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVpyaaegKRRV--------LQEYEVLRTL-HHERLMSLHEAYITPRYLV 2293
Cdd:cd07830     1 YKVIKQLGDGTFGSVYLARNKETGELVAIKKM------KKKFysweecmnLREVKSLRKLnEHPNIVKLKEVFRENDELY 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2294 LIAESC-GNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQal 2372
Cdd:cd07830    75 FVFEYMeGNLYQLMKDRKGKPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAREIRSR-- 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2373 KPLGHRTGTLEFMAPEMV-RGDPIGSATDIWGAGVltyIMLSGYS--PFY----EPD-----------PQETE------- 2427
Cdd:cd07830   153 PPYTDYVSTRWYRAPEILlRSTSYSSPVDIWALGC---IMAELYTlrPLFpgssEIDqlykicsvlgtPTKQDwpegykl 229

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2428 ARIVGGRFDAF------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07830   230 ASKLGFRFPQFaptslhQLIPNASPEAIDLIKDMLRWDPKKRPTASQALQHPYF 283

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270779 [Multi-domain] Cd Length: 285 Bit Score: 91.24 E-value: 1.77e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAEscgnreLL 2305
Cdd:cd05630     9 GKGGFGEVCACQVRATGKMYACKKLEKKRIKKRKgeamALNEKQILEKVNSRFVVSLAYAYETKDALCLVLT------LM 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFR--------YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpYNPQAlKPLGH 2377
Cdd:cd05630    83 NGGDLKFHiyhmgqagFPEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAV-HVPEG-QTIKG 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYE 2420
Cdd:cd05630   161 RVGTVGYMAPEVVKNERYTFSPDWWALGCLLYEMIAGQSPFQQ 203

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270889 [Multi-domain] Cd Length: 259 Bit Score: 90.46 E-value: 2.07e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTL-HHERLMSLHEAYI-TPRYLVLIAESCGNRELLCG 2307
Cdd:cd13987     2 GEGTYGKVLLAVHKGSGTKMALKFVPKPSTKLKDFLREYNISLELsVHPHIIKTYDVAFeTEDYYVFAQEYAPYGDLFSI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 LSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA--LKIVDFGSAQPynpqALKPLGHRTGTLEFM 2385
Cdd:cd13987    82 IPPQVGLPEERVKRCAAQLASALDFMHSKNLVHRDIKPENVLLFDKDCrrVKLCDFGLTRR----VGSTVKRVSGTIPYT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2386 APE---MVRGDPI--GSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARivggRFDAFQLYPNT---------SQSATLF 2451
Cdd:cd13987   158 APEvceAKKNEGFvvDPSIDVWAFGVLLFCCLTGNFPWEKADSDDQFYE----EFVRWQKRKNTavpsqwrrfTPKALRM 233

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2452 LRKVLSVHPWSRPSLQD---CLAHPW 2474
Cdd:cd13987   234 FKKLLAPEPERRCSIKEvfkYLGDRW 259

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270893 [Multi-domain] Cd Length: 268 Bit Score: 90.65 E-value: 2.35e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYaaegKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSD 2310
Cdd:cd13991    16 RGSFGEVHRMEDKQTGFQCAVKKVRL----EVFRAEELMACAGLTSPRVVPLYGAVREGPWVNIFMDLKEGGSLGQLIKE 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2311 RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA-LKIVDFGSAQPYNPQAL-KPL---GHRTGTLEFM 2385
Cdd:cd13991    92 QGCLPEDRALHYLGQALEGLEYLHSRKILHGDVKADNVLLSSDGSdAFLCDFGHAECLDPDGLgKSLftgDYIPGTETHM 171

                         170       180       190
                  ....*....|....*....|....*....|...
gi 564369110 2386 APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd13991   172 APEVVLGKPCDAKVDVWSSCCMMLHMLNGCHPW 204

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271075 [Multi-domain] Cd Length: 288 Bit Score: 90.86 E-value: 2.54e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIV-PYAAEGKRRVLQEYEVLRTLH-HERLMSLHEAYITPRYLVLIAESCGNRELLCGLS 2309
Cdd:cd14173    13 GAYARVQTCINLITNKEYAVKIIeKRPGHSRSRVFREVEMLYQCQgHRNVLELIEFFEEEDKFYLVFEKMRGGSILSHIH 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNAL---KIVDF--GSAQPYN--------PQALKPlg 2376
Cdd:cd14173    93 RRRHFNELEASVVVQDIASALDFLHNKGIAHRDLKPENILCEHPNQVspvKICDFdlGSGIKLNsdcspistPELLTP-- 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 hrTGTLEFMAPEMV-----RGDPIGSATDIWGAGVLTYIMLSGYSPFY------------EPDPQETEARIVGGRFDAFQ 2439
Cdd:cd14173   171 --CGSAEYMAPEVVeafneEASIYDKRCDLWSLGVILYIMLSGYPPFVgrcgsdcgwdrgEACPACQNMLFESIQEGKYE 248

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 564369110 2440 L----YPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14173   249 FpekdWAHISCAAKDLISKLLVRDAKQRLSAAQVLQHPWV 288

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270780 [Multi-domain] Cd Length: 313 Bit Score: 91.19 E-value: 2.68e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELL 2305
Cdd:cd05632    11 GKGGFGEVCACQVRATGKMYACKRLEKKRIKKRKgesmALNEKQILEKVNSQFVVNLAYAYETKDALCLVLTIMNGGDLK 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFR--YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYnPQALKPLGhRTGTLE 2383
Cdd:cd05632    91 FHIYNMGNpgFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAVKI-PEGESIRG-RVGTVG 168

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 564369110 2384 FMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd05632   169 YMAPEVLNNQRYTLSPDYWGLGCLIYEMIEGQSPF 203

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173748 [Multi-domain] Cd Length: 372 Bit Score: 92.50 E-value: 2.96e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAE---GKRRVLQEYEVLRTLHHERLMS----LHEAYITP-RYLVLIAEScgnre 2303
Cdd:cd07853    11 GAFGVVWSVTDPRDGKRVALKKMPNVFQnlvSCKRVFRELKMLCFFKHDNVLSaldiLQPPHIDPfEEIYVVTEL----- 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2304 LLCGLSDRF----RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRT 2379
Cdd:cd07853    86 MQSDLHKIIvspqPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEEPDESKHMTQEV 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDP-----------------------QETEARIVGGRF 2435
Cdd:cd07853   166 VTQYYRAPEILMGSRhYTSAVDIWSVGCIFAELLGRRILFQAQSPiqqldlitdllgtpsleamrsacEGARAHILRGPH 245

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2436 DA------FQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQDAYL 2480
Cdd:cd07853   246 KPpslpvlYTLSSQATHEAVHLLCRMLVFDPDKRISAADALAHPYLDEGRL 296

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270825 [Multi-domain] Cd Length: 282 Bit Score: 90.41 E-value: 3.04e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQ-HDCVLYFHEA-FERRRG-LVIVTE 945
Cdd:cd07831     1 YKILGKIGEGTFSEVLKAQSRKTGKYYAIKCMKKHFKSLEQVNnlREIQALRRLSpHPNILRLIEVlFDRKTGrLALVFE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERM-ARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggeEQVRICDFGNAQELTpGEPQ 1024
Cdd:cd07831    81 LMDMNLYELIkGRKRPLPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKD-----DILKLADFGSCRGIY-SKPP 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQF-GTPEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFVGEN--DRTTLM------------------NIRNY 1082
Cdd:cd07831   155 YTEYiSTRWYRAPECLLTDGYYGPkMDIWAVGCVFFEILSLFPLFPGTNelDQIAKIhdvlgtpdaevlkkfrksRHMNY 234

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 564369110 1083 NVAFEETTFLS-----LSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07831   235 NFPSKKGTGLRkllpnASAEGLDLLKKLLAYDpDERITAKQALRHPYF 282

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270742 [Multi-domain] Cd Length: 323 Bit Score: 91.51 E-value: 3.09e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPyaaegKRRVLQEYEVLRTLHHERLMSLHE----------AYITPRYLVLIAESCG 2300
Cdd:cd05590     5 KGSFGKVMLARLKESGRLYAVKVLK-----KDVILQDDDVECTMTEKRILSLARnhpfltqlycCFQTPDRLFFVMEFVN 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQP--YNPQALKPLghr 2378
Cdd:cd05590    80 GGDLMFHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEgiFNGKTTSTF--- 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFyepdPQETEARIVGGRFDAFQLYPN-TSQSATLFLRKVLS 2457
Cdd:cd05590   157 CGTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPF----EAENEDDLFEAILNDEVVYPTwLSQDAVDILKAFMT 232

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 564369110 2458 VHPWSR-PSLQD-----CLAHPWLQDAYLMKLRRQTLT 2489
Cdd:cd05590   233 KNPTMRlGSLTLggeeaILRHPFFKELDWEKLNRRQIE 270

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270891 [Multi-domain] Cd Length: 289 Bit Score: 90.59 E-value: 3.33e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR----EARLLARLQHDCVLYFHEAFErrrGLVIVT-------- 944
Cdd:cd13989     1 LGSGGFGYVTLWKHQDTGEYVAIKKCRQELSPSDKNRErwclEVQIMKKLNHPNVVSARDVPP---ELEKLSpndlplla 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 -ELCTEELLERMARKPTVC----ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGaGGEEQVRICDFGNAQELT 1019
Cdd:cd13989    78 mEYCSGGDLRKVLNQPENCcglkESEVRTLLSDISSAISYLHENRIIHRDLKPENIVLQQG-GGRVIYKLIDLGYAKELD 156

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 564369110 1020 PGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd13989   157 QGSLCTSFVGTLQYLAPELFESKKYTCTVDYWSFGTLAFECITGYRPF 204

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132975 [Multi-domain] Cd Length: 292 Bit Score: 90.48 E-value: 3.67e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR-EARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd06644    11 NEVWEIIGELGDGAFGKVYKAKNKETGALAAAKVIETKSEEELEDYMvEIEILATCNHPYIVKLLGAFYWDGKLWIMIEF 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 C----TEELLERMARKPTvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGaggeeQVRICDFG-NAQELTP 1020
Cdd:cd06644    91 CpggaVDAIMLELDRGLT--EPQIQVICRQMLEALQYLHSMKIIHRDLKAGNvLLTLDG-----DIKLADFGvSAKNVKT 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYCQFGTPEFVAPEIV-----NQSPVSGVTDIWPVGvVAFLCLTGISPFVGE-NDRTTLMNIRNYnvafEETTFLSL 1094
Cdd:cd06644   164 LQRRDSFIGTPYWMAPEVVmcetmKDTPYDYKADIWSLG-ITLIEMAQIEPPHHElNPMRVLLKIAKS----EPPTLSQP 238

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 1095 SR---EARGFLIKVLVQD-RLRPTAEETLEHPWFKT 1126
Cdd:cd06644   239 SKwsmEFRDFLKTALDKHpETRPSAAQLLEHPFVSS 274

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270753 [Multi-domain] Cd Length: 339 Bit Score: 91.62 E-value: 3.80e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREAR-----LLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd05602     9 FHFLKVIGKGSFGKVLLARHKSDEKFYAVKVLQKKAILKKKEEKHIMsernvLLKNVKHPFLVGLHFSFQTTDKLYFVLD 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE-LTPGEP 1023
Cdd:cd05602    89 YINGgELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILL-DSQG---HIVLTDFGLCKEnIEPNGT 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREARGFLI 1103
Cdd:cd05602   165 TSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKPLQLKP----NITNSARHLLE 240


                  ....*....
gi 564369110 1104 KVLVQDRLR 1112
Cdd:cd05602   241 GLLQKDRTK 249

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271022 [Multi-domain] Cd Length: 256 Bit Score: 89.35 E-value: 3.99e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVA-KIVPYAAEGKRRVL--QEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGL 2308
Cdd:cd14120     4 GAFAVVFKGRHRKKPDLPVAiKCITKKNLSKSQNLlgKEIKILKELSHENVVALLDCQETSSSVYLVMEYCNGGDLADYL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2309 SDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA---------LKIVDFGSAQPYNPQALKplGHRT 2379
Cdd:cd14120    84 QAKGTLSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLSHNSGrkpspndirLKIADFGFARFLQDGMMA--ATLC 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRfdafQLYPN----TSQSATLFLRKV 2455
Cdd:cd14120   162 GSPMYMAPEVIMSLQYDAKADLWSIGTIVYQCLTGKAPFQAQTPQELKAFYEKNA----NLRPNipsgTSPALKDLLLGL 237

                         250
                  ....*....|....*...
gi 564369110 2456 LSVHPWSRPSLQDCLAHP 2473
Cdd:cd14120   238 LKRNPKDRIDFEDFFSHP 255

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270817 [Multi-domain] Cd Length: 271 Bit Score: 89.76 E-value: 4.30e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEK--ARGRFGVVRSCRENATGRTFVAKIV---PYAAEGKRRVLQ---EYEVLRTLHHERLMSLHEAYI--T 2288
Cdd:cd06651     3 PSAPINWRRGKllGQGAFGRVYLCYDVDTGRELAAKQVqfdPESPETSKEVSAlecEIQLLKNLQHERIVQYYGCLRdrA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2289 PRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYN 2368
Cdd:cd06651    83 EKTLTIFMEYMPGGSVKDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQ 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2369 PQALKPLGHR--TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAfQLYPNTSQ 2446
Cdd:cd06651   163 TICMSGTGIRsvTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKIATQPTNP-QLPSHISE 241

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 2447 SATLFLRKVLsVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd06651   242 HARDFLGCIF-VEARHRPSAEELLRHPFAQ 270

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270831 [Multi-domain] Cd Length: 287 Bit Score: 90.03 E-value: 4.75e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRtFVA--KI-VPYAAEG-KRRVLQEYEVLRTL---HHERLMSLHEAYITPRYlvli 2295
Cdd:cd07838     1 YEEVAEIGEGAYGTVYKARDLQDGR-FVAlkKVrVPLSEEGiPLSTIREIALLKQLesfEHPNVVRLLDVCHGPRT---- 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 aescgNRELLCGLSdrFRYSEDDVATYV-----------------VQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKI 2358
Cdd:cd07838    76 -----DRELKLTLV--FEHVDQDLATYLdkcpkpglppetikdlmRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKL 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2359 VDFGSAQPYNPQ-ALKPLghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPD--------------P 2423
Cdd:cd07838   149 ADFGLARIYSFEmALTSV---VVTLWYRAPEVLLQSSYATPVDMWSVGCIFAELFNRRPLFRGSSeadqlgkifdviglP 225

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2424 QETE-ARIVGGRFDAFQLY---------PNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07838   226 SEEEwPRNSALPRSSFPSYtprpfksfvPEIDEEGLDLLKKMLTFNPHKRISAFEALQHPYF 287

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270881 [Multi-domain] Cd Length: 265 Bit Score: 89.37 E-value: 4.82e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERssGLEFAAKFIPSQAKPKASAR--REARLLARLQHDC---VLYFHEAFERRRGLVIVTELC-T 948
Cdd:cd13979     9 EPLGSGGFGSVYKATYK--GETVAVKIVRRRRKNRASRQsfWAELNAARLRHENivrVLAAETGTDFASLGLIIMEYCgN 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 EELLERMARKPTVCESETRT-YMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTP----GEP 1023
Cdd:cd13979    87 GTLQQLIYEGSEPLPLAHRIlISLDIARALRFCHSHGIVHLDVKPANILI----SEQGVCKLCDFGCSVKLGEgnevGTP 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLM----NIRNYNVAFEETTFlslSREAR 1099
Cdd:cd13979   163 RSHIGGTYTYRAPELLKGERVTPKADIYSFGITLWQMLTRELPYAGLRQHVLYAvvakDLRPDLSGLEDSEF---GQRLR 239

                         250       260
                  ....*....|....*....|..
gi 564369110 1100 GFLIKVLVQD-RLRPTAEETLE 1120
Cdd:cd13979   240 SLISRCWSAQpAERPNADESLL 261

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270828 [Multi-domain] Cd Length: 329 Bit Score: 90.66 E-value: 5.02e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI------PSQAKpkasaR--REARLLARLQHDCVLYFHEAF-----ERR 937
Cdd:cd07834     2 YELLKPIGSGAYGVVCSAYDKRTGRKVAIKKIsnvfddLIDAK-----RilREIKILRHLKHENIIGLLDILrppspEEF 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  938 RGLVIVTELcTEELLERMARKPTVCESE-TRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQ 1016
Cdd:cd07834    77 NDVYIVTEL-METDLHKVIKSPQPLTDDhIQYFLYQILRGLKYLHSAGVIHRDLKPSNILVNS----NCDLKICDFGLAR 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPGEPQycQFGTpEFV------APEIV-NQSPVSGVTDIWPVGVVAFLCLTGISPFVGEN------------------ 1071
Cdd:cd07834   152 GVDPDEDK--GFLT-EYVvtrwyrAPELLlSSKKYTKAIDIWSVGCIFAELLTRKPLFPGRDyidqlnlivevlgtpsee 228

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1072 --DRTTLMNIRNYNVAFEE-------TTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWFK--------TEAKGAEV 1133
Cdd:cd07834   229 dlKFISSEKARNYLKSLPKkpkkplsEVFPGASPEAIDLLEKMLVFNpKKRITADEALAHPYLAqlhdpedePVAKPPFD 308

                         330
                  ....*....|....*.
gi 564369110 1134 STDHLKLFLSRRRWQR 1149
Cdd:cd07834   309 FPFFDDEELTIEELKE 324

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270829 [Multi-domain] Cd Length: 283 Bit Score: 89.66 E-value: 5.08e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTfVA--KI--------VPYAAegkrrvLQEYEVLRTLHHERLMSLHEAYITPRYL 2292
Cdd:cd07835     1 YQKLEKIGEGTYGVVYKARDKLTGEI-VAlkKIrletedegVPSTA------IREISLLKELNHPNIVRLLDVVHSENKL 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLIAE-----------SCGNRELlcglsdrfrySEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDF 2361
Cdd:cd07835    74 YLVFEfldldlkkymdSSPLTGL----------DPPLIKSYLYQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADF 143

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 564369110 2362 GSAQPYN-PqaLKPLGHRTGTLEFMAPEMVRGDPIGS-ATDIWGAG 2405
Cdd:cd07835   144 GLARAFGvP--VRTYTHEVVTLWYRAPEILLGSKHYStPVDIWSVG 187

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270884 [Multi-domain] Cd Length: 269 Bit Score: 89.25 E-value: 6.02e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 LSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA-----LKIVDFGSAQ--PYNPQALKPLGHRTG 2380
Cdd:cd13982    90 ESKLFLRPGLEPVRLLRQIASGLAHLHSLNIVHRDLKPQNILISTPNAhgnvrAMISDFGLCKklDVGRSSFSRRSGVAG 169

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVRGDPIGSAT---DIWGAGVLTYIMLSGYS-PFyePDPQETEARIVGGRFDAFQLYPNTSQS--ATLFLRK 2454
Cdd:cd13982   170 TSGWIAPEMLSGSTKRRQTravDIFSLGCVFYYVLSGGShPF--GDKLEREANILKGKYSLDKLLSLGEHGpeAQDLIER 247

                         170
                  ....*....|....*....
gi 564369110 2455 VLSVHPWSRPSLQDCLAHP 2473
Cdd:cd13982   248 MIDFDPEKRPSAEEVLNHP 266

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270836 [Multi-domain] Cd Length: 286 Bit Score: 89.79 E-value: 6.37e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV---PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd07846     3 YENLGLVGEGSYGMVMKCRHKETGQIVAIKKFlesEDDKMVKKIAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELlcglSDRFRY----SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYN-PQALkp 2374
Cdd:cd07846    83 DHTVL----DDLEKYpnglDESRVRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTLAaPGEV-- 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGySPFYEPDP-------------------QETEAR---IV 2431
Cdd:cd07846   157 YTDYVATRWYRAPELLVGDTkYGKAVDVWAVGCLVTEMLTG-EPLFPGDSdidqlyhiikclgnliprhQELFQKnplFA 235

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 2432 GGRFDAFQ-------LYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd07846   236 GVRLPEVKeveplerRYPKLSGVVIDLAKKCLHIDPDKRPSCSELLHHEF 285

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270818 [Multi-domain] Cd Length: 264 Bit Score: 88.95 E-value: 7.11e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIV---PYAAEGKRRV--LQ-EYEVLRTLHHERLMSLHEAYITP--RYLVLIAESCGN 2301
Cdd:cd06652    11 GQGAFGRVYLCYDADTGRELAVKQVqfdPESPETSKEVnaLEcEIQLLKNLLHERIVQYYGCLRDPqeRTLSIFMEYMPG 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHR--T 2379
Cdd:cd06652    91 GSIKDQLKSYGALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQTICLSGTGMKsvT 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAfQLYPNTSQSATLFLRKVLsVH 2459
Cdd:cd06652   171 GTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPTNP-QLPAHVSDHCRDFLKRIF-VE 248

                         250
                  ....*....|...
gi 564369110 2460 PWSRPSLQDCLAH 2472
Cdd:cd06652   249 AKLRPSADELLRH 261

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270950 [Multi-domain] Cd Length: 281 Bit Score: 89.55 E-value: 7.17e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLSDYYDIhQEIGRGAFSYLRRVVERSSGLEFAAKFI--PSQAKPKASARREARLLARLQHDCVL-YFH-------EAF 934
Cdd:cd14048     3 RFLTDFEPI-QCLGRGGFGVVFEAKNKVDDCNYAVKRIrlPNNELAREKVLREVRALAKLDHPGIVrYFNawlerppEGW 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  935 ERRRG---LVIVTELCTEELLERMARKPTVCESETRTYM----RQVLEGIGYLHQSHVLHLDVKPENLLV-WDGAggeeq 1006
Cdd:cd14048    82 QEKMDevyLYIQMQLCRKENLKDWMNRRCTMESRELFVClnifKQIASAVEYLHSKGLIHRDLKPSNVFFsLDDV----- 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1007 VRICDFGNAQELTPGEPQYC-------------QFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCltgISPFVGENDR 1073
Cdd:cd14048   157 VKVGDFGLVTAMDQGEPEQTvltpmpayakhtgQVGTRLYMSPEQIHGNQYSEKVDIFALGLILFEL---IYSFSTQMER 233

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 1074 T-TLMNIRNYNVAfeeTTFLSLSREARGFLIKVLVQDRL-RPTAEETLEH 1121
Cdd:cd14048   234 IrTLTDVRKLKFP---ALFTNKYPEERDMVQQMLSPSPSeRPEAHEVIEH 280

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 83.39 E-value: 7.43e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  763 DVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEEN-ECSLVVLSAGSQDGGVYTCTARNLAGEVSCKAE 841
Cdd:cd20973     6 DKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDgLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAE 85


                  ...
gi 564369110  842 LSV 844
Cdd:cd20973    86 LTV 88

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.

Pssm-ID: 270774 [Multi-domain] Cd Length: 409 Bit Score: 91.61 E-value: 7.72e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd05624    82 RGAFGEVAVVKMKNTERIYAMKILNKWEMLKRAetacFREERNVLVNGDCQWITTLHYAFQDENYLYLVMDYYVGGDLLT 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSdRF--RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEF 2384
Cdd:cd05624   162 LLS-KFedKLPEDMARFYIGEMVLAIHSIHQLHYVHRDIKPDNVLLDMNGHIRLADFGSCLKMNDDGTVQSSVAVGTPDY 240

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2385 MAPEMVRG-----DPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV 2431
Cdd:cd05624   241 ISPEILQAmedgmGKYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIM 292

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270858 [Multi-domain] Cd Length: 256 Bit Score: 88.71 E-value: 8.20e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI---PSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd08218     2 YVRIKKIGEGSFGKALLVKSKEDGKQYVIKEInisKMSPKEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMDYC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 T-EELLERMARKPTVC--ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENL-LVWDGAggeeqVRICDFGNAQEL-TPGE 1022
Cdd:cd08218    82 DgGDLYKRINAQRGVLfpEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIfLTKDGI-----IKLGDFGIARVLnSTVE 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 1023 PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI 1079
Cdd:cd08218   157 LARTCIGTPYYLSPEICENKPYNNKSDIWALGCVLYEMCTLKHAFEAGNMKNLVLKI 213

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270941 [Multi-domain] Cd Length: 289 Bit Score: 89.21 E-value: 8.20e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLV-----IVTELCTE 949
Cdd:cd14039     1 LGTGGFGNVCLYQNQETGEKIAIKSCRLELSVKNKDRwcHEIQIMKKLNHPNVVKACDVPEEMNFLVndvplLAMEYCSG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVC----ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgAGGEEQVRICDFGNAQELTPGEPQY 1025
Cdd:cd14039    81 GDLRKLLNKPENCcglkESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVLQE-INGKIVHKIIDLGYAKDLDQGSLCT 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 564369110 1026 CQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFV 1068
Cdd:cd14039   160 SFVGTLQYLAPELFENKSYTVTVDYWSFGTMVFECIAGFRPFL 202

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270948 [Multi-domain] Cd Length: 278 Bit Score: 88.97 E-value: 8.46e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLSDYYDIhQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLVI 942
Cdd:cd14046     3 RYLTDFEEL-QVLGKGAFGQVVKVRNKLDGRYYAIKKIKLRSESKNNSRilREVMLLSRLNHQHVVRYYQAWIERANLYI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  943 VTELCTE----ELLERMARKPTVcesETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNA--- 1015
Cdd:cd14046    82 QMEYCEKstlrDLIDSGLFQDTD---RLWRLFRQILEGLAYIHSQGIIHRDLKPVNIFL-DSNG---NVKIGDFGLAtsn 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1016 ----------------QELTPGEPQYCQFGTPEFVAPEIvnQSPVSGV----TDIWPVGVVAF-LCLtgisPFVGENDR- 1073
Cdd:cd14046   155 klnvelatqdinkstsAALGSSGDLTGNVGTALYVAPEV--QSGTKSTynekVDMYSLGIIFFeMCY----PFSTGMERv 228

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 1074 TTLMNIRNYNVAFEEtTFLSLSREARGFLIKVLVQ--DRLRPTAEETLEH 1121
Cdd:cd14046   229 QILTALRSVSIEFPP-DFDDNKHSKQAKLIRWLLNhdPAKRPSAQELLKS 277

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.

Pssm-ID: 132987 [Multi-domain] Cd Length: 297 Bit Score: 89.40 E-value: 9.53e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHD-CVLYFHEAFERRRGLVIVTELCTE 949
Cdd:cd06656    21 YTRFEKIGQGASGTVYTAIDIATGQEVAIKQMNLQQQPKKELIINEILVMRENKNpNIVNYLDSYLVGDELWVVMEYLAG 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQYCQF- 1028
Cdd:cd06656   101 GSLTDVVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILL----GMDGSVKLTDFGFCAQITPEQSKRSTMv 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLmnirnYNVAFEETTFLS----LSREARGFLIK 1104
Cdd:cd06656   177 GTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRAL-----YLIATNGTPELQnperLSAVFRDFLNR 251

                         250       260
                  ....*....|....*....|..
gi 564369110 1105 VLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd06656   252 CLEMDvDRRGSAKELLQHPFLK 273

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270755 [Multi-domain] Cd Length: 326 Bit Score: 90.02 E-value: 9.58e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKI----VPYAAEGKRRVLQEYEVL-RTLHHERLMSLHEAYITPRYLVLIAESCGNRELL 2305
Cdd:cd05604     6 KGSFGKVLLAKRKRDGKYYAVKVlqkkVILNRKEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTDKLYFVLDFVNGGELF 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHrTGTLEFM 2385
Cdd:cd05604    86 FHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCKEGISNSDTTTTF-CGTPEYL 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2386 APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggrFDAFQLYPNTSQSATLFLRKVLSVHPWSR-- 2463
Cdd:cd05604   165 APEVIRKQPYDNTVDWWCLGSVLYEMLYGLPPFYCRDTAEMYENIL---HKPLVLRPGISLTAWSILEELLEKDRQLRlg 241

                         250       260
                  ....*....|....*....|....*...
gi 564369110 2464 --PSLQDCLAHPWLQDAYLMKLRRQTLT 2489
Cdd:cd05604   242 akEDFLEIKNHPFFESINWTDLVQKKIP 269

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270766 [Multi-domain] Cd Length: 341 Bit Score: 90.06 E-value: 1.01e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyaaegKRRVLQEYEVLRTLHHERLMS----------LHEAYITPRYL 2292
Cdd:cd05615    12 FNFLMVLGKGSFGKVMLAERKGSDELYAIKILK-----KDVVIQDDDVECTMVEKRVLAlqdkppfltqLHSCFQTVDRL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYnpqAL 2372
Cdd:cd05615    87 YFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCKEH---MV 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2373 KPLGHRT--GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqlYPNT-SQSAT 2449
Cdd:cd05615   164 EGVTTRTfcGTPDYIAPEIIAYQPYGRSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVS----YPKSlSKEAV 239

                         250
                  ....*....|....
gi 564369110 2450 LFLRKVLSVHPWSR 2463
Cdd:cd05615   240 SICKGLMTKHPAKR 253

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143363 [Multi-domain] Cd Length: 337 Bit Score: 90.12 E-value: 1.02e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGK---RRVLQEYEVLRTLHHERLMSLHEAYITPR-------YLVL------ 2294
Cdd:cd07858    15 RGAYGIVCSAKNSETNEKVAIKKIANAFDNRidaKRTLREIKLLRHLDHENVIAIKDIMPPPHreafndvYIVYelmdtd 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2295 ---IAEScgNRELlcglsdrfrySEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNpqa 2371
Cdd:cd07858    95 lhqIIRS--SQTL----------SDDHCQYFLYQLLRGLKYIHSANVLHRDLKPSNLLLNANCDLKICDFGLARTTS--- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 lkplghrtGTLEFM----------APEMV-RGDPIGSATDIWGAGVLtYIMLSGYSPFY-----------------EPDP 2423
Cdd:cd07858   160 --------EKGDFMteyvvtrwyrAPELLlNCSEYTTAIDVWSVGCI-FAELLGRKPLFpgkdyvhqlklitellgSPSE 230

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2424 QETE------ARI------VGGRFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQDAY 2479
Cdd:cd07858   231 EDLGfirnekARRyirslpYTPRQSFARLFPHANPLAIDLLEKMLVFDPSKRITVEEALAHPYLASLH 298

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270748 [Multi-domain] Cd Length: 331 Bit Score: 89.71 E-value: 1.08e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVpyaaeGKRRVLQEYEVLRtLHHER----------LMSLHEAYITPRYLVLIAE-SC 2299
Cdd:cd05597    11 RGAFGEVAVVKLKSTEKVYAMKIL-----NKWEMLKRAETAC-FREERdvlvngdrrwITKLHYAFQDENYLYLVMDyYC 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNrELLCGLSdRF--RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSaqpynpqALKPLGH 2377
Cdd:cd05597    85 GG-DLLTLLS-KFedRLPEEMARFYLAEMVLAIDSIHQLGYVHRDIKPDNVLLDRNGHIRLADFGS-------CLKLRED 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RT-------GTLEFMAPEMVR--GDPIGS---ATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVG--GRFDaFQLY-P 2442
Cdd:cd05597   156 GTvqssvavGTPDYISPEILQamEDGKGRygpECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNhkEHFS-FPDDeD 234

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 2443 NTSQSATLFLRKVLSV--HPWSRPSLQDCLAHPW 2474
Cdd:cd05597   235 DVSEEAKDLIRRLICSreRRLGQNGIDDFKKHPF 268

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270849 [Multi-domain] Cd Length: 311 Bit Score: 89.30 E-value: 1.09e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAK--IVPYAAEG-KRRVLQEYEVLRTLHHERLMSLHE-AYITPR-------- 2290
Cdd:cd07866    10 YEILGKLGEGTFGEVYKARQIKTGRVVALKkiLMHNEKDGfPITALREIKILKKLKHPNVVPLIDmAVERPDkskrkrgs 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 -YLVL---IAEscgnrelLCGLSD--RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA 2364
Cdd:cd07866    90 vYMVTpymDHD-------LSGLLEnpSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLA 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2365 QPY-----NPQALKPLGHR--TG---TLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGySPFYE------------- 2420
Cdd:cd07866   163 RPYdgpppNPKGGGGGGTRkyTNlvvTRWYRPPELLLGERrYTTAVDIWGIGCVFAEMFTR-RPILQgksdidqlhlifk 241

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2421 ---PDPQET--EARIVGG--RFDAFQLYPNTSQSA--------TLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd07866   242 lcgTPTEETwpGWRSLPGceGVHSFTNYPRTLEERfgklgpegLDLLSKLLSLDPYKRLTASDALEHPY 310

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271111 [Multi-domain] Cd Length: 290 Bit Score: 89.00 E-value: 1.13e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA----KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd14209     1 DDFDRIKTLGTGSFGRVMLVRHKETGNYYAMKILDKQKvvklKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 EL-CTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEP 1023
Cdd:cd14209    81 EYvPGGEMFSHLRRIGRFSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLI-DQQG---YIKVTDFGFAKRVKGRTW 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFeETTFLSLSREARGFLI 1103
Cdd:cd14209   157 TLC--GTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRF-PSHFSSDLKDLLRNLL 233

                         250       260
                  ....*....|....*....|....*.
gi 564369110 1104 KVLVQDR---LRPTAEETLEHPWFKT 1126
Cdd:cd14209   234 QVDLTKRfgnLKNGVNDIKNHKWFAT 259

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271022 [Multi-domain] Cd Length: 256 Bit Score: 88.19 E-value: 1.16e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFS--YLRRVVERSSgLEFAAKFIPSQ--AKPKASARREARLLARLQHDCV--LYFHEafERRRGLVIVTELCTE- 949
Cdd:cd14120     1 IGHGAFAvvFKGRHRKKPD-LPVAIKCITKKnlSKSQNLLGKEIKILKELSHENVvaLLDCQ--ETSSSVYLVMEYCNGg 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAG-----GEEQVRICDFGNAQELTPGEPQ 1024
Cdd:cd14120    78 DLADYLQAKGTLSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLSHNSGrkpspNDIRLKIADFGFARFLQDGMMA 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 564369110 1025 YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14120   158 ATLCGSPMYMAPEVIMSLQYDAKADLWSIGTIVYQCLTGKAPF 200

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271076 [Multi-domain] Cd Length: 289 Bit Score: 88.93 E-value: 1.26e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIV-PYAAEGKRRVLQEYEVLRTLH-HERLMSLHEAYITPRYLVLIAESCGNRELLCGL 2308
Cdd:cd14174    12 EGAYAKVQGCVSLQNGKEYAVKIIeKNAGHSRSRVFREVETLYQCQgNKNILELIEFFEDDTRFYLVFEKLRGGSILAHI 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2309 SDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNAL---KIVDF--GSAQPYN----PQALKPLGHRT 2379
Cdd:cd14174    92 QKRKHFNEREASRVVRDIASALDFLHTKGIAHRDLKPENILCESPDKVspvKICDFdlGSGVKLNsactPITTPELTTPC 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 GTLEFMAPEMV-----RGDPIGSATDIWGAGVLTYIMLSGYSPFYEP-------DPQETEARIVGGRFDAFQ-------- 2439
Cdd:cd14174   172 GSAEYMAPEVVevftdEATFYDKRCDLWSLGVILYIMLSGYPPFVGHcgtdcgwDRGEVCRVCQNKLFESIQegkyefpd 251

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 564369110 2440 -LYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd14174   252 kDWSHISSEAKDLISKLLVRDAKERLSAAQVLQHPWVQ 289

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270895 [Multi-domain] Cd Length: 267 Bit Score: 88.18 E-value: 1.46e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--------PSQAKPKASARREARLLARL-QHDCVLYFHEAFERRRGL 940
Cdd:cd13993     1 RYQLISPIGEGAYGVVYLAVDLRTGRKYAIKCLyksgpnskDGNDFQKLPQLREIDLHRRVsRHPNIITLHDVFETEVAI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTE-ELLERM-ARKPTVCESE-TRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgAGGEEQVRICDFGnaqe 1017
Cdd:cd13993    81 YIVLEYCPNgDLFEAItENRIYVGKTElIKNVFLQLIDAVKHCHSLGIYHRDIKPENILL---SQDEGTVKLCDFG---- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1018 LTPGEPQYCQF--GTPEFVAPEIVNQSPVSGVT------DIWPVGVVaFLCLT-GISPF--VGENDRTTLMNIRNYNVAF 1086
Cdd:cd13993   154 LATTEKISMDFgvGSEFYMAPECFDEVGRSLKGypcaagDIWSLGII-LLNLTfGRNPWkiASESDPIFYDYYLNSPNLF 232

                         250
                  ....*....|.
gi 564369110 1087 EetTFLSLSRE 1097
Cdd:cd13993   233 D--VILPMSDD 241

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270885 [Multi-domain] Cd Length: 258 Bit Score: 87.67 E-value: 1.54e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2225 FLEEKARGRFGVVRSCRENATGRTfVA----KIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITP--RYLVLIAES 2298
Cdd:cd13983     5 FNEVLGRGSFKTVYRAFDTEEGIE-VAwneiKLRKLPKAERQRFKQEIEILKSLKHPNIIKFYDSWESKskKEVIFITEL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRH--VLHLDIKPDNLLL-AADNALKIVDFGSAqpynpqALKPL 2375
Cdd:cd13983    84 MTSGTLKQYLKRFKRLKLKVIKSWCRQILEGLNYLHTRDppIIHRDLKCDNIFInGNTGEVKIGDLGLA------TLLRQ 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRT---GTLEFMAPEMVRGDpIGSATDIWGAGVLTYIMLSGYSPFYE-PDPQETEARIVGGRFDAfQLYPNTSQSATLF 2451
Cdd:cd13983   158 SFAKsviGTPEFMAPEMYEEH-YDEKVDIYAFGMCLLEMATGEYPYSEcTNAAQIYKKVTSGIKPE-SLSKVKDPELKDF 235

                         250       260
                  ....*....|....*....|....
gi 564369110 2452 LRKVLsVHPWSRPSLQDCLAHPWL 2475
Cdd:cd13983   236 IEKCL-KPPDERPSARELLEHPFF 258

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270849 [Multi-domain] Cd Length: 311 Bit Score: 88.91 E-value: 1.58e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  866 RLSDYyDIHQEIGRGAFSYLRRVVERSSGLEFAAK-FIPSQAKPKA--SARREARLLARLQHDCVLYF-------HEAFE 935
Cdd:cd07866     6 KLRDY-EILGKLGEGTFGEVYKARQIKTGRVVALKkILMHNEKDGFpiTALREIKILKKLKHPNVVPLidmaverPDKSK 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  936 RRRGLVIVTELCTEELLERMARKPTV--CESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFG 1013
Cdd:cd07866    85 RKRGSVYMVTPYMDHDLSGLLENPSVklTESQIKCYMLQLLEGINYLHENHILHRDIKAANILI-DNQG---ILKIADFG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1014 NAQ--------------------------------ELTPGEPQY----------CQFGtpefvapEIVNQSPV-SGVTDI 1050
Cdd:cd07866   161 LARpydgpppnpkggggggtrkytnlvvtrwyrppELLLGERRYttavdiwgigCVFA-------EMFTRRPIlQGKSDI 233

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1051 WPVGVVAFLCLT-------GISPFVG-ENDRTTLMNIRNYnvafeETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEH 1121
Cdd:cd07866   234 DQLHLIFKLCGTpteetwpGWRSLPGcEGVHSFTNYPRTL-----EERFGKLGPEGLDLLSKLLSLDpYKRLTASDALEH 308


                  ...
gi 564369110 1122 PWF 1124
Cdd:cd07866   309 PYF 311

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270899 [Multi-domain] Cd Length: 252 Bit Score: 87.44 E-value: 1.75e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2225 FLEEKARGRFGVVRSCRENATGRTFVAK--IVPYAAEGKR-RVLQEYEVLRTL-HHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd13997     4 ELEQIGSGSFSEVFKVRSKVDGCLYAVKksKKPFRGPKERaRALREVEAHAALgQHPNIVRYYSSWEEGGHLYIQMELCE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NREL---LCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ--PYNPQAlkpl 2375
Cdd:cd13997    84 NGSLqdaLEELSPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATrlETSGDV---- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 ghRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYsPFYEPDPQETEARiVGGRFDAFQlyPNTSQSATLFLRK 2454
Cdd:cd13997   160 --EEGDSRYLAPELLNENYtHLPKADIFSLGVTVYEAATGE-PLPRNGQQWQQLR-QGKLPLPPG--LVLSQELTRLLKV 233

                         250
                  ....*....|....*....
gi 564369110 2455 VLSVHPWSRPSLQDCLAHP 2473
Cdd:cd13997   234 MLDPDPTRRPTADQLLAHD 252

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270858 [Multi-domain] Cd Length: 256 Bit Score: 87.56 E-value: 2.00e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAK---IVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd08218     2 YVRIKKIGEGSFGKALLVKSKEDGKQYVIKeinISKMSPKEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMDYC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELlCGLSDRFR---YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAlkPLG 2376
Cdd:cd08218    82 DGGDL-YKRINAQRgvlFPEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNSTV--ELA 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 hRT--GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRfdafqlYPNTSQSATLFLRK 2454
Cdd:cd08218   159 -RTciGTPYYLSPEICENKPYNNKSDIWALGCVLYEMCTLKHAFEAGNMKNLVLKIIRGS------YPPVPSRYSYDLRS 231

                         250       260
                  ....*....|....*....|....*
gi 564369110 2455 VLSV----HPWSRPSLQDCLAHPWL 2475
Cdd:cd08218   232 LVSQlfkrNPRDRPSINSILEKPFI 256

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270940 [Multi-domain] Cd Length: 290 Bit Score: 88.10 E-value: 2.13e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHEAFERRRGL------VIVTELCT 948
Cdd:cd14038     2 LGTGGFGNVLRWINQETGEQVAIKQCRQELSPKNRERwcLEIQIMKRLNHPNVVAARDVPEGLQKLapndlpLLAMEYCQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 EELLERMARKPTVC----ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGaggEEQV--RICDFGNAQELTPGE 1022
Cdd:cd14038    82 GGDLRKYLNQFENCcglrEGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQQG---EQRLihKIIDLGYAKELDQGS 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 564369110 1023 PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFV 1068
Cdd:cd14038   159 LCTSFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFL 204

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270737 [Multi-domain] Cd Length: 313 Bit Score: 88.40 E-value: 2.43e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKR----RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd05585     4 KGSFGKVMQVRKKDTSRIYALKTIRKAHIVSRsevtHTLAERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFINGGELFH 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpYNPQALKPLGHRTGTLEFMA 2386
Cdd:cd05585    84 HLQREGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYTGHIALCDFGLCK-LNMKDDDKTNTFCGTPEYLA 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2387 PEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGgrfDAFQLYPNTSQSATLFLRKVLSVHPWSR--- 2463
Cdd:cd05585   163 PELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKILQ---EPLRFPDGFDRDAKDLLIGLLNRDPTKRlgy 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 564369110 2464 PSLQDCLAHPWLQDAYLMKLRRQTL--TF---------TTNRLKEFLGE 2501
Cdd:cd05585   240 NGAQEIKNHPFFDQIDWKRLLMKKIqpPFkpavenaidTSNFDEEFTRE 288

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270811 [Multi-domain] Cd Length: 283 Bit Score: 87.77 E-value: 2.52e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR-EARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd06643     5 DFWEIVGELGDGAFGKVYKAQNKETGILAAAKVIDTKSEEELEDYMvEIDILASCDHPNIVKLLDAFYYENNLWILIEFC 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 ----TEELLERMARKPTvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGaggeeQVRICDFGNAQELTPGE 1022
Cdd:cd06643    85 aggaVDAVMLELERPLT--EPQIRVVCKQTLEALVYLHENKIIHRDLKAGNiLFTLDG-----DIKLADFGVSAKNTRTL 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQF-GTPEFVAPEIV-----NQSPVSGVTDIWPVGvVAFLCLTGISPFVGE-NDRTTLMNIrnynVAFEETTFLSLS 1095
Cdd:cd06643   158 QRRDSFiGTPYWMAPEVVmcetsKDRPYDYKADVWSLG-VTLIEMAQIEPPHHElNPMRVLLKI----AKSEPPTLAQPS 232

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 1096 R---EARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd06643   233 RwspEFKDFLRKCLEKNvDARWTTSQLLQHPF 264

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132971 [Multi-domain] Cd Length: 277 Bit Score: 87.42 E-value: 2.72e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPY--AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIA 2296
Cdd:cd06640     2 PEELFTKLERIGKGSFGEVFKGIDNRTQQVVAIKIIDLeeAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLcglsDRFR---YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALK 2373
Cdd:cd06640    82 EYLGGGSAL----DLLRagpFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIK 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2374 PlGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvgGRFDAFQLYPNTSQSATLFLR 2453
Cdd:cd06640   158 R-NTFVGTPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPPNSDMHPMRVLFLI--PKNNPPTLVGDFSKPFKEFID 234

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 564369110 2454 KVLSVHPWSRPSLQDCLAHPWL-----QDAYLMKL 2483
Cdd:cd06640   235 ACLNKDPSFRPTAKELLKHKFIvknakKTSYLTEL 269

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271103 [Multi-domain] Cd Length: 271 Bit Score: 87.37 E-value: 2.79e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERS-SGLEFAAKFIPSQ--AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-ELL 952
Cdd:cd14201    14 VGHGAFAVVFKGRHRKkTDWEVAIKSINKKnlSKSQILLGKEIKILKELQHENIVALYDVQEMPNSVFLVMEYCNGgDLA 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEE------QVRICDFGNAQELTPGEPQYC 1026
Cdd:cd14201    94 DYLQAKGTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILL-SYASRKKssvsgiRIKIADFGFARYLQSNMMAAT 172

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 564369110 1027 QFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14201   173 LCGSPMYMAPEVIMSQHYDAKADLWSIGTVIYQCLVGKPPF 213

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270759 [Multi-domain] Cd Length: 288 Bit Score: 87.63 E-value: 2.90e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQ----EYEVLRTLHHERLMSLHEAYITPRYLVLIAEscgnreLLC 2306
Cdd:cd05608    11 KGGFGEVSACQMRATGKLYACKKLNKKRLKKRKGYEgamvEKRILAKVHSRFIVSLAYAFQTKTDLCLVMT------IMN 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFR----------YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLG 2376
Cdd:cd05608    85 GGDLRYHiynvdeenpgFQEPRACFYTAQIISGLEHLHQRRIIYRDLKPENVLLDDDGNVRISDLGLAVELKDGQTKTKG 164

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 564369110 2377 HrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd05608   165 Y-AGTPGFMAPELLLGEEYDYSVDYFTLGVTLYEMIAARGPF 205

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270744 [Multi-domain] Cd Length: 320 Bit Score: 88.21 E-value: 3.06e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2262 RRVLqeyeVLRTlHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHL 2341
Cdd:cd05592    46 RRVL----ALAS-QHPFLTHLFCTFQTESHLFFVMEYLNGGDLMFHIQQSGRFDEDRARFYGAEIICGLQFLHSRGIIYR 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2342 DIKPDNLLLAADNALKIVDFGSAQPynpqalKPLGHRT-----GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYS 2416
Cdd:cd05592   121 DLKLDNVLLDREGHIKIADFGMCKE------NIYGENKastfcGTPDYIAPEILKGQKYNQSVDWWSFGVLLYEMLIGQS 194

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2417 PFYEPDPQETEARIVGGRfdafQLYPNT-SQSATLFLRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd05592   195 PFHGEDEDELFWSICNDT----PHYPRWlTKEAASCLSLLLERNPEKRLGVPECPAGD 248

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173750 [Multi-domain] Cd Length: 332 Bit Score: 88.62 E-value: 3.09e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2222 PYTFLEEKARGRFGVVRSCR--ENATGRTFVAKIVPYAAEGK---RRVLQEyevLRTLHHERlmslHEAYITPRYLVLIA 2296
Cdd:cd07857     1 RYELIKELGQGAYGIVCSARnaETSEEETVAIKKITNVFSKKilaKRALRE---LKLLRHFR----GHKNITCLYDMDIV 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELL-------CGLSDRFR----YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ 2365
Cdd:cd07857    74 FPGNFNELYlyeelmeADLHQIIRsgqpLTDAHFQSFIYQILCGLKYIHSANVLHRDLKPGNLLVNADCELKICDFGLAR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2366 PYNPQALKPLGHRTG---TLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSGySPFYE-----------------PDpQ 2424
Cdd:cd07857   154 GFSENPGENAGFMTEyvaTRWYRAPEiMLSFQSYTKAIDVWSVGCILAELLGR-KPVFKgkdyvdqlnqilqvlgtPD-E 231

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2425 ETEARIVGGRFDAF-------------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07857   232 ETLSRIGSPKAQNYirslpnipkkpfeSIFPNANPLALDLLEKLLAFDPTKRISVEEALEHPYL 295

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270861 [Multi-domain] Cd Length: 260 Bit Score: 86.71 E-value: 3.49e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAF--SYLRRVVERSSGLEFAA-KFIP-SQAKPKAS--ARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd08222     2 YRVVRKLGSGNFgtVYLVSDLKATADEELKVlKEISvGELQPDETvdANREAKLLSKLDHPAIVKFHDSFVEKESFCIVT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELC-----TEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeqVRICDFGNAQELT 1019
Cdd:cd08222    82 EYCeggdlDDKISEYKKSGTTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFLKNNV-----IKVGDFGISRILM 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAF--LCLTgiSPFVGENdrttLMNIRnYNVAFEETTFLS--L 1094
Cdd:cd08222   157 GTSDLATTFtGTPYYMSPEVLKHEGYNSKSDIWSLGCILYemCCLK--HAFDGQN----LLSVM-YKIVEGETPSLPdkY 229

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1095 SREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd08222   230 SKELNAIYSRMLNKDpALRPSAAEILKIPF 259

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

Pssm-ID: 270901 [Multi-domain] Cd Length: 245 Bit Score: 86.44 E-value: 3.63e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFS------YLRRVV------ERSSGLEFAAKFipsqakpkasaRREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd13999     1 IGSGSFGevykgkWRGTDVaikklkVEDDNDELLKEF-----------RREVSILSKLRHPNIVQFIGACLSPPPLCIVT 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCT----EELLERMARKPTVceSETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTP 1020
Cdd:cd13999    70 EYMPggslYDLLHKKKIPLSW--SLRLKIALDIARGMNYLHSPPIIHRDLKSLNILL-DENF---TVKIADFGLSRIKNS 143

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1021 GEPQYCQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDR 1073
Cdd:cd13999   144 TTEKMTGVvGTPRWMAPEVLRGEPYTEKADVYSFGIVLWELLTGEVPFKELSPI 197

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173720 [Multi-domain] Cd Length: 285 Bit Score: 87.36 E-value: 3.71e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAEscgnreLLC 2306
Cdd:cd05631    10 KGGFGEVCACQVRATGKMYACKKLEKKRIKKRKgeamALNEKRILEKVNSRFVVSLAYAYETKDALCLVLT------IMN 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFR--------YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYnPQALKPLGhR 2378
Cdd:cd05631    84 GGDLKFHiynmgnpgFDEQRAIFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLAVQI-PEGETVRG-R 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQ----ETEARIvggRFDAFQLYPNTSQSATLFLRK 2454
Cdd:cd05631   162 VGTVGYMAPEVINNEKYTFSPDWWGLGCLIYEMIQGQSPFRKRKERvkreEVDRRV---KEDQEEYSEKFSEDAKSICRM 238


                  ....*....
gi 564369110 2455 VLSVHPWSR 2463
Cdd:cd05631   239 LLTKNPKER 247

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270809 [Multi-domain] Cd Length: 277 Bit Score: 87.05 E-value: 3.84e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPY--AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIA 2296
Cdd:cd06641     2 PEELFTKLEKIGKGSFGEVFKGIDNRTQKVVAIKIIDLeeAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLcGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPlG 2376
Cdd:cd06641    82 EYLGGGSAL-DLLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQIKR-N 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 HRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvgGRFDAFQLYPNTSQSATLFLRKVL 2456
Cdd:cd06641   160 *FVGTPFWMAPEVIKQSAYDSKADIWSLGITAIELARGEPPHSELHPMKVLFLI--PKNNPPTLEGNYSKPLKEFVEACL 237

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 564369110 2457 SVHPWSRPSLQDCLAHpwlqdAYLMKLRRQT--LTFTTNRLKEF 2498
Cdd:cd06641   238 NKEPSFRPTAKELLKH-----KFILRNAKKTsyLTELIDRYKRW 276

mitogen-activated protein kinase kinase; Provisional

Pssm-ID: 215036 [Multi-domain] Cd Length: 353 Bit Score: 88.34 E-value: 4.28e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2197 LSPAKEVVSSPTPESTTLRQGPPQKPYTFLEEKAR---GRFGVVRSCRENATGRTFVAKIVPYAAEG--KRRVLQEYEVL 2271
Cdd:PLN00034   47 LPPPSSSSSSSSSSSASGSAPSAAKSLSELERVNRigsGAGGTVYKVIHRPTGRLYALKVIYGNHEDtvRRQICREIEIL 126

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2272 RTLHHERLMSLHEAYitprylvliaESCGNRELLC------GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKP 2345
Cdd:PLN00034  127 RDVNHPNVVKCHDMF----------DHNGEIQVLLefmdggSLEGTHIADEQFLADVARQILSGIAYLHRRHIVHRDIKP 196

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2346 DNLLLAADNALKIVDFGSAQPYNpQALKPLGHRTGTLEFMAPEMVRGDP-----IGSATDIWGAGVLTYIMLSGYSPFYe 2420
Cdd:PLN00034  197 SNLLINSAKNVKIADFGVSRILA-QTMDPCNSSVGTIAYMSPERINTDLnhgayDGYAGDIWSLGVSILEFYLGRFPFG- 274

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2421 pdpqeteariVGGRFDAFQLY------------PNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:PLN00034  275 ----------VGRQGDWASLMcaicmsqppeapATASREFRHFISCCLQREPAKRWSAMQLLQHPFI 331

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270747 [Multi-domain] Cd Length: 352 Bit Score: 88.59 E-value: 4.37e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2205 SSPTPESTTLRqgPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLM 2280
Cdd:cd05596    12 EKPVNEITKLR--MNAEDFDVIKVIGRGAFGEVQLVRHKSTKKVYAMKLLSKFEMIKRSdsafFWEERDIMAHANSEWIV 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2281 SLHEAYITPRYLVLIAE--SCGNrelLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKI 2358
Cdd:cd05596    90 QLHYAFQDDKYLYMVMDymPGGD---LVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFVHRDVKPDNMLLDASGHLKL 166

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 2359 VDFGSAQPYNPQALKPLGHRTGTLEFMAPEMVR---GDPI-GSATDIWGAGVLTYIMLSGYSPFY 2419
Cdd:cd05596   167 ADFGTCMKMDKDGLVRSDTAVGTPDYISPEVLKsqgGDGVyGRECDWWSVGVFLYEMLVGDTPFY 231

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 81.15 E-value: 4.48e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   458 PDFLRPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRRMTQYRDIHRLVFPAVGPQHAGVYKSVIANKLG 537
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 564369110   538 KAACYAHLYV 547
Cdd:pfam07679   81 EAEASAELTV 90

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

Pssm-ID: 462242 [Multi-domain] Cd Length: 258 Bit Score: 86.40 E-value: 4.63e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  2224 TFLEEKARGRFGVVRSCRENATG---RTFVA-KIVP--YAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:pfam07714    2 TLGEKLGEGAFGEVYKGTLKGEGentKIKVAvKTLKegADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVTE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  2298 SCGNRELLCGL-SDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPL 2375
Cdd:pfam07714   82 YMPGGDLLDFLrKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGlSRDIYDDDYYRKR 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  2376 GHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPFYEPDPQETEARIVGGRfdafQLYPNTSQSATLF--L 2452
Cdd:pfam07714  162 GGGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTlGEQPYPGMSNEEVLEFLEDGY----RLPQPENCPDELYdlM 237

                          250       260
                   ....*....|....*....|
gi 564369110  2453 RKVLSVHPWSRPSLQDCLAH 2472
Cdd:pfam07714  238 KQCWAYDPEDRPTFSELVED 257

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 81.01 E-value: 4.86e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    341 EDVEVLEGRAARLDCKISGTPPPSVTWTHFGH-PVNESENLRLRQDGGLHSLHIARVGSEDEGLYEVSATNTHGQAHCSA 419
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGkLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 564369110    420 QLYV 423
Cdd:smart00410   82 TLTV 85

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270844 [Multi-domain] Cd Length: 284 Bit Score: 86.79 E-value: 4.98e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2226 LEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK---RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCgNR 2302
Cdd:cd07860     5 VEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEgvpSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFL-HQ 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 EL--------LCGLSDRFryseddVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNpQALKP 2374
Cdd:cd07860    84 DLkkfmdasaLTGIPLPL------IKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFG-VPVRT 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHRTGTLEFMAPEMVRGDPIGS-ATDIWGAGVLTYIMLSGYSPFyepdPQETEA-------RIVG-------------- 2432
Cdd:cd07860   157 YTHEVVTLWYRAPEILLGCKYYStAVDIWSLGCIFAEMVTRRALF----PGDSEIdqlfrifRTLGtpdevvwpgvtsmp 232

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2433 ---------GRFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd07860   233 dykpsfpkwARQDFSKVVPPLDEDGRDLLSQMLHYDPNKRISAKAALAHPF 283

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173748 [Multi-domain] Cd Length: 372 Bit Score: 88.26 E-value: 6.19e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQHDCVL------------YFHEAFerrrglv 941
Cdd:cd07853     8 IGYGAFGVVWSVTDPRDGKRVALKKMPNVFQNLVSCKRvfrELKMLCFFKHDNVLsaldilqpphidPFEEIY------- 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPG 1021
Cdd:cd07853    81 VVTELMQSDLHKIIVSPQPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLV----NSNCVLKICDFGLARVEEPD 156

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 564369110 1022 EPQYCqfgTPEFV-----APEIVNQSP-VSGVTDIWPVGVV 1056
Cdd:cd07853   157 ESKHM---TQEVVtqyyrAPEILMGSRhYTSAVDIWSVGCI 194

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270788 [Multi-domain] Cd Length: 259 Bit Score: 85.82 E-value: 6.43e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPK-ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE 949
Cdd:cd06613     2 YELIQRIGSGTYGDVYKARNIATGELAAVKVIKLEPGDDfEIIQQEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCGG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYM-RQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPQYCQF 1028
Cdd:cd06613    82 GSLQDIYQVTGPLSELQIAYVcRETLKGLAYLHSTGKIHRDIKGANILLTEDG----DVKLADFGVSAQLTATIAKRKSF 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 -GTPEFVAPEIVN---QSPVSGVTDIWPVGVVAF-----------------LCLTGISPFvgenDRTTLMNIRNYNVAFE 1087
Cdd:cd06613   158 iGTPYWMAPEVAAverKGGYDGKCDIWALGITAIelaelqppmfdlhpmraLFLIPKSNF----DPPKLKDKEKWSPDFH 233

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 1088 EttflslsreargFLIKVLVQD-RLRPTAEETLEHP 1122
Cdd:cd06613   234 D------------FIKKCLTKNpKKRPTATKLLQHP 257

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270978 [Multi-domain] Cd Length: 270 Bit Score: 86.38 E-value: 6.44e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLR-----RVVERSSGLEFAAKFIPS--QAKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLV 941
Cdd:cd14076     3 YILGRTLGEGEFGKVKlgwplPKANHRSGVQVAIKLIRRdtQQENCQTSKimREINILKGLTHPNIVRLLDVLKTKKYIG 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTP 1020
Cdd:cd14076    83 IVLEFVSGgELFDYILARRRLKDSVACRLFAQLISGVAYLHKKGVVHRDLKLENLLL----DKNRNLVITDFGFANTFDH 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYCQF--GTPEFVAPEIVN-QSPVSGV-TDIWPVGVVAFLCLTGISPF-------VGENDRTTLMNIRNYNVAFEEt 1089
Cdd:cd14076   159 FNGDLMSTscGSPCYAAPELVVsDSMYAGRkADIWSCGVILYAMLAGYLPFdddphnpNGDNVPRLYRYICNTPLIFPE- 237

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 564369110 1090 tflSLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14076   238 ---YVTPKARDLLRRILVPNpRKRIRLSAIMRHAW 269

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270798 [Multi-domain] Cd Length: 267 Bit Score: 86.05 E-value: 6.77e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAK--FIPS-QAKPKASAR-------REARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd06628     8 IGSGSFGSVYLGMNASSGELMAVKqvELPSvSAENKDRKKsmldalqREIALLRELQHENIVQYLGSSSDANHLNIFLEY 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 C----TEELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGeeqVRICDFGNAQEL---- 1018
Cdd:cd06628    88 VpggsVATLLNNYGAFE---ESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILV-DNKGG---IKISDFGISKKLeans 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1019 ---TPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAfeetTFLS-L 1094
Cdd:cd06628   161 lstKNNGARPSLQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLTGTHPFPDCTQMQAIFKIGENASP----TIPSnI 236

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1095 SREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd06628   237 SSEARDFLEKTFEIDhNKRPTADELLKHPF 266

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270768 [Multi-domain] Cd Length: 357 Bit Score: 88.15 E-value: 6.95e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2210 ESTTLRQGPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVpyaaegKRRVLQEYEVLRTLHHER----------- 2278
Cdd:cd05617     4 DGIKISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVV------KKELVHDDEDIDWVQTEKhvfeqassnpf 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2279 LMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKI 2358
Cdd:cd05617    78 LVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKL 157

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2359 VDFGSAQpynpQALKPlGHRT----GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd05617   158 TDYGMCK----EGLGP-GDTTstfcGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPF 216

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270754 [Multi-domain] Cd Length: 321 Bit Score: 87.33 E-value: 7.13e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKAS------ARREArLLARLQHDCVLYFHEAFERRRGLVIVTELCTE- 949
Cdd:cd05603     3 IGKGSFGKVLLAKRKCDGKFYAVKVLQKKTILKKKeqnhimAERNV-LLKNLKHPFLVGLHYSFQTSEKLYFVLDYVNGg 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQF- 1028
Cdd:cd05603    82 ELFFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILL-DCQG---HVVLTDFGLCKEGMEPEETTSTFc 157

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd05603   158 GTPEYLAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPF 196

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270952 [Multi-domain] Cd Length: 249 Bit Score: 85.05 E-value: 9.91e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEG---KRRVLQEYEVLRTLH-HERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd14050     3 FTILSKLGEGSFGEVFKVRSREDGKLYAVKRSRSRFRGekdRKRKLEEVERHEKLGeHPNCVRFIKAWEEKGILYIQTEL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGnRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-----------SAQPY 2367
Cdd:cd14050    83 CD-TSLQQYCEETHSLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGlvveldkedihDAQEG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2368 NPQalkplghrtgtleFMAPEMVRGDPiGSATDIWGAG-----VLTYIMLSGYSPFYEP-----DPQETEARIvggrfda 2437
Cdd:cd14050   162 DPR-------------YMAPELLQGSF-TKAADIFSLGitileLACNLELPSGGDGWHQlrqgyLPEEFTAGL------- 220

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 2438 fqlypntSQSATLFLRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd14050   221 -------SPELRSIIKLMMDPDPERRPTAEDLLALP 249

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270890 [Multi-domain] Cd Length: 316 Bit Score: 86.78 E-value: 1.02e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAK-FIP-SQAKPKASARREARLLARLQHDCV--LYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd13988     1 LGQGATANVFRGRHKKTGDLYAVKvFNNlSFMRPLDVQMREFEVLKKLNHKNIvkLFAIEEELTTRHKVLVMELCPCGSL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARKPT----VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELTPGEPQYCQF 1028
Cdd:cd13988    81 YTVLEEPSnaygLPESEFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMRVIGEDGQSVYKLTDFGAARELEDDEQFVSLY 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 1029 GTPEFVAPEIVN--------QSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd13988   161 GTEEYLHPDMYEravlrkdhQKKYGATVDLWSIGVTFYHAATGSLPF 207

serine/threonine kinase US3; Provisional

Pssm-ID: 165478 [Multi-domain] Cd Length: 391 Bit Score: 87.74 E-value: 1.18e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2213 TLRQGPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKivpyaaEGKRR-VLQEYEVLRTLHHERLMSLHEAY----- 2286
Cdd:PHA03212   84 EARAGIEKAGFSILETFTPGAEGFAFACIDNKTCEHVVIK------AGQRGgTATEAHILRAINHPSIIQLKGTFtynkf 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2287 ---ITPRYlvliaescgNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGS 2363
Cdd:PHA03212  158 tclILPRY---------KTDLYCYLAAKRNIAICDILAIERSVLRAIQYLHENRIIHRDIKAENIFINHPGDVCLGDFGA 228

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2364 A-QPYNPQALKPLGHrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPD 2422
Cdd:PHA03212  229 AcFPVDINANKYYGW-AGTIATNAPELLARDPYGPAVDIWSAGIVLFEMATCHDSLFEKD 287

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270784 [Multi-domain] Cd Length: 258 Bit Score: 85.19 E-value: 1.25e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2221 KPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPY----AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIA 2296
Cdd:cd06607     1 KIFEDLREIGHGSFGAVYYARNKRTSEVVAIKKMSYsgkqSTEKWQDIIKEVKFLRQLRHPNTIEYKGCYLREHTAWLVM 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCgnrelLCGLSD-----RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpqA 2371
Cdd:cd06607    81 EYC-----LGSASDivevhKKPLQEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSA------S 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 LK-PLGHRTGTLEFMAPE----MVRGDPIGSAtDIWGAGVlTYIMLSGYS-PFYEPDPQETEARIvgGRFDAFQLYPNT- 2444
Cdd:cd06607   150 LVcPANSFVGTPYWMAPEvilaMDEGQYDGKV-DVWSLGI-TCIELAERKpPLFNMNAMSALYHI--AQNDSPTLSSGEw 225

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 2445 SQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd06607   226 SDDFRNFVDSCLQKIPQDRPSAEDLLKHPFVT 257

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270839 [Multi-domain] Cd Length: 336 Bit Score: 86.59 E-value: 1.48e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHE-----AFERRRG 939
Cdd:cd07849     3 VGPRYQNLSYIGEGAYGMVCSAVHKPTGQKVAIKKISPFEHQTYCLRtlREIKILLRFKHENIIGILDiqrppTFESFKD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  940 LVIVTELcTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLV---WDgaggeeqVRICDFGNAQ 1016
Cdd:cd07849    83 VYIVQEL-METDLYKLIKTQHLSNDHIQYFLYQILRGLKYIHSANVLHRDLKPSNLLLntnCD-------LKICDFGLAR 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPGEPQYcQFGTpEFV------APEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI---------- 1079
Cdd:cd07849   155 IADPEHDHT-GFLT-EYVatrwyrAPEImLNSKGYTKAIDIWSVGCILAEMLSNRPLFPGKDYLHQLNLIlgilgtpsqe 232

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110 1080 ----------RNY--------NVAFEEtTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd07849   233 dlnciislkaRNYikslpfkpKVPWNK-LFPNADPKALDLLDKMLTFNpHKRITVEEALAHPY 294

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270820 [Multi-domain] Cd Length: 296 Bit Score: 85.93 E-value: 1.50e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHD-CVLYFHEAFERRRGLVIVTELCTE 949
Cdd:cd06654    22 YTRFEKIGQGASGTVYTAMDVATGQEVAIRQMNLQQQPKKELIINEILVMRENKNpNIVNYLDSYLVGDELWVVMEYLAG 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQYCQF- 1028
Cdd:cd06654   102 GSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILL----GMDGSVKLTDFGFCAQITPEQSKRSTMv 177

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLmnirnYNVAFEETTFLS----LSREARGFLIK 1104
Cdd:cd06654   178 GTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRAL-----YLIATNGTPELQnpekLSAIFRDFLNR 252

                         250       260
                  ....*....|....*....|..
gi 564369110 1105 VLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd06654   253 CLEMDvEKRGSAKELLQHQFLK 274

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270741 [Multi-domain] Cd Length: 326 Bit Score: 86.20 E-value: 1.63e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKivpyaAEGKRRVLQE------------YEVLRTLHHERLMSLHEAYITPRYLVLIAE- 2297
Cdd:cd05589     9 RGHFGKVLLAEYKPTGELFAIK-----ALKKGDIIARdeveslmcekriFETVNSARHPFLVNLFACFQTPEHVCFVMEy 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFrySEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpynpQALKPlGH 2377
Cdd:cd05589    84 AAGGDLMMHIHEDVF--SEPRAVFYAACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCK----EGMGF-GD 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RT----GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFyepdPQETEARIvggrFDAF----QLYPN-TSQSA 2448
Cdd:cd05589   157 RTstfcGTPEFLAPEVLTDTSYTRAVDWWGLGVLIYEMLVGESPF----PGDDEEEV----FDSIvndeVRYPRfLSTEA 228

                         250
                  ....*....|....*
gi 564369110 2449 TLFLRKVLSVHPWSR 2463
Cdd:cd05589   229 ISIMRRLLRKNPERR 243

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270765 [Multi-domain] Cd Length: 332 Bit Score: 86.51 E-value: 1.75e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFS---YLRRVVERSSGLEFAAKF-----IPSQAKPKASARREARLLARL-QHDCVLYFHEAFERRRGL- 940
Cdd:cd05614     2 FELLKVLGTGAYGkvfLVRKVSGHDANKLYAMKVlrkaaLVQKAKTVEHTRTERNVLEHVrQSPFLVTLHYAFQTDAKLh 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTP 1020
Cdd:cd05614    82 LILDYVSGGELFTHLYQRDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILL----DSEGHVVLTDFGLSKEFLT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQ--YCQFGTPEFVAPEIV-NQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSRE 1097
Cdd:cd05614   158 EEKErtYSFCGTIEYMAPEIIrGKSGHGKAVDWWSLGILMFELLTGASPFTLEGEKNTQSEVSRRILKCDPPFPSFIGPV 237

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 1098 ARGFLIKVLVQD---RL--RPT-AEETLEHPWFK 1125
Cdd:cd05614   238 ARDLLQKLLCKDpkkRLgaGPQgAQEIKEHPFFK 271

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270801 [Multi-domain] Cd Length: 266 Bit Score: 84.80 E-value: 2.00e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVrSCRENATGRTFVAKIVPYAAEGKRRVLQEYE-------VLRTLHHERLM-----SLHEAYITPRYLVLIAES 2298
Cdd:cd06631    11 KGAYGTV-YCGLTSTGQLIAVKQVELDTSDKEKAEKEYEklqeevdLLKTLKHVNIVgylgtCLEDNVVSIFMEFVPGGS 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNrellcgLSDRFRYSEDDV-ATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY--------NP 2369
Cdd:cd06631    90 IAS------ILARFGALEEPVfCRYTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKRLcinlssgsQS 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSAT 2449
Cdd:cd06631   164 QLLKSM---RGTPYWMAPEVINETGHGRKSDIWSIGCTVFEMATGKPPWADMNPMAAIFAIGSGRKPVPRLPDKFSPEAR 240

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2450 LFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06631   241 DFVHACLTRDQDERPSAEQLLKHPFI 266

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270793 [Multi-domain] Cd Length: 287 Bit Score: 85.17 E-value: 2.18e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHEAF--ERRRGLVIVTELCTEELL 952
Cdd:cd06621     9 LGEGAGGSVTKCRLRNTKTIFALKTITTDPNPDVQKQilRELEINKSCASPYIVKYYGAFldEQDSSIGIAMEYCEGGSL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARKptVCESETRTYMR-------QVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELtpGEPQY 1025
Cdd:cd06621    89 DSIYKK--VKKKGGRIGEKvlgkiaeSVLKGLSYLHSRKIIHRDIKPSNILL----TRKGQVKLCDFGVSGEL--VNSLA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 CQF-GTPEFVAPEIVNQSPVSGVTDIWPVGV----VAFLCLtgisPFVGENDR--------TTLMNIRNYNVAFEETTFL 1092
Cdd:cd06621   161 GTFtGTSYYMAPERIQGGPYSITSDVWSLGLtlleVAQNRF----PFPPEGEPplgpiellSYIVNMPNPELKDEPENGI 236

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 564369110 1093 SLSREARGFLIKVLVQDRL-RPTAEETLEHPWFKTEAK 1129
Cdd:cd06621   237 KWSESFKDFIEKCLEKDGTrRPGPWQMLAHPWIKAQEK 274

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270787 [Multi-domain] Cd Length: 267 Bit Score: 84.33 E-value: 2.60e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV---PYAAEGKRrVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd06610     3 YELIEVIGSGATAVVYAAYCLPKKEKVAIKRIdleKCQTSMDE-LRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELLCGLSDRFRYS---EDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPL 2375
Cdd:cd06610    82 SGGSLLDIMKSSYPRGgldEAIIATVLKEVLKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGvSASLATGGDRTRK 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRT--GTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggrFDAFQLYPNT------SQ 2446
Cdd:cd06610   162 VRKTfvGTPCWMAPEvMEQVRGYDFKADIWSFGITAIELATGAAPYSKYPPMKVLMLTL---QNDPPSLETGadykkySK 238

                         250       260
                  ....*....|....*....|....*..
gi 564369110 2447 SATLFLRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd06610   239 SFRKMISLCLQKDPSKRPTAEELLKHK 265

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270755 [Multi-domain] Cd Length: 326 Bit Score: 85.40 E-value: 2.84e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIpsqAKPKASARREAR--------LLARLQHDCVLYFHEAFERRRGLVIVTELCT 948
Cdd:cd05604     4 IGKGSFGKVLLAKRKRDGKYYAVKVL---QKKVILNRKEQKhimaernvLLKNVKHPFLVGLHYSFQTTDKLYFVLDFVN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 E-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQ 1027
Cdd:cd05604    81 GgELFFHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILL-DSQG---HIVLTDFGLCKEGISNSDTTTT 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 F-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYnvafEETTFLSLSREARGFLIKVL 1106
Cdd:cd05604   157 FcGTPEYLAPEVIRKQPYDNTVDWWCLGSVLYEMLYGLPPFYCRDTAEMYENILHK----PLVLRPGISLTAWSILEELL 232

                         250       260
                  ....*....|....*....|....*
gi 564369110 1107 VQDR-----LRPTAEETLEHPWFKT 1126
Cdd:cd05604   233 EKDRqlrlgAKEDFLEIKNHPFFES 257

Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-alpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.

Pssm-ID: 270773 [Multi-domain] Cd Length: 409 Bit Score: 86.99 E-value: 2.96e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2220 QKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd05623    71 KEDFEILKVIGRGAFGEVAVVKLKNADKVFAMKILNKWEMLKRAetacFREERDVLVNGDSQWITTLHYAFQDDNNLYLV 150

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSdRF--RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALK 2373
Cdd:cd05623   151 MDYYVGGDLLTLLS-KFedRLPEDMARFYLAEMVLAIDSVHQLHYVHRDIKPDNILMDMNGHIRLADFGSCLKLMEDGTV 229

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2374 PLGHRTGTLEFMAPEMVRG-----DPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRfDAFQlYP----NT 2444
Cdd:cd05623   230 QSSVAVGTPDYISPEILQAmedgkGKYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHK-ERFQ-FPtqvtDV 307

                         250       260       270
                  ....*....|....*....|....*....|...
gi 564369110 2445 SQSATLFLRKVLSV--HPWSRPSLQDCLAHPWL 2475
Cdd:cd05623   308 SENAKDLIRRLICSreHRLGQNGIEDFKNHPFF 340

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270848 [Multi-domain] Cd Length: 310 Bit Score: 85.11 E-value: 3.61e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEGKR---RVLQEYEVLRTLHHERLMSLHEAYITPR----------YLVLiaES 2298
Cdd:cd07865    23 GTFGEVFKARHRKTGQIVALKKVLMENEKEGfpiTALREIKILQLLKHENVVNLIEICRTKAtpynrykgsiYLVF--EF 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRelLCGLSD--RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYN-PQALKP- 2374
Cdd:cd07865   101 CEHD--LAGLLSnkNVKFTLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLARAFSlAKNSQPn 178

                         170       180       190
                  ....*....|....*....|....*....|...
gi 564369110 2375 -LGHRTGTLEFMAPEMVRGD-PIGSATDIWGAG 2405
Cdd:cd07865   179 rYTNRVVTLWYRPPELLLGErDYGPPIDMWGAG 211

cAMP-dependent protein kinase catalytic subunit; Provisional

Pssm-ID: 173616 [Multi-domain] Cd Length: 340 Bit Score: 85.42 E-value: 3.73e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2264 VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDI 2343
Cdd:PTZ00426   78 VFSERKILNYINHPFCVNLYGSFKDESYLYLVLEFVIGGEFFTFLRRNKRFPNDVGCFYAAQIVLIFEYLQSLNIVYRDL 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2344 KPDNLLLAADNALKIVDFGSAQPYNPQALKplghRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDP 2423
Cdd:PTZ00426  158 KPENLLLDKDGFIKMTDFGFAKVVDTRTYT----LCGTPEYIAPEILLNVGHGKAADWWTLGIFIYEILVGCPPFYANEP 233

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2424 QETEARIVGGrfdaFQLYPNTSQSATLFLRKVLSVHPWS------RPSLQDCLAHPWLQD 2477
Cdd:PTZ00426  234 LLIYQKILEG----IIYFPKFLDNNCKHLMKKLLSHDLTkrygnlKKGAQNVKEHPWFGN 289

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271101 [Multi-domain] Cd Length: 286 Bit Score: 84.25 E-value: 3.99e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--------------------------PSQAK-PKASARREARLLARLQ 923
Cdd:cd14199     4 YKLKDEIGKGSYGVVKLAYNEDDNTYYAMKVLskkklmrqagfprrppprgaraapegCTQPRgPIERVYQEIAILKKLD 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  924 HDCVLYFHEAFE--RRRGLVIVTELCTE-ELLERMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdg 1000
Cdd:cd14199    84 HPNVVKLVEVLDdpSEDHLYMVFELVKQgPVMEVPTLKP-LSEDQARFYFQDLIKGIEYLHYQKIIHRDVKPSNLLV--- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1001 aGGEEQVRICDFGNAQELTPGEPQYCQ-FGTPEFVAPEIVNQSP--VSG-VTDIWPVGVVAFLCLTGISPFVGENDRTTL 1076
Cdd:cd14199   160 -GEDGHIKIADFGVSNEFEGSDALLTNtVGTPAFMAPETLSETRkiFSGkALDVWAMGVTLYCFVFGQCPFMDERILSLH 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 564369110 1077 MNIRNYNVAFEETTflSLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd14199   239 SKIKTQPLEFPDQP--DISDDLKDLLFRMLDKNpESRISVPEIKLHPW 284

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270772 [Multi-domain] Cd Length: 405 Bit Score: 86.21 E-value: 4.07e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR----REARLLARLQHDCVLYFHEAFERRRGL 940
Cdd:cd05622    69 RMKAEDYEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSDSaffwEERDIMAFANSPWVVQLFYAFQDDRYL 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTP 1020
Cdd:cd05622   149 YMVMEYMPGGDLVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLL-DKSG---HLKLADFGTCMKMNK 224

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYCQ--FGTPEFVAPEIVNQSPVSGV----TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSL 1094
Cdd:cd05622   225 EGMVRCDtaVGTPDYISPEVLKSQGGDGYygreCDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMNHKNSLTFPDDNDI 304

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 564369110 1095 SREARGfLIKVLVQDRL----RPTAEETLEHPWFKTE 1127
Cdd:cd05622   305 SKEAKN-LICAFLTDREvrlgRNGVEEIKRHLFFKND 340

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270739 [Multi-domain] Cd Length: 320 Bit Score: 84.75 E-value: 4.20e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  969 YMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQF-GTPEFVAPEIVNQSPVSGV 1047
Cdd:cd05587   102 YAAEIAVGLFFLHSKGIIYRDLKLDNVML-DAEG---HIKIADFGMCKEGIFGGKTTRTFcGTPDYIAPEIIAYQPYGKS 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1048 TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREA----RGFLIKVLVQdRL--RPTAEETL-E 1120
Cdd:cd05587   178 VDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPK----SLSKEAvsicKGLLTKHPAK-RLgcGPTGERDIkE 252


                  ....*.
gi 564369110 1121 HPWFKT 1126
Cdd:cd05587   253 HPFFRR 258

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 78.39 E-value: 4.22e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  337 TRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDG-GLHSLHIARVGSEDEGLYEVSATNTHGQA 415
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdGLCSLIISDVCGDDSGKYTCKAVNSLGEA 80


                  ....*...
gi 564369110  416 HCSAQLYV 423
Cdd:cd20973    81 TCSAELTV 88

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143341 [Multi-domain] Cd Length: 284 Bit Score: 84.07 E-value: 4.33e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFI--PSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd07836     6 EKLGEGTYATVYKGRNRTTGEIVALKEIhlDAEEGTPSTAIREISLMKELKHENIVRLHDVIHTENKLMLVFEYMDKDLK 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARKPTVCE---SETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQeltpgepqycQFG 1029
Cdd:cd07836    86 KYMDTHGVRGAldpNTVKSFTYQLLKGIAFCHENRVLHRDLKPQNLLI----NKRGELKLADFGLAR----------AFG 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1030 TP------EFV-----APEIVNQSPV-SGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRN---------------- 1081
Cdd:cd07836   152 IPvntfsnEVVtlwyrAPDVLLGSRTySTSIDIWSVGCIMAEMITGRPLFPGTNNEDQLLKIFRimgtptestwpgisql 231

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 1082 --YNVAFE-------ETTFLSLSREARGFLIKVL-VQDRLRPTAEETLEHPWF 1124
Cdd:cd07836   232 peYKPTFPryppqdlQQLFPHADPLGIDLLHRLLqLNPELRISAHDALQHPWF 284

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270859 [Multi-domain] Cd Length: 256 Bit Score: 83.63 E-value: 4.37e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFS--YL-RRVVERSsglEFAAKFIPSQAKPK---ASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd08220     2 YEKIRVVGRGAYGtvYLcRRKDDNK---LVIIKQIPVEQMTKeerQAALNEVKVLSMLHHPNIIEYYESFLEDKALMIVM 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTEELLERMARKPT---VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGaggEEQVRICDFGNAQELTPG 1021
Cdd:cd08220    79 EYAPGGTLFEYIQQRKgslLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLNKK---RTVVKIGDFGISKILSSK 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 EPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFlslSREARGF 1101
Cdd:cd08220   156 SKAYTVVGTPCYISPELCEGKPYNQKSDIWALGCVLYELASLKRAFEAANLPALVLKIMRGTFAPISDRY---SEELRHL 232

                         250       260
                  ....*....|....*....|..
gi 564369110 1102 LIKVLVQD-RLRPTAEETLEHP 1122
Cdd:cd08220   233 ILSMLHLDpNKRPTLSEIMAQP 254

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270772 [Multi-domain] Cd Length: 405 Bit Score: 86.21 E-value: 4.75e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd05622    75 YEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSdsafFWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEY 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLcGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHR 2378
Cdd:cd05622   155 MPGGDLV-NLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMNKEGMVRCDTA 233

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2379 TGTLEFMAPEMVR---GDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV 2431
Cdd:cd05622   234 VGTPDYISPEVLKsqgGDGyYGRECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIM 290

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270764 [Multi-domain] Cd Length: 290 Bit Score: 84.28 E-value: 4.80e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFS---YLRRVVERSSGLEFAAKF-----IPSQAKPKASARREARLLARL-QHDCVLYFHEAFERRRGL- 940
Cdd:cd05613     2 FELLKVLGTGAYGkvfLVRKVSGHDAGKLYAMKVlkkatIVQKAKTAEHTRTERQVLEHIrQSPFLVTLHYAFQTDTKLh 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTP 1020
Cdd:cd05613    82 LILDYINGGELFTHLSQRERFTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILL-DSSG---HVVLTDFGLSKEFLL 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQ--YCQFGTPEFVAPEIVN--QSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSR 1096
Cdd:cd05613   158 DENEraYSFCGTIEYMAPEIVRggDSGHDKAVDWWSLGVLMYELLTGASPFTVDGEKNSQAEISRRILKSEPPYPQEMSA 237

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 564369110 1097 EARGFLIKVLVQD---RL--RPT-AEETLEHPWFK 1125
Cdd:cd05613   238 LAKDIIQRLLMKDpkkRLgcGPNgADEIKKHPFFQ 272

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271103 [Multi-domain] Cd Length: 271 Bit Score: 83.52 E-value: 5.34e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2266 QEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKP 2345
Cdd:cd14201    54 KEIKILKELQHENIVALYDVQEMPNSVFLVMEYCNGGDLADYLQAKGTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKP 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2346 DNLLLAADN---------ALKIVDFGSAQPYNPQALKplGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYS 2416
Cdd:cd14201   134 QNILLSYASrkkssvsgiRIKIADFGFARYLQSNMMA--ATLCGSPMYMAPEVIMSQHYDAKADLWSIGTVIYQCLVGKP 211


                  ....*....
gi 564369110 2417 PFYEPDPQE 2425
Cdd:cd14201   212 PFQANSPQD 220

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270921 [Multi-domain] Cd Length: 252 Bit Score: 83.04 E-value: 5.52e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRFR-----YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA-LKIVDFGSAQ--PYNPQALKPlghRTGT 2381
Cdd:cd14019    89 DDFRdfyrkMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGkGVLVDFGLAQreEDRPEQRAP---RAGT 165

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2382 LEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSG-YSPFYEPDPQETEARIVG--GRFDAFQLypntsqsatlfLRKVLS 2457
Cdd:cd14019   166 RGFRAPEvLFKCPHQTTAIDIWSAGVILLSILSGrFPFFFSSDDIDALAEIATifGSDEAYDL-----------LDKLLE 234

                         170
                  ....*....|....*...
gi 564369110 2458 VHPWSRPSLQDCLAHPWL 2475
Cdd:cd14019   235 LDPSKRITAEEALKHPFF 252

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270761 [Multi-domain] Cd Length: 349 Bit Score: 84.93 E-value: 5.71e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2218 PPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYA------------AEGKRRVLQEYEVLRTLHHErLMSLHEA 2285
Cdd:cd05610     1 PSIEEFVIVKPISRGAFGKVYLGRKKNNSKLYAVKVVKKAdminknmvhqvqAERDALALSKSPFIVHLYYS-LQSANNV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2286 YITPRYLVliaesCGNRELLCGLsdrFRYSEDDVAT-YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-- 2362
Cdd:cd05610    80 YLVMEYLI-----GGDVKSLLHI---YGYFDEEMAVkYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGls 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2363 ------------------SAQPYNPQALKP---------LG------HRT-----------------GTLEFMAPEMVRG 2392
Cdd:cd05610   152 kvtlnrelnmmdilttpsMAKPKNDYSRTPgqvlslissLGfntptpYRTpksvrrgaarvegerilGTPDYLAPELLLG 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2393 DPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRF---DAFQLYPNTSQSATLFLrkvLSVHPWSRPSLQDC 2469
Cdd:cd05610   232 KPHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILNRDIpwpEGEEELSVNAQNAIEIL---LTMDPTKRAGLKEL 308

                         330       340
                  ....*....|....*....|.
gi 564369110 2470 LAHPWLQDAYLMKLRRQTLTF 2490
Cdd:cd05610   309 KQHPLFHGVDWENLQNQTMPF 329

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270809 [Multi-domain] Cd Length: 277 Bit Score: 83.58 E-value: 5.78e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA--SARREARLLARLQHDCVLYFHEAFERRRGLVIVTE-LCTEEL 951
Cdd:cd06641    10 EKIGKGSFGEVFKGIDNRTQKVVAIKIIDLEEAEDEieDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEyLGGGSA 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPQYCQF-GT 1030
Cdd:cd06641    90 LDLLEPGP-LDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHG----EVKLADFGVAGQLTDTQIKRN*FvGT 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1031 PEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFlslSREARGFLIKVLVQD- 1109
Cdd:cd06641   165 PFWMAPEVIKQSAYDSKADIWSLGITAIELARGEPPHSELHPMKVLFLIPKNNPPTLEGNY---SKPLKEFVEACLNKEp 241

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 564369110 1110 RLRPTAEETLEHPWFKTEAKgaevSTDHLKLFLSR-RRWQ 1148
Cdd:cd06641   242 SFRPTAKELLKHKFILRNAK----KTSYLTELIDRyKRWK 277

Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group is composed of fungal NDR-like proteins including Saccharomyces cerevisiae CBK1 (or CBK1p), Schizosaccharomyces pombe Orb6 (or Orb6p), Ustilago maydis Ukc1 (or Ukc1p), and Neurospora crassa Cot1. Like NDR kinase, group members contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. CBK1 is an essential component in the RAM (regulation of Ace2p activity and cellular morphogenesis) network. CBK1 and Orb6 play similar roles in coordinating cell morphology with cell cycle progression. Ukc1 is involved in morphogenesis, pathogenicity, and pigment formation. Cot1 plays a role in polar tip extension.The fungal NDR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270778 [Multi-domain] Cd Length: 377 Bit Score: 85.29 E-value: 7.06e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAK-FIPSQAKPK---ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE-LCTEEL 951
Cdd:cd05629     9 IGKGAFGEVRLVQKKDTGKIYAMKtLLKSEMFKKdqlAHVKAERDVLAESDSPWVVSLYYSFQDAQYLYLIMEfLPGGDL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFG------------------ 1013
Cdd:cd05629    89 MTMLIKYDTFSEDVTRFYMAECVLAIEAVHKLGFIHRDIKPDNILI-DRGG---HIKLSDFGlstgfhkqhdsayyqkll 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1014 -----------------NAQELTPGEPQ-------------YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTG 1063
Cdd:cd05629   165 qgksnknridnrnsvavDSINLTMSSKDqiatwkknrrlmaYSTVGTPDYIAPEIFLQQGYGQECDWWSLGAIMFECLIG 244

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1064 ISPFVGENDRTTLMNIrnynVAFEET-TF---LSLSREARGfLIKVLVQD---RL-RPTAEETLEHPWFK 1125
Cdd:cd05629   245 WPPFCSENSHETYRKI----INWRETlYFpddIHLSVEAED-LIRRLITNaenRLgRGGAHEIKSHPFFR 309

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270948 [Multi-domain] Cd Length: 278 Bit Score: 83.19 E-value: 7.32e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGK--RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGL 2308
Cdd:cd14046    16 KGAFGQVVKVRNKLDGRYYAIKKIKLRSESKnnSRILREVMLLSRLNHQHVVRYYQAWIERANLYIQMEYCEKSTLRDLI 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2309 SDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA-----------QPYN---PQALKP 2374
Cdd:cd14046    96 DSGLFQDTDRLWRLFRQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLAtsnklnvelatQDINkstSAALGS 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHRT---GTLEFMAPEMVRGDP--IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSAT 2449
Cdd:cd14046   176 SGDLTgnvGTALYVAPEVQSGTKstYNEKVDMYSLGIIFFEMCYPFSTGMERVQILTALRSVSIEFPPDFDDNKHSKQAK 255

                         250       260
                  ....*....|....*....|...
gi 564369110 2450 LfLRKVLSVHPWSRPSLQDCLAH 2472
Cdd:cd14046   256 L-IRWLLNHDPAKRPSAQELLKS 277

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270852 [Multi-domain] Cd Length: 286 Bit Score: 83.47 E-value: 7.78e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA--SARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd07870     6 EKLGEGSYATVYKGISRINGQLVALKVISMKTEEGVpfTAIREASLLKGLKHANIVLLHDIIHTKETLTFVFEYMHTDLA 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARKPTVCES-ETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGEeqVRICDFGNAQELT-PGEPQYCQFGT 1030
Cdd:cd07870    86 QYMIQHPGGLHPyNVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLI--SYLGE--LKLADFGLARAKSiPSQTYSSEVVT 161

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 564369110 1031 PEFVAPEIV-NQSPVSGVTDIWPVGVVAFLCLTGISPFVGEND 1072
Cdd:cd07870   162 LWYRPPDVLlGATDYSSALDIWGAGCIFIEMLQGQPAFPGVSD 204

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270949 [Multi-domain] Cd Length: 267 Bit Score: 82.92 E-value: 8.60e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYaaeGKRRVLQEYEVLRTLHHERLMSLHEAYITP------------- 2289
Cdd:cd14047     8 FKEIELIGSGGFGQVFKAKHRIDGKTYAIKRVKL---NNEKAEREVKALAKLDHPNIVRYNGCWDGFdydpetsssnssr 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2290 ---RYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVV--QLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-S 2363
Cdd:cd14047    85 sktKCLFIQMEFCEKGTLESWIEKRNGEKLDKVLALEIfeQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDFGlV 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2364 AQPYNPQalkPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARivGGRF-DAF-QLY 2441
Cdd:cd14047   165 TSLKNDG---KRTKSKGTLSYMSPEQISSQDYGKEVDIYALGLILFELLHVCDSAFEKSKFWTDLR--NGILpDIFdKRY 239

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 2442 PNTSQsatlFLRKVLSVHPWSRPSLQDCLAH 2472
Cdd:cd14047   240 KIEKT----IIKKMLSKKPEDRPNASEILRT 266

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270853 [Multi-domain] Cd Length: 288 Bit Score: 83.52 E-value: 8.79e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAE--GKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE--- 2297
Cdd:cd07871     7 YVKLDKLGEGTYATVFKGRSKLTENLVALKEIRLEHEegAPCTAIREVSLLKNLKHANIVTLHDIIHTERCLTLVFEyld 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 --------SCGNreLLCglsdrfrysEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP 2369
Cdd:cd07871    87 sdlkqyldNCGN--LMS---------MHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLARAKSV 155

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QAlKPLGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd07871   156 PT-KTYSNEVVTLWYRPPDVLLGSTeYSTPIDMWGVGCILYEMATGRPMF 204

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132971 [Multi-domain] Cd Length: 277 Bit Score: 83.18 E-value: 9.20e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA--SARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd06640    10 ERIGKGSFGEVFKGIDNRTQQVVAIKIIDLEEAEDEieDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEYLGGGSA 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEPQYCQF-GTP 1031
Cdd:cd06640    90 LDLLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSE----QGDVKLADFGVAGQLTDTQIKRNTFvGTP 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1032 EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAfeeTTFLSLSREARGFLIKVLVQD-R 1110
Cdd:cd06640   166 FWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPPNSDMHPMRVLFLIPKNNPP---TLVGDFSKPFKEFIDACLNKDpS 242

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 564369110 1111 LRPTAEETLEHPWFKTEAKgaevSTDHLKLFLSR-RRWQ 1148
Cdd:cd06640   243 FRPTAKELLKHKFIVKNAK----KTSYLTELIDRfKRWK 277

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271104 [Multi-domain] Cd Length: 267 Bit Score: 82.75 E-value: 1.01e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2266 QEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKP 2345
Cdd:cd14202    50 KEIKILKELKHENIVALYDFQEIANSVYLVMEYCNGGDLADYLHTMRTLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKP 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2346 DNLLLAADNA---------LKIVDFGSAQPYNPQALKplGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYS 2416
Cdd:cd14202   130 QNILLSYSGGrksnpnnirIKIADFGFARYLQNNMMA--ATLCGSPMYMAPEVIMSQHYDAKADLWSIGTIIYQCLTGKA 207

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2417 PFYEPDPQETEARIVGGRfdafQLYPNTSQSATLFLRK----VLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd14202   208 PFQASSPQDLRLFYEKNK----SLSPNIPRETSSHLRQlllgLLQRNQKDRMDFDEFFHHPFLD 267

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270962 [Multi-domain] Cd Length: 242 Bit Score: 81.93 E-value: 1.04e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2240 CRENATGRTFVAKIVPYAAE-GKRRVLQ---EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLS--DRFR 2313
Cdd:cd14060     1 CGGGSFGSVYRAIWVSQDKEvAVKKLLKiekEAEILSVLSHRNIIQFYGAILEAPNYGIVTEYASYGSLFDYLNsnESEE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2314 YSEDDVATYVVQLLQGLDYLHGR---HVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLghrTGTLEFMAPEMV 2390
Cdd:cd14060    81 MDMDQIMTWATDIAKGMHYLHMEapvKVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHMSL---VGTFPWMAPEVI 157

                         170       180
                  ....*....|....*....|....*...
gi 564369110 2391 RGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd14060   158 QSLPVSETCDTYSYGVVLWEMLTREVPF 185

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270739 [Multi-domain] Cd Length: 320 Bit Score: 83.60 E-value: 1.05e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPyaaegKRRVLQEYEVLRTLHHER----------LMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd05587     6 KGSFGKVMLAERKGTDELYAIKILK-----KDVIIQDDDVECTMVEKRvlalsgkppfLTQLHSCFQTMDRLYFVMEYVN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPyNPQALKPLGHRTG 2380
Cdd:cd05587    81 GGDLMYHIQQVGKFKEPVAVFYAAEIAVGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKE-GIFGGKTTRTFCG 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVggrfDAFQLYPNT-SQSATLFLRKVLSVH 2459
Cdd:cd05587   160 TPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIM----EHNVSYPKSlSKEAVSICKGLLTKH 235


                  ....
gi 564369110 2460 PWSR 2463
Cdd:cd05587   236 PAKR 239

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143374 [Multi-domain] Cd Length: 303 Bit Score: 83.20 E-value: 1.16e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA--SARREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd07869     4 ADSYEKLEKLGEGSYATVYKGKSKVNGKLVALKVIRLQEEEGTpfTAIREASLLKGLKHANIVLLHDIIHTKETLTLVFE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPTVCESET-RTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQ-ELTPGEP 1023
Cdd:cd07869    84 YVHTDLCQYMDKHPGGLHPENvKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTG----ELKLADFGLARaKSVPSHT 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEND------------------------------ 1072
Cdd:cd07869   160 YSNEVVTLWYRPPDVlLGSTEYSTCLDMWGVGCIFVEMIQGVAAFPGMKDiqdqleriflvlgtpnedtwpgvhslphfk 239

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1073 --RTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQDRLrpTAEETLEHPWF 1124
Cdd:cd07869   240 peRFTLYSPKNLRQAWNKLSYVNHAEDLASKLLQCFPKNRL--SAQAALSHEYF 291

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270835 [Multi-domain] Cd Length: 286 Bit Score: 82.81 E-value: 1.24e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2265 LQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGnrellcglSDRFRYSED--------DVATYVVQLLQGLDYLHGR 2336
Cdd:cd07844    46 IREASLLKDLKHANIVTLHDIIHTKKTLTLVFEYLD--------TDLKQYMDDcggglsmhNVRLFLFQLLRGLAYCHQR 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2337 HVLHLDIKPDNLLLAADNALKIVDFGSAQPYN-PQalKPLGHRTGTLEFMAPEMVRGDPIGSAT-DIWGAGVLTYIMLSG 2414
Cdd:cd07844   118 RVLHRDLKPQNLLISERGELKLADFGLARAKSvPS--KTYSNEVVTLWYRPPDVLLGSTEYSTSlDMWGVGCIFYEMATG 195


                  ....
gi 564369110 2415 YSPF 2418
Cdd:cd07844   196 RPLF 199

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143359 [Multi-domain] Cd Length: 342 Bit Score: 84.06 E-value: 1.27e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIhQEIGRGAFSYLRRVVERSSGLEFAAKFIP-SQAKPKASARREARLLARLQHDCVLYFHEAF--------ERRR 938
Cdd:cd07854     5 SRYMDL-RPLGCGSNGLVFSAVDSDCDKRVAVKKIVlTDPQSVKHALREIKIIRRLDHDNIVKVYEVLgpsgsdltEDVG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  939 GLV------IVTElCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQV-RICD 1011
Cdd:cd07854    84 SLTelnsvyIVQE-YMETDLANVLEQGPLSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANVFI----NTEDLVlKIGD 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1012 FGNAQELtpgEPQYCQFG-------TPEFVAPEIVnQSP--VSGVTDIWPVGVVAFLCLTGISPFVG------------- 1069
Cdd:cd07854   159 FGLARIV---DPHYSHKGylseglvTKWYRSPRLL-LSPnnYTKAIDMWAAGCIFAEMLTGKPLFAGaheleqmqliles 234

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1070 -----ENDRTTLMNIRNYNVAFEET--------TFLSLSREARGFLIKVLV---QDRLrpTAEETLEHPWFK 1125
Cdd:cd07854   235 vpvvrEEDRNELLNVIPSFVRNDGGeprrplrdLLPGVNPEALDFLEQILTfnpMDRL--TAEEALMHPYMS 304

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270954 [Multi-domain] Cd Length: 278 Bit Score: 82.47 E-value: 1.39e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRE-NATGRTFVAKI--VPYA-AEGKRRVLQEYEVLRTLH---HERLMSLHEAYITPRYLVLIAESCGNREL 2304
Cdd:cd14052    11 GEFSQVYKVSErVPTGKVYAVKKlkPNYAgAKDRLRRLEEVSILRELTldgHDNIVQLIDSWEYHGHLYIQTELCENGSL 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 ---LCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYnpqalkPLG---HR 2378
Cdd:cd14052    91 dvfLSELGLLGRLDEFRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVW------PLIrgiER 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRGDPIGSATDIWGAGVltyIMLSGYSPFYEPDPQETEARIVGGRF-DAFQLYPNTSQSATLF------ 2451
Cdd:cd14052   165 EGDREYIAPEILSEHMYDKPADIFSLGL---ILLEAAANVVLPDNGDAWQKLRSGDLsDAPRLSSTDLHSASSPssnppp 241

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 564369110 2452 ---------------LRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd14052   242 dppnmpilsgsldrvVRWMLSPEPDRRPTADDVLATP 278

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 76.85 E-value: 1.44e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  333 APLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDGGLHSLHIARVGSEDEGLYEVSATNTH 412
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                          90
                  ....*....|.
gi 564369110  413 GQAHCSAQLYV 423
Cdd:cd20972    81 GSDTTSAEIFV 91

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.

Pssm-ID: 197581 [Multi-domain] Cd Length: 257 Bit Score: 81.81 E-value: 1.64e-16

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    875 QEIGRGAFSYLRR----VVERSSGLEFAAKFIPSQAKPKASA--RREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT 948
Cdd:smart00219    5 KKLGEGAFGEVYKgklkGKGGKKKVEVAVKTLKEDASEQQIEefLREARIMRKLDHPNVVKLLGVCTEEEPLYIVMEYME 84

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    949 E-ELLERM-ARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEpQYC 1026
Cdd:smart00219   85 GgDLLSYLrKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLV----GENLVVKISDFGLSRDLYDDD-YYR 159

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110   1027 QFGTPEFV---APEIVNQSPVSGVTDIWPVGVVAF-LCLTGISPFVGENDRTTLMNIRNYN 1083
Cdd:smart00219  160 KRGGKLPIrwmAPESLKEGKFTSKSDVWSFGVLLWeIFTLGEQPYPGMSNEEVLEYLKNGY 220

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270811 [Multi-domain] Cd Length: 283 Bit Score: 82.38 E-value: 1.75e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK-RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd06643     3 PEDFWEIVGELGDGAFGKVYKAQNKETGILAAAKVIDTKSEEElEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFR-YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQpyNPQALKPL 2375
Cdd:cd06643    83 FCAGGAVDAVMLELERpLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGvSAK--NTRTLQRR 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRTGTLEFMAPEMV-----RGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATL 2450
Cdd:cd06643   161 DSFIGTPYWMAPEVVmcetsKDRPYDYKADVWSLGVTLIEMAQIEPPHHELNPMRVLLKIAKSEPPTLAQPSRWSPEFKD 240

                         250       260
                  ....*....|....*....|....*
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06643   241 FLRKCLEKNVDARWTTSQLLQHPFV 265

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270822 [Multi-domain] Cd Length: 277 Bit Score: 82.14 E-value: 1.76e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFI--PSQAKPKASARREARLLARLQH---DCVLYFHEAFERRRGLVIVTELCTEEL 951
Cdd:cd06917     9 VGRGSYGAVYRGYHVKTGRVVALKVLnlDTDDDDVSDIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWIIMDYCEGGS 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQYCQF-GT 1030
Cdd:cd06917    89 IRTLMRAGPIAERYIAVIMREVLVALKFIHKDGIIHRDIKAANILV----TNTGNVKLCDFGVAASLNQNSSKRSTFvGT 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1031 PEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFVGEND-RTTLMNIRNYNVAFEETTFlslSREARGFLIKVLVQ 1108
Cdd:cd06917   165 PYWMAPEVITEGKYYDTkADIWSLGITTYEMATGNPPYSDVDAlRAVMLIPKSKPPRLEGNGY---SPLLKEFVAACLDE 241

                         250       260
                  ....*....|....*....|..
gi 564369110 1109 D-RLRPTAEETLEHPWFKTEAK 1129
Cdd:cd06917   242 EpKDRLSADELLKSKWIKQHSK 263

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270806 [Multi-domain] Cd Length: 282 Bit Score: 81.98 E-value: 2.12e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTL-HHERLMSLHEAYITPR------Y 2291
Cdd:cd06636    14 PAGIFELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDVTEDEEEEIKLEINMLKKYsHHRNIATYYGAFIKKSppghddQ 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2292 LVLIAESCGNREL--LCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynP 2369
Cdd:cd06636    94 LWLVMEFCGAGSVtdLVKNTKGNALKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVS----A 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLGHRT---GTLEFMAPEMVRGDPIGSAT-----DIWGAGVLTYIMLSGYSPFYEPDPQEtearivggrfdAFQLY 2441
Cdd:cd06636   170 QLDRTVGRRNtfiGTPYWMAPEVIACDENPDATydyrsDIWSLGITAIEMAEGAPPLCDMHPMR-----------ALFLI 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 564369110 2442 PNT----------SQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06636   239 PRNpppklkskkwSKKFIDFIEGCLVKNYLSRPSTEQLLKHPFI 282

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270771 [Multi-domain] Cd Length: 379 Bit Score: 83.90 E-value: 2.27e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR----REARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd05621    54 YDVVKVIGRGAFGEVQLVRHKASQKVYAMKLLSKFEMIKRSDSaffwEERDIMAFANSPWVVQLFCAFQDDKYLYMVMEY 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYC 1026
Cdd:cd05621   134 MPGGDLVNLMSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLL-DKYG---HLKLADFGTCMKMDETGMVHC 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 Q--FGTPEFVAPEIVNQSPVSGV----TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARG 1100
Cdd:cd05621   210 DtaVGTPDYISPEVLKSQGGDGYygreCDWWSVGVFLFEMLVGDTPFYADSLVGTYSKIMDHKNSLNFPDDVEISKHAKN 289

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 1101 fLIKVLVQDRL----RPTAEETLEHPWFKTE 1127
Cdd:cd05621   290 -LICAFLTDREvrlgRNGVEEIKQHPFFRND 319

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270842 [Multi-domain] Cd Length: 336 Bit Score: 83.18 E-value: 2.27e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  866 RLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQHDCVLYFHEAFERR----- 937
Cdd:cd07855     2 DVGDRYEPIETIGSGAYGVVCSAIDTKSGQKVAIKKIPNAFDVVTTAKRtlrELKILRHFKHDNIIAIRDILRPKvpyad 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  938 -RGLVIVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQ 1016
Cdd:cd07855    82 fKDVYVVLDLMESDLHHIIHSDQPLTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLV----NENCELKIGDFGMAR 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPGEPQYCQFGTpEFV------APEIVNQSP-VSGVTDIWPVGVV---------------------AFLCLTG----- 1063
Cdd:cd07855   158 GLCTSPEEHKYFMT-EYVatrwyrAPELMLSLPeYTQAIDMWSVGCIfaemlgrrqlfpgknyvhqlqLILTVLGtpsqa 236

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 1064 -ISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWFKT 1126
Cdd:cd07855   237 vINAIGADRVRRYIQNLPNKQPVPWETLYPKADQQALDLLSQMLRFDpSERITVAEALQHPFLAK 301

serine/threonine protein kinase; Provisional

Pssm-ID: 240344 [Multi-domain] Cd Length: 496 Bit Score: 84.54 E-value: 2.53e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVP---YAAEGKRRVLQEYEVLRTLHHERLMSLHE--AYITPR--------YLVLIAES 2298
Cdd:PTZ00283   43 GATGTVLCAKRVSDGEPFAVKVVDmegMSEADKNRAQAEVCCLLNCDFFSIVKCHEdfAKKDPRnpenvlmiALVLDYAN 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGN-RELLCGLSDRFR-YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLG 2376
Cdd:PTZ00283  123 AGDlRQEIKSRAKTNRtFREHEAGLLFIQVLLAVHHVHSKHMIHRDIKSANILLCSNGLVKLGDFGFSKMYAATVSDDVG 202

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 hRT--GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAfqLYPNTSQSATLFLRK 2454
Cdd:PTZ00283  203 -RTfcGTPYYVAPEIWRRKPYSKKADMFSLGVLLYELLTLKRPFDGENMEEVMHKTLAGRYDP--LPPSISPEMQEIVTA 279

                         250
                  ....*....|....*....
gi 564369110 2455 VLSVHPWSRPSLQDCLAHP 2473
Cdd:PTZ00283  280 LLSSDPKRRPSSSKLLNMP 298

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173710 [Multi-domain] Cd Length: 316 Bit Score: 82.68 E-value: 2.59e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKivpyaAEGKRRVLQEYEVLRTLHHERLMSL----------HEAYITPRYLVLIAESCG 2300
Cdd:cd05620     5 KGSFGKVLLAELKGKGEYFAVK-----ALKKDVVLIDDDVECTMVEKRVLALawenpflthlYCTFQTKEHLFFVMEFLN 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPyNPQALKPLGHRTG 2380
Cdd:cd05620    80 GGDLMFHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKE-NVFGDNRASTFCG 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 2381 TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQE 2425
Cdd:cd05620   159 TPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDE 203

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270860 [Multi-domain] Cd Length: 256 Bit Score: 81.32 E-value: 2.69e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2261 KRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC--GNrellcgLSDRFR------YSEDDVATYVVQLLQGLDY 2332
Cdd:cd08221    43 RRDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYCngGN------LHDKIAqqknqlFPEEVVLWYLYQIVSAVSH 116

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2333 LHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpqalKPLGHR-------TGTLEFMAPEMVRGDPIGSATDIWGAG 2405
Cdd:cd08221   117 IHKAGILHRDIKTLNIFLTKADLVKLGDFGIS--------KVLDSEssmaesiVGTPYYMSPELVQGVKYNFKSDIWAVG 188

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2406 VLTYIMLSGYSPFYEPDPQETEARIVGGRFDafQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd08221   189 CVLYELLTLKRTFDATNPLRLAVKIVQGEYE--DIDEQYSEEIIQLVHDCLHQDPEDRPTAEELLERPLL 256

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270857 [Multi-domain] Cd Length: 265 Bit Score: 81.43 E-value: 2.70e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA---KPKASARREARLLARLQHD-CVLYFHEAFERRRGLV-IVTE 945
Cdd:cd08217     2 YEVLETIGKGSFGTVRKVRRKSDGKILVWKEIDYGKmseKEKQQLVSEVNILRELKHPnIVRYYDRIVDRANTTLyIVME 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPT-----VCESETRTYMRQVLEGIGYLH-----QSHVLHLDVKPENLLVwDGAGGeeqVRICDFGNA 1015
Cdd:cd08217    82 YCEGGDLAQLIKKCKkenqyIPEEFIWKIFTQLLLALYECHnrsvgGGKILHRDLKPANIFL-DSDNN---VKLGDFGLA 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1016 QELTpGEPQYCQ--FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAF-LClTGISPFVGENDRTTLMNIRnynvafeETTFL 1092
Cdd:cd08217   158 RVLS-HDSSFAKtyVGTPYYMSPELLNEQSYDEKSDIWSLGCLIYeLC-ALHPPFQAANQLELAKKIK-------EGKFP 228

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 1093 SL----SREARGfLIKVL--VQDRLRPTAEETLEHP 1122
Cdd:cd08217   229 RIpsrySSELNE-VIKSMlnVDPDKRPSVEELLQLP 263

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270740 [Multi-domain] Cd Length: 328 Bit Score: 82.47 E-value: 3.48e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2276 HERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA 2355
Cdd:cd05588    55 HPFLVGLHSCFQTESRLFFVIEFVNGGDLMFHMQRQRRLPEEHARFYSAEISLALNFLHEKGIIYRDLKLDNVLLDSEGH 134

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2356 LKIVDFGSAQpynpQALKPlGHRT----GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd05588   135 IKLTDYGMCK----EGLRP-GDTTstfcGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMLAGRSPF 196

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270744 [Multi-domain] Cd Length: 320 Bit Score: 82.05 E-value: 3.61e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQF-GTPEFVAPEIV-- 1039
Cdd:cd05592    95 EDRARFYGAEIICGLQFLHSRGIIYRDLKLDNVLL-DREG---HIKIADFGMCKENIYGENKASTFcGTPDYIAPEILkg 170

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1040 ---NQSpvsgvTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREARGFLIKVLVQD---RL-- 1111
Cdd:cd05592   171 qkyNQS-----VDWWSFGVLLYEMLIGQSPFHGEDEDELFWSICNDTPHYPRW----LTKEAASCLSLLLERNpekRLgv 241

                         170
                  ....*....|....*.
gi 564369110 1112 -RPTAEETLEHPWFKT 1126
Cdd:cd05592   242 pECPAGDIRDHPFFKT 257

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271067 [Multi-domain] Cd Length: 263 Bit Score: 80.98 E-value: 3.68e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2247 RTFVAKIVPyaaegkrrvlQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR-ELLCGLSDRFRYSEDDVATYVVQ 2325
Cdd:cd14165    41 DDFVEKFLP----------RELEILARLNHKSIIKTYEIFETSDGKVYIVMELGVQgDLLEFIKLRGALPEDVARKMFHQ 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2326 LLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAL-KPLGHRT--GTLEFMAPEMVRGDPIG-SATDI 2401
Cdd:cd14165   111 LSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRCLRDENgRIVLSKTfcGSAAYAAPEVLQGIPYDpRIYDI 190

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2402 WGAGVLTYIMLSGYSPFYEPDPQET-----EARIvggrfdAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14165   191 WSLGVILYIMVCGSMPYDDSNVKKMlkiqkEHRV------RFPRSKNLTSECKDLIYRLLQPDVSQRLCIDEVLSHPWL 263

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270852 [Multi-domain] Cd Length: 286 Bit Score: 81.55 E-value: 3.70e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKI--------VPYAAegkrrvLQEYEVLRTLHHERLMSLHEAYITPRYLVL 2294
Cdd:cd07870     2 YLNLEKLGEGSYATVYKGISRINGQLVALKVismkteegVPFTA------IREASLLKGLKHANIVLLHDIIHTKETLTF 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2295 IaescgnrellcglsdrFRYSEDDVATYVVQ----------------LLQGLDYLHGRHVLHLDIKPDNLLLAADNALKI 2358
Cdd:cd07870    76 V----------------FEYMHTDLAQYMIQhpgglhpynvrlfmfqLLRGLAYIHGQHILHRDLKPQNLLISYLGELKL 139

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2359 VDFGSA-------QPYNPQALkplghrtgTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSG---------------- 2414
Cdd:cd07870   140 ADFGLAraksipsQTYSSEVV--------TLWYRPPDVLLGATdYSSALDIWGAGCIFIEMLQGqpafpgvsdvfeqlek 211

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2415 ---------------------YSPFYEPDPQETEARIVGGRFDAfqlYPNTSQSATlflrKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd07870   212 iwtvlgvptedtwpgvsklpnYKPEWFLPCKPQQLRVVWKRLSR---PPKAEDLAS----QMLMMFPKDRISAQDALLHP 284


                  ..
gi 564369110 2474 WL 2475
Cdd:cd07870   285 YF 286

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 75.92 E-value: 3.92e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  334 PLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESE---NLRLRQDGGLHSLHIARVGSEDEGLYEVSATN 410
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|....
gi 564369110  411 THGQAHCSAQLYVE 424
Cdd:cd20951    81 IHGEASSSASVVVE 94

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270746 [Multi-domain] Cd Length: 356 Bit Score: 82.77 E-value: 3.97e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQ---AKPK-ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-EL 951
Cdd:cd05594    33 LGKGTFGKVILVKEKATGRYYAMKILKKEvivAKDEvAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGgEL 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLH-QSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE-LTPGEPQYCQFG 1029
Cdd:cd05594   113 FFHLSRERVFSEDRARFYGAEIVSALDYLHsEKNVVYRDLKLENLML-DKDG---HIKITDFGLCKEgIKDGATMKTFCG 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1030 TPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREARGFLIKVLVQD 1109
Cdd:cd05594   189 TPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRT----LSPEAKSLLSGLLKKD 264

                         250       260
                  ....*....|....*....|.
gi 564369110 1110 RLR------PTAEETLEHPWF 1124
Cdd:cd05594   265 PKQrlgggpDDAKEIMQHKFF 285

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270769 [Multi-domain] Cd Length: 364 Bit Score: 82.77 E-value: 4.33e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAA----EGKRRVLQEYEVL-RTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd05618    22 FDLLRVIGRGSYAKVLLVRLKKTERIYAMKVVKKELvnddEDIDWVQTEKHVFeQASNHPFLVGLHSCFQTESRLFFVIE 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpynpQALKPlGH 2377
Cdd:cd05618   102 YVNGGDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCK----EGLRP-GD 176

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 2378 RT----GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd05618   177 TTstfcGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPF 221

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173750 [Multi-domain] Cd Length: 332 Bit Score: 82.07 E-value: 4.38e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYL--RRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQH-----------DCVLYFHEAFer 936
Cdd:cd07857     1 RYELIKELGQGAYGIVcsARNAETSEEETVAIKKITNVFSKKILAKRALRELKLLRHfrghknitclyDMDIVFPGNF-- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  937 rRGLVIVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGEeqVRICDFGNAQ 1016
Cdd:cd07857    79 -NELYLYEELMEADLHQIIRSGQPLTDAHFQSFIYQILCGLKYIHSANVLHRDLKPGNLLV--NADCE--LKICDFGLAR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPGEPQYCQFGTpEFV------APEIV--NQSPVSGVtDIWPVGVVAFLCLTGISPFVGEN---------------DR 1073
Cdd:cd07857   154 GFSENPGENAGFMT-EYVatrwyrAPEIMlsFQSYTKAI-DVWSVGCILAELLGRKPVFKGKDyvdqlnqilqvlgtpDE 231

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110 1074 TTLMNI---RNYNVAFE---------ETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd07857   232 ETLSRIgspKAQNYIRSlpnipkkpfESIFPNANPLALDLLEKLLAFDpTKRISVEEALEHPY 294

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270794 [Multi-domain] Cd Length: 268 Bit Score: 80.92 E-value: 4.41e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeeQVRICDFGNAQELTPGEPQYCQF-GTPEFVAPEIVNQ 1041
Cdd:cd06624   107 ENTIGYYTKQILEGLKYLHDNKIVHRDIKGDNVLVNTYSG---VVKISDFGTSKRLAGINPCTETFtGTLQYMAPEVIDK 183

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1042 SP--VSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMnirnYNVAFEET---TFLSLSREARGFLIKVLVQDRL-RPTA 1115
Cdd:cd06624   184 GQrgYGPPADIWSLGCTIIEMATGKPPFIELGEPQAAM----FKVGMFKIhpeIPESLSEEAKSFILRCFEPDPDkRATA 259


                  ....*..
gi 564369110 1116 EETLEHP 1122
Cdd:cd06624   260 SDLLQDP 266

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 75.22 E-value: 4.98e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 218
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 564369110  219 GARQCEARLEV 229
Cdd:cd05744    81 GENSFNAELVV 91

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143344 [Multi-domain] Cd Length: 284 Bit Score: 80.94 E-value: 5.08e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPY--AAEG-KRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd07839     2 YEKLEKIGEGTYGTVFKAKNRETHEIVALKRVRLddDDEGvPSSALREICLLKELKHKNIVRLYDVLHSDKKLTLVFEYC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNrellcglsDRFRY-----SEDD---VATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYN-Pq 2370
Cdd:cd07839    82 DQ--------DLKKYfdscnGDIDpeiVKSFMFQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLARAFGiP- 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 aLKPLGHRTGTLEFMAPEMVRGDPIGSAT-DIWGAGVLTYIMLSGYSPFY 2419
Cdd:cd07839   153 -VRCYSAEVVTLWYRPPDVLFGAKLYSTSiDMWSAGCIFAELANAGRPLF 201

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR1 (also called STK38) plays a role in proper centrosome duplication. It is highly expressed in thymus, muscle, lung and spleen. It is not an essential protein because mice deficient of NDR1 remain viable and fertile. However, these mice develop T-cell lymphomas and appear to be hypersenstive to carcinogenic treatment. NDR1 appears to also act as a tumor suppressor. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270777 [Multi-domain] Cd Length: 376 Bit Score: 82.39 E-value: 5.50e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPS----QAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE-LCTEEL 951
Cdd:cd05628     9 IGRGAFGEVRLVQKKDTGHVYAMKILRKadmlEKEQVGHIRAERDILVEADSLWVVKMFYSFQDKLNLYLIMEfLPGGDM 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFG---------------NAQ 1016
Cdd:cd05628    89 MTLLMKKDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLL-DSKG---HVKLSDFGlctglkkahrtefyrNLN 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPG---------------------EPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTT 1075
Cdd:cd05628   165 HSLPSdftfqnmnskrkaetwkrnrrQLAFSTVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSETPQET 244

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 1076 LMNIRNYNVAFEETTFLSLSREARGFLIKVLVQDRLR---PTAEETLEHPWFK 1125
Cdd:cd05628   245 YKKVMNWKETLIFPPEVPISEKAKDLILRFCCEWEHRigaPGVEEIKTNPFFE 297

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270737 [Multi-domain] Cd Length: 313 Bit Score: 81.46 E-value: 5.64e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAK-----FIPSQAKPKASARrEARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-E 950
Cdd:cd05585     2 IGKGSFGKVMQVRKKDTSRIYALKtirkaHIVSRSEVTHTLA-ERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFINGgE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  951 LLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFG----NAQElTPGEPQYC 1026
Cdd:cd05585    81 LFHHLQREGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILL-DYTG---HIALCDFGlcklNMKD-DDKTNTFC 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 qfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREARGFLIKVL 1106
Cdd:cd05585   156 --GTPEYLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKILQEPLRFPD----GFDRDAKDLLIGLL 229

                         250       260
                  ....*....|....*....|....*
gi 564369110 1107 VQDrlrPT-------AEETLEHPWF 1124
Cdd:cd05585   230 NRD---PTkrlgyngAQEIKNHPFF 251

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143385 [Multi-domain] Cd Length: 343 Bit Score: 81.92 E-value: 5.93e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAK--FIPSQAKPKAS-ARREARLLARLQHDCVLYFHEAF------ERRRG 939
Cdd:cd07880    15 DRYRDLKQVGSGAYGTVCSALDRRTGAKVAIKklYRPFQSELFAKrAYRELRLLKHMKHENVIGLLDVFtpdlslDRFHD 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  940 LVIVTELCTEELLERMaRKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELT 1019
Cdd:cd07880    95 FYLVMPFMGTDLGKLM-KHEKLSEDRIQFLVYQMLKGLKYIHAAGIIHRDLKPGNLAVNE----DCELKILDFGLARQTD 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCQfgTPEFVAPE-IVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI------------------- 1079
Cdd:cd07880   170 SEMTGYVV--TRWYRAPEvILNWMHYTQTVDIWSVGCIMAEMLTGKPLFKGHDHLDQLMEImkvtgtpskefvqklqsed 247

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1080 -RNYNVA---FEETTFLSLSREARGFLIKVL-----VQDRLRPTAEETLEHPWF--------KTEAKGAEVSTDHLKLFL 1142
Cdd:cd07880   248 aKNYVKKlprFRKKDFRSLLPNANPLAVNVLekmlvLDAESRITAAEALAHPYFeefhdpedETEAPPYDDSFDEVDQSL 327

                         330       340
                  ....*....|....*....|
gi 564369110 1143 SrrRWQRsqISYKCHLVLRP 1162
Cdd:cd07880   328 E--EWKR--LTFTEILSFQP 343

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.

Pssm-ID: 270774 [Multi-domain] Cd Length: 409 Bit Score: 82.75 E-value: 6.19e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRV----VERSSGLEFAAKFIPSQAKPKASARREARLLarLQHDC--VLYFHEAFERRRGLVI 942
Cdd:cd05624    72 DDFEIIKVIGRGAFGEVAVVkmknTERIYAMKILNKWEMLKRAETACFREERNVL--VNGDCqwITTLHYAFQDENYLYL 149

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  943 VTEL-CTEELLERMAR-KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTP 1020
Cdd:cd05624   150 VMDYyVGGDLLTLLSKfEDKLPEDMARFYIGEMVLAIHSIHQLHYVHRDIKPDNVLL-DMNG---HIRLADFGSCLKMND 225

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 -GEPQ-YCQFGTPEFVAPEIVnQSPVSGV------TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFL 1092
Cdd:cd05624   226 dGTVQsSVAVGTPDYISPEIL-QAMEDGMgkygpeCDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHEERFQFPSHV 304

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 564369110 1093 S-LSREARGfLIKVLVQDRLRPTAEETLE----HPWFK 1125
Cdd:cd05624   305 TdVSEEAKD-LIQRLICSRERRLGQNGIEdfkkHAFFE 341

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270756 [Multi-domain] Cd Length: 285 Bit Score: 80.86 E-value: 6.27e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAEscgnreLLC 2306
Cdd:cd05605    10 KGGFGEVCACQVRATGKMYACKKLEKKRIKKRKgeamALNEKQILEKVNSRFVVSLAYAYETKDALCLVLT------IMN 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFR--------YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQalKPLGHR 2378
Cdd:cd05605    84 GGDLKFHiynmgnpgFEEERAVFYAAEITCGLEHLHSERIVYRDLKPENILLDDHGHVRISDLGLAVEIPEG--ETIRGR 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFY----EPDPQETEARIvggRFDAFQLYPNTSQSATLFLRK 2454
Cdd:cd05605   162 VGTVGYMAPEVVKNERYTFSPDWWGLGCLIYEMIEGQAPFRarkeKVKREEVDRRV---KEDQEEYSEKFSEEAKSICSQ 238

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 564369110 2455 VLSVHPWSR-----PSLQDCLAHPWLQDAYLMKLR 2484
Cdd:cd05605   239 LLQKDPKTRlgcrgEGAEDVKSHPFFKSINFKRLE 273

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270807 [Multi-domain] Cd Length: 296 Bit Score: 80.92 E-value: 6.43e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTL-HHERLMSLHEAYITPR------Y 2291
Cdd:cd06637     4 PAGIFELVELVGNGTYGQVYKGRHVKTGQLAAIKVMDVTGDEEEEIKQEINMLKKYsHHRNIATYYGAFIKKNppgmddQ 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2292 LVLIAESCGNREL--LCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynP 2369
Cdd:cd06637    84 LWLVMEFCGAGSVtdLIKNTKGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVS----A 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLGHRT---GTLEFMAPEMVRGDPIGSAT-----DIWGAGVLTYIMLSGYSPFYEPDPQetEARIVGGRFDAFQLY 2441
Cdd:cd06637   160 QLDRTVGRRNtfiGTPYWMAPEVIACDENPDATydfksDLWSLGITAIEMAEGAPPLCDMHPM--RALFLIPRNPAPRLK 237

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 564369110 2442 PNT-SQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd06637   238 SKKwSKKFQSFIESCLVKNHSQRPSTEQLMKHPFIRD 274

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143374 [Multi-domain] Cd Length: 303 Bit Score: 81.28 E-value: 6.45e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKR--RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd07869     7 YEKLEKLGEGSYATVYKGKSKVNGKLVALKVIRLQEEEGTpfTAIREASLLKGLKHANIVLLHDIIHTKETLTLVFEYVH 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRelLCGLSDRFR--YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAlKPLGHR 2378
Cdd:cd07869    87 TD--LCQYMDKHPggLHPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLARAKSVPS-HTYSNE 163

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 564369110 2379 TGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd07869   164 VVTLWYRPPDVLLGSTeYSTCLDMWGVGCIFVEMIQGVAAF 204

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270813 [Multi-domain] Cd Length: 268 Bit Score: 80.07 E-value: 7.10e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd06646     7 PQHDYELIQRVGSGTYGDVYKARNLHTGELAAVKIIKLEPGDDFSLIQqEIFMVKECKHCNIVAYFGSYLSREKLWICME 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGH 2377
Cdd:cd06646    87 YCGGGSLQDIYHVTGPLSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKITATIAKRKSF 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 rTGTLEFMAPEMVRGDPIGSAT---DIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATL--FL 2452
Cdd:cd06646   167 -IGTPYWMAPEVAAVEKNGGYNqlcDIWAVGITAIELAELQPPMFDLHPMRALFLMSKSNFQPPKLKDKTKWSSTFhnFV 245

                         250       260
                  ....*....|....*....|
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAH 2472
Cdd:cd06646   246 KISLTKNPKKRPTAERLLTH 265

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173741 [Multi-domain] Cd Length: 293 Bit Score: 80.73 E-value: 7.58e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEGKR---RVLQEYEVLRTLHHERLMSLHE----AYITPRYLVLIAESCGNREL 2304
Cdd:cd07843    16 GTYGVVYRARDKKTGEIVALKKLKMEKEKEGfpiTSLREINILLKLQHPNIVTVKEvvvgSNLDKIYMVMEYVEHDLKSL 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 LCGLSDRFRYSEddVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYnPQALKPLGHRTGTLEF 2384
Cdd:cd07843    96 METMKQPFLQSE--VKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLAREY-GSPLKPYTQLVVTLWY 172

                         170       180
                  ....*....|....*....|..
gi 564369110 2385 MAPEMVRGDPI-GSATDIWGAG 2405
Cdd:cd07843   173 RAPELLLGAKEySTAIDMWSVG 194

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270770 [Multi-domain] Cd Length: 331 Bit Score: 81.12 E-value: 8.16e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPyaaegKRRVLQEYEVLRTLHHERLMSL---HE-------AYITPRYLVLIAESCG 2300
Cdd:cd05619    15 KGSFGKVFLAELKGTNQFFAIKALK-----KDVVLMDDDVECTMVEKRVLSLaweHPflthlfcTFQTKENLFFVMEYLN 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPyNPQALKPLGHRTG 2380
Cdd:cd05619    90 GGDLMFHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKE-NMLGDAKTSTFCG 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvggRFDAfQLYPN-TSQSATLFLRKVLSVH 2459
Cdd:cd05619   169 TPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGQDEEELFQSI---RMDN-PFYPRwLEKEAKDILVKLFVRE 244

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 2460 PWSRPSLQ-DCLAHPWLQDAYLMKLRRQTL-----------TFTTNRLKEFLGEQ 2502
Cdd:cd05619   245 PERRLGVRgDIRQHPFFREINWEALEEREIeppfkpkvkspFDCSNFDKEFLNEK 299

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270792 [Multi-domain] Cd Length: 286 Bit Score: 80.18 E-value: 8.56e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2226 LEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK--RRVLQEYEVLRTLHHERLMSLHEAYITPR-YLVLIAESCGnr 2302
Cdd:cd06620    10 LKDLGAGNGGSVSKVLHIPTGTIMAKKVIHIDAKSSvrKQILRELQILHECHSPYIVSFYGAFLNENnNIIICMEYMD-- 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ellCGLSDRF-----RYSEDDVATYVVQLLQGLDYLHGRH-VLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPL 2375
Cdd:cd06620    88 ---CGSLDKIlkkkgPFPEEVLGKIAVAVLEGLTYLYNVHrIIHRDIKPSNILVNSKGQIKLCDFGvSGELINSIADTFV 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRTgtleFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNT----------- 2444
Cdd:cd06620   165 GTST----YMSPERIQGGKYSVKSDVWSLGLSIIELALGEFPFAGSNDDDDGYNGPMGILDLLQRIVNEppprlpkdrif 240

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 2445 SQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd06620   241 PKDLRDFVDRCLLKDPRERPSPQLLLDHDPFIQA 274

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270792 [Multi-domain] Cd Length: 286 Bit Score: 80.18 E-value: 8.56e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHEAFERRRG-LVIVTELCTEEL 951
Cdd:cd06620    11 KDLGAGNGGSVSKVLHIPTGTIMAKKVIHIDAKSSVRKQilRELQILHECHSPYIVSFYGAFLNENNnIIICMEYMDCGS 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMR-QVLEGIGYLH-QSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQycQF- 1028
Cdd:cd06620    91 LDKILKKKGPFPEEVLGKIAvAVLEGLTYLYnVHRIIHRDIKPSNILV-NSKG---QIKLCDFGVSGELINSIAD--TFv 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVnQSPVSGV-TDIWPVGVVAFLCLTGISPFVGEND----RTTLMNIRN--YNVAFEETTFLSLSR----E 1097
Cdd:cd06620   165 GTSTYMSPERI-QGGKYSVkSDVWSLGLSIIELALGEFPFAGSNDdddgYNGPMGILDllQRIVNEPPPRLPKDRifpkD 243

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 564369110 1098 ARGFLIKVLVQD-RLRPTAEETLEHPWFKTEAKGAEV 1133
Cdd:cd06620   244 LRDFVDRCLLKDpRERPSPQLLLDHDPFIQAVRASDV 280

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270738 [Multi-domain] Cd Length: 330 Bit Score: 81.08 E-value: 9.73e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPS----QAKPKASARREARLLAR-LQHDC--VLYFHEAFERRRGLVIVTE-LCT 948
Cdd:cd05586     1 IGKGTFGQVYQVRKKDTRRIYAMKVLSKkvivAKKEVAHTIGERNILVRtALDESpfIVGLKFSFQTPTDLYLVTDyMSG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQ-ELTPGEPQYCQ 1027
Cdd:cd05586    81 GELFWHLQKEGRFSEDRAKFYIAELVLALEHLHKNDIVYRDLKPENILL-DANG---HIALCDFGLSKaDLTDNKTTNTF 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 FGTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTflsLSREARGFLIKVL 1106
Cdd:cd05586   157 CGTTEYLAPEVlLDEKGYTKMVDFWSLGVLVFEMCCGWSPFYAEDTQQMYRNIAFGKVRFPKDV---LSDEGRSFVKGLL 233

                         250       260
                  ....*....|....*....|....
gi 564369110 1107 ---VQDRLRPT--AEETLEHPWFK 1125
Cdd:cd05586   234 nrnPKHRLGAHddAVELKEHPFFA 257

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270832 [Multi-domain] Cd Length: 291 Bit Score: 80.30 E-value: 1.07e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGlEFAA--KFIPSQAK---PKASARrEARLLARLQHDCVLYFHE-----AFERRRGL 940
Cdd:cd07840     1 YEKIAQIGEGTYGQVYKARNKKTG-ELVAlkKIRMENEKegfPITAIR-EIKLLQKLDHPNVVRLKEivtskGSAKYKGS 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 V-IVTELCtEELLERMARKPTV--CESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE 1017
Cdd:cd07840    79 IyMVFEYM-DHDLTGLLDNPEVkfTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILI-NNDG---VLKLADFGLARP 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1018 LTPGEPQYCqfgTPEFV-----APEIvnqspVSGVT------DIWPVGVVAFLCLTGISPFVGENDRTTLMNI------- 1079
Cdd:cd07840   154 YTKENNADY---TNRVItlwyrPPEL-----LLGATrygpevDMWSVGCILAELFTGKPIFQGKTELEQLEKIfelcgsp 225

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 1080 --------------------RNYNVAFEETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07840   226 teenwpgvsdlpwfenlkpkKPYKRRLREVFKNVIDPSALDLLDKLLTLDpKKRISADQALQHEYF 291

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173742 [Multi-domain] Cd Length: 309 Bit Score: 80.49 E-value: 1.23e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEgKRRV----LQEYEVLRTLHHERLMSLHEAyITPRYL---VLIAESCgnREL 2304
Cdd:cd07845    18 GTYGIVYRARDTTSGEIVALKKVRMDNE-RDGIpissLREITLLLNLRHPNIVELKEV-VVGKHLdsiFLVMEYC--EQD 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 LCGLSDRFR--YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAlKPLGHRTGTL 2382
Cdd:cd07845    94 LASLLDNMPtpFSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLARTYGLPA-KPMTPKVVTL 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMVRG-DPIGSATDIWGAGVLTYIMLSGySPFYepdPQETEA---------------RIVGGrFDAF-------- 2438
Cdd:cd07845   173 WYRAPELLLGcTTYTTAIDMWAVGCILAELLAH-KPLL---PGKSEIeqldliiqllgtpneSIWPG-FSDLplvgkftl 247

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 564369110 2439 --QLYPN-------TSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd07845   248 pkQPYNNlkhkfpwLSEAGLRLLNFLLMYDPKKRATAEEALESSYFKEK 296

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.

Pssm-ID: 214568 [Multi-domain] Cd Length: 258 Bit Score: 79.13 E-value: 1.28e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    875 QEIGRGAFS--YLRRVVERSSGLEF--AAKFIPSQAKPKASA--RREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT 948
Cdd:smart00221    5 KKLGEGAFGevYKGTLKGKGDGKEVevAVKTLKEDASEQQIEefLREARIMRKLDHPNIVKLLGVCTEEEPLMIVMEYMP 84

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    949 E-ELLE--RMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEpQY 1025
Cdd:smart00221   85 GgDLLDylRKNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLV----GENLVVKISDFGLSRDLYDDD-YY 159

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110   1026 CQFGTPEFV---APEIVNQSPVSGVTDIWPVGVVAF-LCLTGISPFVGENDRTTLMNIRNYN 1083
Cdd:smart00221  160 KVKGGKLPIrwmAPESLKEGKFTSKSDVWSFGVLLWeIFTLGEEPYPGMSNAEVLEYLKKGY 221

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK2, also called beta-adrenergic receptor kinase (beta-ARK) or beta-ARK1, is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRK2 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. TheGRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271125 [Multi-domain] Cd Length: 321 Bit Score: 80.48 E-value: 1.31e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVpyaaEGKRRVLQEYEVLRTlhHERLM-------------SLHEAYITPRYLVLIA 2296
Cdd:cd14223     9 GRGGFGEVYGCRKADTGKMYAMKCL----DKKRIKMKQGETLAL--NERIMlslvstgdcpfivCMSYAFHTPDKLSFIL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQalKPLG 2376
Cdd:cd14223    83 DLMNGGDLHYHLSQHGVFSEAEMRFYAAEIILGLEHMHSRFVVYRDLKPANILLDEFGHVRISDLGLACDFSKK--KPHA 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 2377 hRTGTLEFMAPEMV-RGDPIGSATDIWGAGVLTYIMLSGYSPFYE 2420
Cdd:cd14223   161 -SVGTHGYMAPEVLqKGVAYDSSADWFSLGCMLFKLLRGHSPFRQ 204

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271036 [Multi-domain] Cd Length: 332 Bit Score: 80.69 E-value: 1.38e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  864 GRRLSDYYDIHQEIGRGAFSylrRVVE---RSSGLEFAAKFIPSQAKPKASARREARLLARLQHD-------CVLyFHEA 933
Cdd:cd14134     7 GDLLTNRYKILRLLGEGTFG---KVLEcwdRKRKRYVAVKIIRNVEKYREAAKIEIDVLETLAEKdpngkshCVQ-LRDW 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  934 FERRRGLVIVTELCTEELLERMAR---KPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGA--------- 1001
Cdd:cd14134    83 FDYRGHMCIVFELLGPSLYDFLKKnnyGP-FPLEHVQHIAKQLLEAVAFLHDLKLTHTDLKPENILLVDSDyvkvynpkk 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1002 GGEE------QVRICDFGNAqeltpgepqycQF---------GTPEFVAPEIV-----NQSpvsgvTDIWPVGVVAFLCL 1061
Cdd:cd14134   162 KRQIrvpkstDIKLIDFGSA-----------TFddeyhssivSTRHYRAPEVIlglgwSYP-----CDVWSIGCILVELY 225

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1062 TGISPFVGENDRTTL--M--------------------------------------NIRNYNVAFEETTFLSLSREARGF 1101
Cdd:cd14134   226 TGELLFQTHDNLEHLamMerilgplpkrmirrakkgakyfyfyhgrldwpegsssgRSIKRVCKPLKRLMLLVDPEHRLL 305

                         330       340
                  ....*....|....*....|....*..
gi 564369110 1102 --LI-KVLVQDR-LRPTAEETLEHPWF 1124
Cdd:cd14134   306 fdLIrKMLEYDPsKRITAKEALKHPFF 332

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270781 [Multi-domain] Cd Length: 346 Bit Score: 80.88 E-value: 1.49e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVpyaaEGKRRVLQEYEVLRTlhHERLM-------------SLHEAYITPRYLVLIA 2296
Cdd:cd05633    14 GRGGFGEVYGCRKADTGKMYAMKCL----DKKRIKMKQGETLAL--NERIMlslvstgdcpfivCMTYAFHTPDKLCFIL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQalKPLG 2376
Cdd:cd05633    88 DLMNGGDLHYHLSQHGVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSKK--KPHA 165

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 2377 hRTGTLEFMAPEMV-RGDPIGSATDIWGAGVLTYIMLSGYSPFYE 2420
Cdd:cd05633   166 -SVGTHGYMAPEVLqKGTAYDSSADWFSLGCMLFKLLRGHSPFRQ 209

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270884 [Multi-domain] Cd Length: 269 Bit Score: 79.24 E-value: 1.50e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  912 ARREARLL-ARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMARKPTVCESETRTY-----MRQVLEGIGYLHQSHV 985
Cdd:cd13982    41 ADREVQLLrESDEHPNVIRYFCTEKDRQFLYIALELCAASLQDLVESPRESKLFLRPGLepvrlLRQIASGLAHLHSLNI 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  986 LHLDVKPENLLV-WDGAGGEEQVRICDFGNAQELTPGEPQYCQF----GTPEFVAPEIVNQSPVSGVT---DIWPVGVVA 1057
Cdd:cd13982   121 VHRDLKPQNILIsTPNAHGNVRAMISDFGLCKKLDVGRSSFSRRsgvaGTSGWIAPEMLSGSTKRRQTravDIFSLGCVF 200

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 1058 FLCLTGIS-PFvGENDRttlmniRNYNVAFEETTFLSLSRE-ARGFLIKVLVQD------RLRPTAEETLEHPWF 1124
Cdd:cd13982   201 YYVLSGGShPF-GDKLE------REANILKGKYSLDKLLSLgEHGPEAQDLIERmidfdpEKRPSAEEVLNHPFF 268

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 73.69 E-value: 1.64e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    147 DQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEAR 226
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82


                    ...
gi 564369110    227 LEV 229
Cdd:smart00410   83 LTV 85

protein kinase A catalytic subunit; Provisional

Pssm-ID: 140289 [Multi-domain] Cd Length: 329 Bit Score: 80.25 E-value: 1.74e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  866 RLSDYyDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA----KPKASARREARLLARLQHDCVLYFHEAFERRRGLV 941
Cdd:PTZ00263   16 KLSDF-EMGETLGTGSFGRVRIAKHKGTGEYYAIKCLKKREilkmKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVY 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTp 1020
Cdd:PTZ00263   95 FLLEFVVGgELFTHLRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLL-DNKG---HVKVTDFGFAKKVP- 169

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 gEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGE 1070
Cdd:PTZ00263  170 -DRTFTLCGTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDD 218

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270861 [Multi-domain] Cd Length: 260 Bit Score: 79.00 E-value: 1.82e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2233 RFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEV-----------------LRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd08222     1 RYRVVRKLGSGNFGTVYLVSDLKATADEELKVLKEISVgelqpdetvdanreaklLSKLDHPAIVKFHDSFVEKESFCIV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRFR----YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLaADNALKIVDFGSAQPYnpqa 2371
Cdd:cd08222    81 TEYCEGGDLDDKISEYKKsgttIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFL-KNNVIKVGDFGISRIL---- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 lkpLGHR------TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGrfDAFQLYPNTS 2445
Cdd:cd08222   156 ---MGTSdlattfTGTPYYMSPEVLKHEGYNSKSDIWSLGCILYEMCCLKHAFDGQNLLSVMYKIVEG--ETPSLPDKYS 230

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 2446 QSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd08222   231 KELNAIYSRMLNKDPALRPSAAEILKIPFI 260

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270810 [Multi-domain] Cd Length: 277 Bit Score: 79.33 E-value: 1.83e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPY--AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIA 2296
Cdd:cd06642     2 PEELFTKLERIGKGSFGEVYKGIDNRTKEVVAIKIIDLeeAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLcGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPlG 2376
Cdd:cd06642    82 EYLGGGSAL-DLLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKR-N 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 HRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQlyPNTSQSATLFLRKVL 2456
Cdd:cd06642   160 TFVGTPFWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNSPPTLE--GQHSKPFKEFVEACL 237

                         250
                  ....*....|....*....
gi 564369110 2457 SVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06642   238 NKDPRFRPTAKELLKHKFI 256

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270825 [Multi-domain] Cd Length: 282 Bit Score: 79.24 E-value: 2.11e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRV--LQEYEVLRTL-HHERLMSLHEayitprylVLIAESC 2299
Cdd:cd07831     1 YKILGKIGEGTFSEVLKAQSRKTGKYYAIKCMKKHFKSLEQVnnLREIQALRRLsPHPNILRLIE--------VLFDRKT 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELLCGLSD---------RFRY-SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNaLKIVDFGSA----- 2364
Cdd:cd07831    73 GRLALVFELMDmnlyelikgRKRPlPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKDDI-LKLADFGSCrgiys 151

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2365 -QPYNpqalkplgHRTGTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLS 2413
Cdd:cd07831   152 kPPYT--------EYISTRWYRAPEcLLTDGYYGPKMDIWAVGCVFFEILS 194

NIMA-related protein kinase; Provisional

Pssm-ID: 140293 [Multi-domain] Cd Length: 478 Bit Score: 81.60 E-value: 2.25e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2292 LVLIAE--SCG--NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY 2367
Cdd:PTZ00267  140 LLLIMEygSGGdlNKQIKQRLKEHLPFQEYEVGLLFYQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFSKQY 219

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2368 NPQ-ALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLypNTSQ 2446
Cdd:PTZ00267  220 SDSvSLDVASSFCGTPYYLAPELWERKRYSKKADMWSLGVILYELLTLHRPFKGPSQREIMQQVLYGKYDPFPC--PVSS 297

                         170       180
                  ....*....|....*....|....
gi 564369110 2447 SATLFLRKVLSVHPWSRPSLQDCL 2470
Cdd:PTZ00267  298 GMKALLDPLLSKNPALRPTTQQLL 321

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270749 [Multi-domain] Cd Length: 333 Bit Score: 80.05 E-value: 2.35e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2311 RFRYSEDDVAT-YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG---------SAQPYNPQALkplghrTG 2380
Cdd:cd05598    94 KKGIFEEDLARfYIAELVCAIESVHKMGFIHRDIKPDNILIDRDGHIKLTDFGlctgfrwthDSKYYLAHSL------VG 167

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRfDAFQL--YPNTSQSATLFLRKVLSV 2458
Cdd:cd05598   168 TPNYIAPEVLLRTGYTQLCDWWSVGVILYEMLVGQPPFLAQTPAETQLKVINWR-TTLKIphEANLSPEAKDLILRLCCD 246

                         170       180       190
                  ....*....|....*....|....*....|.
gi 564369110 2459 HP--WSRPSLQDCLAHPWLQDAYLMKLRRQT 2487
Cdd:cd05598   247 AEdrLGRNGADEIKAHPFFAGIDWEKLRKQK 277

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 73.30 E-value: 2.41e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  458 PDFLRPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQ-SSDDRRMTQYRDIHRLVFPAVGPQHAGVYKSVIANKL 536
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRpDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 564369110  537 GKAACYAHLYV 547
Cdd:cd05744    81 GENSFNAELVV 91

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143359 [Multi-domain] Cd Length: 342 Bit Score: 79.82 E-value: 2.63e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2247 RTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAyITP---------RYLVLIAESCGNREL----LCGLSDRFR 2313
Cdd:cd07854    32 RVAVKKIVLTDPQSVKHALREIKIIRRLDHDNIVKVYEV-LGPsgsdltedvGSLTELNSVYIVQEYmetdLANVLEQGP 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2314 YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADN-ALKIVDFGSAQPYNPQaLKPLGHRTGTLE---FMAPEM 2389
Cdd:cd07854   111 LSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANVFINTEDlVLKIGDFGLARIVDPH-YSHKGYLSEGLVtkwYRSPRL 189

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2390 V-RGDPIGSATDIWGAGVLTYIMLSGYSPF-------------------YEPDPQE---TEARIVGG-----RFDAFQLY 2441
Cdd:cd07854   190 LlSPNNYTKAIDMWAAGCIFAEMLTGKPLFagaheleqmqlilesvpvvREEDRNEllnVIPSFVRNdggepRRPLRDLL 269

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 2442 PNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd07854   270 PGVNPEALDFLEQILTFNPMDRLTAEEALMHPYMSC 305

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270805 [Multi-domain] Cd Length: 317 Bit Score: 79.32 E-value: 2.89e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFS--YLRRVVERSsglEFAAKFIPSQAKPKASAR-----REARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd06635    31 REIGHGSFGavYFARDVRTS---EVVAIKKMSYSGKQSNEKwqdiiKEVKFLQRIKHPNSIEYKGCYLREHTAWLVMEYC 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 ---TEELLErMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPq 1024
Cdd:cd06635   108 lgsASDLLE-VHKKP-LQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPG----QVKLADFGSASIASPANS- 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 ycQFGTPEFVAPEIV---NQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI-RNYNVAFEETTFLSLSREARG 1100
Cdd:cd06635   181 --FVGTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIaQNESPTLQSNEWSDYFRNFVD 258

                         250       260
                  ....*....|....*....|....*..
gi 564369110 1101 FLIKVLVQDrlRPTAEETLEHPWFKTE 1127
Cdd:cd06635   259 SCLQKIPQD--RPTSEELLKHMFVLRE 283

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270760 [Multi-domain] Cd Length: 280 Bit Score: 78.60 E-value: 2.94e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA------KPKASARREarLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd05609     2 FETIKLISNGAYGAVYLVRHRETRQRFAMKKINKQNlilrnqIQQVFVERD--ILTFAENPFVVSMYCSFETKRHLCMVM 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELC----TEELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGeeQVRICDFG------- 1013
Cdd:cd05609    80 EYVeggdCATLLKNIGPLP---VDMARMYFAETVLALEYLHSYGIVHRDLKPDNLLI--TSMG--HIKLTDFGlskiglm 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1014 --------NAQELTPGEPQYCQ-FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNV 1084
Cdd:cd05609   153 slttnlyeGHIEKDTREFLDKQvCGTPEYIAPEVILRQGYGKPVDWWAMGIILYEFLVGCVPFFGDTPEELFGQVISDEI 232

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 1085 AFEETTfLSLSREARGFLIKVLVQD---RLRPT-AEETLEHPWFK 1125
Cdd:cd05609   233 EWPEGD-DALPDDAQDLITRLLQQNpleRLGTGgAEEVKQHPFFQ 276

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270863 [Multi-domain] Cd Length: 262 Bit Score: 78.08 E-value: 3.50e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAK----FIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd08224     2 YEIEKKIGKGQFSVVYRARCLLDGRLVALKkvqiFEMMDAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLEL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTEELLERMAR-----KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGeeQVRICDFGNAQELTPG 1021
Cdd:cd08224    82 ADAGDLSRLIKhfkkqKRLIPERTIWKYFVQLCSALEHMHSKRIMHRDIKPANVFI--TANG--VVKLGDLGLGRFFSSK 157

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1022 EPQ-YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEN 1071
Cdd:cd08224   158 TTAaHSLVGTPYYMSPERIREQGYDFKSDIWSLGCLLYEMAALQSPFYGEK 208

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270808 [Multi-domain] Cd Length: 291 Bit Score: 78.50 E-value: 3.56e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARL-QHDCVLYFHEAFERRRGLV----- 941
Cdd:cd06639    21 SDTWDIIETIGKGTYGKVYKVTNKKDGSLAAVKILDPISDVDEEIEAEYNILRSLpNHPNVVKFYGMFYKADQYVggqlw 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCT----EELLERMARKPTVCESETRTY-MRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeeqVRICDFGNAQ 1016
Cdd:cd06639   101 LVLELCNggsvTELVKGLLKCGQRLDEAMISYiLYGALLGLQHLHNNRIIHRDVKGNNILLTTEGG----VKLVDFGVSA 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPGE-PQYCQFGTPEFVAPEIVN-----QSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI-RNynvafEET 1089
Cdd:cd06639   177 QLTSARlRRNTSVGTPFWMAPEVIAceqqyDYSYDARCDVWSLGITAIELADGDPPLFDMHPVKALFKIpRN-----PPP 251

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 564369110 1090 TFLSLSREARG---FLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd06639   252 TLLNPEKWCRGfshFISQCLIKDfEKRPSVTHLLEHPFIK 291

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270810 [Multi-domain] Cd Length: 277 Bit Score: 78.18 E-value: 3.90e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA--SARREARLLARLQHDCVLYFHEAFERRRGLVIVTE-LCTEEL 951
Cdd:cd06642    10 ERIGKGSFGEVYKGIDNRTKEVVAIKIIDLEEAEDEieDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEyLGGGSA 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEPQYCQF-GT 1030
Cdd:cd06642    90 LDLLKPGP-LEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSE----QGDVKLADFGVAGQLTDTQIKRNTFvGT 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1031 PEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFlslSREARGFLIKVLVQD- 1109
Cdd:cd06642   165 PFWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNSPPTLEGQH---SKPFKEFVEACLNKDp 241

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 564369110 1110 RLRPTAEETLEHPWFKTEAKGAEVSTDhlkLFLSRRRWQ 1148
Cdd:cd06642   242 RFRPTAKELLKHKFITRYTKKTSFLTE---LIDRYKRWK 277

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270727 [Multi-domain] Cd Length: 323 Bit Score: 78.90 E-value: 4.02e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFS--YLRRvvERSSGLEFAAKFIPSQAKPKasaRREAR--------LLARLQHDCVLYFHEAFERRRGLVIVTE- 945
Cdd:cd05575     3 IGKGSFGkvLLAR--HKAEGKLYAVKVLQKKAILK---RNEVKhimaernvLLKNVKHPFLVGLHYSFQTKDKLYFVLDy 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE-LTPGEP- 1023
Cdd:cd05575    78 VNGGELFFHLQRERHFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILL-DSQG---HVVLTDFGLCKEgIEPSDTt 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 -QYCqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENdrTTLM--NIRNYNVAFEEttflSLSREARG 1100
Cdd:cd05575   154 sTFC--GTPEYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRD--TAEMydNILHKPLRLRT----NVSPSARD 225

                         250
                  ....*....|
gi 564369110 1101 FLIKVLVQDR 1110
Cdd:cd05575   226 LLEGLLQKDR 235

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132953 [Multi-domain] Cd Length: 286 Bit Score: 78.35 E-value: 4.07e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2225 FLEEKARGRFGVVRSCRENATGRTFVAKIVpyaaegkRRVLQEYEvLRTLHHErLMSLHEA---YITPRYLVLIAESC-- 2299
Cdd:cd06622     5 VLDELGKGNYGSVYKVLHRPTGVTMAMKEI-------RLELDESK-FNQIIME-LDILHKAvspYIVDFYGAFFIEGAvy 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 --------GNRE-LLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRH-VLHLDIKPDNLLLAADNALKIVDFG-SAQPYN 2368
Cdd:cd06622    76 mcmeymdaGSLDkLYAGGVATEGIPEDVLRRITYAVVKGLKFLKEEHnIIHRDVKPTNVLVNGNGQVKLCDFGvSGNLVA 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2369 PQALKPLGHRTgtleFMAPEMVR-GDPIGSAT-----DIWGAGVLTYIMLSGYSPFyepdPQETEAR-------IVGGrf 2435
Cdd:cd06622   156 SLAKTNIGCQS----YMAPERIKsGGPNQNPTytvqsDVWSLGLSILEMALGRYPY----PPETYANifaqlsaIVDG-- 225

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 2436 DAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWlqdayLMKLRRQTL---TFTTNRLKE 2497
Cdd:cd06622   226 DPPTLPSGYSDDAQDFVAKCLNKIPNRRPTYAQLLEHPW-----LVKYKNADVdmaEWVTGALKR 285

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270729 [Multi-domain] Cd Length: 278 Bit Score: 78.34 E-value: 4.09e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQ----AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd05577     1 LGRGGFGEVCACQVKATGKMYACKKLDKKrikkKKGETMALNEKIILEKVSSPFIVSLAYAFETKDKLCLVLTLMNGGDL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 E---RMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQFG 1029
Cdd:cd05577    81 KyhiYNVGTRGFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILL-DDHG---HVRISDLGLAVEFKGGKKIKGRVG 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1030 TPEFVAPEIV-NQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQ 1108
Cdd:cd05577   157 THGYMAPEVLqKEVAYDFSVDWFALGCMLYEMIAGRSPFRQRKEKVDKEELKRRTLEMAVEYPDSFSPEARSLCEGLLQK 236

                         250       260
                  ....*....|....*....|....
gi 564369110 1109 D---RL---RPTAEETLEHPWFKT 1126
Cdd:cd05577   237 DperRLgcrGGSADEVKEHPFFRS 260

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR2 (also called STK38-like) plays a role in proper centrosome duplication. In addition, it is involved in regulating neuronal growth and differentiation, as well as in facilitating neurite outgrowth. NDR2 is also implicated in fear conditioning as it contributes to the coupling of neuronal morphological changes with fear-memory consolidation. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270776 [Multi-domain] Cd Length: 366 Bit Score: 79.72 E-value: 4.13e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYA----AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELL 2305
Cdd:cd05627    11 GRGAFGEVRLVQKKDTGHIYAMKILRKAdmleKEQVAHIRAERDILVEADGAWVVKMFYSFQDKRNLYLIMEFLPGGDMM 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ--------------PYNPQA 2371
Cdd:cd05627    91 TLLMKKDTLSEEATQFYIAETVLAIDAIHQLGFIHRDIKPDNLLLDAKGHVKLSDFGLCTglkkahrtefyrnlTHNPPS 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 -------------------LKPLGHRT-GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV 2431
Cdd:cd05627   171 dfsfqnmnskrkaetwkknRRQLAYSTvGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSETPQETYRKVM 250


                  ...
gi 564369110 2432 GGR 2434
Cdd:cd05627   251 NWK 253

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270780 [Multi-domain] Cd Length: 313 Bit Score: 78.86 E-value: 4.26e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA----KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd05632     2 NTFRQYRVLGKGGFGEVCACQVRATGKMYACKRLEKKRikkrKGESMALNEKQILEKVNSQFVVNLAYAYETKDALCLVL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTEELLE----RMArKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTP 1020
Cdd:cd05632    82 TIMNGGDLKfhiyNMG-NPGFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDD----YGHIRISDLGLAVKIPE 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARG 1100
Cdd:cd05632   157 GESIRGRVGTVGYMAPEVLNNQRYTLSPDYWGLGCLIYEMIEGQSPFRGRKEKVKREEVDRRVLETEEVYSAKFSEEAKS 236

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 1101 FLIKVLVQD---RL---RPTAEETLEHPWFK 1125
Cdd:cd05632   237 ICKMLLTKDpkqRLgcqEEGAGEVKRHPFFR 267

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 271050 [Multi-domain] Cd Length: 258 Bit Score: 77.72 E-value: 4.32e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2264 VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRH---VLH 2340
Cdd:cd14148    40 VRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGGALNRALAGK-KVPPHVLVNWAVQIARGMNYLHNEAivpIIH 118

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2341 LDIKPDNLLLA--------ADNALKIVDFGSAQPYnpqalkplgHRT------GTLEFMAPEMVRGDPIGSATDIWGAGV 2406
Cdd:cd14148   119 RDLKSSNILILepienddlSGKTLKITDFGLAREW---------HKTtkmsaaGTYAWMAPEVIRLSLFSKSSDVWSFGV 189

                         170
                  ....*....|....*.
gi 564369110 2407 LTYIMLSGYSPFYEPD 2422
Cdd:cd14148   190 LLWELLTGEVPYREID 205

Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-alpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.

Pssm-ID: 270773 [Multi-domain] Cd Length: 409 Bit Score: 80.06 E-value: 4.54e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPK----ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd05623    74 FEILKVIGRGAFGEVAVVKLKNADKVFAMKILNKWEMLKraetACFREERDVLVNGDSQWITTLHYAFQDDNNLYLVMDY 153

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 -CTEELLERMAR-KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTP-GEP 1023
Cdd:cd05623   154 yVGGDLLTLLSKfEDRLPEDMARFYLAEMVLAIDSVHQLHYVHRDIKPDNILM-DMNG---HIRLADFGSCLKLMEdGTV 229

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 Q-YCQFGTPEFVAPEIVN-----QSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSRE 1097
Cdd:cd05623   230 QsSVAVGTPDYISPEILQamedgKGKYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHKERFQFPTQVTDVSE 309

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 1098 ARGFLIKVLVQDRLRPTAEETLE----HPWF 1124
Cdd:cd05623   310 NAKDLIRRLICSREHRLGQNGIEdfknHPFF 340

serine/threonine kinase US3; Provisional

Pssm-ID: 177557 [Multi-domain] Cd Length: 357 Bit Score: 79.53 E-value: 4.55e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2234 FGVVRSCRENATGRTFVAK------IVPYAAEGKRRVLQEYEVLRTLHHERLMSLHE--AYITPRYLVLIAESCgnrELL 2305
Cdd:PHA03209   68 YTVIKTLTPGSEGRVFVATkpgqpdPVVLKIGQKGTTLIEAMLLQNVNHPSVIRMKDtlVSGAITCMVLPHYSS---DLY 144

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFR-YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpYNPQALKPLGhRTGTLEF 2384
Cdd:PHA03209  145 TYLTKRSRpLPIDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFINDVDQVCIGDLGAAQ-FPVVAPAFLG-LAGTVET 222

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 2385 MAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGR 2434
Cdd:PHA03209  223 NAPEVLARDKYNSKADIWSAGIVLFEMLAYPSTIFEDPPSTPEEYVKSCH 272

Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The beta-ARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270757 [Multi-domain] Cd Length: 279 Bit Score: 77.86 E-value: 4.81e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVpyaaEGKRRVLQEYEVLRTlhHERLM--------------SLHEAYITPRYLVLIA 2296
Cdd:cd05606     4 RGGFGEVYGCRKADTGKMYAMKCL----DKKRIKMKQGETLAL--NERIMlslvstggdcpfivCMTYAFQTPDKLCFIL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQalKPlg 2376
Cdd:cd05606    78 DLMNGGDLHYHLSQHGVFSEAEMRFYAAEVILGLEHMHNRFIVYRDLKPANILLDEHGHVRISDLGLACDFSKK--KP-- 153

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 564369110 2377 HRT-GTLEFMAPEMV-RGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd05606   154 HASvGTHGYMAPEVLqKGVAYDSSADWFSLGCMLYKLLKGHSPF 197

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 72.62 E-value: 5.41e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQASCASSLA 80
Cdd:cd20972    11 QEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSVGSDTTSAEIF 90


                  .
gi 564369110   81 V 81
Cdd:cd20972    91 V 91

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143356 [Multi-domain] Cd Length: 343 Bit Score: 78.87 E-value: 6.14e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--PSQAKPKAS-ARREARLLARLQHDCVL----YFH--EAFERRRG 939
Cdd:cd07851    15 DRYQNLSPVGSGAYGQVCSAFDTKTGRKVAIKKLsrPFQSAIHAKrTYRELRLLKHMKHENVIglldVFTpaSSLEDFQD 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  940 LVIVTELCTEELLERMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQ--- 1016
Cdd:cd07851    95 VYLVTHLMGADLNNIVKCQK-LSDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSNLAV----NEDCELKILDFGLARhtd 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 -ELTpgepQYCQfgTPEFVAPEIV------NQSpvsgvTDIWPVGVVAFLCLTGISPFVGEN--DR-TTLMNI------- 1079
Cdd:cd07851   170 dEMT----GYVA--TRWYRAPEIMlnwmhyNQT-----VDIWSVGCIMAELLTGKTLFPGSDhiDQlKRIMNLvgtpdee 238

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1080 ----------RNYNVAFEETT-------FLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd07851   239 llkkissesaRNYIQSLPQMPkkdfkevFSGANPLAIDLLEKMLVLDpDKRITAAEALAHPYLA 302

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270741 [Multi-domain] Cd Length: 326 Bit Score: 78.50 E-value: 6.21e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  964 SETRT--YMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE-LTPGE--PQYCqfGTPEFVAPEI 1038
Cdd:cd05589    99 SEPRAvfYAACVVLGLQFLHEHKIVYRDLKLDNLLL-DTEG---YVKIADFGLCKEgMGFGDrtSTFC--GTPEFLAPEV 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1039 VNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttFLSLsrEARGFLIKVLVQD---RL---R 1112
Cdd:cd05589   173 LTDTSYTRAVDWWGLGVLIYEMLVGESPFPGDDEEEVFDSIVNDEVRYPR--FLST--EAISIMRRLLRKNperRLgasE 248

                         170
                  ....*....|....
gi 564369110 1113 PTAEETLEHPWFKT 1126
Cdd:cd05589   249 RDAEDVKKQPFFRN 262

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270862 [Multi-domain] Cd Length: 257 Bit Score: 77.09 E-value: 6.72e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR---VLQEYEVLRTLHHERLMSLHEAYITPR-YLVLIAES 2298
Cdd:cd08223     2 YQFLRVIGKGSYGEVWLVRHKRDRKQYVIKKLNLKNASKRErkaAEQEAKLLSKLKHPNIVSYKESFEGEDgFLYIVMGF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDR--FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAlKPLG 2376
Cdd:cd08223    82 CEGGDLYTRLKEQkgVLLEERQVVEWFVQIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARVLESSS-DMAT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 HRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafQLYPNTSQSATLFLRKVL 2456
Cdd:cd08223   161 TLIGTPYYMSPELFSNKPYNHKSDVWALGCCVYEMATLKHAFNAKDMNSLVYKILEGKLP--PMPKQYSPELGELIKAML 238

                         250
                  ....*....|....*....
gi 564369110 2457 SVHPWSRPSLQDCLAHPWL 2475
Cdd:cd08223   239 HQDPEKRPSVKRILRQPYI 257

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143382 [Multi-domain] Cd Length: 345 Bit Score: 78.54 E-value: 6.86e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--PSQAKPKAS-ARREARLLARLQHDCVLYFHEAFERRRGL----- 940
Cdd:cd07877    17 ERYQNLSPVGSGAYGSVCAAFDTKTGLRVAVKKLsrPFQSIIHAKrTYRELRLLKHMKHENVIGLLDVFTPARSLeefnd 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 -VIVTELCTEELlERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELT 1019
Cdd:cd07877    97 vYLVTHLMGADL-NNIVKCQKLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDC----ELKILDFGLARHTD 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCqfGTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI------------------- 1079
Cdd:cd07877   172 DEMTGYV--ATRWYRAPEImLNWMHYNQTVDIWSVGCIMAELLTGRTLFPGTDHIDQLKLIlrlvgtpgaellkkisses 249

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1080 -RNYNVAFE-------ETTFLSLSREARGFLIKVLVQDR-LRPTAEETLEHPWF 1124
Cdd:cd07877   250 aRNYIQSLTqmpkmnfANVFIGANPLAVDLLEKMLVLDSdKRITAAQALAHAYF 303

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270770 [Multi-domain] Cd Length: 331 Bit Score: 78.43 E-value: 6.92e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA----KPKASARREARLLA-RLQHDCVLYFHEAFERRRGLVIV 943
Cdd:cd05619     5 EDFVLHKMLGKGSFGKVFLAELKGTNQFFAIKALKKDVvlmdDDVECTMVEKRVLSlAWEHPFLTHLFCTFQTKENLFFV 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TE-LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGE 1022
Cdd:cd05619    85 MEyLNGGDLMFHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILL-DKDG---HIKIADFGMCKENMLGD 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREARGF 1101
Cdd:cd05619   161 AKTSTFcGTPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGQDEEELFQSIRMDNPFYPRW----LEKEAKDI 236

                         250       260
                  ....*....|....*....|....*.
gi 564369110 1102 LIKVLVQ--DRLRPTAEETLEHPWFK 1125
Cdd:cd05619   237 LVKLFVRepERRLGVRGDIRQHPFFR 262

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270845 [Multi-domain] Cd Length: 285 Bit Score: 77.46 E-value: 7.14e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRtFVA--KI--------VPYAAegkrrvLQEYEVLRTLHHERLMSLHEAYITPRYL 2292
Cdd:cd07861     2 YTKIEKIGEGTYGVVYKGRNKKTGQ-IVAmkKIrleseeegVPSTA------IREISLLKELQHPNIVCLEDVLMQENRL 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLIAE--SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYN-P 2369
Cdd:cd07861    75 YLVFEflSMDLKKYLDSLPKGKYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLARAFGiP 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 qaLKPLGHRTGTLEFMAPEMVRGDPIGSA-TDIWGAGVLTYIMLSGYSPFYE---------------------------- 2420
Cdd:cd07861   155 --VRVYTHEVVTLWYRAPEVLLGSPRYSTpVDIWSIGTIFAEMATKKPLFHGdseidqlfrifrilgtptediwpgvtsl 232

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 2421 PDPQETEARIVGGRFDAFqlYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07861   233 PDYKNTFPKWKKGSLRTA--VKNLDEDGLDLLEKMLIYDPAKRISAKKALVHPYF 285

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270949 [Multi-domain] Cd Length: 267 Bit Score: 77.15 E-value: 7.83e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  866 RLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAK---FIPSQAKpkasarREARLLARLQH-DCVLYFH---------- 931
Cdd:cd14047     3 RFRQDFKEIELIGSGGFGQVFKAKHRIDGKTYAIKrvkLNNEKAE------REVKALAKLDHpNIVRYNGcwdgfdydpe 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  932 -----EAFERRRGLVIVTELCT----EELLERMaRKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgag 1002
Cdd:cd14047    77 tsssnSSRSKTKCLFIQMEFCEkgtlESWIEKR-NGEKLDKVLALEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVD--- 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 1003 gEEQVRICDFGNAQELTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAF 1058
Cdd:cd14047   153 -TGKVKIGDFGLVTSLKNDGKRTKSKGTLSYMSPEQISSQDYGKEVDIYALGLILF 207

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270854 [Multi-domain] Cd Length: 297 Bit Score: 77.74 E-value: 7.96e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2265 LQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNrellcglsDRFRYSED--------DVATYVVQLLQGLDYLHGR 2336
Cdd:cd07873    48 IREVSLLKDLKHANIVTLHDIIHTEKSLTLVFEYLDK--------DLKQYLDDcgnsinmhNVKLFLFQLLRGLAYCHRR 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2337 HVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAlKPLGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGy 2415
Cdd:cd07873   120 KVLHRDLKPQNLLINERGELKLADFGLARAKSIPT-KTYSNEVVTLWYRPPDILLGSTdYSTQIDMWGVGCIFYEMSTG- 197

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2416 SPFYEPDPQETEA----RIVGG-----------------------RFDAFQLY-PNTSQSATLFLRKVLSVHPWSRPSLQ 2467
Cdd:cd07873   198 RPLFPGSTVEEQLhfifRILGTpteetwpgilsneefksynypkyRADALHNHaPRLDSDGADLLSKLLQFEGRKRISAE 277


                  ....*....
gi 564369110 2468 DCLAHPWLQ 2476
Cdd:cd07873   278 EAMKHPYFH 286

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271038 [Multi-domain] Cd Length: 320 Bit Score: 78.00 E-value: 8.25e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2325 QLLQGLDYLHGR-HVLHLDIKPDNLLLAADNA-LKIVDFGSAQPYNPqalkplgHRTG---TLEFMAPEMVRGDPIGSAT 2399
Cdd:cd14136   127 QVLQGLDYLHTKcGIIHTDIKPENVLLCISKIeVKIADLGNACWTDK-------HFTEdiqTRQYRSPEVILGAGYGTPA 199

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2400 DIWGAGVLTYIMLSGYSPFyepDPQETE---------ARIVG--GRFDAfQLYPNTSQSATLF-----LRKVLSVHPWS- 2462
Cdd:cd14136   200 DIWSTACMAFELATGDYLF---DPHSGEdysrdedhlALIIEllGRIPR-SIILSGKYSREFFnrkgeLRHISKLKPWPl 275

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 2463 --------------------------------RPSLQDCLAHPWL 2475
Cdd:cd14136   276 edvlvekykwskeeakefasfllpmleydpekRATAAQCLQHPWL 320

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271065 [Multi-domain] Cd Length: 257 Bit Score: 76.95 E-value: 8.25e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2261 KRRVLQEYEVLRTLHHERLMSLHEAYITPR---YLVL-IAEScgnrellcglSDRFRY-------SEDDVATYVVQLLQG 2329
Cdd:cd14163    44 QRFLPRELQIVERLDHKNIIHVYEMLESADgkiYLVMeLAED----------GDVFDCvlhggplPEHRAKALFRQLVEA 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2330 LDYLHGRHVLHLDIKPDNLLLAADNaLKIVDFGSAQpynpqaLKPLGHRT------GTLEFMAPEMVRGDPIGSAT-DIW 2402
Cdd:cd14163   114 IRYCHGCGVAHRDLKCENALLQGFT-LKLTDFGFAK------QLPKGGRElsqtfcGSTAYAAPEVLQGVPHDSRKgDIW 186

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2403 GAGVLTYIMLSGYSPFYEPD-PQETEARIVGGRFDAfqlYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14163   187 SMGVVLYVMLCAQLPFDDTDiPKMLCQQQKGVSLPG---HLGVSRTCQDLLKRLLEPDMVLRPSIEEVSWHPWL 257

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270865 [Multi-domain] Cd Length: 268 Bit Score: 76.99 E-value: 8.34e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2258 AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE--SCGNrellcgLSDRFRY--------SEDDVATYVVQLL 2327
Cdd:cd08228    43 AKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVLElaDAGD------LSQMIKYfkkqkrliPERTVWKYFVQLC 116

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2328 QGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKplGHR-TGTLEFMAPEMVRGDPIGSATDIWGAGV 2406
Cdd:cd08228   117 SAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTA--AHSlVGTPYYMSPERIHENGYNFKSDIWSLGC 194

                         170
                  ....*....|...
gi 564369110 2407 LTYIMLSGYSPFY 2419
Cdd:cd08228   195 LLYEMAALQSPFY 207

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270771 [Multi-domain] Cd Length: 379 Bit Score: 78.89 E-value: 9.16e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR----VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELL 2305
Cdd:cd05621    61 GRGAFGEVQLVRHKASQKVYAMKLLSKFEMIKRSdsafFWEERDIMAFANSPWVVQLFCAFQDDKYLYMVMEYMPGGDLV 140

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 cGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEFM 2385
Cdd:cd05621   141 -NLMSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKYGHLKLADFGTCMKMDETGMVHCDTAVGTPDYI 219

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 2386 APEMVR---GDP-IGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV 2431
Cdd:cd05621   220 SPEVLKsqgGDGyYGRECDWWSVGVFLFEMLVGDTPFYADSLVGTYSKIM 269

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270834 [Multi-domain] Cd Length: 316 Bit Score: 77.71 E-value: 9.58e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFS--YLRRVVERSSGLEFAAKFIPSQAKPKA----SARREARLLARLQHDCVLYFHEAF--ERRRGLVI 942
Cdd:cd07842     2 YEIEGCIGRGTYGrvYKAKRKNGKDGKEYAIKKFKGDKEQYTgisqSACREIALLRELKHENVVSLVEVFleHADKSVYL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  943 VTELCTEELLE-----RMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWdgAGGEEQ--VRICDFGNA 1015
Cdd:cd07842    82 LFDYAEHDLWQiikfhRQAKRVSIPPSMVKSLLWQILNGIHYLHSNWVLHRDLKPANILVM--GEGPERgvVKIGDLGLA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1016 QEL-TPGEPQYCqfGTPEFV-----APEIVNQSP-VSGVTDIWPVGVVAFLCLTGISPFVGEND---------RTTLMNI 1079
Cdd:cd07842   160 RLFnAPLKPLAD--LDPVVVtiwyrAPELLLGARhYTKAIDIWAIGCIFAELLTLEPIFKGREAkikksnpfqRDQLERI 237

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 1080 ---------------------RNYNVAFEETTF------------LSLSREARGFLIKVLVQDRL-RPTAEETLEHPWF 1124
Cdd:cd07842   238 fevlgtptekdwpdikkmpeyDTLKSDTKASTYpnsllakwmhkhKKPDSQGFDLLRKLLEYDPTkRITAEEALEHPYF 316

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270799 [Multi-domain] Cd Length: 270 Bit Score: 77.04 E-value: 9.84e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLV-WDGAggeeqVRICDFG---NAQELTPGEPQYCQFGTPEFVAPEI 1038
Cdd:cd06629   107 EDLVRFFTRQILDGLAYLHSKGILHRDLKADNILVdLEGI-----CKISDFGiskKSDDIYGNNGATSMQGSVFWMAPEV 181

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1039 V--NQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIK-VLVQDRLRPTA 1115
Cdd:cd06629   182 IhsQGQGYSAKVDIWSLGCVVLEMLAGRRPWSDDEAIAAMFKLGNKRSAPPVPEDVNLSPEALDFLNAcFAIDPRDRPTA 261


                  ....*...
gi 564369110 1116 EETLEHPW 1123
Cdd:cd06629   262 AELLSHPF 269

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270939 [Multi-domain] Cd Length: 277 Bit Score: 76.94 E-value: 9.87e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2224 TFLEEKARGRFGVVRSCRENATGRTFVAK--IVPyAAEGKRRVLQEYEVLRTLH-HERLMSLHEAYITPR----YLVLI- 2295
Cdd:cd14037     6 TIEKYLAEGGFAHVYLVKTSNGGNRAALKrvYVN-DEHDLNVCKREIEIMKRLSgHKNIVGYIDSSANRSgngvYEVLLl 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRF--RYSEDDVATYVVQLLQGLDYLHGRH--VLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQA 2371
Cdd:cd14037    85 MEYCKGGGVIDLMNQRLqtGLTESEILKIFCDVCEAVAAMHYLKppLIHRDLKVENVLISDSGNYKLCDFGSATTKILPP 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 LKPLG--------HRTGTLEFMAPEMV---RGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPqeteARIVGGRFdAFQL 2440
Cdd:cd14037   165 QTKQGvtyveediKKYTTLQYRAPEMIdlyRGKPITEKSDIWALGCLLYKLCFYTTPFEESGQ----LAILNGNF-TFPD 239

                         250       260
                  ....*....|....*....|....*
gi 564369110 2441 YPNTSQSATLFLRKVLSVHPWSRPS 2465
Cdd:cd14037   240 NSRYSKRLHKLIRYMLEEDPEKRPN 264

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 71.38 E-value: 9.88e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110      1 MVVAPGADVLLKCIITANPPPQVSWKKDG-SVLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQASCASSL 79
Cdd:smart00410    4 VTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83


                    ..
gi 564369110     80 AV 81
Cdd:smart00410   84 TV 85

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271052 [Multi-domain] Cd Length: 265 Bit Score: 76.59 E-value: 1.03e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2226 LEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMsLHEAYITPRYLVLIAESCGNREL- 2304
Cdd:cd14150     5 LKRIGTGSFGTVFRGKWHGDVAVKILKVTEPTPEQLQAFKNEMQVLRKTRHVNIL-LFMGFMTRPNFAIITQWCEGSSLy 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 --LCGLSDRFR-YSEDDVATyvvQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP-QALKPLGHRTG 2380
Cdd:cd14150    84 rhLHVTETRFDtMQLIDVAR---QTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLATVKTRwSGSQQVEQPSG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVR---GDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRF---DAFQLYPNTSQSATLFLRK 2454
Cdd:cd14150   161 SILWMAPEVIRmqdTNPYSFQSDVYAYGVVLYELMSGTLPYSNINNRDQIIFMVGRGYlspDLSKLSSNCPKAMKRLLID 240

                         250
                  ....*....|....*..
gi 564369110 2455 VLSVHPWSRPSLQDCLA 2471
Cdd:cd14150   241 CLKFKREERPLFPQILV 257

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 71.68 E-value: 1.09e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRP--DQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVN 216
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPssIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|....
gi 564369110  217 EYGARQCEARLEVR 230
Cdd:cd20951    81 IHGEASSSASVVVE 94

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270801 [Multi-domain] Cd Length: 266 Bit Score: 76.71 E-value: 1.10e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  967 RTYMRQVLEGIGYLHQSHVLHLDVKPENL-LVWDGAggeeqVRICDFGNAQEL-------TPGEPQYCQFGTPEFVAPEI 1038
Cdd:cd06631   106 CRYTKQILEGVAYLHNNNVIHRDIKGNNImLMPNGV-----IKLIDFGCAKRLcinlssgSQSQLLKSMRGTPYWMAPEV 180

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1039 VNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTfLSLSREARGFLIKVLVQD-RLRPTAEE 1117
Cdd:cd06631   181 INETGHGRKSDIWSIGCTVFEMATGKPPWADMNPMAAIFAIGSGRKPVPRLP-DKFSPEARDFVHACLTRDqDERPSAEQ 259


                  ....*.
gi 564369110 1118 TLEHPW 1123
Cdd:cd06631   260 LLKHPF 265

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270815 [Multi-domain] Cd Length: 261 Bit Score: 76.33 E-value: 1.41e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGaggeeQVRICDFGNAQELTPGEPQYCQF-GTPEFVAPEIVN 1040
Cdd:cd06648   102 EEQIATVCRAVLKALSFLHSQGVIHRDIKSDSiLLTSDG-----RVKLSDFGFCAQVSKEVPRRKSLvGTPYWMAPEVIS 176

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1041 QSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTfLSLSREARGFLIKVLVQDRL-RPTAEETL 1119
Cdd:cd06648   177 RLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRIRDNEPPKLKNL-HKVSPRLRSFLDRMLVRDPAqRATAAELL 255


                  ....*.
gi 564369110 1120 EHPWFK 1125
Cdd:cd06648   256 NHPFLA 261

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270889 [Multi-domain] Cd Length: 259 Bit Score: 76.21 E-value: 1.45e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQ-HDCVL-YFHEAFERRRGLVIVTELCTE-ELLE 953
Cdd:cd13987     1 LGEGTYGKVLLAVHKGSGTKMALKFVPKPSTKLKDFLREYNISLELSvHPHIIkTYDVAFETEDYYVFAQEYAPYgDLFS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  954 rmARKPTVCESETRTY--MRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeEQVRICDFGNAQELtpGEPQYCQFGTP 1031
Cdd:cd13987    81 --IIPPQVGLPEERVKrcAAQLASALDFMHSKNLVHRDIKPENVLLFDKDC--RRVKLCDFGLTRRV--GSTVKRVSGTI 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 564369110 1032 EFVAPEIVNQSP-----VSGVTDIWPVGVVAFLCLTGISP 1066
Cdd:cd13987   155 PYTAPEVCEAKKnegfvVDPSIDVWAFGVLLFCCLTGNFP 194

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271033 [Multi-domain] Cd Length: 271 Bit Score: 76.10 E-value: 1.59e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2265 LQEYEVLRTL-HHERLMSLHEAYITPR--YLVLIAEsCGNRELLCGLSDRFRYSEDD--VATYVVQLLQGLDYLHGRHVL 2339
Cdd:cd14131    47 KNEIELLKKLkGSDRIIQLYDYEVTDEddYLYMVME-CGEIDLATILKKKRPKPIDPnfIRYYWKQMLEAVHTIHEEGIV 125

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2340 HLDIKPDNLLLAaDNALKIVDFGSA---QPYNPQALKPlgHRTGTLEFMAPEMVRGD----------PIGSATDIWGAGV 2406
Cdd:cd14131   126 HSDLKPANFLLV-KGRLKLIDFGIAkaiQNDTTSIVRD--SQVGTLNYMSPEAIKDTsasgegkpksKIGRPSDVWSLGC 202

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2407 LTYIMLSGYSPFYE-PDPQETEARIVGGRFDAFqlYPN-TSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14131   203 ILYQMVYGKTPFQHiTNPIAKLQAIIDPNHEIE--FPDiPNPDLIDVMKRCLQRDPKKRPSIPELLNHPFL 271

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270803 [Multi-domain] Cd Length: 313 Bit Score: 77.00 E-value: 1.62e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAA----EGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVL 2294
Cdd:cd06633    19 PEEIFVDLHEIGHGSFGAVYFATNSHTNEVVAIKKMSYSGkqtnEKWQDIIKEVKFLQQLKHPNTIEYKGCYLKDHTAWL 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2295 IAESCgnrelLCGLSDRFR-----YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynp 2369
Cdd:cd06633    99 VMEYC-----LGSASDLLEvhkkpLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSA----- 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLGHRTGTLEFMAPEMVRGDPIGS---ATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvgGRFDAFQLYPNT-S 2445
Cdd:cd06633   169 SIASPANSFVGTPYWMAPEVILAMDEGQydgKVDIWSLGITCIELAERKPPLFNMNAMSALYHI--AQNDSPTLQSNEwT 246

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 2446 QSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd06633   247 DSFRGFVDYCLQKIPQERPSSAELLRHDFVR 277

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270960 [Multi-domain] Cd Length: 253 Bit Score: 75.94 E-value: 1.70e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRScrenATGRTF-VA-KIVPYAAEgKRRVLQEYEVLRTLHHERLMSLHEAYIT--PRYLVLIAESCGN-RELL 2305
Cdd:cd14058     3 RGSFGVVCK----ARWRNQiVAvKIIESESE-KKAFEVEVRQLSRVDHPNIIKLYGACSNqkPVCLVMEYAEGGSlYNVL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFRYSEDDVATYVVQLLQGLDYLHG---RHVLHLDIKPDNLLLAADNA-LKIVDFGSAQPYNPQalkpLGHRTGT 2381
Cdd:cd14058    78 HGKEPKPIYTAAHAMSWALQCAKGVAYLHSmkpKALIHRDLKPPNLLLTNGGTvLKICDFGTACDISTH----MTNNKGS 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2382 LEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYE---PDPQETEARIVGGRFDAFQLYPNTSQSatlFLRKVLSV 2458
Cdd:cd14058   154 AAWMAPEVFEGSKYSEKCDVFSWGIILWEVITRRKPFDHiggPAFRIMWAVHNGERPPLIKNCPKPIES---LMTRCWSK 230

                         250
                  ....*....|
gi 564369110 2459 HPWSRPSLQD 2468
Cdd:cd14058   231 DPEKRPSMKE 240

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270747 [Multi-domain] Cd Length: 352 Bit Score: 77.42 E-value: 1.79e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR----REARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd05596    28 FDVIKVIGRGAFGEVQLVRHKSTKKVYAMKLLSKFEMIKRSDSaffwEERDIMAHANSEWIVQLHYAFQDDKYLYMVMDY 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYC 1026
Cdd:cd05596   108 MPGGDLVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFVHRDVKPDNMLL-DASG---HLKLADFGTCMKMDKDGLVRS 183

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 Q--FGTPEFVAPEIVNQSPVSGV----TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARG 1100
Cdd:cd05596   184 DtaVGTPDYISPEVLKSQGGDGVygreCDWWSVGVFLYEMLVGDTPFYADSLVGTYGKIMNHKNSLQFPDDVEISKDAKS 263

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1101 FLIKVLV--QDRL-RPTAEETLEHPWFKTE 1127
Cdd:cd05596   264 LICAFLTdrEVRLgRNGIEEIKAHPFFKND 293

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270963 [Multi-domain] Cd Length: 258 Bit Score: 75.89 E-value: 1.80e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2263 RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRH---VL 2339
Cdd:cd14061    39 NVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGGALNRVLAGR-KIPPHVLVDWAIQIARGMNYLHNEApvpII 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2340 HLDIKPDNLLLA--------ADNALKIVDFGSAQPYnpqalkplgHRT------GTLEFMAPEMVRGDPIGSATDIWGAG 2405
Cdd:cd14061   118 HRDLKSSNILILeaienedlENKTLKITDFGLAREW---------HKTtrmsaaGTYAWMAPEVIKSSTFSKASDVWSYG 188

                         170
                  ....*....|....*...
gi 564369110 2406 VLTYIMLSGYSPFYEPDP 2423
Cdd:cd14061   189 VLLWELLTGEVPYKGIDG 206

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143385 [Multi-domain] Cd Length: 343 Bit Score: 77.30 E-value: 1.86e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV--PYAAE-GKRRVLQEYEVLRTLHHERLMSLHEAYiTPR--------- 2290
Cdd:cd07880    17 YRDLKQVGSGAYGTVCSALDRRTGAKVAIKKLyrPFQSElFAKRAYRELRLLKHMKHENVIGLLDVF-TPDlsldrfhdf 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 YLVL--IAESCGNrellcgLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpyn 2368
Cdd:cd07880    96 YLVMpfMGTDLGK------LMKHEKLSEDRIQFLVYQMLKGLKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLAR--- 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2369 pQALKPLGHRTGTLEFMAPEMVRGDPIGSAT-DIWGAGVLTYIMLSGYSPFYEPD--------------P--------QE 2425
Cdd:cd07880   167 -QTDSEMTGYVVTRWYRAPEVILNWMHYTQTvDIWSVGCIMAEMLTGKPLFKGHDhldqlmeimkvtgtPskefvqklQS 245

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2426 TEARIVGGRFDAFQ------LYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd07880   246 EDAKNYVKKLPRFRkkdfrsLLPNANPLAVNVLEKMLVLDAESRITAAEALAHPYFEE 303

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173759 [Multi-domain] Cd Length: 255 Bit Score: 75.78 E-value: 1.88e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFG-VVRSCRENATGRTFVAKI-VPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd08219     2 YNVLRVVGEGSFGrALLVQHVNSDQKYAMKEIrLPKSSSAVEDSRKEAVLLAKMKHPNIVAFKESFEADGHLYIVMEYCD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSD-RFR-YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY-NPQALKPLgh 2377
Cdd:cd08219    82 GGDLMQKIKLqRGKlFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLtSPGAYACT-- 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAfqLYPNTSQSATLFLRKVLS 2457
Cdd:cd08219   160 YVGTPYYVPPEIWENMPYNNKSDIWSLGCILYELCTLKHPFQANSWKNLILKVCQGSYKP--LPSHYSYELRSLIKQMFK 237

                         250
                  ....*....|....
gi 564369110 2458 VHPWSRPSLQDCLA 2471
Cdd:cd08219   238 RNPRSRPSATTILS 251

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270812 [Multi-domain] Cd Length: 272 Bit Score: 75.85 E-value: 2.00e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPY-AAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd06645     9 PQEDFELIQRIGSGTYGDVYKARNVNTGELAAIKVIKLePGEDFAVVQQEIIMMKDCKHSNIVAYFGSYLRRDKLWICME 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynPQALKPLGH 2377
Cdd:cd06645    89 FCGGGSLQDIYHVTGPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVS----AQITATIAK 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2378 RT---GTLEFMAPEMV---RGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYPNTSQSATL- 2450
Cdd:cd06645   165 RKsfiGTPYWMAPEVAaveRKGGYNQLCDIWAVGITAIELAELQPPMFDLHPMRALFLMTKSNFQPPKLKDKMKWSNSFh 244

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2451 -FLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06645   245 hFVKMALTKNPKKRPTAEKLLQHPFV 270

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271039 [Multi-domain] Cd Length: 293 Bit Score: 76.39 E-value: 2.01e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2218 PPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRvlqEYEVLRTLHHERLMSLHEAYITPrylvliaE 2297
Cdd:cd14137     1 PVEISYTIEKVIGSGSFGVVYQAKLLETGEVVAIKKVLQDKRYKNR---ELQIMRRLKHPNIVKLKYFFYSS-------G 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLC--------GLSDRFR-YSED-------DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA-LKIVD 2360
Cdd:cd14137    71 EKKDEVYLNlvmeympeTLYRVIRhYSKNkqtipiiYVKLYSYQLFRGLAYLHSLGICHRDIKPQNLLVDPETGvLKLCD 150


                  ....*
gi 564369110 2361 FGSAQ 2365
Cdd:cd14137   151 FGSAK 155

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143363 [Multi-domain] Cd Length: 337 Bit Score: 77.03 E-value: 2.32e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQH-------DCVLYFH-EAFErrrGLVIVTE 945
Cdd:cd07858    13 IGRGAYGIVCSAKNSETNEKVAIKKIANAFDNRIDAKRtlrEIKLLRHLDHenviaikDIMPPPHrEAFN---DVYIVYE 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQelTPGEPQy 1025
Cdd:cd07858    90 LMDTDLHQIIRSSQTLSDDHCQYFLYQLLRGLKYIHSANVLHRDLKPSNLLL----NANCDLKICDFGLAR--TTSEKG- 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1026 cQFGTPEFV-----APE-IVNQSPVSGVTDIWPVGVVaFLCLTGISPF----------------VGENDRTTLMNIRNYN 1083
Cdd:cd07858   163 -DFMTEYVVtrwyrAPElLLNCSEYTTAIDVWSVGCI-FAELLGRKPLfpgkdyvhqlklitelLGSPSEEDLGFIRNEK 240

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 1084 -------------VAFEEtTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07858   241 arryirslpytprQSFAR-LFPHANPLAIDLLEKMLVFDpSKRITVEEALAHPYL 294

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132989 [Multi-domain] Cd Length: 292 Bit Score: 75.85 E-value: 2.82e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR-REARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd06658    22 EYLDSFIKIGEGSTGIVCIATEKHTGKQVAVKKMDLRKQQRRELLfNEVVIMRDYHHENVVDMYNSYLVGDELWVVMEFL 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGaggeeQVRICDFGNAQELTPGEPQYC 1026
Cdd:cd06658   102 EGGALTDIVTHTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSiLLTSDG-----RIKLSDFGFCAQVSKEVPKRK 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 QF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNyNVAFEETTFLSLSREARGFLIKV 1105
Cdd:cd06658   177 SLvGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRD-NLPPRVKDSHKVSSVLRGFLDLM 255

                         250       260
                  ....*....|....*....|.
gi 564369110 1106 LVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd06658   256 LVREpSQRATAQELLQHPFLK 276

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132969 [Multi-domain] Cd Length: 286 Bit Score: 75.82 E-value: 2.89e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  868 SDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQ-HDCVLYFHEAFERRR-----GLV 941
Cdd:cd06638    17 SDTWEIIETIGKGTYGKVFKVLNKKNGSKAAVKILDPIHDIDEEIEAEYNILKALSdHPNVVKFYGMYYKKDvkngdQLW 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCT----EELLERMARKPTVCESETRTY-MRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeeqVRICDFGNAQ 1016
Cdd:cd06638    97 LVLELCNggsvTDLVKGFLKRGERMEEPIIAYiLHEALMGLQHLHVNKTIHRDVKGNNILLTTEGG----VKLVDFGVSA 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPGE-PQYCQFGTPEFVAPEIVN-----QSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI-RNYNVAFEET 1089
Cdd:cd06638   173 QLTSTRlRRNTSVGTPFWMAPEVIAceqqlDSTYDARCDVWSLGITAIELGDGDPPLADLHPMRALFKIpRNPPPTLHQP 252

                         250       260       270
                  ....*....|....*....|....*....|...
gi 564369110 1090 TFlsLSREARGFLIKVLVQD-RLRPTAEETLEH 1121
Cdd:cd06638   253 EL--WSNEFNDFIRKCLTKDyEKRPTVSDLLQH 283

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270748 [Multi-domain] Cd Length: 331 Bit Score: 76.62 E-value: 2.92e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKfIPSQA----KPKASARREAR-LLARLQHDCVLYFHEAFERRRGLVIV 943
Cdd:cd05597     1 DDFEILKVIGRGAFGEVAVVKLKSTEKVYAMK-ILNKWemlkRAETACFREERdVLVNGDRRWITKLHYAFQDENYLYLV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TEL-CTEELLERMAR-KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPG 1021
Cdd:cd05597    80 MDYyCGGDLLTLLSKfEDRLPEEMARFYLAEMVLAIDSIHQLGYVHRDIKPDNVLL-DRNG---HIRLADFGSCLKLRED 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 EPQYCQ--FGTPEFVAPEIVnQSPVSGV------TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFE-ETTFL 1092
Cdd:cd05597   156 GTVQSSvaVGTPDYISPEIL-QAMEDGKgrygpeCDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHKEHFSfPDDED 234

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 564369110 1093 SLSREARGfLIKVLVQD---RL-RPTAEETLEHPWFK 1125
Cdd:cd05597   235 DVSEEAKD-LIRRLICSrerRLgQNGIDDFKKHPFFE 270

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270766 [Multi-domain] Cd Length: 341 Bit Score: 76.57 E-value: 2.96e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  866 RLSDYyDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPS----QAKPKASARREARLLARLQHDCVL-YFHEAFERRRGL 940
Cdd:cd05615     8 RLTDF-NFLMVLGKGSFGKVMLAERKGSDELYAIKILKKdvviQDDDVECTMVEKRVLALQDKPPFLtQLHSCFQTVDRL 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQE-L 1018
Cdd:cd05615    87 YFVMEYVNGgDLMYHIQQVGKFKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVML----DSEGHIKIADFGMCKEhM 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1019 TPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREA 1098
Cdd:cd05615   163 VEGVTTRTFCGTPDYIAPEIIAYQPYGRSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPK----SLSKEA 238

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 1099 ----RGFLIKVLVQdRL--RPTAEETL-EHPWFK 1125
Cdd:cd05615   239 vsicKGLMTKHPAK-RLgcGPEGERDIrEHAFFR 271

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271047 [Multi-domain] Cd Length: 270 Bit Score: 75.46 E-value: 3.10e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2264 VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRH---VLH 2340
Cdd:cd14145    52 VRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSGK-RIPPDILVNWAVQIARGMNYLHCEAivpVIH 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2341 LDIKPDNLLLA--------ADNALKIVDFGSAQPYnpqalkplgHRT------GTLEFMAPEMVRGDPIGSATDIWGAGV 2406
Cdd:cd14145   131 RDLKSSNILILekvengdlSNKILKITDFGLAREW---------HRTtkmsaaGTYAWMAPEVIRSSMFSKGSDVWSYGV 201

                         170
                  ....*....|..
gi 564369110 2407 LTYIMLSGYSPF 2418
Cdd:cd14145   202 LLWELLTGEVPF 213

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 70.11 E-value: 3.12e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQSVR-EGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEaEGGLcrlRILAAERGDAGFYTCKAVNE 217
Cdd:cd20978     1 PKFIQKPEKNVVVkGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE-DGTL---TIINVQPEDTGYYGCVATNE 76

                          90
                  ....*....|..
gi 564369110  218 YGARQCEARLEV 229
Cdd:cd20978    77 IGDIYTETLLHV 88

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270877 [Multi-domain] Cd Length: 262 Bit Score: 75.22 E-value: 3.47e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2227 EEKARGRFGVVRSCRE-NATGRTFVAKIVPYAAEGKRRVLQEYEVLRTL-HHERLMSLHEAYITPRY-------LVLIAE 2297
Cdd:cd13975     6 RELGRGQYGVVYACDSwGGHFPCALKSVVPPDDKHWNDLALEFHYTRSLpKHERIVSLHGSVIDYSYgggssiaVLLIME 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCgNRELLCGLsdRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpynPQALKpLGH 2377
Cdd:cd13975    86 RL-HRDLYTGI--KAGLSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLGFCK---PEAMM-SGS 158

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 564369110 2378 RTGTLEFMAPEMVRGDpIGSATDIWGAGVLTYIMLSG 2414
Cdd:cd13975   159 IVGTPIHMAPELFSGK-YDNSVDVYAFGILFWYLCAG 194

mitogen-activated protein kinase kinase; Provisional

Pssm-ID: 215036 [Multi-domain] Cd Length: 353 Bit Score: 76.40 E-value: 3.68e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKP--KASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLE- 953
Cdd:PLN00034   82 IGSGAGGTVYKVIHRPTGRLYALKVIYGNHEDtvRRQICREIEILRDVNHPNVVKCHDMFDHNGEIQVLLEFMDGGSLEg 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  954 -RMARkptvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGaggeEQVRICDFGNAQELTPG-EPQYCQFGTP 1031
Cdd:PLN00034  162 tHIAD-----EQFLADVARQILSGIAYLHRRHIVHRDIKPSNLLINSA----KNVKIADFGVSRILAQTmDPCNSSVGTI 232

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1032 EFVAPEIVNQSPVSG-----VTDIWPVGVVAFLCLTGISPF-VG-ENDRTTLMNIRNYNVAFEETTflSLSREARGFLIK 1104
Cdd:PLN00034  233 AYMSPERINTDLNHGaydgyAGDIWSLGVSILEFYLGRFPFgVGrQGDWASLMCAICMSQPPEAPA--TASREFRHFISC 310

                         250       260
                  ....*....|....*....|
gi 564369110 1105 VLVQD-RLRPTAEETLEHPW 1123
Cdd:PLN00034  311 CLQREpAKRWSAMQLLQHPF 330

serine/threonine kinase US3; Provisional

Pssm-ID: 165473 [Multi-domain] Cd Length: 392 Bit Score: 77.19 E-value: 3.73e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVA---------KIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYitprylvliaescGN 2301
Cdd:PHA03207   91 RMQYNILSSLTPGSEGEVFVCtkhgdeqrkKVIVKAVTGGKTPGREIDILKTISHRAIINLIHAY-------------RW 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYsedDVATYV-------------VQ--LLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA-- 2364
Cdd:PHA03207  158 KSTVCMVMPKYKC---DLFTYVdrsgplpleqaitIQrrLLEALAYLHGRGIIHRDVKTENIFLDEPENAVLGDFGAAck 234

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2365 ---QPYNPQALKplghRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFY 2419
Cdd:PHA03207  235 ldaHPDTPQCYG----WSGTLETNSPELLALDPYCAKTDIWSAGLVLFEMSVKNVTLF 288

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270726 [Multi-domain] Cd Length: 316 Bit Score: 76.12 E-value: 3.83e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFS--YLrrVVERSSGLEFAAKFIPSQAKPKAS----ARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT-E 949
Cdd:cd05574     9 LGKGDVGrvYL--VRLKGTGKLFAMKVLDKEEMIKRNkvkrVLTEREILATLDHPFLPTLYASFQTSTHLCFVMDYCPgG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVC--ESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGaggeeQVRICDFG----NAQELTPGE 1022
Cdd:cd05574    87 ELFRLLQKQPGKRlpEEVARFYAAEVLLALEYLHLLGFVYRDLKPENiLLHESG-----HIMLTDFDlskqSSVTPPPVR 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQF--------------------------GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTL 1076
Cdd:cd05574   162 KSLRKGsrrssvksieketfvaepsarsnsfvGTEEYIAPEVIKGDGHGSAVDWWTLGILLYEMLYGTTPFKGSNRDETF 241

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1077 MNIRNYNVAFEETtfLSLSREARGFLIKVLVQD---RL--RPTAEETLEHPWFK 1125
Cdd:cd05574   242 SNILKKELTFPES--PPVSSEAKDLIRKLLVKDpskRLgsKRGASEIKRHPFFR 293

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270961 [Multi-domain] Cd Length: 237 Bit Score: 74.45 E-value: 4.00e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  915 EARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPE 993
Cdd:cd14059    31 DIKHLRKLNHPNIIKFKGVCTQAPCYCILMEYCPYgQLYEVLRAGREITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSP 110

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110  994 NLLVwdgaGGEEQVRICDFGNAQELTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14059   111 NVLV----TYNDVLKISDFGTSKELSEKSTKMSFAGTVAWMAPEVIRNEPCSEKVDIWSFGVVLWELLTGEIPY 180

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270756 [Multi-domain] Cd Length: 285 Bit Score: 75.47 E-value: 4.02e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQFGTPEFVAPEIVNQS 1042
Cdd:cd05605   101 EERAVFYAAEITCGLEHLHSERIVYRDLKPENILL-DDHG---HVRISDLGLAVEIPEGETIRGRVGTVGYMAPEVVKNE 176

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1043 PVSGVTDIWPVGVVAFLCLTGISPFVG--------ENDRTTLMNIRNYNVAFEEttflslsrEARGFLIKVLVQD---RL 1111
Cdd:cd05605   177 RYTFSPDWWGLGCLIYEMIEGQAPFRArkekvkreEVDRRVKEDQEEYSEKFSE--------EAKSICSQLLQKDpktRL 248

                         170
                  ....*....|....*...
gi 564369110 1112 ---RPTAEETLEHPWFKT 1126
Cdd:cd05605   249 gcrGEGAEDVKSHPFFKS 266

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270751 [Multi-domain] Cd Length: 386 Bit Score: 76.99 E-value: 4.03e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2262 RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE-SCGN--RELLCGLSdrfRYSEDDVATYVVQLLQGLDYLHGRHV 2338
Cdd:cd05600    56 NHVLTERDILTTTNSPWLVKLLYAFQDPENVYLAMEyVPGGdfRTLLNNSG---ILSEEHARFYIAEMFAAISSLHQLGY 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2339 LHLDIKPDNLLLAADNALKIVDFGSAQPY-----------NPQALK--PLGHRT-----------------------GTL 2382
Cdd:cd05600   133 IHRDLKPENFLIDSSGHIKLTDFGLASGTlspkkiesmkiRLEEVKntAFLELTakerrniyramrkedqnyansvvGSP 212

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV-------GGRFDAFQLYPNTSQSATLFLRKV 2455
Cdd:cd05600   213 DYMAPEVLRGEGYDLTVDYWSLGCILFECLVGFPPFSGSTPNETWANLYhwkktlqRPVYTDPDLEFNLSDEAWDLITKL 292

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 2456 LSVHPWSRPSLQDCLAHPWLQDAYLMKLRRQT 2487
Cdd:cd05600   293 ITDPQDRLQSPEQIKNHPFFKNIDWDRLREGS 324

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270822 [Multi-domain] Cd Length: 277 Bit Score: 75.20 E-value: 4.29e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2222 PYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK--RRVLQEYEVLRTLHH---ERLMSLHEAYITPRYLVLIA 2296
Cdd:cd06917     2 LYRRLELVGRGSYGAVYRGYHVKTGRVVALKVLNLDTDDDdvSDIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWIIM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLCgLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKplg 2376
Cdd:cd06917    82 DYCEGGSIRT-LMRAGPIAERYIAVIMREVLVALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNSSK--- 157

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2377 hRT---GTLEFMAPEMVR-GDPIGSATDIWGAGVLTYIMLSGYSPFYEPDP 2423
Cdd:cd06917   158 -RStfvGTPYWMAPEVITeGKYYDTKADIWSLGITTYEMATGNPPYSDVDA 207

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270743 [Multi-domain] Cd Length: 321 Bit Score: 75.99 E-value: 4.58e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPyaaegKRRVLQEYEVLRTLHHER----------LMSLHEAYITPRYLVLIAESCG 2300
Cdd:cd05591     5 KGSFGKVMLAERKGTDEVYAIKVLK-----KDVILQDDDVDCTMTEKRilalaakhpfLTALHSCFQTKDRLFFVMEYVN 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2301 NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpynpQALKPlGHRT- 2379
Cdd:cd05591    80 GGDLMFQIQRARKFDEPRARFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCK----EGILN-GKTTt 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2380 ---GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFyEPDPQEtearivggrfDAFQ-------LYPN-TSQSA 2448
Cdd:cd05591   155 tfcGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPF-EADNED----------DLFEsilhddvLYPVwLSKEA 223

                         250
                  ....*....|....*
gi 564369110 2449 TLFLRKVLSVHPWSR 2463
Cdd:cd05591   224 VSILKAFMTKNPAKR 238

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270821 [Multi-domain] Cd Length: 297 Bit Score: 75.41 E-value: 4.59e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIpsqaKPKASARRE-----ARLLARLQHDCVLYFHEAFERRRGLVIVT 944
Cdd:cd06659    22 LLENYVKIGEGSTGVVCIAREKHSGRQVAVKMM----DLRKQQRREllfneVVIMRDYQHPNVVEMYKSYLVGEELWVLM 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGaggeeQVRICDFGNAQELTPGEP 1023
Cdd:cd06659    98 EYLQGGALTDIVSQTRLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSiLLTLDG-----RVKLSDFGFCAQISKDVP 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNyNVAFEETTFLSLSREARGFL 1102
Cdd:cd06659   173 KRKSLvGTPYWMAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKRLRD-SPPPKLKNSHKASPVLRDFL 251

                         250       260
                  ....*....|....*....|...
gi 564369110 1103 IKVLVQDRL-RPTAEETLEHPWF 1124
Cdd:cd06659   252 ERMLVRDPQeRATAQELLDHPFL 274

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143364 [Multi-domain] Cd Length: 338 Bit Score: 75.97 E-value: 5.69e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAE---GKRRVLQEYEVLRTLHHERLMSLHEAYITPR-------YL 2292
Cdd:cd07859     2 YKIQEVIGKGSYGVVCSAIDTHTGEKVAIKKINDVFEhvsDATRILREIKLLRLLRHPDIVEIKHIMLPPSrrefkdiYV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLiaescgnrELLCGLSDRFRYSEDDVAT-----YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY 2367
Cdd:cd07859    82 VF--------ELMESDLHQVIKANDDLTPehhqfFLYQLLRALKYIHTANVFHRDLKPKNILANADCKLKICDFGLARVA 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2368 ---NPQALKPLGHrTGTLEFMAPEMVrgdpiGS-------ATDIWGAGVLTYIMLSGYSPFYEPD--------------- 2422
Cdd:cd07859   154 fndTPTAIFWTDY-VATRWYRAPELC-----GSffskytpAIDIWSIGCIFAEVLTGKPLFPGKNvvhqldlitdllgtp 227

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2423 PQETEARIVGGRFDAF-------------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd07859   228 SPETISRVRNEKARRYlssmrkkqpvpfsQKFPNADPLALRLLERLLAFDPKDRPTAEEALADPYFK 294

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271037 [Multi-domain] Cd Length: 318 Bit Score: 75.34 E-value: 5.77e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERS-SGLEFAAKFIPSQAKPKASARREARLLARL-QHD------CV-LYFHeaFERRRGL 940
Cdd:cd14135     1 RYRVYGYLGKGVFSNVVRARDLArGNQEVAIKIIRNNELMHKAGLKELEILKKLnDADpddkkhCIrLLRH--FEHKNHL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTE---LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgagGEEQ--VRICDFGNA 1015
Cdd:cd14135    79 CLVFEslsMNLREVLKKYGKNVGLNIKAVRSYAQQLFLALKHLKKCNILHADIKPDNILV-----NEKKntLKLCDFGSA 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 1016 QELTPGEPqycqfgTPEFV-----APEIVNQSPVSGVTDIWPVGVVAFLCLTG 1063
Cdd:cd14135   154 SDIGENEI------TPYLVsrfyrAPEIILGLPYDYPIDMWSVGCTLYELYTG 200

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270933 [Multi-domain] Cd Length: 275 Bit Score: 74.76 E-value: 6.15e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIhqEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQHDCVLYFHEAFER----RRGLVIV 943
Cdd:cd14031    14 FDI--ELGRGAFKTVYKGLDTETWVEVAWCELQDRKLTKAEQQRfkeEAEMLKGLQHPNIVRFYDSWESvlkgKKCIVLV 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTEELLERMARKPTVCESET-RTYMRQVLEGIGYLHQSH--VLHLDVKPENLLVwdgAGGEEQVRICDFGNAQELTP 1020
Cdd:cd14031    92 TELMTSGTLKTYLKRFKVMKPKVlRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFI---TGPTGSVKIGDLGLATLMRT 168

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 1021 GEPQYCqFGTPEFVAPEIVNQSPVSGVtDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14031   169 SFAKSV-IGTPEFMAPEMYEEHYDESV-DVYAFGMCMLEMATSEYPY 213

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270803 [Multi-domain] Cd Length: 313 Bit Score: 75.46 E-value: 6.38e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHqEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR----REARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd06633    23 FVDLH-EIGHGSFGAVYFATNSHTNEVVAIKKMSYSGKQTNEKWqdiiKEVKFLQQLKHPNTIEYKGCYLKDHTAWLVME 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LC---TEELLErMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGE 1022
Cdd:cd06633   102 YClgsASDLLE-VHKKP-LQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPG----QVKLADFGSASIASPAN 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PqycQFGTPEFVAPEIV---NQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLmnirnYNVAFEETTFLS---LSR 1096
Cdd:cd06633   176 S---FVGTPYWMAPEVIlamDEGQYDGKVDIWSLGITCIELAERKPPLFNMNAMSAL-----YHIAQNDSPTLQsneWTD 247

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 1097 EARGFL---IKVLVQDrlRPTAEETLEHPWFKTE 1127
Cdd:cd06633   248 SFRGFVdycLQKIPQE--RPSSAELLRHDFVRRE 279

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270951 [Multi-domain] Cd Length: 284 Bit Score: 74.85 E-value: 6.51e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTF-VAKIVPYAAEGK--RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVL-IAESCGNRELL 2305
Cdd:cd14049    15 GKGGYGKVYKVRNKLDGQYYaIKKILIKKVTKRdcMKVLREVKVLAGLQHPNIVGYHTAWMEHVQLMLyIQMQLCELSLW 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDR---FRYSED----------DVATYVV-QLLQGLDYLHGRHVLHLDIKPDNLLL-AADNALKIVDFGSAQP---- 2366
Cdd:cd14049    95 DWIVERnkrPCEEEFksapytpvdvDVTTKILqQLLEGVTYIHSMGIVHRDLKPRNIFLhGSDIHVRIGDFGLACPdilq 174

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2367 -----YNPQALKPLGH--RTGTLEFMAPEMVRGDPIGSATDIWGAGVltyIMLSGYSPF 2418
Cdd:cd14049   175 dgndsTTMSRLNGLTHtsGVGTCLYAAPEQLEGSHYDFKSDMYSIGV---ILLELFQPF 230

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270914 [Multi-domain] Cd Length: 254 Bit Score: 73.93 E-value: 7.23e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  900 KFIPSQAKPKASA-RREARL-------LARLQHDCVLYFHEAFERRRG------LVIVTELCT----EELLERMarkPTV 961
Cdd:cd14012    25 KFLTSQEYFKTSNgKKQIQLlekelesLKKLRHPNLVSYLAFSIERRGrsdgwkVYLLTEYAPggslSELLDSV---GSV 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  962 CESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEEQVRICDFG---------NAQELTPGEPQYcqfgtpe 1032
Cdd:cd14012   102 PLDTARRWTLQLLEALEYLHRNGVVHKSLHAGNVLL-DRDAGTGIVKLTDYSlgktlldmcSRGSLDEFKQTY------- 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1033 FVAPEIVNQS-PVSGVTDIWPVGVVAFLCLTGISPFVgendrttlmnirNYNVAFEETTFLSLSREARGFLIKVLVQD-R 1110
Cdd:cd14012   174 WLPPELAQGSkSPTRKTDVWDLGLLFLQMLFGLDVLE------------KYTSPNPVLVSLDLSASLQDFLSKCLSLDpK 241

                         250
                  ....*....|..
gi 564369110 1111 LRPTAEETLEHP 1122
Cdd:cd14012   242 KRPTALELLPHE 253

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 69.06 E-value: 7.30e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    3 VAPGADVLLKCIITANPPPQVSWKKDGSVL--HSEGRLLIRaEGERHTLLLREAQAADAGSYTATATNELGQASCASSLA 80
Cdd:cd05744    12 VQEGRLCRFDCKVSGLPTPDLFWQLNGKPVrpDSAHKMLVR-ENGRHSLIIEPVTKRDAGIYTCIARNRAGENSFNAELV 90


                  .
gi 564369110   81 V 81
Cdd:cd05744    91 V 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 68.75 E-value: 7.31e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110  1848 PPVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVScKDGRQLLSIPRASKRHAGLYECSATN 1926
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSL-SGSNSTLTISNVTRSDAGTYTCVASN 78

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143377 [Multi-domain] Cd Length: 309 Bit Score: 75.03 E-value: 7.74e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAE--GKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE--- 2297
Cdd:cd07872     8 YIKLEKLGEGTYATVFKGRSKLTENLVALKEIRLEHEegAPCTAIREVSLLKDLKHANIVTLHDIVHTDKSLTLVFEyld 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 --------SCGNRellcglsdrfrYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP 2369
Cdd:cd07872    88 kdlkqymdDCGNI-----------MSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARAKSV 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110 2370 QAlKPLGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYIMLSGySPFYEPDPQETEARIV 2431
Cdd:cd07872   157 PT-KTYSNEVVTLWYRPPDVLLGSSeYSTQIDMWGVGCIFFEMASG-RPLFPGSTVEDELHLI 217

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270860 [Multi-domain] Cd Length: 256 Bit Score: 74.00 E-value: 8.05e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAF--SYLRRVVERSS-------GLEFAAKfipsqaKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd08221     8 LGRGAFgeAVLYRKTEDNSlvvwkevNLSRLSE------KERRDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TE-ELLERMARKPTVCESETRT--YMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGaggeEQVRICDFGNAQELTpGEPQ 1024
Cdd:cd08221    82 NGgNLHDKIAQQKNQLFPEEVVlwYLYQIVSAVSHIHKAGILHRDIKTLNIFLTKA----DLVKLGDFGISKVLD-SESS 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1025 YCQ--FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFlslSREARGFL 1102
Cdd:cd08221   157 MAEsiVGTPYYMSPELVQGVKYNFKSDIWAVGCVLYELLTLKRTFDATNPLRLAVKIVQGEYEDIDEQY---SEEIIQLV 233

                         250       260
                  ....*....|....*....|...
gi 564369110 1103 IKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd08221   234 HDCLHQDpEDRPTAEELLERPLL 256

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270751 [Multi-domain] Cd Length: 386 Bit Score: 75.84 E-value: 8.26e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE-LTPGE--------------PQYCQ 1027
Cdd:cd05600   110 EEHARFYIAEMFAAISSLHQLGYIHRDLKPENFLI-DSSG---HIKLTDFGLASGtLSPKKiesmkirleevkntAFLEL 185

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 F-----------------------GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNV 1084
Cdd:cd05600   186 TakerrniyramrkedqnyansvvGSPDYMAPEVLRGEGYDLTVDYWSLGCILFECLVGFPPFSGSTPNETWANLYHWKK 265

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 564369110 1085 AFEETTF------LSLSREARGFLIKVLV--QDRLRPTaEETLEHPWFK 1125
Cdd:cd05600   266 TLQRPVYtdpdleFNLSDEAWDLITKLITdpQDRLQSP-EQIKNHPFFK 313

serine/threonine-protein kinase 1; Provisional

Pssm-ID: 223069 [Multi-domain] Cd Length: 267 Bit Score: 74.12 E-value: 8.27e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  951 LLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLvWDGAggEEQVRICDFGNAQ-ELTPGepqyCQFG 1029
Cdd:PHA03390   96 LFDLLKKEGKLSEAEVKKIIRQLVEALNDLHKHNIIHNDIKLENVL-YDRA--KDRIYLCDYGLCKiIGTPS----CYDG 168

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1030 TPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRT---TLMNIRNYNvafeETTFLS-LSREARGFLIKV 1105
Cdd:PHA03390  169 TLDYFSPEKIKGHNYDVSFDWWAVGVLTYELLTGKHPFKEDEDEEldlESLLKRQQK----KLPFIKnVSKNANDFVQSM 244

                         170       180
                  ....*....|....*....|...
gi 564369110 1106 LVQD---RLRpTAEETLEHPWFK 1125
Cdd:PHA03390  245 LKYNinyRLT-NYNEIIKHPFLK 266

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR1 (also called STK38) plays a role in proper centrosome duplication. It is highly expressed in thymus, muscle, lung and spleen. It is not an essential protein because mice deficient of NDR1 remain viable and fertile. However, these mice develop T-cell lymphomas and appear to be hypersenstive to carcinogenic treatment. NDR1 appears to also act as a tumor suppressor. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270777 [Multi-domain] Cd Length: 376 Bit Score: 75.85 E-value: 8.30e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYA----AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELL 2305
Cdd:cd05628    10 GRGAFGEVRLVQKKDTGHVYAMKILRKAdmleKEQVGHIRAERDILVEADSLWVVKMFYSFQDKLNLYLIMEFLPGGDMM 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 CGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA----QPYNPQALKPLGHR--- 2378
Cdd:cd05628    90 TLLMKKDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLLDSKGHVKLSDFGLCtglkKAHRTEFYRNLNHSlps 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2379 ---------------------------TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV 2431
Cdd:cd05628   170 dftfqnmnskrkaetwkrnrrqlafstVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSETPQETYKKVM 249


                  ...
gi 564369110 2432 GGR 2434
Cdd:cd05628   250 NWK 252

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173720 [Multi-domain] Cd Length: 285 Bit Score: 74.26 E-value: 8.62e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQA----KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd05631     8 LGKGGFGEVCACQVRATGKMYACKKLEKKRikkrKGEAMALNEKRILEKVNSRFVVSLAYAYETKDALCLVLTIMNGGDL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 E----RMArKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQF 1028
Cdd:cd05631    88 KfhiyNMG-NPGFDEQRAIFYAAELCCGLEDLQRERIVYRDLKPENILL-DDRG---HIRISDLGLAVQIPEGETVRGRV 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQ 1108
Cdd:cd05631   163 GTVGYMAPEVINNEKYTFSPDWWGLGCLIYEMIQGQSPFRKRKERVKREEVDRRVKEDQEEYSEKFSEDAKSICRMLLTK 242

                         250       260
                  ....*....|....*....|....
gi 564369110 1109 D---RLRPT---AEETLEHPWFKT 1126
Cdd:cd05631   243 NpkeRLGCRgngAAGVKQHPIFKN 266

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270779 [Multi-domain] Cd Length: 285 Bit Score: 74.29 E-value: 9.26e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQA----KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-EL 951
Cdd:cd05630     8 LGKGGFGEVCACQVRATGKMYACKKLEKKRikkrKGEAMALNEKQILEKVNSRFVVSLAYAYETKDALCLVLTLMNGgDL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRT--YMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPQYCQFG 1029
Cdd:cd05630    88 KFHIYHMGQAGFPEARAvfYAAEICCGLEDLHRERIVYRDLKPENILLDDHG----HIRISDLGLAVHVPEGQTIKGRVG 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1030 TPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARGFLIKVLVQD 1109
Cdd:cd05630   164 TVGYMAPEVVKNERYTFSPDWWALGCLLYEMIAGQSPFQQRKKKIKREEVERLVKEVPEEYSEKFSPQARSLCSMLLCKD 243

                         250       260
                  ....*....|....*....|..
gi 564369110 1110 RLR------PTAEETLEHPWFK 1125
Cdd:cd05630   244 PAErlgcrgGGAREVKEHPLFK 265

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 68.76 E-value: 9.28e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  144 SLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQC 223
Cdd:cd20973     3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATC 82


                  ....*.
gi 564369110  224 EARLEV 229
Cdd:cd20973    83 SAELTV 88

cyclin-dependent protein kinase; Provisional

Pssm-ID: 240233 [Multi-domain] Cd Length: 335 Bit Score: 75.18 E-value: 9.38e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2264 VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNrELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDI 2343
Cdd:PTZ00024   67 TLRELKIMNEIKHENIMGLVDVYVEGDFINLVMDIMAS-DLKKVVDRKIRLTESQVKCILLQILNGLNVLHKWYFMHRDL 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2344 KPDNLLLAADNALKIVDFGSAQPY-------------NPQALKPLGHRTGTLEFMAPEMVRG-DPIGSATDIWGAGVLTY 2409
Cdd:PTZ00024  146 SPANIFINSKGICKIADFGLARRYgyppysdtlskdeTMQRREEMTSKVVTLWYRAPELLMGaEKYHFAVDMWSVGCIFA 225

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2410 IMLSGYSPFyepdPQETEARIVGGRF------------DAFQL-----------------YPNTSQSATLFLRKVLSVHP 2460
Cdd:PTZ00024  226 ELLTGKPLF----PGENEIDQLGRIFellgtpnednwpQAKKLplyteftprkpkdlktiFPNASDDAIDLLQSLLKLNP 301

                         250
                  ....*....|....*.
gi 564369110 2461 WSRPSLQDCLAHPWLQ 2476
Cdd:PTZ00024  302 LERISAKEALKHEYFK 317

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270634 [Multi-domain] Cd Length: 284 Bit Score: 73.95 E-value: 1.25e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2224 TFLEEKARGRFGVVRSCR-----ENATGRTFVAKIVPYAAEGKRRVLQ-EYEVLRTLHHErlmslheaYITPryLVLIAE 2297
Cdd:cd05038     7 KFIKQLGEGHFGSVELCRydplgDNTGEQVAVKSLQPSGEEQHMSDFKrEIEILRTLDHE--------YIVK--YKGVCE 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLC--------GLSDRFRYSEDDVAT-----YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA 2364
Cdd:cd05038    77 SPGRRSLRLimeylpsgSLRDYLQRHRDQIDLkrlllFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLA 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2365 Q--PYNPQALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQ 2424
Cdd:cd05038   157 KvlPEDKEYYYVKEPGESPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGDPSQSPPAL 218

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173741 [Multi-domain] Cd Length: 293 Bit Score: 73.80 E-value: 1.35e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  914 REARLLARLQHDCVLYFHEAF--ERRRGLVIVTELCTEEL---LERMarKPTVCESETRTYMRQVLEGIGYLHQSHVLHL 988
Cdd:cd07843    53 REINILLKLQHPNIVTVKEVVvgSNLDKIYMVMEYVEHDLkslMETM--KQPFLQSEVKCLMLQLLSGVAHLHDNWILHR 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  989 DVKPENLLVwDGAGgeeQVRICDFGNAQELtpGEP--QYcqfgTPEFV-----APEIVNQSPV-SGVTDIWPVGVVAFLC 1060
Cdd:cd07843   131 DLKTSNLLL-NNRG---ILKICDFGLAREY--GSPlkPY----TQLVVtlwyrAPELLLGAKEySTAIDMWSVGCIFAEL 200

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1061 LTGISPFVGENDRTTLMNI---------RNY----------NVAFEETT-------FLSLSREARGF--LIKVLVQD-RL 1111
Cdd:cd07843   201 LTKKPLFPGKSEIDQLNKIfkllgtpteKIWpgfselpgakKKTFTKYPynqlrkkFPALSLSDNGFdlLNRLLTYDpAK 280

                         250
                  ....*....|...
gi 564369110 1112 RPTAEETLEHPWF 1124
Cdd:cd07843   281 RISAEDALKHPYF 293

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 67.98 E-value: 1.41e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110   138 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLcRLRILAAERGDAGFYTCKAVN 216
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNS-TLTISNVTRSDAGTYTCVASN 78

cyclin-dependent kinase A; Provisional

Pssm-ID: 177649 [Multi-domain] Cd Length: 294 Bit Score: 73.70 E-value: 1.48e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK---RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:PLN00009    4 YEKVEKIGEGTYGVVYKARDRVTNETIALKKIRLEQEDEgvpSTAIREISLLKEMQHGNIVRLQDVVHSEKRLYLVFEYL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 G-NRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLL-AADNALKIVDFGSAQPYNPqALKPLGH 2377
Cdd:PLN00009   84 DlDLKKHMDSSPDFAKNPRLIKTYLYQILRGIAYCHSHRVLHRDLKPQNLLIdRRTNALKLADFGLARAFGI-PVRTFTH 162

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGSA-TDIWGAGVLTYIMLS 2413
Cdd:PLN00009  163 EVVTLWYRAPEILLGSRHYSTpVDIWSVGCIFAEMVN 199

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270880 [Multi-domain] Cd Length: 263 Bit Score: 73.26 E-value: 1.53e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCReNATGRTFVA-KIVPYA---AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN---RE 2303
Cdd:cd13978     3 SGGFGTVSKAR-HVSWFGMVAiKCLHSSpncIEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENgslKS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2304 LL------CGLSDRFRYseddvatyVVQLLQGLDYLHG--RHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPL 2375
Cdd:cd13978    82 LLereiqdVPWSLRFRI--------IHEIALGMNFLHNmdPPLLHHDLKPENILLDNHFHVKISDFGLSKLGMKSISANR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2376 GHRT----GTLEFMAPE---MVRGDPiGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV--GGR-----FDAFQLY 2441
Cdd:cd13978   154 RRGTenlgGTPIYMAPEafdDFNKKP-TSKSDVYSFAIVIWAVLTRKEPFENAINPLLIMQIVskGDRpslddIGRLKQI 232

                         250       260       270
                  ....*....|....*....|....*....|..
gi 564369110 2442 PNTSQSATLfLRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd13978   233 ENVQELISL-MIRCWDGNPDARPTFLECLDRL 263

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 67.92 E-value: 1.67e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    762 EDVEVGPGETARFAVVVEGKPLPDIMWYKD-EVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLAGEVSCKA 840
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQgGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 564369110    841 ELSV 844
Cdd:smart00410   82 TLTV 85

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143368 [Multi-domain] Cd Length: 288 Bit Score: 73.46 E-value: 1.72e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA---SARREARLLARLqhdcvlyfhEAFERRRgLVIVTELC 947
Cdd:cd07863     2 YEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVQTNEDGlplSTVREVALLKRL---------EAFDHPN-IVRLMDVC 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TEELLERMARKPTVCE---SETRTY-----------------MRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQV 1007
Cdd:cd07863    72 ATSRTDRETKVTLVFEhvdQDLRTYldkvpppglpaetikdlMRQFLRGLDFLHANCIVHRDLKPENILVTSGG----QV 147

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 1008 RICDFGNAQELTpgepqyCQFG-TPEFV-----APEIVNQSPVSGVTDIWPVGVV 1056
Cdd:cd07863   148 KLADFGLARIYS------CQMAlTPVVVtlwyrAPEVLLQSTYATPVDMWSVGCI 196

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173742 [Multi-domain] Cd Length: 309 Bit Score: 73.94 E-value: 1.74e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  911 SARREARLLARLQHDCVLYFHEAFERRR--GLVIVTELCTEE---LLERMARKPTvcESETRTYMRQVLEGIGYLHQSHV 985
Cdd:cd07845    52 SSLREITLLLNLRHPNIVELKEVVVGKHldSIFLVMEYCEQDlasLLDNMPTPFS--ESQVKCLMLQLLRGLQYLHENFI 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  986 LHLDVKPENLLVWDGAggeeQVRICDFGNAQelTPGEPqyCQFGTPEFV-----APEIVNQSPV-SGVTDIWPVGVVAFL 1059
Cdd:cd07845   130 IHRDLKVSNLLLTDKG----CLKIADFGLAR--TYGLP--AKPMTPKVVtlwyrAPELLLGCTTyTTAIDMWAVGCILAE 201

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1060 CLTGISPFVGE----------------NDR-----TTLMNIRNYNVA-----FEETTFLSLSREARGFLIKVLVQD-RLR 1112
Cdd:cd07845   202 LLAHKPLLPGKseieqldliiqllgtpNESiwpgfSDLPLVGKFTLPkqpynNLKHKFPWLSEAGLRLLNFLLMYDpKKR 281

                         250
                  ....*....|....
gi 564369110 1113 PTAEETLEHPWFKT 1126
Cdd:cd07845   282 ATAEEALESSYFKE 295

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270888 [Multi-domain] Cd Length: 282 Bit Score: 73.48 E-value: 1.78e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTF-VAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPR-------YLVL 2294
Cdd:cd13986     2 YRIQRLLGEGGFSFVYLVEDLSTGRLYaLKKILCHSKEDVKEAMREIENYRLFNHPNILRLLDSQIVKEaggkkevYLLL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2295 IAESCGNrelLCGLSDRFR-----YSEDDVATYVVQLLQGLDYLH---GRHVLHLDIKPDNLLLAADNALKIVDFGSAQP 2366
Cdd:cd13986    82 PYYKRGS---LQDEIERRLvkgtfFPEDRILHIFLGICRGLKAMHepeLVPYAHRDIKPGNVLLSEDDEPILMDLGSMNP 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2367 --------YNPQALKPLGHRTGTLEFMAPEM--VRGDP-IGSATDIWGAGVLTYIMLSGYSPF-YEPDPQETEARIVGGR 2434
Cdd:cd13986   159 arieiegrREALALQDWAAEHCTMPYRAPELfdVKSHCtIDEKTDIWSLGCTLYALMYGESPFeRIFQKGDSLALAVLSG 238

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 564369110 2435 FDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAH 2472
Cdd:cd13986   239 NYSFPDNSRYSEELHQLVKSMLVVNPAERPSIDDLLSR 276

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270951 [Multi-domain] Cd Length: 284 Bit Score: 73.31 E-value: 1.87e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLSDYYDIHQeIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR---REARLLARLQHDCVLYFHEAFERRRGLV 941
Cdd:cd14049     3 RYLNEFEEIAR-LGKGGYGKVYKVRNKLDGQYYAIKKILIKKVTKRDCMkvlREVKVLAGLQHPNIVGYHTAWMEHVQLM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 --IVTELCTEELLERMA-RKPTVCESETRT-------------YMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgAGGEE 1005
Cdd:cd14049    82 lyIQMQLCELSLWDWIVeRNKRPCEEEFKSapytpvdvdvttkILQQLLEGVTYIHSMGIVHRDLKPRNIFL---HGSDI 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1006 QVRICDFGNA-------------QELTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAflcLTGISPFVGEND 1072
Cdd:cd14049   159 HVRIGDFGLAcpdilqdgndsttMSRLNGLTHTSGVGTCLYAAPEQLEGSHYDFKSDMYSIGVIL---LELFQPFGTEME 235

                         250
                  ....*....|
gi 564369110 1073 RT-TLMNIRN 1081
Cdd:cd14049   236 RAeVLTQLRN 245

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270834 [Multi-domain] Cd Length: 316 Bit Score: 73.86 E-value: 1.97e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2267 EYEVLRTLHHERLMSLHEAYITPR----YLVliaescgnrellcglsdrFRYSEDD---------------VATYVV--- 2324
Cdd:cd07842    52 EIALLRELKHENVVSLVEVFLEHAdksvYLL------------------FDYAEHDlwqiikfhrqakrvsIPPSMVksl 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2325 --QLLQGLDYLHGRHVLHLDIKPDNLLLAADN----ALKIVDFGSAQPYNPqALKPLGHRTG---TLEFMAPEMVrgdpI 2395
Cdd:cd07842   114 lwQILNGIHYLHSNWVLHRDLKPANILVMGEGpergVVKIGDLGLARLFNA-PLKPLADLDPvvvTIWYRAPELL----L 188

                         170
                  ....*....|....*
gi 564369110 2396 GS-----ATDIWGAG 2405
Cdd:cd07842   189 GArhytkAIDIWAIG 203

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271107 [Multi-domain] Cd Length: 284 Bit Score: 73.13 E-value: 2.04e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2225 FLEEKARGRFGVVRSCR----ENATGRTF-VAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITP--RYLVLIAE 2297
Cdd:cd14205     8 FLQQLGKGNFGSVEMCRydplQDNTGEVVaVKKLQHSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAgrRNLRLIME 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SC--GN-RELLCGLSDRFRYSEddVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ--PYNPQAL 2372
Cdd:cd14205    88 YLpyGSlRDYLQKHKERIDHIK--LLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKvlPQDKEYY 165

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 2373 KPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSgYSPFYEPDPQE 2425
Cdd:cd14205   166 KVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFT-YIEKSKSPPAE 217

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270805 [Multi-domain] Cd Length: 317 Bit Score: 73.93 E-value: 2.17e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAA----EGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVL 2294
Cdd:cd06635    23 PEKLFSDLREIGHGSFGAVYFARDVRTSEVVAIKKMSYSGkqsnEKWQDIIKEVKFLQRIKHPNSIEYKGCYLREHTAWL 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2295 IAESC-GNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpQALK 2373
Cdd:cd06635   103 VMEYClGSASDLLEVHKK-PLQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSA-----SIAS 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2374 PLGHRTGTLEFMAPEMVRGDPIGS---ATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQlYPNTSQSATL 2450
Cdd:cd06635   177 PANSFVGTPYWMAPEVILAMDEGQydgKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNESPTLQ-SNEWSDYFRN 255

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd06635   256 FVDSCLQKIPQDRPTSEELLKHMFVL 281

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270844 [Multi-domain] Cd Length: 284 Bit Score: 72.92 E-value: 2.28e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFI----PSQAKPkASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEE 950
Cdd:cd07860     6 EKIGEGTYGVVYKARNKLTGEVVALKKIrldtETEGVP-STAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQD 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  951 LLERMARKPT--VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQeltpgepqycQF 1028
Cdd:cd07860    85 LKKFMDASALtgIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLI-NTEG---AIKLADFGLAR----------AF 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1029 GTP------EFV-----APEIVNQSPV-SGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI----------------- 1079
Cdd:cd07860   151 GVPvrtythEVVtlwyrAPEILLGCKYySTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIfrtlgtpdevvwpgvts 230

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1080 -RNYNVAFE-------ETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07860   231 mPDYKPSFPkwarqdfSKVVPPLDEDGRDLLSQMLHYDpNKRISAKAALAHPFF 284

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3). PIM3 can inhibit apoptosis and promote cell survival and protein translation, therefore, it can enhance the proliferation of normal and cancer cells. Mice deficient with PIM3 show minimal effects, suggesting that PIM3 msy not be essential. Since its expression is enhanced in several cancers, it may make a good molecular target for cancer drugs. The PIM3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271004 [Multi-domain] Cd Length: 253 Bit Score: 72.30 E-value: 2.31e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA-LKIVDFGSAQPYNPQALKPLghrTG 2380
Cdd:cd14102    90 KDLFDFITEKGALDEDTARGFFRQVLEAVRHCYSCGVVHRDIKDENLLVDLRTGeLKLIDFGSGALLKDTVYTDF---DG 166

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVRGDPI-GSATDIWGAGVLTYIMLSGYSPFyepdpqETEARIVGGRFDAFQLYPNTSQSatlFLRKVLSVH 2459
Cdd:cd14102   167 TRVYSPPEWIRYHRYhGRSATVWSLGVLLYDMVCGDIPF------EQDEEILRGRLYFRRRVSPECQQ---LIKWCLSLR 237

                         170
                  ....*....|....*.
gi 564369110 2460 PWSRPSLQDCLAHPWL 2475
Cdd:cd14102   238 PSDRPTLEQIFDHPWM 253

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173729 [Multi-domain] Cd Length: 283 Bit Score: 72.84 E-value: 2.42e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFSYLRRVVERSSGLEFAAKFIPSQAkpkaSARREARLLARLQ-----HDCV--LYFHEAFERRRGLVIVTEL-- 946
Cdd:cd06617     8 ELGRGAYGVVDKMRHVPTGTIMAVKRIRATV----NSQEQKRLLMDLDismrsVDCPytVTFYGALFREGDVWICMEVmd 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 -CTEELLERMARKP-TVCESETRTYMRQVLEGIGYLH-QSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEP 1023
Cdd:cd06617    84 tSLDKFYKKVYDKGlTIPEDILGKIAVSIVKALEYLHsKLSVIHRDVKPSNVLI-NRNG---QVKLCDFGISGYLVDSVA 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQFGTPEFVAPEIVN----QSPVSGVTDIWPVGVVAFLCLTGISPFvgENDRTTLMNIRnyNVAFEETTFL---SLSR 1096
Cdd:cd06617   160 KTIDAGCKPYMAPERINpelnQKGYDVKSDVWSLGITMIELATGRFPY--DSWKTPFQQLK--QVVEEPSPQLpaeKFSP 235

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1097 EARGFLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd06617   236 EFQDFVNKCLKKNyKERPNYPELLQHPFFE 265

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271033 [Multi-domain] Cd Length: 271 Bit Score: 72.63 E-value: 2.44e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVeRSSGLEFAAK---FIPSQAKPKASARREARLLARLQH-DCV--LYFHEAFERRRGLVIV 943
Cdd:cd14131     2 PYEILKQLGKGGSSKVYKVL-NPKKKIYALKrvdLEGADEQTLQSYKNEIELLKKLKGsDRIiqLYDYEVTDEDDYLYMV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TElCTEELLERMARK---PTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGaggeeQVRICDFGNA---QE 1017
Cdd:cd14131    81 ME-CGEIDLATILKKkrpKPIDPNFIRYYWKQMLEAVHTIHEEGIVHSDLKPANFLLVKG-----RLKLIDFGIAkaiQN 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1018 LTPGEPQYCQFGTPEFVAPEIVNQS-------PVSGV---TDIWPVGVVAFLCLTGISPFVG-ENDRTTLMNIRNYNVAF 1086
Cdd:cd14131   155 DTTSIVRDSQVGTLNYMSPEAIKDTsasgegkPKSKIgrpSDVWSLGCILYQMVYGKTPFQHiTNPIAKLQAIIDPNHEI 234

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 564369110 1087 EettFLSLSREargFLIKV----LVQD-RLRPTAEETLEHP 1122
Cdd:cd14131   235 E---FPDIPNP---DLIDVmkrcLQRDpKKRPSIPELLNHP 269

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

Pssm-ID: 271112 [Multi-domain] Cd Length: 311 Bit Score: 73.35 E-value: 2.56e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQH------DCVLYFHEAFERRRGLVIVT 944
Cdd:cd14210    15 YEVLSVLGKGSFGQVVKCLDHKTGQLVAIKIIRNKKRFHQQALVEVKILKHLNDndpddkHNIVRYKDSFIFRGHLCIVF 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELC---TEELLERMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaGGEEQVRICDFG-----NAQ 1016
Cdd:cd14210    95 ELLsinLYELLKSNNFQG-LSLSLIRKFAKQILQALQFLHKLNIIHCDLKPENILLKQ--PSKSSIKVIDFGsscfeGEK 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTpgepqYCQ--FgtpeFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEN---------------DRTTLMNI 1079
Cdd:cd14210   172 VYT-----YIQsrF----YRAPEVILGLPYDTAIDMWSLGCILAELYTGYPLFPGENeeeqlacimevlgvpPKSLIDKA 242

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 1080 RNYNVAFEETTFLSLSREARG-----------------------FLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd14210   243 SRRKKFFDSNGKPRPTTNSKGkkrrpgskslaqvlkcddpsfldFLKKCLRWDpSERMTPEEALQHPWI 311

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270804 [Multi-domain] Cd Length: 308 Bit Score: 73.52 E-value: 2.61e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAA----EGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVL 2294
Cdd:cd06634    13 PEKLFSDLREIGHGSFGAVYFARDVRNNEVVAIKKMSYSGkqsnEKWQDIIKEVKFLQKLRHPNTIEYRGCYLREHTAWL 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2295 IAESC-GNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpQALK 2373
Cdd:cd06634    93 VMEYClGSASDLLEVHKK-PLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSA-----SIMA 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2374 PLGHRTGTLEFMAPEMVRGDPIGS---ATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQlYPNTSQSATL 2450
Cdd:cd06634   167 PANSFVGTPYWMAPEVILAMDEGQydgKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNESPALQ-SGHWSEYFRN 245

                         250       260
                  ....*....|....*....|....*.
gi 564369110 2451 FLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd06634   246 FVDSCLQKIPQDRPTSDVLLKHRFLL 271

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270804 [Multi-domain] Cd Length: 308 Bit Score: 73.52 E-value: 2.63e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFS--YLRRVVeRSSGLEFAAKFIPSQAKPKASAR---REARLLARLQHDCVLYFHEAFERRRGLVIVTELC-- 947
Cdd:cd06634    21 REIGHGSFGavYFARDV-RNNEVVAIKKMSYSGKQSNEKWQdiiKEVKFLQKLRHPNTIEYRGCYLREHTAWLVMEYClg 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 -TEELLErMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPqyc 1026
Cdd:cd06634   100 sASDLLE-VHKKP-LQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPG----LVKLGDFGSASIMAPANS--- 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 QFGTPEFVAPEIV---NQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLmnirnYNVAFEETTFLS---LSREARG 1100
Cdd:cd06634   171 FVGTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSAL-----YHIAQNESPALQsghWSEYFRN 245

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1101 FL---IKVLVQDrlRPTAEETLEHPWFKTE 1127
Cdd:cd06634   246 FVdscLQKIPQD--RPTSDVLLKHRFLLRE 273

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270865 [Multi-domain] Cd Length: 268 Bit Score: 72.75 E-value: 2.66e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVV----ERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd08228     4 FQIEKKIGRGQFSEVYRATclldRKPVALKKVQIFEMMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVLEL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTEELLERM-----ARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGEeqVRICDFGNAQELTP- 1020
Cdd:cd08228    84 ADAGDLSQMikyfkKQKRLIPERTVWKYFVQLCSAVEHMHSRRVMHRDIKPANVFI--TATGV--VKLGDLGLGRFFSSk 159

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 1021 GEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENdrttlMNIRNYNVAFEETTFLSLSRE 1097
Cdd:cd08228   160 TTAAHSLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYGDK-----MNLFSLCQKIEQCDYPPLPTE 231

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270891 [Multi-domain] Cd Length: 289 Bit Score: 72.48 E-value: 3.58e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEG----KRRVLQEYEVLRTLHHERLMSL-----HEAYITPRYLVLIA-ESC-- 2299
Cdd:cd13989     4 GGFGYVTLWKHQDTGEYVAIKKCRQELSPsdknRERWCLEVQIMKKLNHPNVVSArdvppELEKLSPNDLPLLAmEYCsg 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GN-RELL------CGLSdrfrysEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA---LKIVDFGSAQPYNP 2369
Cdd:cd13989    84 GDlRKVLnqpencCGLK------ESEVRTLLSDISSAISYLHENRIIHRDLKPENIVLQQGGGrviYKLIDLGYAKELDQ 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 564369110 2370 QALkpLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd13989   158 GSL--CTSFVGTLQYLAPELFESKKYTCTVDYWSFGTLAFECITGYRPF 204

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270866 [Multi-domain] Cd Length: 292 Bit Score: 72.76 E-value: 3.64e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2258 AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGL----SDRFRYSEDDVATYVVQLLQGLDYL 2333
Cdd:cd08229    65 AKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLELADAGDLSRMIkhfkKQKRLIPEKTVWKYFVQLCSALEHM 144

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2334 HGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKplGHR-TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIML 2412
Cdd:cd08229   145 HSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTA--AHSlVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMA 222


                  ....*..
gi 564369110 2413 SGYSPFY 2419
Cdd:cd08229   223 ALQSPFY 229

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270758 [Multi-domain] Cd Length: 286 Bit Score: 72.63 E-value: 3.66e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR----EARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd05607     3 YFYEFRVLGKGGFGEVCAVQVKNTGQMYACKKLDKKRLKKKSGEKmallEKEILEKVNSPFIVSLAYAFETKTHLCLVMS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRT--YMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGE 1022
Cdd:cd05607    83 LMNGgDLKYHIYNVGERGIEMERVifYSAQITCGILHLHSLKIVYRDMKPENVLLDDNG----NCRLSDLGLAVEVKEGK 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYN----VAFEETTFLSLSREA 1098
Cdd:cd05607   159 PITQRAGTNGYMAPEILKEESYSYPVDWFAMGCSIYEMVAGRTPFRDHKEKVSKEELKRRTledeVKFEHQNFTEEAKDI 238

                         250       260       270
                  ....*....|....*....|....*....|
gi 564369110 1099 RGFLIKVLVQDRL--RPTAEETLEHPWFKT 1126
Cdd:cd05607   239 CRLFLAKKPENRLgsRTNDDDPRKHEFFKS 268

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270968 [Multi-domain] Cd Length: 272 Bit Score: 72.31 E-value: 3.68e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENaTGRTFVAKIVP--YAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCG 2307
Cdd:cd14066     2 GSGGFGTVYKGVLE-NGTVVAVKRLNemNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLEDR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 LSDRF---------RYSeddVAtyvVQLLQGLDYLHG---RHVLHLDIKPDNLLLAADNALKIVDFGSAQ--PYNPQALK 2373
Cdd:cd14066    81 LHCHKgspplpwpqRLK---IA---KGIARGLEYLHEecpPPIIHGDIKSSNILLDEDFEPKLTDFGLARliPPSESVSK 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2374 pLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV 2431
Cdd:cd14066   155 -TSAVKGTIGYLAPEYIRTGRVSTKSDVYSFGVVLLELLTGKPAVDENRENASRKDLV 211

Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GAK, also called auxilin-2, contains an N-terminal kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of PTEN-like, clathrin-binding, and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor. It also interacts with the androgen receptor, acting as a transcriptional coactivator, and its expression is significantly increased with the progression of prostate cancer. The GAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270938 [Multi-domain] Cd Length: 282 Bit Score: 72.54 E-value: 3.71e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAK-IVPYAAEGKRRVLQEYEVLRTLH-HERLMSL-HEAYITPR--------YLVLiAES 2298
Cdd:cd14036     9 AEGGFAFVYEAQDVGTGKEYALKrLLSNEEEKNKAIIQEINFMKKLSgHPNIVQFcSAASIGKEesdqgqaeYLLL-TEL 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNR--ELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRH--VLHLDIKPDNLLLAADNALKIVDFGSA--QPYNPQAL 2372
Cdd:cd14036    88 CKGQlvDFVKKVEAPGPFSPDTVLKIFYQTCRAVQHMHKQSppIIHRDLKIENLLIGNQGQIKLCDFGSAttEAHYPDYS 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2373 KPLGHRT---------GTLEFMAPEMV---RGDPIGSATDIWGAGVLTYIMLSGYSPFYEpdpqETEARIVGGRFdafqL 2440
Cdd:cd14036   168 WSAQKRSlvedeitrnTTPMYRTPEMIdlySNYPIGEKQDIWALGCILYLLCFRKHPFED----GAKLRIINAKY----T 239

                         250       260       270
                  ....*....|....*....|....*....|...
gi 564369110 2441 YPNTSQSATLF---LRKVLSVHPWSRPSLQDCL 2470
Cdd:cd14036   240 IPPNDTQYTVFhdlIRSTLKVNPEERLSITEIV 272

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270743 [Multi-domain] Cd Length: 321 Bit Score: 72.91 E-value: 3.75e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  915 EARLLA-RLQHDCVLYFHEAFERRRGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKP 992
Cdd:cd05591    45 EKRILAlAAKHPFLTALHSCFQTKDRLFFVMEYVNGgDLMFQIQRARKFDEPRARFYAAEVTLALMFLHRHGVIYRDLKL 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  993 ENLLVwDGAGgeeQVRICDFGNAQE-LTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEN 1071
Cdd:cd05591   125 DNILL-DAEG---HCKLADFGMCKEgILNGKTTTTFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADN 200

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110 1072 DRTTLMNIRNYNVAFEettfLSLSREA----RGFLIKVLVQdRL-----RPTAEETLEHPWFK 1125
Cdd:cd05591   201 EDDLFESILHDDVLYP----VWLSKEAvsilKAFMTKNPAK-RLgcvasQGGEDAIRQHPFFR 258

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143384 [Multi-domain] Cd Length: 342 Bit Score: 73.40 E-value: 3.81e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2221 KPYTFLEEKARGRFGVVRSCRENATGRTFVAKIV--PYAAE-GKRRVLQEYEVLRTLHHERLMSLHEAYITPR------- 2290
Cdd:cd07879    15 ERYTSLKQVGSGAYGSVCSAIDKRTGEKVAIKKLsrPFQSEiFAKRAYRELTLLKHMQHENVIGLLDVFTSAVsgdefqd 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 -YLVLIAESCGNRELLcGLsdrfRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP 2369
Cdd:cd07879    95 fYLVMPYMQTDLQKIM-GH----PLSEDKVQYLVYQMLCGLKYIHSAGIIHRDLKPGNLAVNEDCELKILDFGLARHADA 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QAlkplghrTG---TLEFMAPEMVRGDPIGSAT-DIWGAGVLTYIMLSGYSPFYEPD--PQETEARIVGG---------- 2433
Cdd:cd07879   170 EM-------TGyvvTRWYRAPEVILNWMHYNQTvDIWSVGCIMAEMLTGKTLFKGKDylDQLTQILKVTGvpgpefvqkl 242

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2434 ----------------RFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd07879   243 edkaaksyikslpkypRKDFSTLFPKASPQAVDLLEKMLELDVDKRLTATEALEHPYFD 301

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270767 [Multi-domain] Cd Length: 323 Bit Score: 73.11 E-value: 3.98e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  969 YMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQE-LTPGEPQYCQFGTPEFVAPEIVNQSPVSGV 1047
Cdd:cd05616   106 YAAEIAIGLFFLQSKGIIYRDLKLDNVML----DSEGHIKIADFGMCKEnIWDGVTTKTFCGTPDYIAPEIIAYQPYGKS 181

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1048 TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREA 1098
Cdd:cd05616   182 VDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPK----SMSKEA 228

serine/threonine-protein kinase 1; Provisional

Pssm-ID: 223069 [Multi-domain] Cd Length: 267 Bit Score: 71.81 E-value: 4.04e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVpyaaegKRRVLQEYEVLrtLHHerLMS-------LHEAYITPRYLVLIAE--SCGNR 2302
Cdd:PHA03390   27 GKFGKVSVLKHKPTQKLFVQKII------KAKNFNAIEPM--VHQ--LMKdnpnfikLYYSVTTLKGHVLIMDyiKDGDL 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDRFrySEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLL-AADNALKIVDFGSAQPYNPQalkplGHRTGT 2381
Cdd:PHA03390   97 FDLLKKEGKL--SEAEVKKIIRQLVEALNDLHKHNIIHNDIKLENVLYdRAKDRIYLCDYGLCKIIGTP-----SCYDGT 169

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 564369110 2382 LEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFyEPDPQE 2425
Cdd:PHA03390  170 LDYFSPEKIKGHNYDVSFDWWAVGVLTYELLTGKHPF-KEDEDE 212

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270831 [Multi-domain] Cd Length: 287 Bit Score: 72.31 E-value: 4.77e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAK---FIPSQAKPKASARREARLLARLQH-DC--------VLYFHEAfERRR 938
Cdd:cd07838     1 YEEVAEIGEGAYGTVYKARDLQDGRFVALKkvrVPLSEEGIPLSTIREIALLKQLESfEHpnvvrlldVCHGPRT-DREL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  939 GLVIVTELCTEEL---LERMArKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNA 1015
Cdd:cd07838    80 KLTLVFEHVDQDLatyLDKCP-KPGLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILV----TSDGQVKLADFGLA 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1016 Q------ELTPgepqycQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVaFLCLTGISP-FVGENDRTTLMNIRNY------ 1082
Cdd:cd07838   155 RiysfemALTS------VVVTLWYRAPEVLLQSSYATPVDMWSVGCI-FAELFNRRPlFRGSSEADQLGKIFDViglpse 227

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1083 -----NVAFEETTF------------LSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07838   228 eewprNSALPRSSFpsytprpfksfvPEIDEEGLDLLKKMLTFNpHKRISAFEALQHPYF 287

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270623 [Multi-domain] Cd Length: 262 Bit Score: 71.80 E-value: 4.88e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSC--RENATGRTFVA-KIVPYAAEGKRRV--LQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELL 2305
Cdd:cd00192     5 EGAFGEVYKGklKGGDGKTVDVAvKTLKEDASESERKdfLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGGDLL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 ---------CGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQalkpLG 2376
Cdd:cd00192    85 dflrksrpvFPSPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDD----DY 160

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110 2377 HRTGTLE-----FMAPEMVRGDPIGSATDIWGAGVLTY-IMLSGYSPFYEPDPQETEARIVGG 2433
Cdd:cd00192   161 YRKKTGGklpirWMAPESLKDGIFTSKSDVWSFGVLLWeIFTLGATPYPGLSNEEVLEYLRKG 223

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143364 [Multi-domain] Cd Length: 338 Bit Score: 72.89 E-value: 4.91e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQH-DCVLYFHEAF--ERR--RGLVI 942
Cdd:cd07859     2 YKIQEVIGKGSYGVVCSAIDTHTGEKVAIKKINDVFEHVSDATRilrEIKLLRLLRHpDIVEIKHIMLppSRRefKDIYV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  943 VTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLvwdgAGGEEQVRICDFGNAQEL---T 1019
Cdd:cd07859    82 VFELMESDLHQVIKANDDLTPEHHQFFLYQLLRALKYIHTANVFHRDLKPKNIL----ANADCKLKICDFGLARVAfndT 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1020 PGEPQYCQF-GTPEFVAPEIVNQ--SPVSGVTDIWPVGVVAFLCLTGISPFVGEN---------------DRTTLMNIRN 1081
Cdd:cd07859   158 PTAIFWTDYvATRWYRAPELCGSffSKYTPAIDIWSIGCIFAEVLTGKPLFPGKNvvhqldlitdllgtpSPETISRVRN 237

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1082 -----YNVAFEETTFLSLSRE-------ARGFLIKVLVQD-RLRPTAEETLEHPWFKTEAKGA-EVSTD---HLKLFLSR 1144
Cdd:cd07859   238 ekarrYLSSMRKKQPVPFSQKfpnadplALRLLERLLAFDpKDRPTAEEALADPYFKGLAKVErEPSAQpitKLEFEFER 317

                         330       340
                  ....*....|....*....|.
gi 564369110 1145 RRWQRSQISykcHLVLRPIPE 1165
Cdd:cd07859   318 RRLTKEDVR---ELIYREILE 335

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 66.75 E-value: 4.98e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  755 PRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAE-SNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLA 833
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPdSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 564369110  834 GEVSCKAELSV 844
Cdd:cd05744    81 GENSFNAELVV 91

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 66.46 E-value: 5.01e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQAS 74
Cdd:cd05748     2 IVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKS 75

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271048 [Multi-domain] Cd Length: 268 Bit Score: 71.61 E-value: 5.11e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEF-AAKFIPSQ--AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLE 953
Cdd:cd14146     2 IGVGGFGKVYRATWKGQEVAVkAARQDPDEdiKATAESVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFARGGTLN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  954 RMARKPTVCESETR----------TYMRQVLEGIGYLHQSHV---LHLDVKPENLLVWDGAG----GEEQVRICDFGNAQ 1016
Cdd:cd14146    82 RALAAANAAPGPRRarripphilvNWAVQIARGMLYLHEEAVvpiLHRDLKSSNILLLEKIEhddiCNKTLKITDFGLAR 161

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 1017 ELTPgEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVG 1069
Cdd:cd14146   162 EWHR-TTKMSAAGTYAWMAPEVIKSSLFSKGSDIWSYGVLLWELLTGEVPYRG 213

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270929 [Multi-domain] Cd Length: 267 Bit Score: 71.76 E-value: 5.24e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTfVAKIV---PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGL 2308
Cdd:cd14027     4 GGFGKVSLCFHRTQGLV-VLKTVytgPNCIEHNEALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2309 sDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAL------------KPLG 2376
Cdd:cd14027    83 -KKVSVPLSVKGRIILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFKMWSKLtkeehneqrevdGTAK 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2377 HRTGTLEFMAPEMVRGDPIGSA--TDIWGAGVLTYIMLSGYSPfYEPDPQETE---ARIVGGRFDAFQLYPNTSQSATLF 2451
Cdd:cd14027   162 KNAGTLYYMAPEHLNDVNAKPTekSDVYSFAIVLWAIFANKEP-YENAINEDQiimCIKSGNRPDVDDITEYCPREIIDL 240

                         250
                  ....*....|....*...
gi 564369110 2452 LRKVLSVHPWSRPSLQDC 2469
Cdd:cd14027   241 MKLCWEANPEARPTFPGI 258

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143356 [Multi-domain] Cd Length: 343 Bit Score: 72.71 E-value: 5.53e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIV--PY-AAEGKRRVLQEYEVLRTLHHERLMSLHEAYiTPR--------- 2290
Cdd:cd07851    17 YQNLSPVGSGAYGQVCSAFDTKTGRKVAIKKLsrPFqSAIHAKRTYRELRLLKHMKHENVIGLLDVF-TPAssledfqdv 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 YLV--LIAESCGNrellcgLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQpyn 2368
Cdd:cd07851    96 YLVthLMGADLNN------IVKCQKLSDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSNLAVNEDCELKILDFGLAR--- 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2369 pQALKPLGHRTGTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARI---VGGRFDAF------ 2438
Cdd:cd07851   167 -HTDDEMTGYVATRWYRAPEiMLNWMHYNQTVDIWSVGCIMAELLTGKTLFPGSDHIDQLKRImnlVGTPDEELlkkiss 245

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 2439 -------------------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07851   246 esarnyiqslpqmpkkdfkEVFSGANPLAIDLLEKMLVLDPDKRITAAEALAHPYL 301

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270902 [Multi-domain] Cd Length: 275 Bit Score: 71.88 E-value: 5.55e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2266 QEYEVLRTLHHERLMSLHEAYITPRYLVLiaescgnrEL--LCGLSDRFRYSEDDVA--------TYVVQLLQGLDYLHG 2335
Cdd:cd14000    59 QELTVLSHLHHPSIVYLLGIGIHPLMLVL--------ELapLGSLDHLLQQDSRSFAslgrtlqqRIALQVADGLRYLHS 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2336 RHVLHLDIKPDNLL---LAADNAL--KIVDFGSAQPYNPQALKPLGhrtGTLEFMAPEMVRGDPI-GSATDIWGAGVLTY 2409
Cdd:cd14000   131 AMIIYRDLKSHNVLvwtLYPNSAIiiKIADYGISRQCCRMGAKGSE---GTPGFRAPEIARGNVIyNEKVDVFSFGMLLY 207

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2410 IMLSGYSPFYEPDPQETEARIVGGRFDAFQlYPNTSQSATL--FLRKVLSVHPWSRPS 2465
Cdd:cd14000   208 EILSGGAPMVGHLKFPNEFDIHGGLRPPLK-QYECAPWPEVevLMKKCWKENPQQRPT 264

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270759 [Multi-domain] Cd Length: 288 Bit Score: 71.84 E-value: 5.69e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPK----ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd05608     9 LGKGGFGEVSACQMRATGKLYACKKLNKKRLKKrkgyEGAMVEKRILAKVHSRFIVSLAYAFQTKTDLCLVMTIMNGGDL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERM-----ARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQ 1027
Cdd:cd05608    89 RYHiynvdEENPGFQEPRACFYTAQIISGLEHLHQRRIIYRDLKPENVLL-DDDG---NVRISDLGLAVELKDGQTKTKG 164

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 564369110 1028 F-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd05608   165 YaGTPGFMAPELLLGEEYDYSVDYFTLGVTLYEMIAARGPF 205

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 66.66 E-value: 5.92e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  334 PLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVN-ESENLRLRQDGGLHSLHIARVGSEDEGLYEVSATNTH 412
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRpDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 564369110  413 GQAHCSAQLYV 423
Cdd:cd20990    81 GQNSFNLELVV 91

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270808 [Multi-domain] Cd Length: 291 Bit Score: 71.95 E-value: 6.07e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2217 GPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTL-HHERLMSLHEAYITPRYLV-- 2293
Cdd:cd06639    18 ADPSDTWDIIETIGKGTYGKVYKVTNKKDGSLAAVKILDPISDVDEEIEAEYNILRSLpNHPNVVKFYGMFYKADQYVgg 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2294 ---LIAESCGN---RELLCGLSDRFRYSEDDVATYVV-QLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQ 2365
Cdd:cd06639    98 qlwLVLELCNGgsvTELVKGLLKCGQRLDEAMISYILyGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGvSAQ 177

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2366 PYNPQALKplGHRTGTLEFMAPEMVRGD-----PIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFqL 2440
Cdd:cd06639   178 LTSARLRR--NTSVGTPFWMAPEVIACEqqydySYDARCDVWSLGITAIELADGDPPLFDMHPVKALFKIPRNPPPTL-L 254

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 564369110 2441 YPNT-SQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd06639   255 NPEKwCRGFSHFISQCLIKDFEKRPSVTHLLEHPFIK 291

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271049 [Multi-domain] Cd Length: 267 Bit Score: 71.60 E-value: 6.45e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2264 VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRH---VLH 2340
Cdd:cd14147    49 VRQEARLFAMLAHPNIIALKAVCLEEPNLCLVMEYAAGGPLSRALAGR-RVPPHVLVNWAVQIARGMHYLHCEAlvpVIH 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2341 LDIKPDNLLLA--------ADNALKIVDFGSAQPYnpqalkplgHRT------GTLEFMAPEMVRGDPIGSATDIWGAGV 2406
Cdd:cd14147   128 RDLKSNNILLLqpienddmEHKTLKITDFGLAREW---------HKTtqmsaaGTYAWMAPEVIKASTFSKGSDVWSFGV 198

                         170
                  ....*....|..
gi 564369110 2407 LTYIMLSGYSPF 2418
Cdd:cd14147   199 LLWELLTGEVPY 210

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270893 [Multi-domain] Cd Length: 268 Bit Score: 71.39 E-value: 6.53e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  874 HQEIGRGAFSYLRRVVERSSGLEFAAKFIPSqakpKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL----CTE 949
Cdd:cd13991    11 QLRIGRGSFGEVHRMEDKQTGFQCAVKKVRL----EVFRAEELMACAGLTSPRVVPLYGAVREGPWVNIFMDLkeggSLG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGAggeeQVRICDFGNAQELTPGEPQYCQF 1028
Cdd:cd13991    87 QLIKEQGCLP---EDRALHYLGQALEGLEYLHSRKILHGDVKADNvLLSSDGS----DAFLCDFGHAECLDPDGLGKSLF 159

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 1029 ------GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd13991   160 tgdyipGTETHMAPEVVLGKPCDAKVDVWSSCCMMLHMLNGCHPW 204

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 66.05 E-value: 6.76e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110     1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATN 68
Cdd:pfam13927   11 VTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270942 [Multi-domain] Cd Length: 299 Bit Score: 72.01 E-value: 6.86e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2262 RRVLQEYEVLRTLHHERLMSLHEAY-ITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLH--GRHV 2338
Cdd:cd14040    55 KHACREYRIHKELDHPRIVKLYDYFsLDTDTFCTVLEYCEGNDLDFYLKQHKLMSEKEARSIVMQIVNALRYLNeiKPPI 134

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2339 LHLDIKPDNLLLAADNA---LKIVDFGSAQ-----PYNPQALKPLGHRTGTLEFMAPE--MVRGDP--IGSATDIWGAGV 2406
Cdd:cd14040   135 IHYDLKPGNILLVDGTAcgeIKITDFGLSKimdddSYGVDGMDLTSQGAGTYWYLPPEcfVVGKEPpkISNKVDVWSVGV 214

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2407 LTYIMLSGYSPFYEPDPQE---TEARIVGGRFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLqdclaHPWLQDAYLMKL 2483
Cdd:cd14040   215 IFFQCLYGRKPFGHNQSQQdilQENTILKATEVQFPVKPVVSNEAKAFIRRCLAYRKEDRFDV-----HQLASDPYLLPH 289


                  ....
gi 564369110 2484 RRQT 2487
Cdd:cd14040   290 MRRS 293

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132988 [Multi-domain] Cd Length: 292 Bit Score: 71.59 E-value: 7.17e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR-REARLLARLQHDCVLYFHEAFERRRGLVIVTELCT 948
Cdd:cd06657    21 YLDNFIKIGEGSTGIVCIATVKSSGKLVAVKKMDLRKQQRRELLfNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLE 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 EELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPEN-LLVWDGaggeeQVRICDFGNAQELTPGEPQYCQ 1027
Cdd:cd06657   101 GGALTDIVTHTRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSiLLTHDG-----RVKLSDFGFCAQVSKEVPRRKS 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 F-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNyNVAFEETTFLSLSREARGFLIKVL 1106
Cdd:cd06657   176 LvGTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRD-NLPPKLKNLHKVSPSLKGFLDRLL 254

                         250
                  ....*....|....*....
gi 564369110 1107 VQD-RLRPTAEETLEHPWF 1124
Cdd:cd06657   255 VRDpAQRATAAELLKHPFL 273

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270950 [Multi-domain] Cd Length: 281 Bit Score: 71.44 E-value: 7.24e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAK--IVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYI-TPR----------YLVLIAE 2297
Cdd:cd14048    16 RGGFGVVFEAKNKVDDCNYAVKriRLPNNELAREKVLREVRALAKLDHPGIVRYFNAWLeRPPegwqekmdevYLYIQMQ 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVAT---YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYN------ 2368
Cdd:cd14048    96 LCRKENLKDWMNRRCTMESRELFVclnIFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLVTAMDqgepeq 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2369 -----PQALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARivGGRFDAF--QLY 2441
Cdd:cd14048   176 tvltpMPAYAKHTGQVGTRLYMSPEQIHGNQYSEKVDIFALGLILFELIYSFSTQMERIRTLTDVR--KLKFPALftNKY 253

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 2442 PNTSQsatlFLRKVLSVHPWSRPSLQDCLAH 2472
Cdd:cd14048   254 PEERD----MVQQMLSPSPSERPEAHEVIEH 280

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270866 [Multi-domain] Cd Length: 292 Bit Score: 71.60 E-value: 7.40e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAK----FIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd08229    26 FRIEKKIGRGQFSEVYRATCLLDGVPVALKkvqiFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLEL 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTEELLERMAR-----KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGeeQVRICDFGNAQELTPG 1021
Cdd:cd08229   106 ADAGDLSRMIKhfkkqKRLIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFI--TATG--VVKLGDLGLGRFFSSK 181

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 E-PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENdrttlMNIRNYNVAFEETTFLSLSREARG 1100
Cdd:cd08229   182 TtAAHSLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYGDK-----MNLYSLCKKIEQCDYPPLPSDHYS 256

                         250
                  ....*....|....*..
gi 564369110 1101 FLIKVLVQDRLRPTAEE 1117
Cdd:cd08229   257 EELRQLVNMCINPDPEK 273

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270963 [Multi-domain] Cd Length: 258 Bit Score: 70.89 E-value: 8.04e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERssGLEFAAKFIPSQ-----AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEEL 951
Cdd:cd14061     2 IGVGGFGKVYRGIWR--GEEVAVKAARQDpdediSVTLENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGGA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARKPTVCESETRTYMRQVLEGIGYLHQSH---VLHLDVKPENLLVWDGAGGEEQ----VRICDFGNAQELTpGEPQ 1024
Cdd:cd14061    80 LNRVLAGRKIPPHVLVDWAIQIARGMNYLHNEApvpIIHRDLKSSNILILEAIENEDLenktLKITDFGLAREWH-KTTR 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 1025 YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVG 1069
Cdd:cd14061   159 MSAAGTYAWMAPEVIKSSTFSKASDVWSYGVLLWELLTGEVPYKG 203

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271060 [Multi-domain] Cd Length: 288 Bit Score: 71.38 E-value: 8.67e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATgRTFVAKIVPYAA----EGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLcg 2307
Cdd:cd14158    26 GGFGVVFKGYINDK-NVAVKKLAAMVDisteDLTKQFEQEIQVMAKCQHENLVELLGYSCDGPQLCLVYTYMPNGSLL-- 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 lsDRFRYSEDDVATYVVQLL-------QGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHR-T 2379
Cdd:cd14158   103 --DRLACLNDTPPLSWHMRCkiaqgtaNGINYLHENNHIHRDIKSANILLDETFVPKISDFGLARASEKFSQTIMTERiV 180

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 564369110 2380 GTLEFMAPEMVRGDpIGSATDIWGAGVLTYIMLSGYSPF-YEPDPQ 2424
Cdd:cd14158   181 GTTAYMAPEALRGE-ITPKSDIFSFGVVLLEIITGLPPVdENRDPQ 225

cyclin-dependent kinase A; Provisional

Pssm-ID: 177649 [Multi-domain] Cd Length: 294 Bit Score: 71.39 E-value: 8.72e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPK---ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:PLN00009    2 DQYEKVEKIGEGTYGVVYKARDRVTNETIALKKIRLEQEDEgvpSTAIREISLLKEMQHGNIVRLQDVVHSEKRLYLVFE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPTVCESET--RTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgAGGEEQVRICDFGNAQeltpgep 1023
Cdd:PLN00009   82 YLDLDLKKHMDSSPDFAKNPRliKTYLYQILRGIAYCHSHRVLHRDLKPQNLLI---DRRTNALKLADFGLAR------- 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 qycQFGTP------EFV-----APEIVNQS-PVSGVTDIWPVGVVaFLCLTGISP-FVGENDRTTLMNI----------- 1079
Cdd:PLN00009  152 ---AFGIPvrtfthEVVtlwyrAPEILLGSrHYSTPVDIWSVGCI-FAEMVNQKPlFPGDSEIDELFKIfrilgtpneet 227

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1080 -------RNYNVAFE-------ETTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:PLN00009  228 wpgvtslPDYKSAFPkwppkdlATVVPTLEPAGVDLLSKMLRLDpSKRITARAALEHEYFK 288

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271048 [Multi-domain] Cd Length: 268 Bit Score: 70.84 E-value: 9.90e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2264 VLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE----SCGNREL-----LCGLSDRFRYSEDDVATYVVQLLQGLDYLH 2334
Cdd:cd14146    40 VRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEfargGTLNRALaaanaAPGPRRARRIPPHILVNWAVQIARGMLYLH 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2335 GRHV---LHLDIKPDNLLL--------AADNALKIVDFGSAQPYnpqalkplgHRT------GTLEFMAPEMVRGDPIGS 2397
Cdd:cd14146   120 EEAVvpiLHRDLKSSNILLlekiehddICNKTLKITDFGLAREW---------HRTtkmsaaGTYAWMAPEVIKSSLFSK 190

                         170       180
                  ....*....|....*....|.
gi 564369110 2398 ATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd14146   191 GSDIWSYGVLLWELLTGEVPY 211

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270880 [Multi-domain] Cd Length: 263 Bit Score: 70.95 E-value: 1.01e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQ---AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT----E 949
Cdd:cd13978     1 LGSGGFGTVSKARHVSWFGMVAIKCLHSSpncIEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMEngslK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERmaRKPTVCESETRTYMRQVLEGIGYLHQSH--VLHLDVKPENLLVWDgaggEEQVRICDFG-----------NAQ 1016
Cdd:cd13978    81 SLLER--EIQDVPWSLRFRIIHEIALGMNFLHNMDppLLHHDLKPENILLDN----HFHVKISDFGlsklgmksisaNRR 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 1017 ELTPGEpqycqFGTPEFVAPEIVN--QSPVSGVTDIWPVGVVAFLCLTGISPFVGE 1070
Cdd:cd13978   155 RGTENL-----GGTPIYMAPEAFDdfNKKPTSKSDVYSFAIVIWAVLTRKEPFENA 205

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271002 [Multi-domain] Cd Length: 254 Bit Score: 70.77 E-value: 1.02e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 RELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA-LKIVDFGSAQPYNPQALKPLghrTG 2380
Cdd:cd14100    91 QDLFDFITERGALPEELARSFFRQVLEAVRHCHNCGVLHRDIKDENILIDLNTGeLKLIDFGSGALLKDTVYTDF---DG 167

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2381 TLEFMAPEMVRGDPI-GSATDIWGAGVLTYIMLSGYSPFyepdpqETEARIVGGrfdafQLY--PNTSQSATLFLRKVLS 2457
Cdd:cd14100   168 TRVYSPPEWIRFHRYhGRSAAVWSLGILLYDMVCGDIPF------EHDEEIIRG-----QVFfrQRVSSECQHLIKWCLA 236

                         170
                  ....*....|....*...
gi 564369110 2458 VHPWSRPSLQDCLAHPWL 2475
Cdd:cd14100   237 LRPSDRPSFEDIQNHPWM 254

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143368 [Multi-domain] Cd Length: 288 Bit Score: 71.15 E-value: 1.05e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRtFVAKI---VPYAAEG-KRRVLQEYEVLRTLhherlmslhEAYITP---RYLVLI 2295
Cdd:cd07863     2 YEPVAEIGVGAYGTVYKARDPHSGH-FVALKsvrVQTNEDGlPLSTVREVALLKRL---------EAFDHPnivRLMDVC 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSdrFRYSEDDVATYV-----------------VQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKI 2358
Cdd:cd07863    72 ATSRTDRETKVTLV--FEHVDQDLRTYLdkvpppglpaetikdlmRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKL 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2359 VDFGSAQPYNPQ-ALKPLghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSgYSPFYEPDpqeTEARIVGGRFDA 2437
Cdd:cd07863   150 ADFGLARIYSCQmALTPV---VVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFR-RKPLFCGN---SEADQLGKIFDL 222

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 2438 FQL----------------------------YPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07863   223 IGLppeddwprdvtlprgafsprgprpvqsvVPEIEESGAQLLLEMLTFNPHKRISAFRALQHPFF 288

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 65.95 E-value: 1.09e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  334 PLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHfghpVNES-----ENLRLRQDG-GLHSLHIARVGSEDEGLYEVS 407
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKK----NNEMlqyntDRISLYQDNcGRICLLIQNANKKDAGWYTVS 76

                          90
                  ....*....|....*.
gi 564369110  408 ATNTHGQAHCSAQLYV 423
Cdd:cd05892    77 AVNEAGVVSCNARLDV 92

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 65.73 E-value: 1.18e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  138 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFaeEAEGGLCRLRILAAERGDAGFYTCKAVNE 217
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRS--TCEAGVGELHIQDVLPEDHGTYTCLAKNA 78

                          90
                  ....*....|..
gi 564369110  218 YGARQCEARLEV 229
Cdd:cd20976    79 AGQVSCSAWVTV 90

serine/threonine kinase US3; Provisional

Pssm-ID: 177557 [Multi-domain] Cd Length: 357 Bit Score: 71.83 E-value: 1.25e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  882 FSYLRRVVERSSGLEFAAKfIPSQAKP-------KASARREARLLARLQHDCVLYFHEAFERRRGLVIV-----TELCTE 949
Cdd:PHA03209   68 YTVIKTLTPGSEGRVFVAT-KPGQPDPvvlkigqKGTTLIEAMLLQNVNHPSVIRMKDTLVSGAITCMVlphysSDLYTY 146

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 eLLERMARKPTvceSETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEPQYCQFG 1029
Cdd:PHA03209  147 -LTKRSRPLPI---DQALIIEKQILEGLRYLHAQRIIHRDVKTENIFIND----VDQVCIGDLGAAQFPVVAPAFLGLAG 218

                         170       180
                  ....*....|....*....|....*....
gi 564369110 1030 TPEFVAPEIVNQSPVSGVTDIWPVGVVAF 1058
Cdd:PHA03209  219 TVETNAPEVLARDKYNSKADIWSAGIVLF 247

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 65.28 E-value: 1.29e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110   755 PRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARN 831
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 65.04 E-value: 1.29e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110    9 VLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQASCAS 77
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132969 [Multi-domain] Cd Length: 286 Bit Score: 70.81 E-value: 1.32e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLH-HERLMSLHEAY-----ITPRYL 2292
Cdd:cd06638    16 PSDTWEIIETIGKGTYGKVFKVLNKKNGSKAAVKILDPIHDIDEEIEAEYNILKALSdHPNVVKFYGMYykkdvKNGDQL 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLIAESCGN---RELLCGLSDRFRYSEDDVATYVV-QLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPY 2367
Cdd:cd06638    96 WLVLELCNGgsvTDLVKGFLKRGERMEEPIIAYILhEALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGvSAQLT 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2368 NPQALKplGHRTGTLEFMAPEMVRGDPIGSAT-----DIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDAFQLYP 2442
Cdd:cd06638   176 STRLRR--NTSVGTPFWMAPEVIACEQQLDSTydarcDVWSLGITAIELGDGDPPLADLHPMRALFKIPRNPPPTLHQPE 253

                         250       260       270
                  ....*....|....*....|....*....|...
gi 564369110 2443 NTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd06638   254 LWSNEFNDFIRKCLTKDYEKRPTVSDLLQHVFI 286

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270758 [Multi-domain] Cd Length: 286 Bit Score: 70.70 E-value: 1.37e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2220 QKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYA----AEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd05607     1 DKYFYEFRVLGKGGFGEVCAVQVKNTGQMYACKKLDKKrlkkKSGEKMALLEKEILEKVNSPFIVSLAYAFETKTHLCLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AEscgnreLLCGLSDRFRYSE--------DDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpY 2367
Cdd:cd05607    81 MS------LMNGGDLKYHIYNvgergiemERVIFYSAQITCGILHLHSLKIVYRDMKPENVLLDDNGNCRLSDLGLA--V 152

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2368 NPQALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFyePDPQETEAR 2429
Cdd:cd05607   153 EVKEGKPITQRAGTNGYMAPEILKEESYSYPVDWFAMGCSIYEMVAGRTPF--RDHKEKVSK 212

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270853 [Multi-domain] Cd Length: 288 Bit Score: 70.81 E-value: 1.38e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  911 SARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMAR-KPTVCESETRTYMRQVLEGIGYLHQSHVLHLD 989
Cdd:cd07871    49 TAIREVSLLKNLKHANIVTLHDIIHTERCLTLVFEYLDSDLKQYLDNcGNLMSMHNVKIFMFQLLRGLSYCHKRKILHRD 128

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  990 VKPENLLVWDGAggeeQVRICDFGNAQ-ELTPGEPQYCQFGTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd07871   129 LKPQNLLINEKG----ELKLADFGLARaKSVPTKTYSNEVVTLWYRPPDVlLGSTEYSTPIDMWGVGCILYEMATGRPMF 204

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1068 VGENDRTTLMNI-RNYNVAFEET-TFLSLSREARGFLIK-------------------------VLVQDRLRPTAEETLE 1120
Cdd:cd07871   205 PGSTVKEELHLIfRLLGTPTEETwPGVTSNEEFRSYLFPqyraqplinhaprldtdgidllsslLLYETKSRISAEAALR 284


                  ....
gi 564369110 1121 HPWF 1124
Cdd:cd07871   285 HSYF 288

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 65.52 E-value: 1.43e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    3 VAPGADVLLKCIITANPPPQVSWKKDG---SVLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQASCASSL 79
Cdd:cd20951    12 VWEKSDAKLRVEVQGKPDPEVKWYKNGvpiDPSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIHGEASSSASV 91


                  ...
gi 564369110   80 AVR 82
Cdd:cd20951    92 VVE 94

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

Pssm-ID: 462242 [Multi-domain] Cd Length: 258 Bit Score: 70.22 E-value: 1.47e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   873 IHQEIGRGAF----SYLRRVVERSSGLEFAAKFIPSQAKPKASA--RREARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:pfam07714    3 LGEKLGEGAFgevyKGTLKGEGENTKIKVAVKTLKEGADEEEREdfLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVTEY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   947 CTE-ELLERM-ARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQ 1024
Cdd:pfam07714   83 MPGgDLLDFLrKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLV----SENLVVKISDFGLSRDIYDDDYY 158

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 564369110  1025 YCQFGTPEFV---APEIVNQSPVSGVTDIWPVGVV 1056
Cdd:pfam07714  159 RKRGGGKLPIkwmAPESLKDGKFTSKSDVWSFGVL 193

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270769 [Multi-domain] Cd Length: 364 Bit Score: 71.99 E-value: 1.47e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRV----VERSSGLEFAAKFIPSQAKPKASARREARLLARLQ-HDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd05618    22 FDLLRVIGRGSYAKVLLVrlkkTERIYAMKVVKKELVNDDEDIDWVQTEKHVFEQASnHPFLVGLHSCFQTESRLFFVIE 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQE-LTPGEP 1023
Cdd:cd05618   102 YVNGgDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLL----DSEGHIKLTDYGMCKEgLRPGDT 177

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF--VGEND 1072
Cdd:cd05618   178 TSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFdiVGSSD 228

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 65.45 E-value: 1.53e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1849 PVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQ--SLRSEPSVVIvSCKDGRQLLSIPRASKRHAGLYECSATN 1926
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQviSTSTLPGVQI-SFSDGRAKLSIPAVTKANSGRYSLTATN 79

                          90
                  ....*....|...
gi 564369110 1927 VLGSITSSCTVAV 1939
Cdd:cd20974    80 GSGQATSTAELLV 92

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173710 [Multi-domain] Cd Length: 316 Bit Score: 71.13 E-value: 1.59e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  969 YMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCQF-GTPEFVAPEIVNQSPVSGV 1047
Cdd:cd05620   101 YAAEIVCGLQFLHSKGIIYRDLKLDNVML-DRDG---HIKIADFGMCKENVFGDNRASTFcGTPDYIAPEILQGLKYTFS 176

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1048 TDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREARGFLIKVLVQD---RLRPTAEETLeHPWF 1124
Cdd:cd05620   177 VDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRW----ITKESKDILEKLFERDptrRLGVVGNIRG-HPFF 251


                  ..
gi 564369110 1125 KT 1126
Cdd:cd05620   252 KT 253

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270784 [Multi-domain] Cd Length: 258 Bit Score: 70.17 E-value: 1.60e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHqEIGRGAFS---YLRRVVERS----SGLEFAAKfipsQAKPK-ASARREARLLARLQHDCVLYFHEAFERRRGLV 941
Cdd:cd06607     3 FEDLR-EIGHGSFGavyYARNKRTSEvvaiKKMSYSGK----QSTEKwQDIIKEVKFLRQLRHPNTIEYKGCYLREHTAW 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELC---TEELLErMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQEL 1018
Cdd:cd06607    78 LVMEYClgsASDIVE-VHKKP-LQEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPG----TVKLADFGSASLV 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1019 TPGEpqycQF-GTPEFVAPEIV---NQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLmnirnYNVAFEETTFLS- 1093
Cdd:cd06607   152 CPAN----SFvGTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSAL-----YHIAQNDSPTLSs 222

                         250       260       270
                  ....*....|....*....|....*....|...
gi 564369110 1094 --LSREARGFLIKVLVQDRL-RPTAEETLEHPW 1123
Cdd:cd06607   223 geWSDDFRNFVDSCLQKIPQdRPSAEDLLKHPF 255

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 65.17 E-value: 1.63e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    2 VVAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNELGQASCASSLAV 81
Cdd:cd04969    13 LAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270807 [Multi-domain] Cd Length: 296 Bit Score: 70.90 E-value: 1.65e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARL-QHDCVLYFHEAFERRR------GLVIV 943
Cdd:cd06637     8 FELVELVGNGTYGQVYKGRHVKTGQLAAIKVMDVTGDEEEEIKQEINMLKKYsHHRNIATYYGAFIKKNppgmddQLWLV 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTEELLERMAR--KPTVCESETRTYM-RQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTP 1020
Cdd:cd06637    88 MEFCGAGSVTDLIKntKGNTLKEEWIAYIcREILRGLSHLHQHKVIHRDIKGQNVLLTENA----EVKLVDFGVSAQLDR 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYCQF-GTPEFVAPEIV--NQSPVSGV---TDIWPVGVVAFLCLTGISPFVGENDRTTLMNI-RNYNVAFEETTFls 1093
Cdd:cd06637   164 TVGRRNTFiGTPYWMAPEVIacDENPDATYdfkSDLWSLGITAIEMAEGAPPLCDMHPMRALFLIpRNPAPRLKSKKW-- 241

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 1094 lSREARGFLIKVLVQDR-LRPTAEETLEHPWFKTEAKGAEVSTdHLKLFLSRRRWQR 1149
Cdd:cd06637   242 -SKKFQSFIESCLVKNHsQRPSTEQLMKHPFIRDQPNERQVRI-QLKDHIDRTKKKR 296

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270964 [Multi-domain] Cd Length: 253 Bit Score: 69.73 E-value: 1.84e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2325 QLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG--------SAQPYNPQAlkplghrTGTLEFMAPEMVR---GD 2393
Cdd:cd14062    97 QTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGlatvktrwSGSQQFEQP-------TGSILWMAPEVIRmqdEN 169

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2394 PIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGG---RFDAFQLYPNTSQSatlfLRKVLS 2457
Cdd:cd14062   170 PYSFQSDVYAFGIVLYELLTGQLPYSHINNRDQILFMVGRgylRPDLSKVRSDTPKA----LRRLME 232

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271051 [Multi-domain] Cd Length: 283 Bit Score: 70.45 E-value: 1.93e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMsLHEAYITPRYLVLIAESCGNREL---LCGL 2308
Cdd:cd14149    23 GSFGTVYKGKWHGDVAVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNIL-LFMGYMTKDNLAIVTQWCEGSSLykhLHVQ 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2309 SDRFR-YSEDDVATyvvQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ-----PYNPQALKPlghrTGTL 2382
Cdd:cd14149   102 ETKFQmFQLIDIAR---QTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATvksrwSGSQQVEQP----TGSI 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2383 EFMAPEMVR---GDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRF---DAFQLYPNTSQSATLFLRKVL 2456
Cdd:cd14149   175 LWMAPEVIRmqdNNPFSFQSDVYSYGIVLYELMTGELPYSHINNRDQIIFMVGRGYaspDLSKLYKNCPKAMKRLVADCI 254

                         250       260
                  ....*....|....*....|....*....
gi 564369110 2457 SVHPWSRPSLQDCLAHPWLQDAYLMKLRR 2485
Cdd:cd14149   255 KKVKEERPLFPQILSSIELLQHSLPKINR 283

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270934 [Multi-domain] Cd Length: 266 Bit Score: 69.72 E-value: 2.10e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIhqEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQHDCVLYFHEAFER----RRGLVIV 943
Cdd:cd14032     5 FDI--ELGRGSFKTVYKGLDTETWVEVAWCELQDRKLTKVERQRfkeEAEMLKGLQHPNIVRFYDFWEScakgKRCIVLV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTEELLERMARKPTVCESET-RTYMRQVLEGIGYLHQSH--VLHLDVKPENLLVwdgAGGEEQVRICDFGNAQeLTP 1020
Cdd:cd14032    83 TELMTSGTLKTYLKRFKVMKPKVlRSWCRQILKGLLFLHTRTppIIHRDLKCDNIFI---TGPTGSVKIGDLGLAT-LKR 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 1021 GEPQYCQFGTPEFVAPEIVNQSPVSGVtDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14032   159 ASFAKSVIGTPEFMAPEMYEEHYDESV-DVYAFGMCMLEMATSEYPY 204

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270791 [Multi-domain] Cd Length: 295 Bit Score: 70.48 E-value: 2.22e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2225 FLEEKARGRFGVVRSCRENATGRTFVAKIVPYA--AEGKRRVLQEYEVLrtlhherLMSLHEAYITPRYLVLIAES---- 2298
Cdd:cd06618    19 NLGEIGSGTCGQVYKMRHKKTGHVMAVKQMRRSgnKEENKRILMDLDVV-------LKSHDCPYIVKCYGYFITDSdvfi 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CgnREL----LCGLSDRFR--YSEDDVATYVVQLLQGLDYLHGRH-VLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQ 2370
Cdd:cd06618    92 C--MELmstcLDKLLKRIQgpIPEDILGKMTVSIVKALHYLKEKHgVIHRDVKPSNILLDESGNVKLCDFGiSGRLVDSK 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 AlkplghRT---GTLEFMAPEMVRGDPIGS---ATDIWGAGVLTYIMLSGYSPFYEPDPQ-ETEARIVGGRFDAFQLYPN 2443
Cdd:cd06618   170 A------KTrsaGCAAYMAPERIDPPDNPKydiRADVWSLGISLVELATGQFPYRNCKTEfEVLTKILNEEPPSLPPNEG 243

                         250       260       270
                  ....*....|....*....|....*....|....
gi 564369110 2444 TSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd06618   244 FSPDFCSFVDLCLTKDHRYRPKYRELLQHPFIRR 277

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 64.83 E-value: 2.34e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   1856 KDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVSCKDGRQLLSIPRASKRHAGLYECSATNVLGSITSSC 1935
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 564369110   1936 TVAV 1939
Cdd:smart00410   82 TLTV 85

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143384 [Multi-domain] Cd Length: 342 Bit Score: 71.09 E-value: 2.37e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQeIGRGAFSYLRRVVERSSGLEFAAKFI--PSQAKPKAS-ARREARLLARLQHDCVLYFHEAFERR------RGL 940
Cdd:cd07879    17 YTSLKQ-VGSGAYGSVCSAIDKRTGEKVAIKKLsrPFQSEIFAKrAYRELTLLKHMQHENVIGLLDVFTSAvsgdefQDF 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTEELLERMARKptVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTP 1020
Cdd:cd07879    96 YLVMPYMQTDLQKIMGHP--LSEDKVQYLVYQMLCGLKYIHSAGIIHRDLKPGNLAVNEDC----ELKILDFGLARHADA 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYCQfgTPEFVAPE-IVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI-------------------- 1079
Cdd:cd07879   170 EMTGYVV--TRWYRAPEvILNWMHYNQTVDIWSVGCIMAEMLTGKTLFKGKDYLDQLTQIlkvtgvpgpefvqkledkaa 247

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1080 RNYNVAFEE-------TTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF--------KTEAKGAEVSTDHLKlfLS 1143
Cdd:cd07879   248 KSYIKSLPKyprkdfsTLFPKASPQAVDLLEKMLELDvDKRLTATEALEHPYFdsfrdadeETEQQPYDDSLENEK--LS 325


                  ....*.
gi 564369110 1144 RRRWQR 1149
Cdd:cd07879   326 VDEWKK 331

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270954 [Multi-domain] Cd Length: 278 Bit Score: 69.76 E-value: 2.66e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERS-SGLEFAAKFI-PSQAKPKASARR--EARLLARLQ---HDCVLYFHEAFERRRGLVIVTELCTE 949
Cdd:cd14052     8 IGSGEFSQVYKVSERVpTGKVYAVKKLkPNYAGAKDRLRRleEVSILRELTldgHDNIVQLIDSWEYHGHLYIQTELCEN 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ----ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGeeqVRICDFGNAQELtPGEPQY 1025
Cdd:cd14052    88 gsldVFLSELGLLGRLDEFRVWKILVELSLGLRFIHDHHFVHLDLKPANVLI-TFEGT---LKIGDFGMATVW-PLIRGI 162

                         170       180       190
                  ....*....|....*....|....*....|...
gi 564369110 1026 CQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAF 1058
Cdd:cd14052   163 EREGDREYIAPEILSEHMYDKPADIFSLGLILL 195

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270897 [Multi-domain] Cd Length: 256 Bit Score: 69.27 E-value: 2.67e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVlqeyEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSD 2310
Cdd:cd13995    14 RGAFGKVYLAQDTKTKKRMACKLIPVEQFKPSDV----EIQACFRHENIAELYGALLWEETVHLFMEAGEGGSVLEKLES 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2311 RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALkIVDFG-SAQ----PYNPQALKplghrtGTLEFM 2385
Cdd:cd13995    90 CGPMREFEIIWVTKHVLKGLDFLHSKNIIHHDIKPSNIVFMSTKAV-LVDFGlSVQmtedVYVPKDLR------GTEIYM 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2386 APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEAR---IVGGRFDAFQLYPNT-SQSATLFLRKVLSVHPW 2461
Cdd:cd13995   163 SPEVILCRGHNTKADIYSLGATIIHMQTGSPPWVRRYPRSAYPSylyIIHKQAPPLEDIAQDcSPAMRELLEAALERNPN 242

                         250
                  ....*....|....
gi 564369110 2462 SRPSLQDCLAHPWL 2475
Cdd:cd13995   243 HRSSAAELLKHEAL 256

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 64.58 E-value: 2.72e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  333 APLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENlRLRQDGGLHSLHIARVGSEDEGLYEVSATNTH 412
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAAD-RSTCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                          90
                  ....*....|.
gi 564369110  413 GQAHCSAQLYV 423
Cdd:cd20976    80 GQVSCSAWVTV 90

serine/threonine-protein kinase PknD;

Pssm-ID: 183880 [Multi-domain] Cd Length: 932 Bit Score: 72.50 E-value: 3.00e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2328 QGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQ-----------------ALKPLGHRTGTLEFMAPEMV 2390
Cdd:PRK13184  124 ATIEYVHSKGVLHRDLKPDNILLGLFGEVVILDWGAAIFKKLEeedlldidvdernicysSMTIPGKIVGTPDYMAPERL 203

                          90       100
                  ....*....|....*....|....*...
gi 564369110 2391 RGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:PRK13184  204 LGVPASESTDIYALGVILYQMLTLSFPY 231

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143344 [Multi-domain] Cd Length: 284 Bit Score: 69.77 E-value: 3.25e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSG---------LEFAAKFIPSqakpkaSARREARLLARLQHDCVLYFHEAFERRRGLV 941
Cdd:cd07839     2 YEKLEKIGEGTYGTVFKAKNRETHeivalkrvrLDDDDEGVPS------SALREICLLKELKHKNIVRLYDVLHSDKKLT 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110  942 IVTELCTEELLERM-ARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQ 1016
Cdd:cd07839    76 LVFEYCDQDLKKYFdSCNGDIDPEIVKSFMFQLLKGLAFCHSHNVLHRDLKPQNLLI----NKNGELKLADFGLAR 147

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 64.53 E-value: 3.45e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  458 PDFLRPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRRMTQYRDIHRLVFPAVGPQHAGVYKSVIANKLG 537
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSVG 81

                          90
                  ....*....|
gi 564369110  538 KAACYAHLYV 547
Cdd:cd20972    82 SDTTSAEIFV 91

Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group is composed of fungal NDR-like proteins including Saccharomyces cerevisiae CBK1 (or CBK1p), Schizosaccharomyces pombe Orb6 (or Orb6p), Ustilago maydis Ukc1 (or Ukc1p), and Neurospora crassa Cot1. Like NDR kinase, group members contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. CBK1 is an essential component in the RAM (regulation of Ace2p activity and cellular morphogenesis) network. CBK1 and Orb6 play similar roles in coordinating cell morphology with cell cycle progression. Ukc1 is involved in morphogenesis, pathogenicity, and pigment formation. Cot1 plays a role in polar tip extension.The fungal NDR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270778 [Multi-domain] Cd Length: 377 Bit Score: 70.65 E-value: 3.49e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYAAEGKR----RVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd05629    11 KGAFGEVRLVQKKDTGKIYAMKTLLKSEMFKKdqlaHVKAERDVLAESDSPWVVSLYYSFQDAQYLYLIMEFLPGGDLMT 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA-------------QPYNPQALK 2373
Cdd:cd05629    91 MLIKYDTFSEDVTRFYMAECVLAIEAVHKLGFIHRDIKPDNILIDRGGHIKLSDFGLStgfhkqhdsayyqKLLQGKSNK 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2374 P--------------------------------LGHRT-GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYE 2420
Cdd:cd05629   171 NridnrnsvavdsinltmsskdqiatwkknrrlMAYSTvGTPDYIAPEIFLQQGYGQECDWWSLGAIMFECLIGWPPFCS 250

                         250
                  ....*....|....
gi 564369110 2421 PDPQETEARIVGGR 2434
Cdd:cd05629   251 ENSHETYRKIINWR 264

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270943 [Multi-domain] Cd Length: 309 Bit Score: 70.09 E-value: 3.60e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2262 RRVLQEYEVLRTLHHERLMSLHEAY-ITPRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRH--V 2338
Cdd:cd14041    55 KHACREYRIHKELDHPRIVKLYDYFsLDTDSFCTVLEYCEGNDLDFYLKQHKLMSEKEARSIIMQIVNALKYLNEIKppI 134

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2339 LHLDIKPDNLLLAADNA---LKIVDFGSAQ-----PYNP-QALKPLGHRTGTLEFMAPE--MVRGDP--IGSATDIWGAG 2405
Cdd:cd14041   135 IHYDLKPGNILLVNGTAcgeIKITDFGLSKimdddSYNSvDGMELTSQGAGTYWYLPPEcfVVGKEPpkISNKVDVWSVG 214

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110 2406 VLTYIMLSGYSPFYEPDPQE---TEARIVGGRFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14041   215 VIFYQCLYGRKPFGHNQSQQdilQENTILKATEVQFPPKPVVTPEAKAFIRRCLAYRKEDRIDVQQLACDPYL 287

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270941 [Multi-domain] Cd Length: 289 Bit Score: 69.56 E-value: 3.72e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2237 VRSCRenatgrtfvakiVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLV-----LIAESCGN---RELL--- 2305
Cdd:cd14039    23 IKSCR------------LELSVKNKDRWCHEIQIMKKLNHPNVVKACDVPEEMNFLVndvplLAMEYCSGgdlRKLLnkp 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2306 ---CGLSdrfrysEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNAL---KIVDFGSAQPYNPQALkpLGHRT 2379
Cdd:cd14039    91 encCGLK------ESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVLQEINGKivhKIIDLGYAKDLDQGSL--CTSFV 162

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 564369110 2380 GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd14039   163 GTLQYLAPELFENKSYTVTVDYWSFGTMVFECIAGFRPF 201

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 63.74 E-value: 3.80e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   341 EDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDGGLHSLHIARVGSEDEGLYEVSATN 410
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 64.36 E-value: 4.12e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  755 PRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLaESNHVSFVY----EENECSLVVLSAGSQDGGVYTCTAR 830
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPI-DPSSIPGKYkiesEYGVHVLHIRRVTVEDSAVYSAVAK 79

                          90
                  ....*....|....
gi 564369110  831 NLAGEVSCKAELSV 844
Cdd:cd20951    80 NIHGEASSSASVVV 93

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 63.82 E-value: 6.22e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110   243 PLQDVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPAlLKCKMHFDGRKCKLLLTSVHEDDSGVYTCKLSTVKDELTC 322
Cdd:pfam07679    6 KPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSS-DRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEA 84


                   ....*.
gi 564369110   323 SARLTV 328
Cdd:pfam07679   85 SAELTV 90

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271053 [Multi-domain] Cd Length: 274 Bit Score: 68.55 E-value: 6.90e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2267 EYEVLRTLHHERLMsLHEAYITPRYLVLIAESCGNRELLCGL-SDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKP 2345
Cdd:cd14151    54 EVGVLRKTRHVNIL-LFMGYSTKPQLAIVTQWCEGSSLYHHLhIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKS 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2346 DNLLLAADNALKIVDFGSAQPYNP-QALKPLGHRTGTLEFMAPEMVR---GDPIGSATDIWGAGVLTYIMLSGYSPFYEP 2421
Cdd:cd14151   133 NNIFLHEDLTVKIGDFGLATVKSRwSGSHQFEQLSGSILWMAPEVIRmqdKNPYSFQSDVYAFGIVLYELMTGQLPYSNI 212

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 2422 DPQETEARIVGGRF---DAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLA 2471
Cdd:cd14151   213 NNRDQIIFMVGRGYlspDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILA 265

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143383 [Multi-domain] Cd Length: 343 Bit Score: 69.31 E-value: 7.11e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKpYTFLEEKARGRFGVVRSCRENATGRTFVAKIV--PYAAE-GKRRVLQEYEVLRTLHHERLMSLHEAYiTPR----- 2290
Cdd:cd07878    14 PER-YQNLTPVGSGAYGSVCSAYDTRLRQKVAVKKLsrPFQSLiHARRTYRELRLLKHMKHENVIGLLDVF-TPAtsien 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 ----YLV--LIAESCGNRELLCGLSDrfryseDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA 2364
Cdd:cd07878    92 fnevYLVtnLMGADLNNIVKCQKLSD------EHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLA 165

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2365 QpynpQALKPLGHRTGTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV 2431
Cdd:cd07878   166 R----QADDEMTGYVATRWYRAPEiMLNWMHYNQTVDIWSVGCIMAELLKGKALFPGNDYIDQLKRIM 229

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 271050 [Multi-domain] Cd Length: 258 Bit Score: 68.09 E-value: 7.51e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASA---RREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLE 953
Cdd:cd14148     2 IGVGGFGKVYKGLWRGEEVAVKAARQDPDEDIAVTAenvRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGGALN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  954 RMARKPTVCESETRTYMRQVLEGIGYLHQSH---VLHLDVKPENLLVWDGAGGEE----QVRICDFGNAQELTPgEPQYC 1026
Cdd:cd14148    82 RALAGKKVPPHVLVNWAVQIARGMNYLHNEAivpIIHRDLKSSNILILEPIENDDlsgkTLKITDFGLAREWHK-TTKMS 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 564369110 1027 QFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14148   161 AAGTYAWMAPEVIRLSLFSKSSDVWSFGVLLWELLTGEVPY 201

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270960 [Multi-domain] Cd Length: 253 Bit Score: 67.85 E-value: 8.63e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSsgLEFAAKFIPSQAKPKAsARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE----ELL 952
Cdd:cd14058     1 VGRGSFGVVCKARWRN--QIVAVKIIESESEKKA-FEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGgslyNVL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARKPTVCESETRTYMRQVLEGIGYLHQ---SHVLHLDVKPENLLVWDGAggeEQVRICDFGNAqeltpgepqyCQF- 1028
Cdd:cd14058    78 HGKEPKPIYTAAHAMSWALQCAKGVAYLHSmkpKALIHRDLKPPNLLLTNGG---TVLKICDFGTA----------CDIs 144

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 564369110 1029 -------GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14058   145 thmtnnkGSAAWMAPEVFEGSKYSEKCDVFSWGIILWEVITRRKPF 190

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271114 [Multi-domain] Cd Length: 330 Bit Score: 68.82 E-value: 8.96e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLH-------HERLMSLHEAYITPRYLVLI 2295
Cdd:cd14212     1 YLVLDLLGQGTFGQVVKCQDLKTNKLVAVKVLKNKPAYFRQAMLEIAILTLLNtkydpedKHHIVRLLDHFMHHGHLCIV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNR--ELLcgLSDRFR-YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA--LKIVDFGSAqpynpq 2370
Cdd:cd14212    81 FELLGVNlyELL--KQNQFRgLSLQLIRKFLQQLLDALSVLKDARIIHCDLKPENILLVNLDSpeIKLIDFGSA------ 152

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 564369110 2371 alkplGHRTGTL-------EFMAPEMVRGDPIGSATDIWGAG 2405
Cdd:cd14212   153 -----CFENYTLytyiqsrFYRSPEVLLGLPYSTAIDMWSLG 189

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 63.25 E-value: 9.11e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    3 VAPGADVLLKCIITANPPPQVSWKKDG-SVLHSEGRLLIRAEGE-RHTLLLREAQAADAGSYTATATNELGQASCASSLA 80
Cdd:cd05892    12 VLEGDPVRLECQISAIPPPQIFWKKNNeMLQYNTDRISLYQDNCgRICLLIQNANKKDAGWYTVSAVNEAGVVSCNARLD 91


                  .
gi 564369110   81 V 81
Cdd:cd05892    92 V 92

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270932 [Multi-domain] Cd Length: 289 Bit Score: 68.54 E-value: 9.42e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIhqEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQHDCVLYFHEAFER----RRGLVIV 943
Cdd:cd14030    29 FDI--EIGRGSFKTVYKGLDTETTVEVAWCELQDRKLSKSERQRfkeEAGMLKGLQHPNIVRFYDSWEStvkgKKCIVLV 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTEELLERMARKPTVCESET-RTYMRQVLEGIGYLHQSH--VLHLDVKPENLLVwdgAGGEEQVRICDFGNAQeLTP 1020
Cdd:cd14030   107 TELMTSGTLKTYLKRFKVMKIKVlRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFI---TGPTGSVKIGDLGLAT-LKR 182

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 1021 GEPQYCQFGTPEFVAPEIVNQSPVSGVtDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14030   183 ASFAKSVIGTPEFMAPEMYEEKYDESV-DVYAFGMCMLEMATSEYPY 228

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 62.80 E-value: 9.84e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLhSEGRLLIRAEgerHTLLLREAQAADAGSYTATATNELGQASCASSLA 80
Cdd:cd05725     7 QVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-PKGRYEILDD---HSLKIRKVTAGDMGSYTCVAENMVGKIEASATLT 82


                  .
gi 564369110   81 V 81
Cdd:cd05725    83 V 83

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270749 [Multi-domain] Cd Length: 333 Bit Score: 68.88 E-value: 9.99e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPS----QAKPKASARREARLLARLQHDCV--LYFheAFERRRGLVI 942
Cdd:cd05598     1 SMFEKIKTIGVGAFGEVSLVRKKDTNALYAMKTLRKkdvlKRNQVAHVKAERDILAEADNEWVvkLYY--SFQDKENLYF 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  943 VTE-LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGnaqeLTPG 1021
Cdd:cd05598    79 VMDyIPGGDLMSLLIKKGIFEEDLARFYIAELVCAIESVHKMGFIHRDIKPDNILI-DRDG---HIKLTDFG----LCTG 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 -----EPQYCQ----FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFL 1092
Cdd:cd05598   151 frwthDSKYYLahslVGTPNYIAPEVLLRTGYTQLCDWWSVGVILYEMLVGQPPFLAQTPAETQLKVINWRTTLKIPHEA 230

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 1093 SLSREARGFLIKVL--VQDRL-RPTAEETLEHPWFK 1125
Cdd:cd05598   231 NLSPEAKDLILRLCcdAEDRLgRNGADEIKAHPFFA 266

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS1 functions as a tumor suppressor and is implicated in cell cycle regulation. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. Promoter methylation, loss of heterozygosity, and missense mutations targeting the LATS1 gene have also been found in human sarcomas and ovarian cancers. In addition, decreased expression of LATS1 is associated with an aggressive phenotype and poor prognosis. LATS1 induces G2 arrest and promotes cytokinesis. It may be a component of the mitotic exit network in higher eukaryotes. The LATS1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270775 [Multi-domain] Cd Length: 382 Bit Score: 69.31 E-value: 1.08e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  910 ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE-LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHL 988
Cdd:cd05625    46 AHVKAERDILAEADNEWVVRLYYSFQDKDNLYFVMDyIPGGDMMSLLIRMGVFPEDLARFYIAELTCAVESVHKMGFIHR 125

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  989 DVKPENLLVwDGAGgeeQVRICDFG----------------------NAQELTP--GEPQYCQ----------------- 1027
Cdd:cd05625   126 DIKPDNILI-DRDG---HIKLTDFGlctgfrwthdskyyqsgdhlrqDSMDFSNewGDPENCRcgdrlkplerraarqhq 201

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 -------FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSREARG 1100
Cdd:cd05625   202 rclahslVGTPNYIAPEVLLRTGYTQLCDWWSVGVILFEMLVGQPPFLAQTPLETQMKVINWQTSLHIPPQAKLSPEASD 281

                         250       260
                  ....*....|....*....|....*....
gi 564369110 1101 FLIKVL--VQDRL-RPTAEETLEHPWFKT 1126
Cdd:cd05625   282 LIIKLCrgPEDRLgKNGADEIKAHPFFKT 310

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270967 [Multi-domain] Cd Length: 252 Bit Score: 67.52 E-value: 1.08e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKfIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL----CTEELL 952
Cdd:cd14065     1 LGKGFFGEVYKVTHRETGKVMVMK-ELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYvnggTLEELL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMarKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVrICDFGNAQELtPGEP--------Q 1024
Cdd:cd14065    80 KSM--DEQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVREANRGRNAV-VADFGLAREM-PDEKtkkpdrkkR 155

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 564369110 1025 YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVafLC 1060
Cdd:cd14065   156 LTVVGSPYWMAPEMLRGESYDEKVDVFSFGIV--LC 189

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270843 [Multi-domain] Cd Length: 328 Bit Score: 68.75 E-value: 1.18e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIhQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR---REARLLARLQHDCVLYFHEAF-ERRRGLVIVTE 945
Cdd:cd07856    12 YSDL-QPVGMGAFGLVCSARDQLTGQNVAVKKIMKPFSTPVLAKrtyRELKLLKHLRHENIISLSDIFiSPLEDIYFVTE 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPtVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPQY 1025
Cdd:cd07856    91 LLGTDLHRLLTSRP-LEKQFIQYFLYQILRGLKYVHSAGVIHRDLKPSNILVNENC----DLKICDFGLARIQDPQMTGY 165

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 1026 CQfgTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEN 1071
Cdd:cd07856   166 VS--TRYYRAPEImLTWQKYDVEVDIWSAGCIFAEMLEGKPLFPGKD 210

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132950 [Multi-domain] Cd Length: 279 Bit Score: 67.98 E-value: 1.26e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2225 FLEEKARGRFGVVRSCRENATGRTFVAKIVPY--AAEGKRRVLQEYEVLrtlhherlMSLHEAYITPRYLVLIAEscgNR 2302
Cdd:cd06619     5 YQEILGHGNGGTVYKAYHLLTRRILAVKVIPLdiTVELQKQIMSELEIL--------YKCDSPYIIGFYGAFFVE---NR 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLC------GLSDRFRYSEDDVATYV-VQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKp 2374
Cdd:cd06619    74 ISICtefmdgGSLDVYRKIPEHVLGRIaVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGvSTQLVNSIAKT- 152

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 564369110 2375 lghRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd06619   153 ---YVGTNAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPY 193

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143382 [Multi-domain] Cd Length: 345 Bit Score: 68.53 E-value: 1.28e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2213 TLRQGPPQkpYTFLEEKARGRFGVVRSCRENATG-RTFVAKIV-PYAAE-GKRRVLQEYEVLRTLHHERLMSLHEAYITP 2289
Cdd:cd07877    11 TIWEVPER--YQNLSPVGSGAYGSVCAAFDTKTGlRVAVKKLSrPFQSIiHAKRTYRELRLLKHMKHENVIGLLDVFTPA 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2290 RYL------VLIAESCG---NRELLCGlsdrfRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVD 2360
Cdd:cd07877    89 RSLeefndvYLVTHLMGadlNNIVKCQ-----KLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILD 163

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2361 FGSAQPYNPQalkpLGHRTGTLEFMAPE-MVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd07877   164 FGLARHTDDE----MTGYVATRWYRAPEiMLNWMHYNQTVDIWSVGCIMAELLTGRTLF 218

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270829 [Multi-domain] Cd Length: 283 Bit Score: 67.70 E-value: 1.29e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  902 IPSqakpkaSARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMARKPTV--CESETRTYMRQVLEGIGY 979
Cdd:cd07835    41 VPS------TAIREISLLKELNHPNIVRLLDVVHSENKLYLVFEFLDLDLKKYMDSSPLTglDPPLIKSYLYQLLQGIAF 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  980 LHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQeltpgepqycQFGTP------EFV-----APEIVNQSP-VSGV 1047
Cdd:cd07835   115 CHSHRVLHRDLKPQNLLI-DTEG---ALKLADFGLAR----------AFGVPvrtythEVVtlwyrAPEILLGSKhYSTP 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1048 TDIWPVGVVAFLCLTGISPFVGENDRTTLMNI------------------RNYNVAF-------EETTFLSLSREARGFL 1102
Cdd:cd07835   181 VDIWSVGCIFAEMVTRRPLFPGDSEIDQLFRIfrtlgtpdedvwpgvtslPDYKPTFpkwarqdLSKVVPSLDEDGLDLL 260

                         250       260
                  ....*....|....*....|...
gi 564369110 1103 IKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07835   261 SQMLVYDpAKRISAKAALQHPYF 283

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 61.96 E-value: 1.35e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  351 ARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDGGLHSLHIARVGSEDEGLYEVSATNTH-GQAHCSA 419
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAgGSASASV 70

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270892 [Multi-domain] Cd Length: 279 Bit Score: 67.73 E-value: 1.43e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  912 ARREARLLARLQHDCVLYFHEAFE-RRRGLVIVTELCT-EELLERMARKPTVCESETRTYMRQVLEGIGYL--HQSHVLH 987
Cdd:cd13990    51 ALREYEIHKSLDHPRIVKLYDVFEiDTDSFCTVLEYCDgNDLDFYLKQHKSIPEREARSIIMQVVSALKYLneIKPPIIH 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  988 LDVKPENLLVWDGAGGEEqVRICDFGNAQ------------ELTPgepqycQF-GTPEFVAPEI--VNQSP--VSGVTDI 1050
Cdd:cd13990   131 YDLKPGNILLHSGNVSGE-IKITDFGLSKimddesynsdgmELTS------QGaGTYWYLPPECfvVGKTPpkISSKVDV 203

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 1051 WPVGVVAFLCLTGISPF-VGENDRTTLMN---IRNYNVAFEETTflSLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd13990   204 WSVGVIFYQMLYGRKPFgHNQSQEAILEEntiLKATEVEFPSKP--VVSSEAKDFIRRCLTYRkEDRPDVLQLANDPY 279

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270835 [Multi-domain] Cd Length: 286 Bit Score: 67.79 E-value: 1.46e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  911 SARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMARKPTVCE-SETRTYMRQVLEGIGYLHQSHVLHLD 989
Cdd:cd07844    44 TAIREASLLKDLKHANIVTLHDIIHTKKTLTLVFEYLDTDLKQYMDDCGGGLSmHNVRLFLFQLLRGLAYCHQRRVLHRD 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  990 VKPENLLVWDgaGGEeqVRICDFGNAQELTPGEPQYcqfgTPEFVA-----PEIVNQSP-VSGVTDIWPVGVVAFLCLTG 1063
Cdd:cd07844   124 LKPQNLLISE--RGE--LKLADFGLARAKSVPSKTY----SNEVVTlwyrpPDVLLGSTeYSTSLDMWGVGCIFYEMATG 195


                  ....*....
gi 564369110 1064 ISPFVGEND 1072
Cdd:cd07844   196 RPLFPGSTD 204

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271002 [Multi-domain] Cd Length: 254 Bit Score: 66.92 E-value: 1.55e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  934 FERRRGLVIVTEL--CTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEeqVRICD 1011
Cdd:cd14100    74 FERPDSFVLVLERpePVQDLFDFITERGALPEELARSFFRQVLEAVRHCHNCGVLHRDIKDENILI-DLNTGE--LKLID 150

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1012 FGNAQELTpgEPQYCQF-GTPEFVAPEIVNQSPVSGVT-DIWPVGVVAFLCLTGISPFvgENDRttlmNIRNYNVAFEEt 1089
Cdd:cd14100   151 FGSGALLK--DTVYTDFdGTRVYSPPEWIRFHRYHGRSaAVWSLGILLYDMVCGDIPF--EHDE----EIIRGQVFFRQ- 221

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 564369110 1090 tflSLSREARgFLIKVLVQDRL--RPTAEETLEHPW 1123
Cdd:cd14100   222 ---RVSSECQ-HLIKWCLALRPsdRPSFEDIQNHPW 253

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270816 [Multi-domain] Cd Length: 319 Bit Score: 68.16 E-value: 1.57e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2226 LEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEG--KRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRE 2303
Cdd:cd06650    10 ISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPaiRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGS 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2304 LLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRH-VLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPLGHRTgt 2381
Cdd:cd06650    90 LDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHkIMHRDVKPSNILVNSRGEIKLCDFGvSGQLIDSMANSFVGTRS-- 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2382 leFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEaRIVGGRFDAFQLYPNTSQSATlfLRKVLSVHPW 2461
Cdd:cd06650   168 --YMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELE-LMFGCQVEGDAAETPPRPRTP--GRPLSSYGMD 242


                  ....*
gi 564369110 2462 SRPSL 2466
Cdd:cd06650   243 SRPPM 247

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270970 [Multi-domain] Cd Length: 252 Bit Score: 66.90 E-value: 1.70e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2262 RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELL-----CGLSDRFRYSeddvatYVVQLLQGLDYLHGR 2336
Cdd:cd14068    32 RLLRQELVVLSHLHHPSLVALLAAGTAPRMLVMELAPKGSLDALlqqdnASLTRTLQHR------IALHVADGLRYLHSA 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2337 HVLHLDIKPDNLL---LAADNAL--KIVDFGSAQPYNPQALKPlghRTGTLEFMAPEMVRGDPI-GSATDIWGAGVLTYI 2410
Cdd:cd14068   106 MIIYRDLKPHNVLlftLYPNCAIiaKIADYGIAQYCCRMGIKT---SEGTPGFRAPEVARGNVIyNQQADVYSFGLLLYD 182


                  ....
gi 564369110 2411 MLSG 2414
Cdd:cd14068   183 ILTC 186

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270636 [Multi-domain] Cd Length: 258 Bit Score: 66.98 E-value: 1.78e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCR-ENATGRTF-VA-----KIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRyLVLIAESCGNREL 2304
Cdd:cd05040     6 GSFGVVRRGEwTTPSGKVIqVAvkclkSDVLSQPNAMDDFLKEVNAMHSLDHPNLIRLYGVVLSSP-LMMVTELAPLGSL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 LcglsDRFRYSEDD--VAT---YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG--SAQPYNPQALKPLGH 2377
Cdd:cd05040    85 L----DRLRKDQGHflISTlcdYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGlmRALPQNEDHYVMQEH 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 564369110 2378 RTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSP 2417
Cdd:cd05040   161 RKVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTyGEEP 201

Unstructured region on SPEG complex protein; SPEG_u2 is a region of natively unstructured but conserved sequence on Striated muscle-specific serine/threonine-protein kinase proteins in higher eukaryotes. It lies between two I-set immunoglobulin, pfam07679, domains. The function is not known.

Pssm-ID: 293256 Cd Length: 57 Bit Score: 60.98 E-value: 2.20e-11

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110    82 RPGASTSPFSSPITSDEEYLSPPEEFPEPGETWSRTPTMKPSPSQDRDSSDSSSKAP 138
Cdd:pfam16650    1 EPGGAKSPFSSPITSDEEYLSPPEEFPEPEEAWHKTPAMKLSPSQAHQAPDTGSKAP 57

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3). PIM3 can inhibit apoptosis and promote cell survival and protein translation, therefore, it can enhance the proliferation of normal and cancer cells. Mice deficient with PIM3 show minimal effects, suggesting that PIM3 msy not be essential. Since its expression is enhanced in several cancers, it may make a good molecular target for cancer drugs. The PIM3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271004 [Multi-domain] Cd Length: 253 Bit Score: 66.52 E-value: 2.24e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  934 FERRRGLVIVTEL--CTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEeqVRICD 1011
Cdd:cd14102    73 YERPDGFLIVMERpePVKDLFDFITEKGALDEDTARGFFRQVLEAVRHCYSCGVVHRDIKDENLLV-DLRTGE--LKLID 149

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1012 FGNAQELTpgEPQYCQF-GTPEFVAPEIVNQSPVSGVT-DIWPVGVVAFLCLTGISPFvgENDRtTLMNIRNYnvaFEEt 1089
Cdd:cd14102   150 FGSGALLK--DTVYTDFdGTRVYSPPEWIRYHRYHGRSaTVWSLGVLLYDMVCGDIPF--EQDE-EILRGRLY---FRR- 220

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 564369110 1090 tflSLSREARGfLIKVLVQDRL--RPTAEETLEHPW 1123
Cdd:cd14102   221 ---RVSPECQQ-LIKWCLSLRPsdRPTLEQIFDHPW 252

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173657 [Multi-domain] Cd Length: 256 Bit Score: 66.44 E-value: 2.27e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2221 KPYTFLEEKARGRFGVVRSCRENatGRTFVA-KIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESC 2299
Cdd:cd05113     4 KDLTFLKELGTGQFGVVKYGKWR--GQYDVAiKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYM 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GNRELLCGLSDRFRYSEddvatyVVQLLQ-------GLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQA 2371
Cdd:cd05113    82 ANGCLLNYLREMRKRFQ------TQQLLEmckdvceAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGlSRYVLDDEY 155

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2372 LKPLGHRTgTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPFYEPDPQETEARIVGGR 2434
Cdd:cd05113   156 TSSVGSKF-PVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSlGKMPYERFTNSETVEHVSQGL 218

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270768 [Multi-domain] Cd Length: 357 Bit Score: 68.12 E-value: 2.28e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKAS----ARREARLLARLQHDCVLY-FHEAFERRRGLVIVTE 945
Cdd:cd05617    17 FDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEdidwVQTEKHVFEQASSNPFLVgLHSCFQTTSRLFLVIE 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQE-LTPGEP 1023
Cdd:cd05617    97 YVNGgDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLL-DADG---HIKLTDYGMCKEgLGPGDT 172

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 564369110 1024 QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd05617   173 TSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPF 216

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270841 [Multi-domain] Cd Length: 337 Bit Score: 67.97 E-value: 2.29e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2322 YVV-QLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA----QPYNPQALKPLGHRTGTLEFMAPEMVrgdpIG 2396
Cdd:cd07852   111 YIMyQLLKALKYLHSGGVIHRDLKPSNILLNSDCRVKLADFGLArslsQLEEDDENPVLTDYVATRWYRAPEIL----LG 186

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2397 S-----ATDIWGAGVLTYIMLSGySPFY-----------------EPDPQETEArIVGG-------------RFDAFQLY 2441
Cdd:cd07852   187 StrytkGVDMWSVGCILGEMLLG-KPLFpgtstlnqlekiievigRPSAEDIES-IQSPfaatmleslppsrPKSLDELF 264

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 564369110 2442 PNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd07852   265 PKASPDALDLLKKLLVFNPNKRLTAEEALRHPYVAQ 300

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270935 [Multi-domain] Cd Length: 261 Bit Score: 66.57 E-value: 2.34e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIhqEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQHDCVLYFHEAFERR-RG---LVIV 943
Cdd:cd14033     5 FNI--EIGRGSFKTVYRGLDTETTVEVAWCELQTRKLSKGERQRfseEVEMLKGLQHPNIVRFYDSWKSTvRGhkcIILV 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTEELLERMAR-----KPTVCESetrtYMRQVLEGIGYLHQSH--VLHLDVKPENLLVwdgAGGEEQVRICDFGNAQ 1016
Cdd:cd14033    83 TELMTSGTLKTYLKrfremKLKLLQR----WSRQILKGLHFLHSRCppILHRDLKCDNIFI---TGPTGSVKIGDLGLAT 155

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1017 eLTPGEPQYCQFGTPEFVAPEIVNQSPVSGVtDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14033   156 -LKRASFAKSVIGTPEFMAPEMYEEKYDEAV-DVYAFGMCILEMATSEYPY 204

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270854 [Multi-domain] Cd Length: 297 Bit Score: 66.95 E-value: 2.73e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  911 SARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMARKPTVCE-SETRTYMRQVLEGIGYLHQSHVLHLD 989
Cdd:cd07873    46 TAIREVSLLKDLKHANIVTLHDIIHTEKSLTLVFEYLDKDLKQYLDDCGNSINmHNVKLFLFQLLRGLAYCHRRKVLHRD 125

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  990 VKPENLLVWDGAggeeQVRICDFGNAQELT-PGEPQYCQFGTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd07873   126 LKPQNLLINERG----ELKLADFGLARAKSiPTKTYSNEVVTLWYRPPDIlLGSTDYSTQIDMWGVGCIFYEMSTGRPLF 201

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1068 VGENDRTTLMNI-RNYNVAFEET--------TFLS-----------------LSREARGFLIKVL-VQDRLRPTAEETLE 1120
Cdd:cd07873   202 PGSTVEEQLHFIfRILGTPTEETwpgilsneEFKSynypkyradalhnhaprLDSDGADLLSKLLqFEGRKRISAEEAMK 281


                  ....
gi 564369110 1121 HPWF 1124
Cdd:cd07873   282 HPYF 285

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173637 [Multi-domain] Cd Length: 256 Bit Score: 66.32 E-value: 2.81e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSgLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL----Ctee 950
Cdd:cd05059    10 KELGSGQFGVVHLGKWRGK-IDVAIKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEYmangC--- 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  951 LLERMARKPTVCESETRTYM-RQVLEGIGYLHQSHVLHLDVKPENLLVwdgagGEEQ-VRICDFGNAQELTpgEPQY-CQ 1027
Cdd:cd05059    86 LLNYLRERRGKFQTEQLLEMcKDVCEAMEYLESNGFIHRDLAARNCLV-----GEQNvVKVSDFGLARYVL--DDEYtSS 158

                         170       180       190
                  ....*....|....*....|....*....|..
gi 564369110 1028 FGTP---EFVAPEIVNQSPVSGVTDIWPVGVV 1056
Cdd:cd05059   159 VGTKfpvKWSPPEVFMYSKFSSKSDVWSFGVL 190

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270845 [Multi-domain] Cd Length: 285 Bit Score: 66.67 E-value: 2.84e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIhQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPK---ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd07861     1 DYTKI-EKIGEGTYGVVYKGRNKKTGQIVAMKKIRLESEEEgvpSTAIREISLLKELQHPNIVCLEDVLMQENRLYLVFE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKPT--VCESET-RTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQeltpge 1022
Cdd:cd07861    80 FLSMDLKKYLDSLPKgkYMDAELvKSYLYQILQGILFCHSRRVLHRDLKPQNLLI-DNKG---VIKLADFGLAR------ 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 pqycQFGTP------EFV-----APEIVNQSP-VSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI----------- 1079
Cdd:cd07861   150 ----AFGIPvrvythEVVtlwyrAPEVLLGSPrYSTPVDIWSIGTIFAEMATKKPLFHGDSEIDQLFRIfrilgtptedi 225

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1080 -------RNYNVAFEE-------TTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWF 1124
Cdd:cd07861   226 wpgvtslPDYKNTFPKwkkgslrTAVKNLDEDGLDLLEKMLIYDpAKRISAKKALVHPYF 285

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132980 [Multi-domain] Cd Length: 331 Bit Score: 67.38 E-value: 2.99e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2226 LEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEG--KRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRE 2303
Cdd:cd06649    10 ISELGAGNGGVVTKVQHKPSGLIMARKLIHLEIKPaiRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGS 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2304 LLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRH-VLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPLGHRTgt 2381
Cdd:cd06649    90 LDQVLKEAKRIPEEILGKVSIAVLRGLAYLREKHqIMHRDVKPSNILVNSRGEIKLCDFGvSGQLIDSMANSFVGTRS-- 167

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 2382 leFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEA 2428
Cdd:cd06649   168 --YMSPERLQGTHYSVQSDIWSMGLSLVELAIGRYPIPPPDAKELEA 212

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270806 [Multi-domain] Cd Length: 282 Bit Score: 66.57 E-value: 3.60e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARL-QHDCVLYFHEAFERRR------GLVIV 943
Cdd:cd06636    18 FELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDVTEDEEEEIKLEINMLKKYsHHRNIATYYGAFIKKSppghddQLWLV 97

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTEELLERMARKP---TVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTP 1020
Cdd:cd06636    98 MEFCGAGSVTDLVKNTkgnALKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENA----EVKLVDFGVSAQLDR 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYCQF-GTPEFVAPEIV--NQSPVSGV---TDIWPVGVVAFLCLTGISPFVGENDRTTLMNI-RNYNVAFEETTFls 1093
Cdd:cd06636   174 TVGRRNTFiGTPYWMAPEVIacDENPDATYdyrSDIWSLGITAIEMAEGAPPLCDMHPMRALFLIpRNPPPKLKSKKW-- 251

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 1094 lSREARGFLIKVLVQDRL-RPTAEETLEHPW 1123
Cdd:cd06636   252 -SKKFIDFIEGCLVKNYLsRPSTEQLLKHPF 281

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270812 [Multi-domain] Cd Length: 272 Bit Score: 66.22 E-value: 3.75e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQ-AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIV 943
Cdd:cd06645     7 RNPQEDFELIQRIGSGTYGDVYKARNVNTGELAAIKVIKLEpGEDFAVVQQEIIMMKDCKHSNIVAYFGSYLRRDKLWIC 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTEELLERMAR-KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGE 1022
Cdd:cd06645    87 MEFCGGGSLQDIYHvTGPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNG----HVKLADFGVSAQITATI 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQF-GTPEFVAPEIVNQSPVSG---VTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNvaFEETTF---LSLS 1095
Cdd:cd06645   163 AKRKSFiGTPYWMAPEVAAVERKGGynqLCDIWAVGITAIELAELQPPMFDLHPMRALFLMTKSN--FQPPKLkdkMKWS 240

                         250       260
                  ....*....|....*....|....*....
gi 564369110 1096 REARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd06645   241 NSFHHFVKMALTKNpKKRPTAEKLLQHPF 269

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270913 [Multi-domain] Cd Length: 287 Bit Score: 66.19 E-value: 4.10e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2325 QLLQGLDYLHGR-HVLHLDIKPDNLLLAADNALKIVDFG---SAQPYNPQALKPLGHRTG-------TLEFMAPEMVRGD 2393
Cdd:cd14011   122 QISEALSFLHNDvKLVHGNICPESVVINSNGEWKLAGFDfciSSEQATDQFPYFREYDPNlpplaqpNLNYLAPEYILSK 201

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2394 PIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEAR--IVGGRFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLA 2471
Cdd:cd14011   202 TCDPASDMFSLGVLIYAIYNKGKPLFDCVNNLLSYKknSNQLRQLSLSLLEKVPEELRDHVKTLLNVTPEVRPDAEQLSK 281


                  ....*.
gi 564369110 2472 HPWLQD 2477
Cdd:cd14011   282 IPFFDD 287

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 61.28 E-value: 4.23e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  458 PDFLRPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRRMTQYRD---IHRLVFPAVGPQHAGVYKSVIAN 534
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESeygVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 564369110  535 KLGKAACYAHLYV 547
Cdd:cd20951    81 IHGEASSSASVVV 93

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270846 [Multi-domain] Cd Length: 290 Bit Score: 66.21 E-value: 4.55e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKI---VPYAAEG-KRRVLQEYEVLR---TLHHERLMSLHEAYITPRylvli 2295
Cdd:cd07862     3 YECVAEIGEGAYGKVFKARDLKNGGRFVALKrvrVQTGEEGmPLSTIREVAVLRhleTFEHPNVVRLFDVCTVSR----- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 aescGNREllCGLSDRFRYSEDDVATYV-----------------VQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKI 2358
Cdd:cd07862    78 ----TDRE--TKLTLVFEHVDQDLTTYLdkvpepgvptetikdmmFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKL 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2359 VDFGSAQPYNPQAlkPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSgYSPFYE-----------------P 2421
Cdd:cd07862   152 ADFGLARIYSFQM--ALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFR-RKPLFRgssdvdqlgkildviglP 228

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2422 DPQETEARIVGGRfDAF---------QLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd07862   229 GEEDWPRDVALPR-QAFhsksaqpieKFVTDIDELGKDLLLKCLTFNPAKRISAYSALSHPY 289

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271109 [Multi-domain] Cd Length: 340 Bit Score: 66.95 E-value: 4.62e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2317 DDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY--NPQALKPlGHRTGTLEFMAPEMVRGDP 2394
Cdd:cd14207   180 EDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIykNPDYVRK-GDARLPLKWMAPESIFDKI 258

                          90       100
                  ....*....|....*....|....*
gi 564369110 2395 IGSATDIWGAGVLTYIMLS-GYSPF 2418
Cdd:cd14207   259 YSTKSDVWSYGVLLWEIFSlGASPY 283

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270760 [Multi-domain] Cd Length: 280 Bit Score: 65.89 E-value: 4.68e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2216 QGPPQKPYTFLEEKARGRFGVVRSCRENATGRTFVakivpyaaegkRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLI 2295
Cdd:cd05609    10 NGAYGAVYLVRHRETRQRFAMKKINKQNLILRNQI-----------QQVFVERDILTFAENPFVVSMYCSFETKRHLCMV 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA----------- 2364
Cdd:cd05609    79 MEYVEGGDCATLLKNIGPLPVDMARMYFAETVLALEYLHSYGIVHRDLKPDNLLITSMGHIKLTDFGLSkiglmslttnl 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2365 -QPYNPQALKPLG--HRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqlY 2441
Cdd:cd05609   159 yEGHIEKDTREFLdkQVCGTPEYIAPEVILRQGYGKPVDWWAMGIILYEFLVGCVPFFGDTPEELFGQVISDEIE----W 234

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 564369110 2442 PNTSQS----ATLFLRKVLSVHPWSR---PSLQDCLAHPWLQD 2477
Cdd:cd05609   235 PEGDDAlpddAQDLITRLLQQNPLERlgtGGAEEVKQHPFFQD 277

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271047 [Multi-domain] Cd Length: 270 Bit Score: 65.83 E-value: 4.83e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEF-AAKFIPSQ--AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLE 953
Cdd:cd14145    14 IGIGGFGKVYRAIWIGDEVAVkAARHDPDEdiSQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLN 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  954 RMARKPTVCESETRTYMRQVLEGIGYLHQSH---VLHLDVKPENLL----VWDGAGGEEQVRICDFGNAQELTPgEPQYC 1026
Cdd:cd14145    94 RVLSGKRIPPDILVNWAVQIARGMNYLHCEAivpVIHRDLKSSNILilekVENGDLSNKILKITDFGLAREWHR-TTKMS 172

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 564369110 1027 QFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVG 1069
Cdd:cd14145   173 AAGTYAWMAPEVIRSSMFSKGSDVWSYGVLLWELLTGEVPFRG 215

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270813 [Multi-domain] Cd Length: 268 Bit Score: 65.82 E-value: 5.02e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKAS-ARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE 949
Cdd:cd06646    11 YELIQRVGSGTYGDVYKARNLHTGELAAVKIIKLEPGDDFSlIQQEIFMVKECKHCNIVAYFGSYLSREKLWICMEYCGG 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMAR-KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPQYCQF 1028
Cdd:cd06646    91 GSLQDIYHvTGPLSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNG----DVKLADFGVAAKITATIAKRKSF 166

                         170       180       190
                  ....*....|....*....|....*....|...
gi 564369110 1029 -GTPEFVAPEIVNQSPVSG---VTDIWPVGVVA 1057
Cdd:cd06646   167 iGTPYWMAPEVAAVEKNGGynqLCDIWAVGITA 199

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270740 [Multi-domain] Cd Length: 328 Bit Score: 66.68 E-value: 5.22e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  931 HEAFERRRGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRI 1009
Cdd:cd05588    62 HSCFQTESRLFFVIEFVNGgDLMFHMQRQRRLPEEHARFYSAEISLALNFLHEKGIIYRDLKLDNVLL-DSEG---HIKL 137

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1010 CDFGNAQE-LTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF--VGENDRTTlMNIRNY--NV 1084
Cdd:cd05588   138 TDYGMCKEgLRPGDTTSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMLAGRSPFdiVGSSDNPD-QNTEDYlfQV 216

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1085 AFEETTFL--SLSREA----RGFLIKVlVQDRL--RPTA--EETLEHPWFKT 1126
Cdd:cd05588   217 ILEKPIRIprSLSVKAasvlKGFLNKN-PAERLgcHPQTgfADIQSHPFFRT 267

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270940 [Multi-domain] Cd Length: 290 Bit Score: 66.14 E-value: 5.24e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2237 VRSCRENATGRTfvakivpyaaegKRRVLQEYEVLRTLHHERLMSLHEA-----YITPRYLVLIA-ESCGNREL------ 2304
Cdd:cd14038    24 IKQCRQELSPKN------------RERWCLEIQIMKRLNHPNVVAARDVpeglqKLAPNDLPLLAmEYCQGGDLrkylnq 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2305 ---LCGLSdrfrysEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA-ADNAL--KIVDFGSAQPYNPQALkpLGHR 2378
Cdd:cd14038    92 fenCCGLR------EGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQqGEQRLihKIIDLGYAKELDQGSL--CTSF 163

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 564369110 2379 TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd14038   164 VGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPF 203

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132953 [Multi-domain] Cd Length: 286 Bit Score: 66.03 E-value: 5.61e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  973 VLEGIGYLHQSH-VLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQY---CQ-FGTPEFVAPEIVNQSPVSGV 1047
Cdd:cd06622   111 VVKGLKFLKEEHnIIHRDVKPTNVLV----NGNGQVKLCDFGVSGNLVASLAKTnigCQsYMAPERIKSGGPNQNPTYTV 186

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1048 -TDIWPVGVVAFLCLTGISPFVGEndrtTLMNIRNYNVAFEETTFLSL----SREARGFLIKVLVQD-RLRPTAEETLEH 1121
Cdd:cd06622   187 qSDVWSLGLSILEMALGRYPYPPE----TYANIFAQLSAIVDGDPPTLpsgySDDAQDFVAKCLNKIpNRRPTYAQLLEH 262

                         170
                  ....*....|..
gi 564369110 1122 PWFKTEaKGAEV 1133
Cdd:cd06622   263 PWLVKY-KNADV 273

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

Pssm-ID: 271112 [Multi-domain] Cd Length: 311 Bit Score: 66.03 E-value: 5.87e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCglSDRFR-YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADN--ALKIVDFGSAQPYNPQALKPLGHRt 2379
Cdd:cd14210   103 ELLK--SNNFQgLSLSLIRKFAKQILQALQFLHKLNIIHCDLKPENILLKQPSksSIKVIDFGSSCFEGEKVYTYIQSR- 179

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 564369110 2380 gtleFM-APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFyepdPQETE 2427
Cdd:cd14210   180 ----FYrAPEVILGLPYDTAIDMWSLGCILAELYTGYPLF----PGENE 220

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271038 [Multi-domain] Cd Length: 320 Bit Score: 66.06 E-value: 6.45e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  864 GRRLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARL--------QHDCVLYFHEAFE 935
Cdd:cd14136     5 GEVYNGRYHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLKCVreadpkdpGREHVVQLLDDFK 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  936 RR----RGLVIVTELCTEELLERMARK-----PTVCeseTRTYMRQVLEGIGYLH-QSHVLHLDVKPENLLVwdgAGGEE 1005
Cdd:cd14136    85 HTgpngTHVCMVFEVLGPNLLKLIKRYnyrgiPLPL---VKKIARQVLQGLDYLHtKCGIIHTDIKPENVLL---CISKI 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1006 QVRICDFGNAqeltpgepqyC----QFG----TPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTG-------------- 1063
Cdd:cd14136   159 EVKIADLGNA----------CwtdkHFTediqTRQYRSPEVILGAGYGTPADIWSTACMAFELATGdylfdphsgedysr 228

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1064 -------ISPFVGE----------------NDRTTLMNIRN------YNVAFEETTFlsLSREAR---GFLIKVLVQD-R 1110
Cdd:cd14136   229 dedhlalIIELLGRiprsiilsgkysreffNRKGELRHISKlkpwplEDVLVEKYKW--SKEEAKefaSFLLPMLEYDpE 306

                         330
                  ....*....|....
gi 564369110 1111 LRPTAEETLEHPWF 1124
Cdd:cd14136   307 KRATAAQCLQHPWL 320

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 60.94 E-value: 6.53e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVR--PDQRRFAEEAEGGLCrLRILAAERGDAGFYTCKAVN 216
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQynTDRISLYQDNCGRIC-LLIQNANKKDAGWYTVSAVN 79

                          90
                  ....*....|...
gi 564369110  217 EYGARQCEARLEV 229
Cdd:cd05892    80 EAGVVSCNARLDV 92

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270847 [Multi-domain] Cd Length: 302 Bit Score: 65.98 E-value: 7.25e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  864 GRRLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA---SARREARLLARLQHDCVLYFHEA------- 933
Cdd:cd07864     2 GKRCVDKFDIIGIIGEGTYGQVYKAKDKDTGELVALKKVRLDNEKEGfpiTAIREIKILRQLNHRSVVNLKEIvtdkqda 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  934 --FERRRG-LVIVTELCTEELLERMARKPT-VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRI 1009
Cdd:cd07864    82 ldFKKDKGaFYLVFEYMDHDLMGLLESGLVhFSEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILL----NNKGQIKL 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1010 CDFGNAQ----------------------ELTPGEPQY----------CQFG-----------TPEFVAPEIVNQSPVSG 1046
Cdd:cd07864   158 ADFGLARlynseesrpytnkvitlwyrppELLLGEERYgpaidvwscgCILGelftkkpifqaNQELAQLELISRLCGSP 237

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 1047 VTDIWPvgvvaflcltGISPFVGENdrtTLMNIRNYNVAFEEtTFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPW 1123
Cdd:cd07864   238 CPAVWP----------DVIKLPYFN---TMKPKKQYRRRLRE-EFSFIPTPALDLLDHMLTLDpSKRCTAEQALNSPW 301

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270791 [Multi-domain] Cd Length: 295 Bit Score: 65.47 E-value: 7.65e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  979 YLHQSH-VLHLDVKPENLLV-WDGaggeeQVRICDFGNAQELTPGEPQYCQFGTPEFVAPEIVNQSPVSGV---TDIWPV 1053
Cdd:cd06618   129 YLKEKHgVIHRDVKPSNILLdESG-----NVKLCDFGISGRLVDSKAKTRSAGCAAYMAPERIDPPDNPKYdirADVWSL 203

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 1054 GVVAFLCLTGISPFVGEN-DRTTLMNIRNynvafEETTFLSL----SREARGFLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd06618   204 GISLVELATGQFPYRNCKtEFEVLTKILN-----EEPPSLPPnegfSPDFCSFVDLCLTKDhRYRPKYRELLQHPFIR 276

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270742 [Multi-domain] Cd Length: 323 Bit Score: 66.08 E-value: 7.72e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFIPS----QAKPKASARREARLL--ARlQHDCVLYFHEAFERRRGLVIVTELCT 948
Cdd:cd05590     1 RVLGKGSFGKVMLARLKESGRLYAVKVLKKdvilQDDDVECTMTEKRILslAR-NHPFLTQLYCCFQTPDRLFFVMEFVN 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  949 E-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQE-LTPGEPQYC 1026
Cdd:cd05590    80 GgDLMFHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLL----DHEGHCKLADFGMCKEgIFNGKTTST 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1027 QFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREARGFLIKVL 1106
Cdd:cd05590   156 FCGTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPTW----LSQDAVDILKAFM 231

                         250       260
                  ....*....|....*....|....*.
gi 564369110 1107 VQD---RLRPTA----EETLEHPWFK 1125
Cdd:cd05590   232 TKNptmRLGSLTlggeEAILRHPFFK 257

Catalytic domain of the Protein Serine/Threonine Kinase, Large Tumor Suppressor 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS2 is an essential mitotic regulator responsible for coordinating accurate cytokinesis completion and governing the stabilization of other mitotic regulators. It is also critical in the maintenance of proper chromosome number, genomic stability, mitotic fidelity, and the integrity of centrosome duplication. Downregulation of LATS2 is associated with poor prognosis in acute lymphoblastic leukemia and breast cancer. The LATS2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173715 [Multi-domain] Cd Length: 381 Bit Score: 66.57 E-value: 8.67e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  910 ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC----TEELLERMARKPtvcESETRTYMRQVLEGIGYLHQSHV 985
Cdd:cd05626    46 AHVKAERDILAEADNEWVVKLYYSFQDKDNLYFVMDYIpggdMMSLLIRMEVFP---EVLARFYIAELTLAIESVHKMGF 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  986 LHLDVKPENLLV-WDGaggeeQVRICDFG---------NAQELTPG--------EP------------------------ 1023
Cdd:cd05626   123 IHRDIKPDNILIdLDG-----HIKLTDFGlctgfrwthNSKYYQKGshirqdsmEPsdlwddvsncrcgdrlktleqrat 197

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 ---QYCQ----FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSLSR 1096
Cdd:cd05626   198 kqhQRCLahslVGTPNYIAPEVLLRKGYTQLCDWWSVGVILFEMLVGQPPFLAPTPTETQLKVINWENTLHIPPQVKLSP 277

                         250       260       270
                  ....*....|....*....|....*....|.
gi 564369110 1097 EARGFLIKVL--VQDRL-RPTAEETLEHPWF 1124
Cdd:cd05626   278 EAVDLITKLCcsAEERLgRNGADDIKAHPFF 308

serine/threonine kinase US3; Provisional

Pssm-ID: 165476 [Multi-domain] Cd Length: 501 Bit Score: 67.03 E-value: 9.26e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2228 EKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCgNRELLcg 2307
Cdd:PHA03210  174 EEAEARRGVNSTNQGKPKCERLIAKRVKAGSRAAIQLENEILALGRLNHENILKIEEILRSEANTYMITQKY-DFDLY-- 250

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 lsdRFRYSED----------DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY-NPQALKPLG 2376
Cdd:PHA03210  251 ---SFMYDEAfdwkdrpllkQTRAIMKQLLCAVEYIHDKKLIHRDIKLENIFLNCDGKIVLGDFGTAMPFeKEREAFDYG 327

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 564369110 2377 HrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS 2413
Cdd:PHA03210  328 W-VGTVATNSPEILAGDGYCEITDIWSCGLILLDMLS 363

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271052 [Multi-domain] Cd Length: 265 Bit Score: 64.65 E-value: 1.03e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  913 RREARLLARLQHDCVLYFHeAFERRRGLVIVTELCTEELLERMARkptVCESETRTYM-----RQVLEGIGYLHQSHVLH 987
Cdd:cd14150    44 KNEMQVLRKTRHVNILLFM-GFMTRPNFAIITQWCEGSSLYRHLH---VTETRFDTMQlidvaRQTAQGMDYLHAKNIIH 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  988 LDVKPENLLVWDGAggeeQVRICDFGNAQELT--PGEPQYCQ-FGTPEFVAPEIV---NQSPVSGVTDIWPVGVVAFLCL 1061
Cdd:cd14150   120 RDLKSNNIFLHEGL----TVKIGDFGLATVKTrwSGSQQVEQpSGSILWMAPEVIrmqDTNPYSFQSDVYAYGVVLYELM 195

                         170       180
                  ....*....|....*....|...
gi 564369110 1062 TGISPF--VGENDRTTLMNIRNY 1082
Cdd:cd14150   196 SGTLPYsnINNRDQIIFMVGRGY 218

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143377 [Multi-domain] Cd Length: 309 Bit Score: 65.40 E-value: 1.13e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  911 SARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMARKPTVCE-SETRTYMRQVLEGIGYLHQSHVLHLD 989
Cdd:cd07872    50 TAIREVSLLKDLKHANIVTLHDIVHTDKSLTLVFEYLDKDLKQYMDDCGNIMSmHNVKIFLYQILRGLAYCHRRKVLHRD 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  990 VKPENLLVWDGAggeeQVRICDFGNAQ-ELTPGEPQYCQFGTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd07872   130 LKPQNLLINERG----ELKLADFGLARaKSVPTKTYSNEVVTLWYRPPDVlLGSSEYSTQIDMWGVGCIFFEMASGRPLF 205

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1068 VGENDRTTLMNI---------------------RNYNV-AFEETTFLS----LSREARGFLIKVL-VQDRLRPTAEETLE 1120
Cdd:cd07872   206 PGSTVEDELHLIfrllgtpteetwpgissndefKNYNFpKYKPQPLINhaprLDTEGIELLTKFLqYESKKRISAEEAMK 285


                  ....*.
gi 564369110 1121 HPWFKT 1126
Cdd:cd07872   286 HAYFRS 291

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 59.27 E-value: 1.23e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110  772 ARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLAGE 835
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGG 64

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270943 [Multi-domain] Cd Length: 309 Bit Score: 65.08 E-value: 1.40e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKF--------IPSQAKPKASARREARLLARLQHDCVLYFHEAFE-RR 937
Cdd:cd14041     4 LNDRYLLLHLLGRGGFSEVYKAFDLTEQRYVAVKIhqlnknwrDEKKENYHKHACREYRIHKELDHPRIVKLYDYFSlDT 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  938 RGLVIVTELCTEELLE-RMARKPTVCESETRTYMRQVLEGIGYLHQSH--VLHLDVKPENLLVWDGAGGEEqVRICDFG- 1013
Cdd:cd14041    84 DSFCTVLEYCEGNDLDfYLKQHKLMSEKEARSIIMQIVNALKYLNEIKppIIHYDLKPGNILLVNGTACGE-IKITDFGl 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1014 ------------NAQELTPGEPqycqfGTPEFVAPE--IVNQSP--VSGVTDIWPVGVVAFLCLTGISPFvGENDRTTLM 1077
Cdd:cd14041   163 skimdddsynsvDGMELTSQGA-----GTYWYLPPEcfVVGKEPpkISNKVDVWSVGVIFYQCLYGRKPF-GHNQSQQDI 236

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 564369110 1078 NIRNYNVAFEETTFLS---LSREARGFLIKVLV---QDRL 1111
Cdd:cd14041   237 LQENTILKATEVQFPPkpvVTPEAKAFIRRCLAyrkEDRI 276

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270962 [Multi-domain] Cd Length: 242 Bit Score: 63.82 E-value: 1.41e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  878 GRGAFSYLRRVVERSSGLEFAAKFIPSQAKpkasarrEARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-ELLERMA 956
Cdd:cd14060     2 GGGSFGSVYRAIWVSQDKEVAVKKLLKIEK-------EAEILSVLSHRNIIQFYGAILEAPNYGIVTEYASYgSLFDYLN 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  957 RKPT--VCESETRTYMRQVLEGIGYLHQS---HVLHLDVKPENLLVwdgaGGEEQVRICDFGnAQELTPGEPQYCQFGTP 1031
Cdd:cd14060    75 SNESeeMDMDQIMTWATDIAKGMHYLHMEapvKVIHRDLKSRNVVI----AADGVLKICDFG-ASRFHSHTTHMSLVGTF 149

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 564369110 1032 EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVG 1069
Cdd:cd14060   150 PWMAPEVIQSLPVSETCDTYSYGVVLWEMLTREVPFKG 187

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270841 [Multi-domain] Cd Length: 337 Bit Score: 65.27 E-value: 1.41e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI------PSQAKpkasaR--REARLLARL-QHDCV---LYFHE 932
Cdd:cd07852     3 KHILRRYEILKKLGKGAYGIVWKAIDKKTGEVVALKKIfdafrnATDAQ-----RtfREIMFLQELnDHPNIiklLNVIR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  933 AfERRRGLVIVTElCTEELLERMARKpTVCESETRTY-MRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICD 1011
Cdd:cd07852    78 A-ENDKDIYLVFE-YMETDLHAVIRA-NILEDIHKQYiMYQLLKALKYLHSGGVIHRDLKPSNILL----NSDCRVKLAD 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1012 FGNAQELTPGEPQYCQFGTPEFVA------PEIVNQSP--VSGVtDIWPVG-VVAFLcLTGISPFVGendrTTLMN---- 1078
Cdd:cd07852   151 FGLARSLSQLEEDDENPVLTDYVAtrwyraPEILLGSTryTKGV-DMWSVGcILGEM-LLGKPLFPG----TSTLNqlek 224

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 1079 ------------IRNYNVAFEET---------------TFLSLSREARGFLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd07852   225 iievigrpsaedIESIQSPFAATmleslppsrpksldeLFPKASPDALDLLKKLLVFNpNKRLTAEEALRHPYVA 299

Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The beta-ARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270757 [Multi-domain] Cd Length: 279 Bit Score: 64.77 E-value: 1.43e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGEPQYCqFGTPEFVAPEIVNQ- 1041
Cdd:cd05606    97 EAEMRFYAAEVILGLEHMHNRFIVYRDLKPANILL-DEHG---HVRISDLGLACDFSKKKPHAS-VGTHGYMAPEVLQKg 171

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1042 SPVSGVTDIWPVGVVAFLCLTGISPFVG-------ENDRTTLmnirNYNVAFEEttflSLSREARGFLIKVL---VQDRL 1111
Cdd:cd05606   172 VAYDSSADWFSLGCMLYKLLKGHSPFRQhktkdkhEIDRMTL----TMNVELPD----SFSPELKSLLEGLLqrdVSKRL 243

                         170
                  ....*....|....*..
gi 564369110 1112 ---RPTAEETLEHPWFK 1125
Cdd:cd05606   244 gclGRGATEVKEHPFFK 260

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270862 [Multi-domain] Cd Length: 257 Bit Score: 64.38 E-value: 1.46e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI---PSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLV-IVTEL 946
Cdd:cd08223     2 YQFLRVIGKGSYGEVWLVRHKRDRKQYVIKKLnlkNASKRERKAAEQEAKLLSKLKHPNIVSYKESFEGEDGFLyIVMGF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CT-EELLERMARKPTVCESEtrtymRQVLE-------GIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQEL 1018
Cdd:cd08223    82 CEgGDLYTRLKEQKGVLLEE-----RQVVEwfvqiamALQYMHERNILHRDLKTQNIFL----TKSNIIKVGDLGIARVL 152

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 564369110 1019 tpgEPQY----CQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLT 1062
Cdd:cd08223   153 ---ESSSdmatTLIGTPYYMSPELFSNKPYNHKSDVWALGCCVYEMAT 197

Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GAK, also called auxilin-2, contains an N-terminal kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of PTEN-like, clathrin-binding, and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor. It also interacts with the androgen receptor, acting as a transcriptional coactivator, and its expression is significantly increased with the progression of prostate cancer. The GAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270938 [Multi-domain] Cd Length: 282 Bit Score: 64.45 E-value: 1.51e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  873 IHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASA-RREARLLARLQ-HDCVLYFHEAF-----ERRRG---LVI 942
Cdd:cd14036     4 IKRVIAEGGFAFVYEAQDVGTGKEYALKRLLSNEEEKNKAiIQEINFMKKLSgHPNIVQFCSAAsigkeESDQGqaeYLL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  943 VTELCTEELLERM----ARKPTVCESETRTYMrQVLEGIGYLHQSH--VLHLDVKPENLLVwdGAGGeeQVRICDFGNA- 1015
Cdd:cd14036    84 LTELCKGQLVDFVkkveAPGPFSPDTVLKIFY-QTCRAVQHMHKQSppIIHRDLKIENLLI--GNQG--QIKLCDFGSAt 158

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1016 -QELTPG-----------EPQYCQFGTPEFVAPEIVN---QSPVSGVTDIWPVG-VVAFLC 1060
Cdd:cd14036   159 tEAHYPDyswsaqkrslvEDEITRNTTPMYRTPEMIDlysNYPIGEKQDIWALGcILYLLC 219

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143383 [Multi-domain] Cd Length: 343 Bit Score: 65.46 E-value: 1.57e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARR---EARLLARLQHDCVLYFHEAF------ERRRGLVIVTELC 947
Cdd:cd07878    23 VGSGAYGSVCSAYDTRLRQKVAVKKLSRPFQSLIHARRtyrELRLLKHMKHENVIGLLDVFtpatsiENFNEVYLVTNLM 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TEELlERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPGEPQYCq 1027
Cdd:cd07878   103 GADL-NNIVKCQKLSDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDC----ELRILDFGLARQADDEMTGYV- 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1028 fGTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPF---------------VGENDRTTLMNI-----RNYNVAF 1086
Cdd:cd07878   177 -ATRWYRAPEImLNWMHYNQTVDIWSVGCIMAELLKGKALFpgndyidqlkrimevVGTPSPEVLKKIssehaRKYIQSL 255

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 564369110 1087 EETTFLSLSREARG-------FLIKVLVQDR-LRPTAEETLEHPWF 1124
Cdd:cd07878   256 PHMPQQDLKKIFRGanplaidLLEKMLVLDSdKRISASEALAHPYF 301

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270761 [Multi-domain] Cd Length: 349 Bit Score: 65.29 E-value: 1.57e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFS--YLRRvvERSSGLEFAAK------FIPSQAKPKASARREARLLARLQHDCVLYFheAFERRRGLVI 942
Cdd:cd05610     6 FVIVKPISRGAFGkvYLGR--KKNNSKLYAVKvvkkadMINKNMVHQVQAERDALALSKSPFIVHLYY--SLQSANNVYL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  943 VTELC----TEELL-------ERMARKptvcesetrtYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICD 1011
Cdd:cd05610    82 VMEYLiggdVKSLLhiygyfdEEMAVK----------YISEVALALDYLHRHGIIHRDLKPDNMLI----SNEGHIKLTD 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1012 FG-------------------------NAQELTPGE------------------PQYCQ-----------FGTPEFVAPE 1037
Cdd:cd05610   148 FGlskvtlnrelnmmdilttpsmakpkNDYSRTPGQvlslisslgfntptpyrtPKSVRrgaarvegeriLGTPDYLAPE 227

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1038 IVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTfLSLSREARGFLIKVLVQDRL-RPTAE 1116
Cdd:cd05610   228 LLLGKPHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILNRDIPWPEGE-EELSVNAQNAIEILLTMDPTkRAGLK 306


                  ....*...
gi 564369110 1117 ETLEHPWF 1124
Cdd:cd05610   307 ELKQHPLF 314

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 59.40 E-value: 1.83e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1849 PVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVSCKD-GRQLLSIPRASKRHAGLYECSATNV 1927
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRISLYQDNcGRICLLIQNANKKDAGWYTVSAVNE 80


                  ....*....
gi 564369110 1928 LGsiTSSCT 1936
Cdd:cd05892    81 AG--VVSCN 87

Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB2 binds and negatively regulates the mitogen activated protein kinase (MAPK) kinases, MKK7 and MEK1, which are activators of the MAPKs, ERK and JNK. It controls the activation of inflammatory monocytes, which is essential in innate immune responses and the pathogenesis of inflammatory diseases such as atherosclerosis. TRB2 expression is down-regulated in human acute myeloid leukaemia (AML), which may lead to enhanced cell survival and pathogenesis of the disease. TRB2 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270924 [Multi-domain] Cd Length: 242 Bit Score: 63.52 E-value: 2.26e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHRTGTLEFMAPEMVR--GDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRFDafqlYPNT-SQSATLF 2451
Cdd:cd14022   143 LSDKHGCPAYVSPEILNtsGSYSGKAADVWSLGVMLYTMLVGRYPFHDIEPSSLFSKIRRGQFN----IPETlSPKAKCL 218

                          90       100
                  ....*....|....*....|....
gi 564369110 2452 LRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14022   219 IRSILRREPSERLTSQEILDHPWF 242

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132946 [Multi-domain] Cd Length: 308 Bit Score: 64.38 E-value: 2.37e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2226 LEEKARGRFGVVRSCRENATGRTFVAKIV--PYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRE 2303
Cdd:cd06615     6 LGELGAGNGGVVTKVLHRPSGLIMARKLIhlEIKPAIRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGS 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2304 LLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGRH-VLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPLGHRTgt 2381
Cdd:cd06615    86 LDQVLKKAGRIPENILGKISIAVLRGLTYLREKHkIMHRDVKPSNILVNSRGEIKLCDFGvSGQLIDSMANSFVGTRS-- 163

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 2382 leFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEA 2428
Cdd:cd06615   164 --YMSPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPIPPPDAKELEA 208

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270636 [Multi-domain] Cd Length: 258 Bit Score: 63.52 E-value: 2.46e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSG---LEFAAKFIPSQAKPKASA----RREARLLARLQHDCVLyfheafeRRRGLVI----- 942
Cdd:cd05040     1 EKLGDGSFGVVRRGEWTTPSgkvIQVAVKCLKSDVLSQPNAmddfLKEVNAMHSLDHPNLI-------RLYGVVLssplm 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  943 -VTELCT-EELLERMaRKP-------TVCEsetrtYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGaggeEQVRICDFG 1013
Cdd:cd05040    74 mVTELAPlGSLLDRL-RKDqghflisTLCD-----YAVQIANGMAYLESKRFIHRDLAARNILLASK----DKVKIGDFG 143

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1014 NAQELTPGEPQYC---QFGTP-EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLT-GISPFVGENDRTTLMNI 1079
Cdd:cd05040   144 LMRALPQNEDHYVmqeHRKVPfAWCAPESLKTRKFSHASDVWMFGVTLWEMFTyGEEPWLGLNGSQILEKI 214

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271034 [Multi-domain] Cd Length: 306 Bit Score: 64.10 E-value: 2.51e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2210 ESTTLRQGPpQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKI---VPyaaegKRRVLQEYEVLRTLH-HERLMSLHEA 2285
Cdd:cd14132     8 ENLNVEWGS-QDDYEIIRKIGRGKYSEVFEGINIGNNEKVVIKVlkpVK-----KKKIKREIKILQNLRgGPNIVKLLDV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2286 YITP--RYLVLIAESCGN---RELLCGLSDrfryseDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA-LKIV 2359
Cdd:cd14132    82 VKDPqsKTPSLIFEYVNNtdfKTLYPTLTD------YDIRYYMYELLKALDYCHSKGIMHRDVKPHNIMIDHEKRkLRLI 155

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2360 DFGSA------QPYNPqalkplghRTGTLEFMAPEMVRG----DPigsATDIWGAGVLTYIMLSGYSPFYE 2420
Cdd:cd14132   156 DWGLAefyhpgQEYNV--------RVASRYYKGPELLVDyqyyDY---SLDMWSLGCMLASMIFRKEPFFH 215

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 59.29 E-value: 2.51e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  334 PLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQD--GGLHSLHIARVGSEDEGLYEVSATNT 411
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLPGVQISfsDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|..
gi 564369110  412 HGQAHCSAQLYV 423
Cdd:cd20974    81 SGQATSTAELLV 92

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270840 [Multi-domain] Cd Length: 337 Bit Score: 64.36 E-value: 2.71e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2262 RRVLQEYEVLRTLHHERLMSLHEAYiTPR---------YLVL---IAESCG--NRELlcglsDRFRYSeddvatYVV-QL 2326
Cdd:cd07850    44 KRAYRELVLMKLVNHKNIIGLLNVF-TPQksleefqdvYLVMelmDANLCQviQMDL-----DHERMS------YLLyQM 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2327 LQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpqalkplghRTGTLEFM-----------APEMVRGDPI 2395
Cdd:cd07850   112 LCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLA-------------RTAGTSFMmtpyvvtryyrAPEVILGMGY 178

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2396 GSATDIWGAGVLTYIMLSGYSPF------------YE----PDP------QETEARIVGGR-------FDAF---QLYPN 2443
Cdd:cd07850   179 KENVDIWSVGCIMGEMIRGTVLFpgtdhidqwnkiIEqlgtPSDefmsrlQPTVRNYVENRpkyagysFEELfpdVLFPP 258

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 564369110 2444 TSQS--------ATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd07850   259 DSEEhnklkasqARDLLSKMLVIDPEKRISVDDALQHPYI 298

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270942 [Multi-domain] Cd Length: 299 Bit Score: 63.92 E-value: 3.01e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGlEFAAKFIPSQAKP---------KASARREARLLARLQHDCVLYFHEAFE-R 936
Cdd:cd14040     4 LNERYLLLHLLGRGGFSEVYKAFDLYEQ-RYAAVKIHQLNKSwrdekkenyHKHACREYRIHKELDHPRIVKLYDYFSlD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  937 RRGLVIVTELCTEELLE-RMARKPTVCESETRTYMRQVLEGIGYLHQ--SHVLHLDVKPENLLVWDGAGGEEqVRICDFG 1013
Cdd:cd14040    83 TDTFCTVLEYCEGNDLDfYLKQHKLMSEKEARSIVMQIVNALRYLNEikPPIIHYDLKPGNILLVDGTACGE-IKITDFG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1014 NAQEL------TPGEPQYCQ-FGTPEFVAPE--IVNQSP--VSGVTDIWPVGVVAFLCLTGISPFvGENDRTTLMNIRNY 1082
Cdd:cd14040   162 LSKIMdddsygVDGMDLTSQgAGTYWYLPPEcfVVGKEPpkISNKVDVWSVGVIFFQCLYGRKPF-GHNQSQQDILQENT 240

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 564369110 1083 NVAFEETTF---LSLSREARGFLIKVLV---QDRL 1111
Cdd:cd14040   241 ILKATEVQFpvkPVVSNEAKAFIRRCLAyrkEDRF 275

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173729 [Multi-domain] Cd Length: 283 Bit Score: 63.60 E-value: 3.06e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2224 TFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK--RRVLQEYEV-LRTLHHerlmslheAYITPRYLVLIAES-- 2298
Cdd:cd06617     4 EVIEELGRGAYGVVDKMRHVPTGTIMAVKRIRATVNSQeqKRLLMDLDIsMRSVDC--------PYTVTFYGALFREGdv 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 --CgnRELLCGLSDRF---------RYSEDDVATYVVQLLQGLDYLHGR-HVLHLDIKPDNLLLAADNALKIVDFG-SAQ 2365
Cdd:cd06617    76 wiC--MEVMDTSLDKFykkvydkglTIPEDILGKIAVSIVKALEYLHSKlSVIHRDVKPSNVLINRNGQVKLCDFGiSGY 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2366 PYNPQAlKPLghRTGTLEFMAPEmvRGDPIGSA------TDIWGAGVLTYIMLSGYSPfYEP--DPQETEARIVGGRFDA 2437
Cdd:cd06617   154 LVDSVA-KTI--DAGCKPYMAPE--RINPELNQkgydvkSDVWSLGITMIELATGRFP-YDSwkTPFQQLKQVVEEPSPQ 227

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 564369110 2438 FqlyPNTSQSATL--FLRKVLSVHPWSRPSLQDCLAHPWLQDA 2478
Cdd:cd06617   228 L---PAEKFSPEFqdFVNKCLKKNYKERPNYPELLQHPFFELH 267

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270681 [Multi-domain] Cd Length: 343 Bit Score: 64.23 E-value: 3.18e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2247 RTFVAKIVPYAAEGKRRVLQEYEV--LRTLHHERLMSL-------HEAYITPRYLVLIAESCGNRELLCglsdRFRYSED 2317
Cdd:cd05103   104 RSKRSEFVPYKTKGARFRQGKDYVgdISVDLKRRLDSItssqssaSSGFVEEKSLSDVEEEEAGQEDLY----KDFLTLE 179

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2318 DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY--NPQALKPlGHRTGTLEFMAPEMVRGDPI 2395
Cdd:cd05103   180 DLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIykDPDYVRK-GDARLPLKWMAPETIFDRVY 258

                         170       180
                  ....*....|....*....|....
gi 564369110 2396 GSATDIWGAGVLTYIMLS-GYSPF 2418
Cdd:cd05103   259 TIQSDVWSFGVLLWEIFSlGASPY 282

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270914 [Multi-domain] Cd Length: 254 Bit Score: 62.76 E-value: 3.66e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2322 YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA---LKIVDFG-SAQPYNPQALKPLGHRTGTLEFmAPEMVRGD-PIG 2396
Cdd:cd14012   109 WTLQLLEALEYLHRNGVVHKSLHAGNVLLDRDAGtgiVKLTDYSlGKTLLDMCSRGSLDEFKQTYWL-PPELAQGSkSPT 187

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2397 SATDIWGAGVLTYIMLSGyspfyepdpqeteaRIVGGRFDAFQLYPNT-SQSATL--FLRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd14012   188 RKTDVWDLGLLFLQMLFG--------------LDVLEKYTSPNPVLVSlDLSASLqdFLSKCLSLDPKKRPTALELLPHE 253

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271037 [Multi-domain] Cd Length: 318 Bit Score: 63.78 E-value: 4.18e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2319 VATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAAD-NALKIVDFGSAQPYNPQALKP-LGHRTgtleFMAPEMVRGDPIG 2396
Cdd:cd14135   107 VRSYAQQLFLALKHLKKCNILHADIKPDNILVNEKkNTLKLCDFGSASDIGENEITPyLVSRF----YRAPEIILGLPYD 182

                          90
                  ....*....|....*...
gi 564369110 2397 SATDIWGAGVLTYIMLSG 2414
Cdd:cd14135   183 YPIDMWSVGCTLYELYTG 200

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 58.56 E-value: 4.19e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  334 PLFTRLLED-VEVLEGRAARLDCKISGTPPPSVTWTHFGHPVN-ESENLRLRQdgglHSLHIARVGSEDEGLYEVSATNT 411
Cdd:cd20978     1 PKFIQKPEKnVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQgPMERATVED----GTLTIINVQPEDTGYYGCVATNE 76

                          90
                  ....*....|..
gi 564369110  412 HGQAHCSAQLYV 423
Cdd:cd20978    77 IGDIYTETLLHV 88

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270848 [Multi-domain] Cd Length: 310 Bit Score: 63.54 E-value: 4.44e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKA---SARREARLLARLQHDCVLYFHE-------AFERRRG- 939
Cdd:cd07865    14 YEKLAKIGQGTFGEVFKARHRKTGQIVALKKVLMENEKEGfpiTALREIKILQLLKHENVVNLIEicrtkatPYNRYKGs 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  940 LVIVTELCTEEL---LERMARKPTvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVW-DGAggeeqVRICDFGNA 1015
Cdd:cd07865    94 IYLVFEFCEHDLaglLSNKNVKFT--LSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITkDGV-----LKLADFGLA 166

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 58.28 E-value: 4.47e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  141 FKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGlcrLRILAAERGDAGFYTCKAVNEYGA 220
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGS---LQIKGAEKSDTGEYTCVALNLSGE 78


                  ....*....
gi 564369110  221 RQCEARLEV 229
Cdd:cd20952    79 ATWSAVLDV 87

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 58.59 E-value: 4.70e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1849 PVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSL--RSEPSVVIVSCKDGRQLLSIPRASKRHAGLYECSATN 1926
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdpSSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 564369110 1927 VLGSITSSCTVAV 1939
Cdd:cd20951    81 IHGEASSSASVVV 93

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 58.29 E-value: 4.94e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  762 EDVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHvSFVYEENECSLVVLSAGSQDGGVYTCTARNLA-GEVSCKA 840
Cdd:cd20970    10 FTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNT-RYIVRENGTTLTIRNIRRSDMGIYLCIASNGVpGSVEKRI 88


                  ....
gi 564369110  841 ELSV 844
Cdd:cd20970    89 TLQV 92

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270639 [Multi-domain] Cd Length: 279 Bit Score: 62.85 E-value: 5.02e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2263 RVLQEYEVLRTLHHERLMSLHEAYI---TPRYLVLIAESCGNRELL---CGLSDRFRY---SEDDVATYVVQLLQGLDYL 2333
Cdd:cd05043    53 MLLQESSLLYGLSHQNLLPILHVCIedgEKPMVLYPYMNWGNLKLFlqqCRLSEANNPqalSTQQLVHMALQIACGMSYL 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2334 HGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLG-HRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIML 2412
Cdd:cd05043   133 HRRGVIHKDIAARNCVIDDELQVKITDNALSRDLFPMDYHCLGdNENRPIKWMSLESLVNKEYSSASDVWSFGVLLWELM 212

                         170       180
                  ....*....|....*....|..
gi 564369110 2413 S-GYSPFYEPDPQETEARIVGG 2433
Cdd:cd05043   213 TlGQTPYVEIDPFEMAAYLKDG 234

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270846 [Multi-domain] Cd Length: 290 Bit Score: 63.13 E-value: 5.67e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAA-KFIPSQAK----PKASARREA--RLLARLQHDCVLYFHEA-----FERRR 938
Cdd:cd07862     3 YECVAEIGEGAYGKVFKARDLKNGGRFVAlKRVRVQTGeegmPLSTIREVAvlRHLETFEHPNVVRLFDVctvsrTDRET 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  939 GLVIVTELCTEELLERMAR--KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQ 1016
Cdd:cd07862    83 KLTLVFEHVDQDLTTYLDKvpEPGVPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSG----QIKLADFGLAR 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 564369110 1017 ELTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVV 1056
Cdd:cd07862   159 IYSFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCI 198

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 58.34 E-value: 5.94e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110  353 LDCKISGTPPPSVTWTHFGHPVneSENLRLRQ------DGGLHS-LHIARVGSEDEGLYEVSATNTHGQAHCSAQLYV 423
Cdd:cd20956    21 LKCVASGNPLPQITWTLDGFPI--PESPRFRVgdyvtsDGDVVSyVNISSVRVEDGGEYTCTATNDVGSVSHSARINV 96

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 57.58 E-value: 7.09e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1855 LKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVSCKDGRQLLSIPRASKRHAGLYECSATNVLGSITSS 1934
Cdd:cd20973     4 LRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCS 83


                  ....*
gi 564369110 1935 CTVAV 1939
Cdd:cd20973    84 AELTV 88

cAMP-dependent protein kinase catalytic subunit; Provisional

Pssm-ID: 173616 [Multi-domain] Cd Length: 340 Bit Score: 63.08 E-value: 8.26e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  915 EARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPE 993
Cdd:PTZ00426   81 ERKILNYINHPFCVNLYGSFKDESYLYLVLEFVIGgEFFTFLRRNKRFPNDVGCFYAAQIVLIFEYLQSLNIVYRDLKPE 160

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  994 NLLVwDGAGGeeqVRICDFGNAQELTPGEPQYCqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDR 1073
Cdd:PTZ00426  161 NLLL-DKDGF---IKMTDFGFAKVVDTRTYTLC--GTPEYIAPEILLNVGHGKAADWWTLGIFIYEILVGCPPFYANEPL 234

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 1074 TTLMNIRNYNVAFEETtflsLSREARGFLIKVLVQD------RLRPTAEETLEHPWF 1124
Cdd:PTZ00426  235 LIYQKILEGIIYFPKF----LDNNCKHLMKKLLSHDltkrygNLKKGAQNVKEHPWF 287

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK2 plays a role in hepatic insulin signaling and glucose metabolism. It is induced by the insulin/Akt pathway as part of the hepatic refeeding reponse, and it directly phosphorylates the SR domain of PGC-1alpha, which results in decreased gluconeogenic gene expression and glucose output. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271117 [Multi-domain] Cd Length: 330 Bit Score: 62.73 E-value: 8.70e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  862 HRGRRLSDYYDIHQEIGRGAFSYLRRVVE-RSSGLEFAAKFIPSQAKPKASARREARLLARL-------QHDCVLYFhEA 933
Cdd:cd14215     5 RSGDWLQERYEIVSTLGEGTFGRVVQCIDhRRGGARVALKIIKNVEKYKEAARLEINVLEKInekdpenKNLCVQMF-DW 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  934 FERRRGLVIVTEL---CTEELLERMARKPTVCEsETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDG---------- 1000
Cdd:cd14215    84 FDYHGHMCISFELlglSTFDFLKENNYLPYPIH-QVRHMAFQVCQAVKFLHDNKLTHTDLKPENILFVNSdyeltynlek 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1001 -----AGGEEQVRICDFGNAQelTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTT 1075
Cdd:cd14215   163 krderSVKSTAIRVVDFGSAT--FDHEHHSTIVSTRHYRAPEVILELGWSQPCDVWSIGCIIFEYYVGFTLFQTHDNREH 240


                  .
gi 564369110 1076 L 1076
Cdd:cd14215   241 L 241

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270830 [Multi-domain] Cd Length: 294 Bit Score: 62.55 E-value: 8.83e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK---RRVLQEYEVLRTLHHE----RLMSLHEAYITPR---YL 2292
Cdd:cd07837     3 YEKLEKIGEGTYGKVYKARDKNTGKLVALKKTRLEMEEEgvpSTALREVSLLQMLSQSiyivRLLDVEHVEENGKpllYL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLIAESCGNRELLcglsDRFRYSEDD------VATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAAD-NALKIVDFGSAQ 2365
Cdd:cd07837    83 VFEYLDTDLKKFI----DSYGRGPHNplpaktIQSFMYQLCKGVAHCHSHGVMHRDLKPQNLLVDKQkGLLKIADLGLGR 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2366 PYNpQALKPLGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLtYIMLSGYSPFYEPDPQETEA----RIVGGRF----- 2435
Cdd:cd07837   159 AFT-IPIKSYTHEIVTLWYRAPEVLLGSThYSTPVDMWSVGCI-FAEMSRKQPLFPGDSELQQLlhifRLLGTPNeevwp 236

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 2436 -----------------DAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd07837   237 gvsklrdwheypqwkpqDLSRAVPDLEPEGVDLLTKMLAYDPAKRISAKAALQHPY 292

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 57.22 E-value: 8.95e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  340 LEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNeSENlRLRQDGGlhSLHIARVGSEDEGLYEVSATNTHGQAHCSA 419
Cdd:cd05728     6 ISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLA-SEN-RIEVEAG--DLRITKLSLSDSGMYQCVAENKHGTIYASA 81


                  ....
gi 564369110  420 QLYV 423
Cdd:cd05728    82 ELAV 85

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270968 [Multi-domain] Cd Length: 272 Bit Score: 61.91 E-value: 8.99e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVeRSSGLEFAAKFIPSQAKP--KASARREARLLARLQHDCVL----YFheaFERRRGLVIVTELCTEE 950
Cdd:cd14066     1 IGSGGFGTVYKGV-LENGTVVAVKRLNEMNCAasKKEFLTELEMLGRLRHPNLVrllgYC---LESDEKLLVYEYMPNGS 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  951 LLERM-ARKPTVCES-ETRTYM-RQVLEGIGYLHQS---HVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEPQ 1024
Cdd:cd14066    77 LEDRLhCHKGSPPLPwPQRLKIaKGIARGLEYLHEEcppPIIHGDIKSSNILLDE----DFEPKLTDFGLARLIPPSESV 152

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1025 YCQ---FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNY 1082
Cdd:cd14066   153 SKTsavKGTIGYLAPEYIRTGRVSTKSDVYSFGVVLLELLTGKPAVDENRENASRKDLVEW 213

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 57.46 E-value: 9.58e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  461 LRPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQ-SSDDRRMTQYRDIhrLVFPAVGPQHAGVYKSVIANKLGKA 539
Cdd:cd04978     3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEpAPEDMRRTVDGRT--LIFSNLQPNDTAVYQCNASNVHGYL 80


                  ....*...
gi 564369110  540 ACYAHLYV 547
Cdd:cd04978    81 LANAFLHV 88

Stk1 family PASTA domain-containing Ser/Thr kinase;

Pssm-ID: 468045 [Multi-domain] Cd Length: 563 Bit Score: 64.05 E-value: 9.99e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 LSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEFMAP 2387
Cdd:NF033483   98 IREHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSSTTMTQTNSVLGTVHYLSP 177

                          90       100       110
                  ....*....|....*....|....*....|.
gi 564369110 2388 EMVRGDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:NF033483  178 EQARGGTVDARSDIYSLGIVLYEMLTGRPPF 208

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 56.57 E-value: 1.07e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110  156 VIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGlCRLRILAAERGDAGFYTCKAVNEYG 219
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGN-GTLTISNVTLEDSGTYTCVASNSAG 63

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 57.21 E-value: 1.11e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1848 PPVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIvSCKDGRQLLSIPRASKRHAGLYECSATNV 1927
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQI-HQEGDLHSLIIAEAFEEDTGRYSCLATNS 79

                          90
                  ....*....|..
gi 564369110 1928 LGSITSSCTVAV 1939
Cdd:cd20972    80 VGSDTTSAEIFV 91

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 57.24 E-value: 1.30e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  757 FESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKD---EVLLAESNHVSFVYEENEcsLVVLSAGSQDGGVYTCTARNLA 833
Cdd:cd05763     2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDggtDFPAARERRMHVMPEDDV--FFIVDVKIEDTGVYSCTAQNSA 79

                          90
                  ....*....|.
gi 564369110  834 GEVSCKAELSV 844
Cdd:cd05763    80 GSISANATLTV 90

serine/threonine kinase US3; Provisional

Pssm-ID: 165473 [Multi-domain] Cd Length: 392 Bit Score: 62.55 E-value: 1.41e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  914 REARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPE 993
Cdd:PHA03207  135 REIDILKTISHRAIINLIHAYRWKSTVCMVMPKYKCDLFTYVDRSGPLPLEQAITIQRRLLEALAYLHGRGIIHRDVKTE 214

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  994 NLLVwdgaGGEEQVRICDFGNAQELT--PGEPQ-YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGE 1070
Cdd:PHA03207  215 NIFL----DEPENAVLGDFGAACKLDahPDTPQcYGWSGTLETNSPELLALDPYCAKTDIWSAGLVLFEMSVKNVTLFGK 290

                         170
                  ....*....|
gi 564369110 1071 NDRTTLMNIR 1080
Cdd:PHA03207  291 QVKSSSSQLR 300

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270816 [Multi-domain] Cd Length: 319 Bit Score: 61.99 E-value: 1.47e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLVIVTEL 946
Cdd:cd06650     5 DDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQiiRELQVLHECNSPYIVGFYGAFYSDGEISICMEH 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 ----CTEELLERMARKPtvcESETRTYMRQVLEGIGYLHQSH-VLHLDVKPENLLVwdGAGGEeqVRICDFGNAQELTPG 1021
Cdd:cd06650    85 mdggSLDQVLKKAGRIP---EQILGKVSIAVIKGLTYLREKHkIMHRDVKPSNILV--NSRGE--IKLCDFGVSGQLIDS 157

                         170       180       190
                  ....*....|....*....|....*....|....
gi 564369110 1022 EPQyCQFGTPEFVAPEIVNQSPVSGVTDIWPVGV 1055
Cdd:cd06650   158 MAN-SFVGTRSYMSPERLQGTHYSVQSDIWSMGL 190

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271003 [Multi-domain] Cd Length: 257 Bit Score: 61.02 E-value: 1.52e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2322 YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA-LKIVDFGSAQPYNPQalkPLGHRTGTLEFMAPEMV-RGDPIGSAT 2399
Cdd:cd14101   113 FFKQVVEAVQHCHSKGVVHRDIKDENILVDLRTGdIKLIDFGSGATLKDS---MYTDFDGTRVYSPPEWIlYHQYHALPA 189

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2400 DIWGAGVLTYIMLSGYSPFyEPDPQETEARIvggRFDAfqlypNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQ 2476
Cdd:cd14101   190 TVWSLGILLYDMVCGDIPF-ERDTDILKAKP---SFNK-----RVSNDCRSLIRSCLAYNPSDRPSLEQILLHPWMM 257

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 57.17 E-value: 1.52e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  766 VGPGETARFAVVVEGKPLPDIMWYK----DEVLLAESNHV-SFVYEENECSLVVLSAGSQDGGVYTCTARNLAGEVSCKA 840
Cdd:cd05765    12 VKVGETASFHCDVTGRPQPEITWEKqvpgKENLIMRPNHVrGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSGGLLRANF 91


                  ....
gi 564369110  841 ELSV 844
Cdd:cd05765    92 PLSV 95

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270781 [Multi-domain] Cd Length: 346 Bit Score: 62.00 E-value: 1.75e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQ---AKPKASARREARLLARL--QHDC--VLYFHEAFERRRGLVIV 943
Cdd:cd05633     7 FSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKrikMKQGETLALNERIMLSLvsTGDCpfIVCMTYAFHTPDKLCFI 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGE 1022
Cdd:cd05633    87 LDLMNGgDLHYHLSQHGVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILL-DEHG---HVRISDLGLACDFSKKK 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PqYCQFGTPEFVAPEIVNQ-SPVSGVTDIWPVGVVAFLCLTGISPF-------VGENDRTTLmnirNYNVAFEETtflsL 1094
Cdd:cd05633   163 P-HASVGTHGYMAPEVLQKgTAYDSSADWFSLGCMLFKLLRGHSPFrqhktkdKHEIDRMTL----TVNVELPDS----F 233

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 564369110 1095 SREARGFLIKVLVQDRLRPT------AEETLEHPWFK 1125
Cdd:cd05633   234 SPELKSLLEGLLQRDVSKRLgchgrgAQEVKEHSFFK 270

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271049 [Multi-domain] Cd Length: 267 Bit Score: 61.20 E-value: 1.80e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  873 IHQEIGRGAFSYLRRVVERSSGLEF-AAKFIPSQ--AKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE 949
Cdd:cd14147     7 LEEVIGIGGFGKVYRGSWRGELVAVkAARQDPDEdiSVTAESVRQEARLFAMLAHPNIIALKAVCLEEPNLCLVMEYAAG 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSH---VLHLDVKPENLLVWDGAGGEEQ----VRICDFGNAQELTPgE 1022
Cdd:cd14147    87 GPLSRALAGRRVPPHVLVNWAVQIARGMHYLHCEAlvpVIHRDLKSNNILLLQPIENDDMehktLKITDFGLAREWHK-T 165

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 1023 PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVG 1069
Cdd:cd14147   166 TQMSAAGTYAWMAPEVIKASTFSKGSDVWSFGVLLWELLTGEVPYRG 212

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.

Pssm-ID: 270668 [Multi-domain] Cd Length: 251 Bit Score: 60.79 E-value: 1.82e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2237 VRSCRENatgrtfvakiVPyaAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLsdrfRYSE 2316
Cdd:cd05085    25 VKTCKED----------LP--QELKIKFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGGDFLSFL----RKKK 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2317 DDVAT-----YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEFMAPEMVR 2391
Cdd:cd05085    89 DELKTkqlvkFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSRQEDDGVYSSSGLKQIPIKWTAPEALN 168

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2392 GDPIGSATDIWGAGVLTYIMLS-GYSPFYEPDPQETEARIVGG-RFDAFQLYPntsQSATLFLRKVLSVHPWSRPSLQD 2468
Cdd:cd05085   169 YGRYSSESDVWSFGILLWETFSlGVCPYPGMTNQQAREQVEKGyRMSAPQRCP---EDIYKIMQRCWDYNPENRPKFSE 244

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 56.44 E-value: 1.85e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  150 VREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCrLRILAAERGDAGFYTCKAVNEYGARqcEARLEV 229
Cdd:cd05748     4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTS-LVIKNAKRSDSGKYTLTLKNSAGEK--SATINV 80


                  .
gi 564369110  230 R 230
Cdd:cd05748    81 K 81

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 56.18 E-value: 1.86e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 564369110  475 AMLECQVTGLPYPTISWFHNGHRIQSSDDRRMTQYRDIHRLVFPAVGPQHAGVYK 529
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYT 55

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270919 [Multi-domain] Cd Length: 263 Bit Score: 60.73 E-value: 1.99e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKfIPSQAKPKASARREARLLARLQ---HDCVLYfhEAFERRRGLVIVTELC 947
Cdd:cd14017     2 WKVVKKIGGGGFGEIYKVRDVVDGEEVAMK-VESKSQPKQVLKMEVAVLKKLQgkpHFCRLI--GCGRTERYNYIVMTLL 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110  948 TEEL--LERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFG 1013
Cdd:cd14017    79 GPNLaeLRRSQPRGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRGPSDERTVYILDFG 146

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 56.03 E-value: 2.01e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110   473 KEAMLECQVTGLPYPTISWFHNGHRIQSSDDRRMTQYRDIHRLVFPAVGPQHAGVYK 529
Cdd:pfam13927   17 ETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYT 73

Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Tribbles Homolog (TRB) proteins interact with many proteins involved in signaling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, differentiation, and gene expression. TRB proteins bind to the middle kinase in mitogen activated protein kinase (MAPK) signaling cascades, MAPK kinases. They regulate the activity of MAPK kinases, and thus, affect MAPK signaling. In Drosophila, Tribbles regulates String, the ortholog of mammalian Cdc25, during morphogenesis. String is implicated in the progression of mitosis during embryonic development. Vertebrates contain three TRB proteins encoded by three separate genes: Tribbles-1 (TRB1 or TRIB1), Tribbles-2 (TRB2 or TRIB2), and Tribbles-3 (TRB3 or TRIB3). The TRB subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270878 [Multi-domain] Cd Length: 242 Bit Score: 60.52 E-value: 2.02e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  883 SYLRRVVERSSGLEFAAKFIP---SQAKPKASARREARLLARLQHDCVLYFHEA---FERRRGlvivtELCTeelLERMA 956
Cdd:cd13976     7 SSLYRCVDIHTGEELVCKVVPvpeCHAVLRAYFRLPSHPNISGVHEVIAGETKAyvfFERDHG-----DLHS---YVRSR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  957 RKptVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggEEQVRICDFGNAQELTPGEPQYC-QFGTPEFVA 1035
Cdd:cd13976    79 KR--LREPEAARLFRQIASAVAHCHRNGIVLRDLKLRKFVFADEE--RTKLRLESLEDAVILEGEDDSLSdKHGCPAYVS 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1036 PEIVN-QSPVSG-VTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREARGFLIKVLVQD-RLR 1112
Cdd:cd13976   155 PEILNsGATYSGkAADVWSLGVILYTMLVGRYPFHDSEPASLFAKIRRGQFAIPET----LSPRARCLIRSLLRREpSER 230

                         250
                  ....*....|..
gi 564369110 1113 PTAEETLEHPWF 1124
Cdd:cd13976   231 LTAEDILLHPWL 242

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270902 [Multi-domain] Cd Length: 275 Bit Score: 61.09 E-value: 2.23e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  907 KPKASARREARLLARLQHDCVLYFHEAFERRRGLVIvtELCT----EELLERMARKP-TVCESETRTYMRQVLEGIGYLH 981
Cdd:cd14000    52 KNFRLLRQELTVLSHLHHPSIVYLLGIGIHPLMLVL--ELAPlgslDHLLQQDSRSFaSLGRTLQQRIALQVADGLRYLH 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  982 QSHVLHLDVKPENLLVWDGAGGEE-QVRICDFGNAQELTPGEPQYCQfGTPEFVAPEIVNQSPV-SGVTDIWPVGVVAFL 1059
Cdd:cd14000   130 SAMIIYRDLKSHNVLVWTLYPNSAiIIKIADYGISRQCCRMGAKGSE-GTPGFRAPEIARGNVIyNEKVDVFSFGMLLYE 208

                         170
                  ....*....|
gi 564369110 1060 CLTGISPFVG 1069
Cdd:cd14000   209 ILSGGAPMVG 218

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271128 [Multi-domain] Cd Length: 339 Bit Score: 61.57 E-value: 2.24e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  864 GRRLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARL-QHD-----CVLYFHEAFERR 937
Cdd:cd14226     8 GEKWMDRYEIDSLIGKGSFGQVVKAYDHVEQEWVAIKIIKNKKAFLNQAQIEVRLLELMnKHDtenkyYIVRLKRHFMFR 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  938 RGLVIVTELCTEEL--LERMARKPTVCESETRTYMRQVLEGIGYLHQ--SHVLHLDVKPENLLVWDGAggEEQVRICDFG 1013
Cdd:cd14226    88 NHLCLVFELLSYNLydLLRNTNFRGVSLNLTRKFAQQLCTALLFLSTpeLSIIHCDLKPENILLCNPK--RSAIKIIDFG 165

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 1014 NAQELTPGEPQYCQ--FgtpeFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI 1079
Cdd:cd14226   166 SSCQLGQRIYQYIQsrF----YRSPEVLLGLPYDLAIDMWSLGCILVEMHTGEPLFSGANEVDQMNKI 229

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270903 [Multi-domain] Cd Length: 292 Bit Score: 61.26 E-value: 2.29e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2250 VAKIVPYAAEGKR-----RVLQEYEVLRTLHHERLMSlHEAYITPR--YLVLIAESCGNrellcGLSDRF--RYSEDDVA 2320
Cdd:cd14001    33 VKKINSKCDKGQRslyqeRLKEEAKILKSLNHPNIVG-FRAFTKSEdgSLCLAMEYGGK-----SLNDLIeeRYEAGLGP 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2321 TYVVQLLQ-------GLDYLHG-RHVLHLDIKPDNLLLAAD-NALKIVDFGSAQPYNPQ---ALKPLGHRTGTLEFMAPE 2388
Cdd:cd14001   107 FPAATILKvalsiarALEYLHNeKKILHGDIKSGNVLIKGDfESVKLCDFGVSLPLTENlevDSDPKAQYVGTEPWKAKE 186

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 564369110 2389 -MVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETE 2427
Cdd:cd14001   187 aLEEGGVITDKADIFAYGLVLWEMMTLSVPHLNLLDIEDD 226

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271056 [Multi-domain] Cd Length: 272 Bit Score: 60.98 E-value: 2.41e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAK-IVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN---RELLC 2306
Cdd:cd14154     3 KGFFGQAIKVTHRETGEVMVMKeLIRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYIPGgtlKDVLK 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSD------RFRYSEDdVATyvvqllqGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA-----QPYNPQALKPL 2375
Cdd:cd14154    83 DMARplpwaqRVRFAKD-IAS-------GMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLArliveERLPSGNMSPS 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 564369110 2376 GHR--------------TGTLEFMAPEMVRGDPIGSATDIWGAGVL 2407
Cdd:cd14154   155 ETLrhlkspdrkkrytvVGNPYWMAPEMLNGRSYDEKVDIFSFGIV 200

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 55.80 E-value: 2.42e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 1866 ATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVScKDGRQLLSIPRASKRHAGLYECSATNVLGSITSS 1934
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRS-ELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270650 [Multi-domain] Cd Length: 257 Bit Score: 60.44 E-value: 2.48e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFSYLRRVVERSSG---LEFAAKFIPSQAKP--KASARREARLLARLQHDCVLyfheafeRRRG------LVIVT 944
Cdd:cd05060     2 ELGHGNFGSVRKGVYLMKSgkeVEVAVKTLKQEHEKagKKEFLREASVMAQLDHPCIV-------RLIGvckgepLMLVM 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEP 1023
Cdd:cd05060    75 ELAPLgPLLKYLKKRREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVN----RHQAKISDFGMSRALGAGSD 150

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 564369110 1024 QYcQFGT----P-EFVAPEIVNQSPVSGVTDIWPVGV 1055
Cdd:cd05060   151 YY-RATTagrwPlKWYAPECINYGKFSSKSDVWSYGV 186

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 56.41 E-value: 2.49e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110    3 VAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLI----RAEGERHTLL-LREAQAADAGSYTATATNELGQAS 74
Cdd:cd20956    13 LQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVgdyvTSDGDVVSYVnISSVRVEDGGEYTCTATNDVGSVS 89

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270667 [Multi-domain] Cd Length: 252 Bit Score: 60.33 E-value: 2.59e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2227 EEKARGRFG--------------VVRSCRENatgrtfvakiVPyaAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYL 2292
Cdd:cd05084     2 ERIGRGNFGevfsgrlradntpvAVKSCRET----------LP--PDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQPI 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2293 VLIAESCGNRELLCGL-SDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQ 2370
Cdd:cd05084    70 YIVMELVQGGDFLTFLrTEGPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGmSREEEDGV 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 ALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPFYEPDPQET-EARIVGGRFDAFQLYPNTSQSa 2448
Cdd:cd05084   150 YAATGGMKQIPVKWTAPEALNYGRYSSESDVWSFGILLWETFSlGAVPYANLSNQQTrEAVEQGVRLPCPENCPDEVYR- 228

                         250
                  ....*....|....*...
gi 564369110 2449 tlFLRKVLSVHPWSRPSL 2466
Cdd:cd05084   229 --LMEQCWEYDPRKRPSF 244

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133230 [Multi-domain] Cd Length: 314 Bit Score: 61.13 E-value: 2.60e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2318 DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQP-YNPQALKPLGHRTGTLEFMAPEMVRGDPIG 2396
Cdd:cd05099   135 DLVSCAYQVARGMEYLESRRCIHRDLAARNVLVTEDNVMKIADFGLARGvHDIDYYKKTSNGRLPVKWMAPEALFDRVYT 214

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2397 SATDIWGAGVLTY-IMLSGYSPfYEPDPQETEARIV--GGRFDAfqlYPNTSQSATLFLRKVLSVHPWSRPSLQ 2467
Cdd:cd05099   215 HQSDVWSFGILMWeIFTLGGSP-YPGIPVEELFKLLreGHRMDK---PSNCTHELYMLMRECWHAVPTQRPTFK 284

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK2, also called beta-adrenergic receptor kinase (beta-ARK) or beta-ARK1, is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRK2 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. TheGRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271125 [Multi-domain] Cd Length: 321 Bit Score: 61.22 E-value: 2.87e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQ---AKPKASARREARLLARL--QHDC--VLYFHEAFERRRGLVIV 943
Cdd:cd14223     2 FSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLDKKrikMKQGETLALNERIMLSLvsTGDCpfIVCMSYAFHTPDKLSFI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTE-ELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNAQELTPGE 1022
Cdd:cd14223    82 LDLMNGgDLHYHLSQHGVFSEAEMRFYAAEIILGLEHMHSRFVVYRDLKPANILL-DEFG---HVRISDLGLACDFSKKK 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PqYCQFGTPEFVAPEIVNQS-PVSGVTDIWPVGVVAFLCLTGISPFVG-------ENDRTTLmnirnyNVAFEETTflSL 1094
Cdd:cd14223   158 P-HASVGTHGYMAPEVLQKGvAYDSSADWFSLGCMLFKLLRGHSPFRQhktkdkhEIDRMTL------TMAVELPD--SF 228

                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 564369110 1095 SREARGFLIKVLVQDRLRPT------AEETLEHPWFKT 1126
Cdd:cd14223   229 SPELRSLLEGLLQRDVNRRLgcmgrgAQEVKEEPFFRG 266

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271123 [Multi-domain] Cd Length: 267 Bit Score: 60.35 E-value: 3.11e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAK-IVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGN---RELLC 2306
Cdd:cd14221     3 KGCFGQAIKVTHRETGEVMVMKeLIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGgtlRGIIK 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSEDdvATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSA--------QPYNPQALKPLGHR 2378
Cdd:cd14221    83 SMDSHYPWSQR--VSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLArlmvdektQPEGLRSLKKPDRK 160

                         170       180       190
                  ....*....|....*....|....*....|....
gi 564369110 2379 -----TGTLEFMAPEMVRGDPIGSATDIWGAGVL 2407
Cdd:cd14221   161 krytvVGNPYWMAPEMINGRSYDEKVDVFSFGIV 194

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 55.67 E-value: 3.27e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110  769 GETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLAGEVS 837
Cdd:cd05748     7 GESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKS 75

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270913 [Multi-domain] Cd Length: 287 Bit Score: 60.41 E-value: 3.36e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  911 SARREARLLARLQHDCVL-YFHEAFERRRGLVIVTELCTEEL---LERMARKPTVC---------ESETRTYMRQVLEGI 977
Cdd:cd14011    48 LLKRGVKQLTRLRHPRILtVQHPLEESRESLAFATEPVFASLanvLGERDNMPSPPpelqdyklyDVEIKYGLLQISEAL 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  978 GYLHQS-HVLHLDVKPENLLVwDGAGgeeQVRICDFG---NAQELTPGEPQYCQFG---------TPEFVAPEIVNQSPV 1044
Cdd:cd14011   128 SFLHNDvKLVHGNICPESVVI-NSNG---EWKLAGFDfciSSEQATDQFPYFREYDpnlpplaqpNLNYLAPEYILSKTC 203

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1045 SGVTDIWPVGVVAF-LCLTGISPFVGENdrttlmNIRNYNVAFEETTFLSLSR------EARGFLIKVL-VQDRLRPTAE 1116
Cdd:cd14011   204 DPASDMFSLGVLIYaIYNKGKPLFDCVN------NLLSYKKNSNQLRQLSLSLlekvpeELRDHVKTLLnVTPEVRPDAE 277


                  ....*...
gi 564369110 1117 ETLEHPWF 1124
Cdd:cd14011   278 QLSKIPFF 285

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 55.58 E-value: 3.58e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    2 VVAPGADVLLKCIITANPPPQVSWKKDG-SVLHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNELGQASCASSLA 80
Cdd:cd20952    10 TVAVGGTVVLNCQATGEPVPTISWLKDGvPLLGKDERITTLENG---SLQIKGAEKSDTGEYTCVALNLSGEATWSAVLD 86


                  .
gi 564369110   81 V 81
Cdd:cd20952    87 V 87

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270647 [Multi-domain] Cd Length: 298 Bit Score: 60.58 E-value: 3.68e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFG-VVRSC----RENATGRTFVAKIVPYAAEG--KRRVLQEYEVLRTL-HHERLMSLHEAYITPRY-LVLIAESC-- 2299
Cdd:cd05054    17 RGAFGkVIQASafgiDKSATCRTVAVKMLKEGATAseHKALMTELKILIHIgHHLNVVNLLGACTKPGGpLMVIVEFCkf 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2300 GN--------RELLCG-----------LSDRFRYSED-----DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA 2355
Cdd:cd05054    97 GNlsnylrskREEFVPyrdkgardveeEEDDDELYKEpltleDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNV 176

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 2356 LKIVDFGSAQPY--NPQALKPLGHRTgTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPF 2418
Cdd:cd05054   177 VKICDFGLARDIykDPDYVRKGDARL-PLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSlGASPY 241

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 55.86 E-value: 3.76e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  458 PDFLR-PLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRrmTQYRDiHRLVFPAVGPQHAGVYKSVIANKL 536
Cdd:cd20978     1 PKFIQkPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMER--ATVED-GTLTIINVQPEDTGYYGCVATNEI 77


                  ..
gi 564369110  537 GK 538
Cdd:cd20978    78 GD 79

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 62.45 E-value: 4.03e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQ---EYEVLRTLHHERLMSLHEAYITP--RYLVLIAE 2297
Cdd:PTZ00266   15 YEVIKKIGNGRFGEVFLVKHKRTQEFFCWKAISYRGLKEREKSQlviEVNVMRELKHKNIVRYIDRFLNKanQKLYILME 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRY----SEDDVATYVVQLLQGLDYLH-------GRHVLHLDIKPDNLLL-----------AADNA 2355
Cdd:PTZ00266   95 FCDAGDLSRNIQKCYKMfgkiEEHAIVDITRQLLHALAYCHnlkdgpnGERVLHRDLKPQNIFLstgirhigkitAQANN 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2356 L------KIVDFGSAQPYnpqALKPLGHR-TGTLEFMAPEMV--RGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDpqeT 2426
Cdd:PTZ00266  175 LngrpiaKIGDFGLSKNI---GIESMAHScVGTPYYWSPELLlhETKSYDDKSDMWALGCIIYELCSGKTPFHKAN---N 248

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 2427 EARIVGGRFDAFQL-YPNTSQSATLFLRKVLSVHPWSRPSLQDCLAH 2472
Cdd:PTZ00266  249 FSQLISELKRGPDLpIKGKSKELNILIKNLLNLSAKERPSALQCLGY 295

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 55.58 E-value: 4.62e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1849 PVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVSCKDGRQLLSIPRASKRHAGLYECSATNVL 1928
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80


                  ....*.
gi 564369110 1929 GSITSS 1934
Cdd:cd05744    81 GENSFN 86

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK3 is a Fas-interacting protein that induces FADD (Fas-associated death domain) phosphorylation and mediates FasL-induced JNK activation. Overexpression of HIPK3 does not affect cell death, however its expression in prostate cancer cells contributes to increased resistance to Fas receptor-mediated apoptosis. HIPK3 also plays a role in regulating steroidogenic gene expression. In response to cAMP, HIPK3 activates the phosphorylation of JNK and c-Jun, leading to increased activity of the transcription factor SF-1 (Steroidogenic factor 1), a key regulator for steroid biosynthesis in the gonad and adrenal gland. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 271131 [Multi-domain] Cd Length: 330 Bit Score: 60.43 E-value: 4.73e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARL------QHDCVLYFhEAFERRRGLVIVT 944
Cdd:cd14229     2 YEVLDFLGRGTFGQVVKCWKRGTNEIVAVKILKNHPSYARQGQIEVGILARLsnenadEFNFVRAY-ECFQHRNHTCLVF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  945 ELCTEEL---LERMARKPTVCESeTRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELTPG 1021
Cdd:cd14229    81 EMLEQNLydfLKQNKFSPLPLKV-IRPILQQVATALKKLKSLGLIHADLKPENIMLVDPVRQPYRVKVIDFGSASHVSKT 159

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 564369110 1022 E-PQYCQfgTPEFVAPEIVNQSPVSGVTDIWPVGVV 1056
Cdd:cd14229   160 VcSTYLQ--SRYYRAPEIILGLPFCEAIDMWSLGCV 193

Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDIK1L is also called STK35 or CLIK-1. It is predominantly a nuclear protein which is capable of autophosphorylation. Through its interaction with the PDZ-LIM protein CLP-36, it is localized to actin stress fibers. The PDIK1L subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270879 [Multi-domain] Cd Length: 322 Bit Score: 60.65 E-value: 4.74e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATG-RTFVAKIVPYAAEGKRRVLQEYEVL-------------------------RTLHH 2276
Cdd:cd13977     2 YSLIREVGRGSYGVVYEAVVRRTGaRVAVKKIRCNAPENVELALREFWALssiqrqhpnviqleecvlqrdglaqRMSHG 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2277 ERLMSLH----------EAYITPR---YLVLIAESCGNRELLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRHVLHLDI 2343
Cdd:cd13977    82 SSKSDLYlllvetslkgERCFDPRsacYLWFVMEFCDGGDMNEYLLSR-RPDRQTNTSFMLQLSSALAFLHRNQIVHRDL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2344 KPDNLLLAADNA---LKIVDFGSAQPYNPQALKP----------LGHRTGTLEFMAPEMVRGDPIGSAtDIWGAGVLTYI 2410
Cdd:cd13977   161 KPDNILISHKRGepiLKVADFGLSKVCSGSGLNPeepanvnkhfLSSACGSDFYMAPEVWEGHYTAKA-DIFALGIIIWA 239


                  ..
gi 564369110 2411 ML 2412
Cdd:cd13977   240 MV 241

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270666 [Multi-domain] Cd Length: 254 Bit Score: 59.50 E-value: 4.77e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2265 LQEYEVLRTLHHERLMSLHeAYITPRYLVLIAESCGNRELLCGLSDRFRYseddvATYVVQLL-------QGLDYLHGRH 2337
Cdd:cd05083    47 LEETAVMTKLQHKNLVRLL-GVILHNGLYIVMELMSKGNLVNFLRSRGRA-----LVPVIQLLqfsldvaEGMEYLESKK 120

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2338 VLHLDIKPDNLLLAADNALKIVDFGSAQPyNPQALKplgHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYS 2416
Cdd:cd05083   121 LVHRDLAARNILVSEDGVAKISDFGLAKV-GSMGVD---NSRLPVKWTAPEALKNKKFSSKSDVWSYGVLLWEVFSyGRA 196

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2417 PFYEPDPQE-TEARIVGGRFDAFQLYPNTSQSatlFLRKVLSVHPWSRPSLQ 2467
Cdd:cd05083   197 PYPKMSVKEvKEAVEKGYRMEPPEGCPPDVYS---IMTSCWEAEPGKRPSFK 245

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors including homeodomain proteins (Nkx and HOX families), Smad1-4, Pax6, c-Myb, AML1, the histone acetyltransferase p300, and the tumor repressor p53, among others. It regulates gene transcription during development and in DNA damage response (DDR), and mediates cell processes such as apoptosis, survival, differentiation, and proliferation. HIPK2 mediates apoptosis by phosphorylating and activating p53 during DDR, resulting in the activation of apoptotic genes. In the absence of p53, HIPK2 targets the anti-apoptotic corepressor C-terminal binding protein (CtBP), leading to CtBP's degradation and the promotion of apoptosis. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271129 [Multi-domain] Cd Length: 355 Bit Score: 60.87 E-value: 4.87e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCV-----LYFHEAFERRRGLV 941
Cdd:cd14227    13 MTNTYEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILARLSTESAddynfVRAYECFQHKNHTC 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTEELLERMARK--PTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELT 1019
Cdd:cd14227    93 LVFEMLEQNLYDFLKQNkfSPLPLKYIRPILQQVATALMKLKSLGLIHADLKPENIMLVDPSRQPYRVKVIDFGSASHVS 172

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 564369110 1020 PGE-PQYCQfgTPEFVAPEIVNQSPVSGVTDIWPVGVV 1056
Cdd:cd14227   173 KAVcSTYLQ--SRYYRAPEIILGLPFCEAIDMWSLGCV 208

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270685 [Multi-domain] Cd Length: 260 Bit Score: 59.49 E-value: 5.08e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2224 TFLEEKARGRFGVVRSCRENATGRTFVAKIVPyAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRE 2303
Cdd:cd05114     7 TFMKELGSGLFGVVRLGKWRAQYKVAIKAIRE-GAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEFMENGC 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2304 LLCGLSDRF-RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ-PYNPQALKPLGHRTgT 2381
Cdd:cd05114    86 LLNYLRQRRgKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRyVLDDQYTSSSGAKF-P 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2382 LEFMAPEMVRGDPIGSATDIWGAGVLTY-IMLSGYSPFYEPDPQETEARIVGGrfdaFQLYPNTSQSATLFLRKVLSVH- 2459
Cdd:cd05114   165 VKWSPPEVFNYSKFSSKSDVWSFGVLMWeVFTEGKMPFESKSNYEVVEMVSRG----HRLYRPKLASKSVYEVMYSCWHe 240

                         250
                  ....*....|..
gi 564369110 2460 -PWSRPSLQDCL 2470
Cdd:cd05114   241 kPEGRPTFADLL 252

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271003 [Multi-domain] Cd Length: 257 Bit Score: 59.48 E-value: 5.08e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIP-------SQAKPKASARREARLLARL----QHDCVLYFHEAFERRRGLVIVTE 945
Cdd:cd14101     8 LGKGGFGTVYAGHRISDGLQVAIKQISrnrvqqwSKLPGVNPVPNEVALLQSVgggpGHRGVIRLLDWFEIPEGFLLVLE 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 --LCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGGEeqVRICDFGNAQELTpgEP 1023
Cdd:cd14101    88 rpQHCQDLFDYITERGALDESLARRFFKQVVEAVQHCHSKGVVHRDIKDENILV-DLRTGD--IKLIDFGSGATLK--DS 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 QYCQF-GTPEFVAPEIVNQSPVSGV-TDIWPVGVVAFLCLTGISPFvgENDRTTLMNIRNYNVafeettflSLSREARGF 1101
Cdd:cd14101   163 MYTDFdGTRVYSPPEWILYHQYHALpATVWSLGILLYDMVCGDIPF--ERDTDILKAKPSFNK--------RVSNDCRSL 232

                         250       260
                  ....*....|....*....|....*
gi 564369110 1102 LIKVLV-QDRLRPTAEETLEHPWFK 1125
Cdd:cd14101   233 IRSCLAyNPSDRPSLEQILLHPWMM 257

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271124 [Multi-domain] Cd Length: 272 Bit Score: 59.96 E-value: 5.20e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAK-IVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE--SCGNRELLCG 2307
Cdd:cd14222     3 KGFFGQAIKVTHKATGKVMVMKeLIRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEfiEGGTLKDFLR 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2308 LSDRFRYSEDdvATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG------SAQPYNPQALKPLGHRT-- 2379
Cdd:cd14222    83 ADDPFPWQQK--VSFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGlsrlivEEKKKPPPDKPTTKKRTlr 160

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 564369110 2380 -----------GTLEFMAPEMVRGDPIGSATDIWGAGVL 2407
Cdd:cd14222   161 kndrkkrytvvGNPYWMAPEMLNGKSYDEKVDIFSFGIV 199

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271034 [Multi-domain] Cd Length: 306 Bit Score: 60.25 E-value: 5.35e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIpsqaKP--KASARREARLLARLQ-HDCVLYFHEAF--ERRRGLVIV 943
Cdd:cd14132    18 DDYEIIRKIGRGKYSEVFEGINIGNNEKVVIKVL----KPvkKKKIKREIKILQNLRgGPNIVKLLDVVkdPQSKTPSLI 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TE-LCTEELLERMarkPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLvWDGAggEEQVRICDFGNAQELTPGE 1022
Cdd:cd14132    94 FEyVNNTDFKTLY---PTLTDYDIRYYMYELLKALDYCHSKGIMHRDVKPHNIM-IDHE--KRKLRLIDWGLAEFYHPGQ 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1023 PQYCQFGTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPFV-GENDRTTLMNI-------------RNYNVAFE 1087
Cdd:cd14132   168 EYNVRVASRYYKGPELlVDYQYYDYSLDMWSLGCMLASMIFRKEPFFhGHDNYDQLVKIakvlgtddlyaylDKYGIELP 247

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 1088 E--------------TTFLSLSR------EARGFLIKVLVQD-RLRPTAEETLEHPWFK 1125
Cdd:cd14132   248 PrlndilgrhskkpwERFVNSENqhlvtpEALDLLDKLLRYDhQERITAKEAMQHPYFD 306

Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Tribbles Homolog (TRB) proteins interact with many proteins involved in signaling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, differentiation, and gene expression. TRB proteins bind to the middle kinase in mitogen activated protein kinase (MAPK) signaling cascades, MAPK kinases. They regulate the activity of MAPK kinases, and thus, affect MAPK signaling. In Drosophila, Tribbles regulates String, the ortholog of mammalian Cdc25, during morphogenesis. String is implicated in the progression of mitosis during embryonic development. Vertebrates contain three TRB proteins encoded by three separate genes: Tribbles-1 (TRB1 or TRIB1), Tribbles-2 (TRB2 or TRIB2), and Tribbles-3 (TRB3 or TRIB3). The TRB subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270878 [Multi-domain] Cd Length: 242 Bit Score: 58.98 E-value: 5.93e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2245 TGRTFVAKIVPyaAEGKRRVLQEYevLRTLHHERLMSLHE--AYITPRYLVLIAEScGNRELLcgLSDRFRYSEDDVATY 2322
Cdd:cd13976    17 TGEELVCKVVP--VPECHAVLRAY--FRLPSHPNISGVHEviAGETKAYVFFERDH-GDLHSY--VRSRKRLREPEAARL 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2323 VVQLLQGLDYLHGRHVLHLDIKPDNLLLAaDNALKIVDFGSAQpyNPQALKP----LGHRTGTLEFMAPEMV--RGDPIG 2396
Cdd:cd13976    90 FRQIASAVAHCHRNGIVLRDLKLRKFVFA-DEERTKLRLESLE--DAVILEGeddsLSDKHGCPAYVSPEILnsGATYSG 166

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2397 SATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvggRFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd13976   167 KAADVWSLGVILYTMLVGRYPFHDSEPASLFAKI---RRGQFAIPETLSPRARCLIRSLLRREPSERLTAEDILLHPWL 242

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK1 has been implicated in regulating eye size, lens formation, and retinal morphogenesis during late embryogenesis. It also contributes to the regulation of haematopoiesis and leukaemogenesis by phosphorylating and repressing the transcription factor c-Myb, which is crucial in T- and B-cell development. In glucose-deprived conditions, HIPK1 phosphorylates Daxx, leading to its relocalization from the nucleus to the cytoplasm, where it binds and stabilizes ASK1 (apoptosis signal-regulating kinase 1), a mitogen-activated protein kinase (MAPK) kinase kinase that activates the JNK and p38 MAPK pathways. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271130 [Multi-domain] Cd Length: 355 Bit Score: 60.49 E-value: 6.70e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  867 LSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYF-----HEAFERRRGLV 941
Cdd:cd14228    13 MTNSYEVLEFLGRGTFGQVAKCWKRSTKEIVAIKILKNHPSYARQGQIEVSILSRLSSENADEYnfvrsYECFQHKNHTC 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTEELLERMARK--PTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELT 1019
Cdd:cd14228    93 LVFEMLEQNLYDFLKQNkfSPLPLKYIRPILQQVATALMKLKSLGLIHADLKPENIMLVDPVRQPYRVKVIDFGSASHVS 172

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 564369110 1020 PGE-PQYCQfgTPEFVAPEIVNQSPVSGVTDIWPVGVV 1056
Cdd:cd14228   173 KAVcSTYLQ--SRYYRAPEIILGLPFCEAIDMWSLGCV 208

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 54.82 E-value: 6.86e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    245 QDVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPALLKCKMHFDGRKCKLLLTSVHEDDSGVYTCKLSTVKDELTCSA 324
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 564369110    325 RLTV 328
Cdd:smart00410   82 TLTV 85

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270635 [Multi-domain] Cd Length: 256 Bit Score: 59.29 E-value: 6.95e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRscRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd05039     4 NKKDLKLGELIGKGEFGDVM--LGDYRGQKVAVKCLKDDSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGNGLYIVTEY 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRY--SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNpqalkpLG 2376
Cdd:cd05039    82 MAKGSLVDYLRSRGRAviTRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAKEAS------SN 155

                         170       180       190
                  ....*....|....*....|....*....|...
gi 564369110 2377 HRTGTL--EFMAPEMVRGDPIGSATDIWGAGVL 2407
Cdd:cd05039   156 QDGGKLpiKWTAPEALREKKFSTKSDVWSFGIL 188

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 55.10 E-value: 7.15e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAE-GGLCRLRILAAERGDAGFYTCKAVNE 217
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDlDGTCSLHTTASTLDDDGNYTIMAANP 80

                          90
                  ....*....|..
gi 564369110  218 YGARQCEARLEV 229
Cdd:cd05893    81 QGRISCTGRLMV 92

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270970 [Multi-domain] Cd Length: 252 Bit Score: 59.20 E-value: 7.52e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERssGLEFAAKFIPSQAKPKAsARREARLLARLQHDCVLYFHEAFERRRGLVIvtELCTEELLERMA 956
Cdd:cd14068     2 LGDGGFGSVYRAVYR--GEDVAVKIFNKHTSFRL-LRQELVVLSHLHHPSLVALLAAGTAPRMLVM--ELAPKGSLDALL 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  957 RKPTVceSETRTYMR----QVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQV-RICDFGNAQELTPGEPQYCQfGTP 1031
Cdd:cd14068    77 QQDNA--SLTRTLQHrialHVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNCAIIaKIADYGIAQYCCRMGIKTSE-GTP 153

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 564369110 1032 EFVAPE------IVNQSpvsgvTDIWPVGVVAFLCLTG 1063
Cdd:cd14068   154 GFRAPEvargnvIYNQQ-----ADVYSFGLLLYDILTC 186

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 54.77 E-value: 7.82e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1870 CLPAACPTPRISWMKDKQSLRSEPSVVIVSckDGRqlLSIPRASKRHAGLYECSATNVLGSITSSCTVAV 1939
Cdd:cd04969    24 CKPKASPKPTISWSKGTELLTNSSRICILP--DGS--LKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270965 [Multi-domain] Cd Length: 271 Bit Score: 59.29 E-value: 8.04e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  872 DIHQEIGRGAFSYLRRvvERSSGlEFAAKFI----PSQAKPKAsARREARLLARLQHDCVLYFHEAFERRRGLVIVTELC 947
Cdd:cd14063     3 EIKEVIGKGRFGRVHR--GRWHG-DVAIKLLnidyLNEEQLEA-FKEEVAAYKNTRHDNLVLFMGACMDPPHLAIVTSLC 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TEELLERMAR--KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGaggeeQVRICDFG--NAQELTPGEP 1023
Cdd:cd14063    79 KGRTLYSLIHerKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFLENG-----RVVITDFGlfSLSGLLQPGR 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 1024 QYCQFGTPE----FVAPEIV----------NQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14063   154 REDTLVIPNgwlcYLAPEIIralspdldfeESLPFTKASDVYAFGTVWYELLAGRWPF 211

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132946 [Multi-domain] Cd Length: 308 Bit Score: 59.37 E-value: 8.74e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKP--KASARREARLLarlqHDC----VLYFHEAFERRRGLVIVTE---- 945
Cdd:cd06615     8 ELGAGNGGVVTKVLHRPSGLIMARKLIHLEIKPaiRNQIIRELKVL----HECnspyIVGFYGAFYSDGEISICMEhmdg 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLERMARKP-------TVCesetrtymrqVLEGIGYLHQSH-VLHLDVKPENLLVwdGAGGEeqVRICDFGNAQE 1017
Cdd:cd06615    84 GSLDQVLKKAGRIPenilgkiSIA----------VLRGLTYLREKHkIMHRDVKPSNILV--NSRGE--IKLCDFGVSGQ 149

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 1018 LTpgEPQYCQF-GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEnDRTTLMNIRNYNV 1084
Cdd:cd06615   150 LI--DSMANSFvGTRSYMSPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPIPPP-DAKELEAMFGRPV 214

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.

Pssm-ID: 270637 [Multi-domain] Cd Length: 251 Bit Score: 58.61 E-value: 9.62e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2237 VRSCRENATgrtfvakivpyaAEGKRRVLQEYEVLRTLHHERLMSLhEAYITPRYLVLIAescgnRELLCG--LSDRFRY 2314
Cdd:cd05041    25 VKTCRETLP------------PDLKRKFLQEARILKQYDHPNIVKL-IGVCVQKQPIMIV-----MELVPGgsLLTFLRK 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2315 SEDDVAtyVVQLLQ-------GLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPLGHRTGTLEFMA 2386
Cdd:cd05041    87 KGARLT--VKQLLQmcldaaaGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGmSREEEDGEYTVSDGLKQIPIKWTA 164

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2387 PEMVRGDPIGSATDIWGAGVLTY-IMLSGYSPFYEPDPQETEARI-VGGRFDAFQLYP 2442
Cdd:cd05041   165 PEALNYGRYTSESDVWSFGILLWeIFSLGATPYPGMSNQQTREQIeSGYRMPAPELCP 222

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271051 [Multi-domain] Cd Length: 283 Bit Score: 59.27 E-value: 9.75e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  913 RREARLLARLQHDCVLYFHeAFERRRGLVIVTELCTEELLERMARkptVCESETRTYM-----RQVLEGIGYLHQSHVLH 987
Cdd:cd14149    56 RNEVAVLRKTRHVNILLFM-GYMTKDNLAIVTQWCEGSSLYKHLH---VQETKFQMFQlidiaRQTAQGMDYLHAKNIIH 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  988 LDVKPENLLVWDGAggeeQVRICDFGNAQELT--PGEPQYCQF-GTPEFVAPEIV---NQSPVSGVTDIWPVGVVAFLCL 1061
Cdd:cd14149   132 RDMKSNNIFLHEGL----TVKIGDFGLATVKSrwSGSQQVEQPtGSILWMAPEVIrmqDNNPFSFQSDVYSYGIVLYELM 207

                         170       180
                  ....*....|....*....|...
gi 564369110 1062 TGISPF--VGENDRTTLMNIRNY 1082
Cdd:cd14149   208 TGELPYshINNRDQIIFMVGRGY 230

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 54.50 E-value: 9.89e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  243 PLQDVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPALlKCKMHFDGR-KCKLLLTSVHEDDSGVYTCKLSTVKDELT 321
Cdd:cd20973     3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESR-RFQIDQDEDgLCSLIISDVCGDDSGKYTCKAVNSLGEAT 81


                  ....*..
gi 564369110  322 CSARLTV 328
Cdd:cd20973    82 CSAELTV 88

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270935 [Multi-domain] Cd Length: 261 Bit Score: 58.86 E-value: 1.08e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2260 GKRRVLQEYEVLRTLHHERLMSLHEAYITP----RYLVLIAESCGNRELLCGLSdRFRYSEDDV-ATYVVQLLQGLDYLH 2334
Cdd:cd14033    43 ERQRFSEEVEMLKGLQHPNIVRFYDSWKSTvrghKCIILVTELMTSGTLKTYLK-RFREMKLKLlQRWSRQILKGLHFLH 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2335 GRH--VLHLDIKPDNLLLAADNA-LKIVDFGSAQPYNPQALKPLghrTGTLEFMAPEMVRgDPIGSATDIWGAGVLTYIM 2411
Cdd:cd14033   122 SRCppILHRDLKCDNIFITGPTGsVKIGDLGLATLKRASFAKSV---IGTPEFMAPEMYE-EKYDEAVDVYAFGMCILEM 197


                  ....*....
gi 564369110 2412 LSGYSPFYE 2420
Cdd:cd14033   198 ATSEYPYSE 206

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 61.11 E-value: 1.11e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1206 PRPLQPEfSGSRVSLTDIPTEDEALGTPEAGAATPMDWQEQGRAPSKDQEAPSPEALPSPGQESPDGPSPRRPELRRGSS 1285
Cdd:PHA03247 2575 PRPSEPA-VTSRARRPDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPR 2653

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1286 AESALPRVGSREPGRSLHKAASVELPQRRsPSPGATRLTRGGLGEgeyaqrlqalrqrlLRGGPEDGKVSGLRGPLLESL 1365
Cdd:PHA03247 2654 DDPAPGRVSRPRRARRLGRAAQASSPPQR-PRRRAARPTVGSLTS--------------LADPPPPPPTPEPAPHALVSA 2718

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1366 GGRARDPRMARAASSEAAPHHQPPPESRGLQKSSSFSQGEAEPRGRHRRAGAPLEIPVArlGARRLQESPSLSALSETQP 1445
Cdd:PHA03247 2719 TPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPAAPAA--GPPRRLTRPAVASLSESRE 2796

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1446 PSPALPSAPKPSITKSPEPSA--ATSRDSPQPPAPQPVPEKIPEPKPEP----------------VRAAKPAQPPLAlqM 1507
Cdd:PHA03247 2797 SLPSPWDPADPPAAVLAPAAAlpPAASPAGPLPPPTSAQPTAPPPPPGPpppslplggsvapggdVRRRPPSRSPAA--K 2874

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1508 PAQSLTPYAQIMQSLQLSSPTLSPQVPPSEPK--PHAAVFARVASPPPGASEKRVPSARIPPVLAEKVRVPTVPPRPGSS 1585
Cdd:PHA03247 2875 PAAPARPPVRRLARPAVSRSTESFALPPDQPErpPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGE 2954

                         410       420
                  ....*....|....*....|..
gi 564369110 1586 LSGSIENLESEAVFEAKFKRSR 1607
Cdd:PHA03247 2955 PSGAVPQPWLGALVPGRVAVPR 2976

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173644 [Multi-domain] Cd Length: 284 Bit Score: 58.79 E-value: 1.12e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATG-----RTFVAKIVPYAAEGKRRVL-QEYEVLRTLHHERLMslheayitpRYLVLIAESCGN---- 2301
Cdd:cd05079    15 GHFGKVELCRYDPEGdntgeQVAVKSLKPESGGNHIADLkKEIEILRNLYHENIV---------KYKGICTEDGGNgikl 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 -RELLCGLS-------DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG--SAQPYNPQA 2371
Cdd:cd05079    86 iMEFLPSGSlkeylprNKNKINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGltKAIETDKEY 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 LKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIML----SGYSPFYE-------PDPQETEARIVGGRFDAFQL 2440
Cdd:cd05079   166 YTVKDDLDSPVFWYAPECLIQSKFYIASDVWSFGVTLYELLtycdSESSPMTLflkmigpTHGQMTVTRLVRVLEEGKRL 245

                         250       260       270
                  ....*....|....*....|....*....|...
gi 564369110 2441 --YPNTSQSATLFLRKVLSVHPWSRPSLQDCLA 2471
Cdd:cd05079   246 prPPNCPEEVYQLMRKCWEFQPSKRTTFQNLIE 278

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270680 [Multi-domain] Cd Length: 336 Bit Score: 59.61 E-value: 1.12e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2317 DDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPY--NPQALKPlGHRTGTLEFMAPEMVRGDP 2394
Cdd:cd05102   172 EDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIykDPDYVRK-GSARLPLKWMAPESIFDKV 250

                          90       100
                  ....*....|....*....|....*
gi 564369110 2395 IGSATDIWGAGVLTYIMLS-GYSPF 2418
Cdd:cd05102   251 YTTQSDVWSFGVLLWEIFSlGASPY 275

Stk1 family PASTA domain-containing Ser/Thr kinase;

Pssm-ID: 468045 [Multi-domain] Cd Length: 563 Bit Score: 60.58 E-value: 1.13e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  864 GRRLSDYYDIHQEIGRG--AFSY------LRRVV-------ERSSGLEFAAKFipsqakpkasaRREARLLARLQHDCV- 927
Cdd:NF033483    2 GKLLGGRYEIGERIGRGgmAEVYlakdtrLDRDVavkvlrpDLARDPEFVARF-----------RREAQSAASLSHPNIv 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  928 ----------LYFheaferrrglvIVTEL---CT-EELLERMARKPTvceSETRTYMRQVLEGIGYLHQSHVLHLDVKPE 993
Cdd:NF033483   71 svydvgedggIPY-----------IVMEYvdgRTlKDYIREHGPLSP---EEAVEIMIQILSALEHAHRNGIVHRDIKPQ 136

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  994 NLLVwdgaGGEEQVRICDFG-----NAQELTpgepqycQ----FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGI 1064
Cdd:NF033483  137 NILI----TKDGRVKVTDFGiaralSSTTMT-------QtnsvLGTVHYLSPEQARGGTVDARSDIYSLGIVLYEMLTGR 205


                  ....*..
gi 564369110 1065 SPFVGEN 1071
Cdd:NF033483  206 PPFDGDS 212

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 54.51 E-value: 1.13e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  138 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVR--PDqrrFAEEAEGGLCRLRILAAERGDAGFYTCKAV 215
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQnsPD---IQIHQEGDLHSLIIAEAFEEDTGRYSCLAT 77

                          90
                  ....*....|....
gi 564369110  216 NEYGARQCEARLEV 229
Cdd:cd20972    78 NSVGSDTTSAEIFV 91

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 54.08 E-value: 1.22e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKK-DGSVLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQAScaSSL 79
Cdd:cd05894     5 IVVVAGNKLRLDVPISGEPAPTVTWSRgDKAFTATEGRVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDH--ASL 82


                  ...
gi 564369110   80 AVR 82
Cdd:cd05894    83 FVK 85

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 54.38 E-value: 1.23e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 1857 DQVLLEGEAATLLCLPAACPTPRISWMKDKQSLrsEPSVVIVSCKDGRQLLSIPRASKRHAGLYECSATNVLGSI 1931
Cdd:cd04978     8 SLVLSPGETGELICEAEGNPQPTITWRLNGVPI--EPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYL 80

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270867 [Multi-domain] Cd Length: 270 Bit Score: 58.67 E-value: 1.24e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAK---FIPSQAKPKASARREAR----------LLARLQHDCVLYFHEAFERR 937
Cdd:cd08528     2 YAVLELLGSGAFGCVYKVRKKSNGQTLLALkeiNMTNPAFGRTEQERDKSvgdiisevniIKEQLRHPNIVRYYKTFLEN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  938 RGLVIVTELCT----EELLERMARKPTVCEsETRTY--MRQVLEGIGYLH-QSHVLHLDVKPENLLVwdgaGGEEQVRIC 1010
Cdd:cd08528    82 DRLYIVMELIEgaplGEHFSSLKEKNEHFT-EDRIWniFVQMVLALRYLHkEKQIVHRDLKPNNIML----GEDDKVTIT 156

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1011 DFGNAQELTPGEPQYCQ-FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRN 1081
Cdd:cd08528   157 DFGLAKQKGPESSKMTSvVGTILYSCPEIVQNEPYGEKADIWALGCILYQMCTLQPPFYSTNMLTLATKIVE 228

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143379 [Multi-domain] Cd Length: 355 Bit Score: 59.33 E-value: 1.29e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2221 KPYTFLEEKARGRFGVVRSCRENATGRTFVAKIV--PYAAEGK-RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd07874    17 KRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLsrPFQNQTHaKRAYRELVLMKCVNHKNIISLLNVFTPQKSLEEFQD 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNREL----LCGLSdRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALk 2373
Cdd:cd07874    97 VYLVMELmdanLCQVI-QMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFM- 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2374 pLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLT------YIMLSG------YSPFYE----PDPQ------------- 2424
Cdd:cd07874   175 -MTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMgemvrhKILFPGrdyidqWNKVIEqlgtPCPEfmkklqptvrnyv 253

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 2425 ETEARIVGGRFDAF---QLYPNTSQSATL-------FLRKVLSVHPWSRPSLQDCLAHPWLQDAY 2479
Cdd:cd07874   254 ENRPKYAGLTFPKLfpdSLFPADSEHNKLkasqardLLSKMLVIDPAKRISVDEALQHPYINVWY 318

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 54.18 E-value: 1.38e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  754 APRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKD-EVLLAESNHVSFvyEENECSLVVLSAGSQDGGVYTCTARNL 832
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNaQPLQYAADRSTC--EAGVGELHIQDVLPEDHGTYTCLAKNA 78

                          90
                  ....*....|..
gi 564369110  833 AGEVSCKAELSV 844
Cdd:cd20976    79 AGQVSCSAWVTV 90

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271057 [Multi-domain] Cd Length: 253 Bit Score: 58.26 E-value: 1.42e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKpKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMA 956
Cdd:cd14155     1 IGSGFFSEVYKVRHRTSGQVMALKMNTLSSN-RANMLREVQLMNRLSHPNILRFMGVCVHQGQLHALTEYINGGNLEQLL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  957 RKPTVCESETRTYMR-QVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVrICDFGNAQEL---TPGEPQYCQFGTPE 1032
Cdd:cd14155    80 DSNEPLSWTVRVKLAlDIARGLSYLHSKGIFHRDLTSKNCLIKRDENGYTAV-VGDFGLAEKIpdySDGKEKLAVVGSPY 158

                         170       180
                  ....*....|....*....|....*...
gi 564369110 1033 FVAPEIVNQSPVSGVTDIWPVGVVafLC 1060
Cdd:cd14155   159 WMAPEVLRGEPYNEKADVFSYGII--LC 184

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 54.05 E-value: 1.43e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1854 KLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVscKDGRQLLSIPRASKRHAGLYECSATN-VLGSIT 1932
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIV--RENGTTLTIRNIRRSDMGIYLCIASNgVPGSVE 85


                  ....*..
gi 564369110 1933 SSCTVAV 1939
Cdd:cd20970    86 KRITLQV 92

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 54.10 E-value: 1.63e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  754 APRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVS---FVYEENEC-SLV-VLSAGSQDGGVYTCT 828
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRvgdYVTSDGDVvSYVnISSVRVEDGGEYTCT 80

                          90
                  ....*....|....*.
gi 564369110  829 ARNLAGEVSCKAELSV 844
Cdd:cd20956    81 ATNDVGSVSHSARINV 96

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. DYRK4 is a testis-specific kinase with restricted expression to postmeiotic spermatids. It may function during spermiogenesis, however, it is not required for male fertility. DYRK4 has also been detected in a human teratocarcinoma cell line induced to produce postmitotic neurons. It may have a role in neuronal differentiation. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. The DYRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271127 [Multi-domain] Cd Length: 341 Bit Score: 58.95 E-value: 1.64e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd14225    45 YEILEVIGKGSFGQVVKALDHKTNEHVAIKIIRNKKRFHHQALVEVKILDALRRKDRDNSHNVIHMKEYFYFRNHLCITF 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLcGLS-------DRFR-YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA--ADNALKIVDFGSAQPYNPQAL 2372
Cdd:cd14225   125 ELL-GMNlyelikkNNFQgFSLSLIRRFAISLLQCLRLLYRERIIHCDLKPENILLRqrGQSSIKVIDFGSSCYEHQRVY 203

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 2373 KPLGHRTgtleFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFyepdPQETEA 2428
Cdd:cd14225   204 TYIQSRF----YRSPEVILGLPYSMAIDMWSLGCILAELYTGYPLF----PGENEV 251

glycogen synthase kinase; Provisional

Pssm-ID: 173333 [Multi-domain] Cd Length: 440 Bit Score: 59.66 E-value: 1.72e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2319 VATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAAD-NALKIVDFGSAQpyNPQAlkplGHRTGTL----EFMAPEMVRGD 2393
Cdd:PTZ00036  172 VKLYSYQLCRALAYIHSKFICHRDLKPQNLLIDPNtHTLKLCDFGSAK--NLLA----GQRSVSYicsrFYRAPELMLGA 245

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2394 P-IGSATDIWGAGVLTYIMLSGYSPFYEPD--------------PQETEARIVGGRF-----------DAFQLYPN-TSQ 2446
Cdd:PTZ00036  246 TnYTTHIDLWSLGCIIAEMILGYPIFSGQSsvdqlvriiqvlgtPTEDQLKEMNPNYadikfpdvkpkDLKKVFPKgTPD 325

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2447 SATLFLRKVLSVHPWSRPSLQDCLAHPWLQD---------AYLMKLrRQTLTFTTNRLKE 2497
Cdd:PTZ00036  326 DAINFISQFLKYEPLKRLNPIEALADPFFDDlrdpciklpKYIDKL-PDLFNFCDAEIKE 384

Catalytic domain of the Protein Serine/Threonine Kinase, Large Tumor Suppressor 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS2 is an essential mitotic regulator responsible for coordinating accurate cytokinesis completion and governing the stabilization of other mitotic regulators. It is also critical in the maintenance of proper chromosome number, genomic stability, mitotic fidelity, and the integrity of centrosome duplication. Downregulation of LATS2 is associated with poor prognosis in acute lymphoblastic leukemia and breast cancer. The LATS2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173715 [Multi-domain] Cd Length: 381 Bit Score: 59.25 E-value: 1.94e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2322 YVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-----------------------SAQPYN---------- 2368
Cdd:cd05626   106 YIAELTLAIESVHKMGFIHRDIKPDNILIDLDGHIKLTDFGlctgfrwthnskyyqkgshirqdSMEPSDlwddvsncrc 185

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 2369 PQALKPLGHRT-------------GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIV 2431
Cdd:cd05626   186 GDRLKTLEQRAtkqhqrclahslvGTPNYIAPEVLLRKGYTQLCDWWSVGVILFEMLVGQPPFLAPTPTETQLKVI 261

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270918 [Multi-domain] Cd Length: 266 Bit Score: 57.85 E-value: 1.97e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyaAEGKRRVL-QEYEVLRTLHHE----RLMSL--HEAYitpRYLVLi 2295
Cdd:cd14016     2 YKLVKKIGSGSFGEVYLGIDLKTGEEVAIKIEK--KDSKHPQLeYEAKVYKLLQGGpgipRLYWFgqEGDY---NVMVM- 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 aescgnrELL-CGLSDRFRY-----SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLL---AADNALKIVDFGSAQP 2366
Cdd:cd14016    76 -------DLLgPSLEDLFNKcgrkfSLKTVLMLADQMISRLEYLHSKGYIHRDIKPENFLMglgKNSNKVYLIDFGLAKK 148


                  .
gi 564369110 2367 Y 2367
Cdd:cd14016   149 Y 149

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 53.96 E-value: 2.07e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  244 LQDVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPALL--KCKMHFDGRKCKLLLTSVHEDDSGVYTCKLSTVKDELT 321
Cdd:cd20951     7 LQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIHGEAS 86


                  ....*...
gi 564369110  322 CSARLTVR 329
Cdd:cd20951    87 SSASVVVE 94

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271113 [Multi-domain] Cd Length: 329 Bit Score: 58.61 E-value: 2.35e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFH-----EAFERRRGLVIVTE 945
Cdd:cd14211     1 YEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILSRLSQENADEFNfvrayECFQHKNHTCLVFE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  946 LCTEELLE-----RMARKPTVCeseTRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGNAQELTP 1020
Cdd:cd14211    81 MLEQNLYDflkqnKFSPLPLKY---IRPILQQVLTALLKLKSLGLIHADLKPENIMLVDPVRQPYRVKVIDFGSASHVSK 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 564369110 1021 GEPQ-YCQfgTPEFVAPEIVNQSPVSGVTDIWPVG-VVAFLCL 1061
Cdd:cd14211   158 AVCStYLQ--SRYYRAPEIILGLPFCEAIDMWSLGcVIAELFL 198

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133248 [Multi-domain] Cd Length: 261 Bit Score: 57.44 E-value: 2.38e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVaKIVPYAAEGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd05148     4 PREEFTLERKLGSGYFGEVWEGLWKNRVRVAI-KILKSDDLLKQQDFQkEVQALKRLRHKHLISLFAVCSVGEPVYIITE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSED-----DVATyvvQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQAL 2372
Cdd:cd05148    83 LMEKGSLLAFLRSPEGQVLPvasliDMAC---QVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKEDVY 159

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2373 KPLGHRTgTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPFYEPDPQETEARIVGG 2433
Cdd:cd05148   160 LSSDKKI-PYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTyGQVPYPGMNNHEVYDQITAG 220

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 53.47 E-value: 2.42e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110  341 EDVEVLEGRAARLDCKISGTPPPSVTWTH-FGHPVNESENLRLRQDGGLH---SLHIARVGSEDEGLYEVSATNTHG 413
Cdd:cd20954     9 VDANVAAGQDVMLHCQADGFPTPTVTWKKaTGSTPGEYKDLLYDPNVRILpngTLVFGHVQKENEGHYLCEAKNGIG 85

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 53.49 E-value: 2.42e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  140 TFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVR---PDQRRFAEEAEGglcrLRILAAERGDAGFYTCKAVN 216
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISasvADMSKYRILADG----LLINKVTQDDTGEYTCRAYQ 76


                  ...
gi 564369110  217 EYG 219
Cdd:cd20949    77 VNS 79

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 53.35 E-value: 2.65e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGERH-TLLLREAQAADAGSYTATATNELGQASCASSL 79
Cdd:cd20973     7 KEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLcSLIISDVCGDDSGKYTCKAVNSLGEATCSAEL 86


                  ..
gi 564369110   80 AV 81
Cdd:cd20973    87 TV 88

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270658 [Multi-domain] Cd Length: 265 Bit Score: 57.73 E-value: 2.66e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPyAAEGKRRVLQEYEVLRTLHHERLMSLHeAYITPRYLVLIAESCGNRELLcglsDR 2311
Cdd:cd05073    22 GQFGEVWMATYNKHTKVAVKTMKP-GSMSVEAFLAEANVMKTLQHDKLVKLH-AVVTKEPIYIITEFMAKGSLL----DF 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2312 FRYSEDD------VATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEFM 2385
Cdd:cd05073    96 LKSDEGSkqplpkLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWT 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2386 APEMVRGDPIGSATDIWGAGV-LTYIMLSGYSPFyepdPQETEARIVGGRFDAFQLYPNTSQSATLF--LRKVLSVHPWS 2462
Cdd:cd05073   176 APEAINFGSFTIKSDVWSFGIlLMEIVTYGRIPY----PGMSNPEVIRALERGYRMPRPENCPEELYniMMRCWKNRPEE 251


                  ....*
gi 564369110 2463 RPSLQ 2467
Cdd:cd05073   252 RPTFE 256

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143381 [Multi-domain] Cd Length: 359 Bit Score: 58.50 E-value: 2.76e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2221 KPYTFLEEKARGRFGVVRSCRENATGRTFVAKIV--PYAAEGK-RRVLQEYEVLRTLHHERLMSLHEAYITPRYLvliaE 2297
Cdd:cd07876    21 KRYQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLsrPFQNQTHaKRAYRELVLLKCVNHKNIISLLNVFTPQKSL----E 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSD-------RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAqpynpq 2370
Cdd:cd07876    97 EFQDVYLVMELMDanlcqviHMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLA------ 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 alkplghRTGTLEFM-----------APEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDP---------------- 2423
Cdd:cd07876   171 -------RTACTNFMmtpyvvtryyrAPEVILGMGYKENVDIWSVGCIMGELVKGSVIFQGTDHidqwnkvieqlgtpsa 243

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2424 ------QETEARIVGGRFD----AF-QLYPN-------------TSQSATLfLRKVLSVHPWSRPSLQDCLAHPWLQDAY 2479
Cdd:cd07876   244 efmnrlQPTVRNYVENRPQypgiSFeELFPDwifpseserdklkTSQARDL-LSKMLVIDPDKRISVDEALRHPYITVWY 322

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 53.36 E-value: 2.83e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110  343 VEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDGGLH-SLHIARVGSEDEGLYEVSATNTHG 413
Cdd:cd05737    11 VTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTvYFTINGVSSEDSGKYGLVVKNKYG 82

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 53.31 E-value: 2.85e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  343 VEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESE-NLRLRQDGGLHSLHIARVGSEDEGLYEVSATNTHGQAHCSAQL 421
Cdd:cd05894     5 IVVVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEgRVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHASLFV 84


                  ..
gi 564369110  422 YV 423
Cdd:cd05894    85 KV 86

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK3 is predominantly expressed in mature spermatozoa, and might play a role in the fertilization process. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271116 [Multi-domain] Cd Length: 331 Bit Score: 58.10 E-value: 3.01e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  864 GRRLSDYYDIHQEIGRGAFSYLRRVVERSSG-LEFAAKFIPSQAKPKASARREARLLARLQHD-------CVLyFHEAFE 935
Cdd:cd14214     8 GDWLQERYEIVGDLGEGTFGKVVECLDHARGkSQVALKIIRNVGKYREAARLEINVLKKIKEKdkenkflCVL-MSDWFN 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  936 RRRGLVIVTELC---TEELLERMARKPTVCeSETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLV----WDGAGGEEQ-- 1006
Cdd:cd14214    87 FHGHMCIAFELLgknTFEFLKENNFQPYPL-PHIRHMAYQLCHALKFLHENQLTHTDLKPENILFvnseFDTLYNESKsc 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1007 ---------VRICDFGNAQelTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLM 1077
Cdd:cd14214   166 eeksvkntsIRVADFGSAT--FDHEHHTTIVATRHYRPPEVILELGWAQPCDVWSLGCILFEYYRGFTLFQTHENREHLV 243


                  ..
gi 564369110 1078 NI 1079
Cdd:cd14214   244 MM 245

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 53.18 E-value: 3.09e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  334 PLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVN-ESENLRLRQD-GGLHSLHIARVGSEDEGLYEVSATNT 411
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISpKSDHYTIQRDlDGTCSLHTTASTLDDDGNYTIMAANP 80

                          90
                  ....*....|..
gi 564369110  412 HGQAHCSAQLYV 423
Cdd:cd05893    81 QGRISCTGRLMV 92

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133243 [Multi-domain] Cd Length: 256 Bit Score: 57.27 E-value: 3.14e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2224 TFLEEKARGRFGVVRscRENATGRTFVA-KIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYI--TPRYLVL--IAES 2298
Cdd:cd05112     7 TFVQEIGSGQFGLVH--LGYWLNKDKVAiKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLeqAPICLVFefMEHG 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CgnrellcgLSDRFR-----YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ-PYNPQAL 2372
Cdd:cd05112    85 C--------LSDYLRtqrglFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRfVLDDQYT 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2373 KPLGHRTgTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPFYEPDPQETEARIVGGrfdaFQLY-PN-TSQSAT 2449
Cdd:cd05112   157 SSTGTKF-PVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDINAG----FRLYkPRlASTHVY 231

                         250
                  ....*....|....*..
gi 564369110 2450 LFLRKVLSVHPWSRPSL 2466
Cdd:cd05112   232 EIMNHCWKERPEDRPSF 248

Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB1 interacts directly with the mitogen activated protein kinase (MAPK) kinase MKK4, an activator of JNK. It regulates vascular smooth muscle cell proliferation and chemotaxis through the JNK signaling pathway. It is found to be down-regulated in human acute myeloid leukaemia (AML) and may play a role in the pathogenesis of the disease. It has also been identified as a potential biomarker for antibody-mediated allograft failure. TRB1 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB1 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270925 [Multi-domain] Cd Length: 242 Bit Score: 56.98 E-value: 3.43e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEE--QVRICDFGNAQeLTPGEPQYC--QFGTPEFVAPEI 1038
Cdd:cd14023    83 EEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSD----EErtQLRLESLEDTH-IMKGEDDALsdKHGCPAYVSPEI 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1039 VNQSPV-SG-VTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEEttflSLSREARGFLIKVLVQD-RLRPTA 1115
Cdd:cd14023   158 LNTTGTySGkSADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPD----HVSPKARCLIRSLLRREpSERLTA 233


                  ....*....
gi 564369110 1116 EETLEHPWF 1124
Cdd:cd14023   234 PEILLHPWF 242

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 59.57 E-value: 3.53e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1228 EALGTPEAGAATPMdWQEQGRAPSKDQEAPSPEALPSPgqespDGPSPRRPELRRGSSAESALPRVGSREPGRSLHKAAS 1307
Cdd:PHA03247 2541 EELASDDAGDPPPP-LPPAAPPAAPDRSVPPPRPAPRP-----SEPAVTSRARRPDAPPQSARPRAPVDDRGDPRGPAPP 2614

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1308 VELP---QRRSPSPGATRLTRGGLGEGEYAQRLQALRqrllrggpedgkvsglrgPLLESLGGRARDPRMARAASSEAAP 1384
Cdd:PHA03247 2615 SPLPpdtHAPDPPPPSPSPAANEPDPHPPPTVPPPER------------------PRDDPAPGRVSRPRRARRLGRAAQA 2676

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1385 hhqpppesrglqksssfsqgEAEPRGRHRRAGAPLEIPVARLGARRLQE-------SPSLSALSETQPPSPALPSAPKPS 1457
Cdd:PHA03247 2677 --------------------SSPPQRPRRRAARPTVGSLTSLADPPPPPptpepapHALVSATPLPPGPAAARQASPALP 2736

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1458 ITKSPEPSAATSRDSPQPPAPQPVPEKIPEPKPEPVRaAKPAQPPLALQMPAQSltpyaqimqslQLSSPTLSPQVPPSE 1537
Cdd:PHA03247 2737 AAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPA-APAAGPPRRLTRPAVA-----------SLSESRESLPSPWDP 2804

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 1538 PKPHAAVFARVASPPPGASekrvPSARIPPVLAEKVRVPTVPPRP 1582
Cdd:PHA03247 2805 ADPPAAVLAPAAALPPAAS----PAGPLPPPTSAQPTAPPPPPGP 2845

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK1 binds with high affinity the alternative splicing factor, SRSF1 (serine/arginine-rich splicing factor 1), and regiospecifically phosphorylates 10-12 serines in its RS domain. It plays a role in the regulation of pre-mRNA splicing, chromatin structure, and germ cell development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271118 [Multi-domain] Cd Length: 349 Bit Score: 58.12 E-value: 3.86e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2246 GRTFVA-KIVPYAAEGKRRVLQEYEVLRTLHH--------ERLMSLHEAY----ITPRYLVLIAESCGNRELLCGLSDRF 2312
Cdd:cd14216    34 GKRFVAmKVVKSAEHYTETALDEIKLLKSVRNsdpndpnrEMVVQLLDDFkisgVNGTHICMVFEVLGHHLLKWIIKSNY 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2313 R-YSEDDVATYVVQLLQGLDYLHGR-HVLHLDIKPDNLLLAAD--------------------------NA----LKIVD 2360
Cdd:cd14216   114 QgLPLPCVKKIIRQVLQGLDYLHTKcRIIHTDIKPENILLSVNeqyirrlaaeatewqrnflvnplepkNAeklkVKIAD 193

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2361 FGSAQPYNpqalKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGySPFYEPDPQETEAR----------- 2429
Cdd:cd14216   194 LGNACWVH----KHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMAFELATG-DYLFEPHSGEDYSRdedhialiiel 268

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2430 --------IVGGRF---------------------------DAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLAHPW 2474
Cdd:cd14216   269 lgkvprklIVAGKYskefftkkgdlkhitklkpwglfevlvEKYEWSQEEAAGFTDFLLPMLELIPEKRATAAECLRHPW 348


                  .
gi 564369110 2475 L 2475
Cdd:cd14216   349 L 349

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271036 [Multi-domain] Cd Length: 332 Bit Score: 57.57 E-value: 3.87e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVpyaaegkRRVlQEY--------EVLRTLHHE------RLMSLHEAYITPRYLVLIAE 2297
Cdd:cd14134    23 GTFGKVLECWDRKRKRYVAVKII-------RNV-EKYreaakieiDVLETLAEKdpngksHCVQLRDWFDYRGHMCIVFE 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 scgnrelLCGLS--DRFR------YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA------------------ 2351
Cdd:cd14134    95 -------LLGPSlyDFLKknnygpFPLEHVQHIAKQLLEAVAFLHDLKLTHTDLKPENILLVdsdyvkvynpkkkrqirv 167

                         170
                  ....*....|....
gi 564369110 2352 -ADNALKIVDFGSA 2364
Cdd:cd14134   168 pKSTDIKLIDFGSA 181

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 52.18 E-value: 3.99e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  352 RLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDGglhSLHIARVGSEDEGLYEVSATNTHGQAHCSAQL 421
Cdd:cd05746     2 QIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEG---YLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

NIMA-related protein kinase; Provisional

Pssm-ID: 140293 [Multi-domain] Cd Length: 478 Bit Score: 58.49 E-value: 4.01e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  899 AKFIP-SQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT-----EELLERMARKPTVCESETRTYMRQ 972
Cdd:PTZ00267   98 AKFVMlNDERQAAYARSELHCLAACDHFGIVKHFDDFKSDDKLLLIMEYGSggdlnKQIKQRLKEHLPFQEYEVGLLFYQ 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  973 VLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELTPG-----EPQYCqfGTPEFVAPEIVNQSPVSGV 1047
Cdd:PTZ00267  178 IVLALDEVHSRKMMHRDLKSANIFLMPTG----IIKLGDFGFSKQYSDSvsldvASSFC--GTPYYLAPELWERKRYSKK 251

                         170       180       190
                  ....*....|....*....|....*....|..
gi 564369110 1048 TDIWPVGVVAFLCLTGISPFVGENDRTTLMNI 1079
Cdd:PTZ00267  252 ADMWSLGVILYELLTLHRPFKGPSQREIMQQV 283

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270657 [Multi-domain] Cd Length: 272 Bit Score: 56.97 E-value: 4.31e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPyAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd05072     5 PRESIKLVKKLGAGQFGEVWMGYYNNSTKVAVKTLKP-GTMSVQAFLEEANLMKTLQHDKLVRLYAVVTKEEPIYIITEY 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGL-SDR-FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLG 2376
Cdd:cd05072    84 MAKGSLLDFLkSDEgGKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVIEDNEYTARE 163

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 564369110 2377 HRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTY-IMLSGYSPF 2418
Cdd:cd05072   164 GAKFPIKWTAPEAINFGSFTIKSDVWSFGILLYeIVTYGKIPY 206

Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PINK1 contains an N-terminal mitochondrial targeting sequence, a catalytic domain, and a C-terminal regulatory region. It plays an important role in maintaining mitochondrial homeostasis. It protects cells against oxidative stress-induced apoptosis by phosphorylating the chaperone TNFR-associated protein 1 (TRAP1), also called Hsp75. Phosphorylated TRAP1 prevents cytochrome c release and peroxide-induced apoptosis. PINK1 interacts with Omi/HtrA2, a serine protease, and Parkin, an E3 ubiquitin ligase, in different pathways to promote mitochondrial health. The parkin gene is the most commonly mutated gene in autosomal recessive familial parkinsonism. Mutations within the catalytic domain of PINK1 are also associated with Parkinson's disease. The PINK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270920 [Multi-domain] Cd Length: 313 Bit Score: 57.50 E-value: 4.81e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2291 YLVLIAESCGNRELLCGLSDRFRYSeddvATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNA----LKIVDFGSAQP 2366
Cdd:cd14018   116 FLVMKNYPCTLRQYLWVNTPSYRLA----RVMILQLLEGVDHLVRHGIAHRDLKSDNILLELDFDgcpwLVIADFGCCLA 191

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 2367 YNPQALK-PLG----HRTGTLEFMAPEMVRGDPiG-------SATDIWGAGVLTYIMLSGYSPFY 2419
Cdd:cd14018   192 DDSIGLQlPFSswyvDRGGNACLMAPEVSTAVP-GpgvvinySKADAWAVGAIAYEIFGLSNPFY 255

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132980 [Multi-domain] Cd Length: 331 Bit Score: 57.37 E-value: 4.82e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLE 953
Cdd:cd06649    12 ELGAGNGGVVTKVQHKPSGLIMARKLIHLEIKPAIRNQiiRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLD 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  954 RMARKPTVCESETRTYMR-QVLEGIGYLHQSH-VLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQyCQFGTP 1031
Cdd:cd06649    92 QVLKEAKRIPEEILGKVSiAVLRGLAYLREKHqIMHRDVKPSNILV----NSRGEIKLCDFGVSGQLIDSMAN-SFVGTR 166

                         170       180
                  ....*....|....*....|....
gi 564369110 1032 EFVAPEIVNQSPVSGVTDIWPVGV 1055
Cdd:cd06649   167 SYMSPERLQGTHYSVQSDIWSMGL 190

Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1a, Xenopus laevis Wee1b (XeWee1b) and similar vertebrate proteins. Members of this subfamily show a wide expression pattern. XeWee1b functions after the first zygotic cell divisions. It is expressed in all tissues and is also present after the gastrulation stage of embryos. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1a subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271040 [Multi-domain] Cd Length: 276 Bit Score: 56.95 E-value: 5.30e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLSDYYDIhQEIGRGAFSYLRRVVERSSGLEFAAKfipSQAKPKA------SARREARLLARL-QHDCVLYFHEAFERR 937
Cdd:cd14138     2 RYATEFHEL-EKIGSGEFGSVFKCVKRLDGCIYAIK---RSKKPLAgsvdeqNALREVYAHAVLgQHSHVVRYYSAWAED 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  938 RGLVIVTELC-----TEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVW-------------- 998
Cdd:cd14138    78 DHMLIQNEYCnggslADAISENYRIMSYFTEPELKDLLLQVARGLKYIHSMSLVHMDIKPSNIFISrtsipnaaseegde 157

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110  999 -DGAGGEEQVRICDFGNAQELTpgEPQyCQFGTPEFVAPEIVNQSPVS-GVTDIWPVGVVAfLCLTGISPFVGENDR 1073
Cdd:cd14138   158 dEWASNKVIFKIGDLGHVTRVS--SPQ-VEEGDSRFLANEVLQENYTHlPKADIFALALTV-VCAAGAEPLPTNGDQ 230

Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDIK1L is also called STK35 or CLIK-1. It is predominantly a nuclear protein which is capable of autophosphorylation. Through its interaction with the PDZ-LIM protein CLP-36, it is localized to actin stress fibers. The PDIK1L subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270879 [Multi-domain] Cd Length: 322 Bit Score: 57.18 E-value: 5.31e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKAS-ARREARLLARLQ--HDCVLYFHEAFERRRGLV------ 941
Cdd:cd13977     2 YSLIREVGRGSYGVVYEAVVRRTGARVAVKKIRCNAPENVElALREFWALSSIQrqHPNVIQLEECVLQRDGLAqrmshg 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 ------------------------------IVTELC-----TEELLERMARKPTvceseTRTYMRQVLEGIGYLHQSHVL 986
Cdd:cd13977    82 ssksdlylllvetslkgercfdprsacylwFVMEFCdggdmNEYLLSRRPDRQT-----NTSFMLQLSSALAFLHRNQIV 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  987 HLDVKPENLLVWDGAgGEEQVRICDFG-----NAQELTPGEP---QYCQF----GTPEFVAPEiVNQSPVSGVTDIWPVG 1054
Cdd:cd13977   157 HRDLKPDNILISHKR-GEPILKVADFGlskvcSGSGLNPEEPanvNKHFLssacGSDFYMAPE-VWEGHYTAKADIFALG 234


                  ..
gi 564369110 1055 VV 1056
Cdd:cd13977   235 II 236

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270830 [Multi-domain] Cd Length: 294 Bit Score: 57.15 E-value: 5.35e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  869 DYYDIHQEIGRGAFSYLRRVVERSSG---------LEFAAKFIPSqakpkaSARREARLLARLQHD-------CVLYFHE 932
Cdd:cd07837     1 DAYEKLEKIGEGTYGKVYKARDKNTGklvalkktrLEMEEEGVPS------TALREVSLLQMLSQSiyivrllDVEHVEE 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  933 afERRRGLVIVTELCTEEL---LERMARKPT--VCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeeQV 1007
Cdd:cd07837    75 --NGKPLLYLVFEYLDTDLkkfIDSYGRGPHnpLPAKTIQSFMYQLCKGVAHCHSHGVMHRDLKPQNLLVDKQKG---LL 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1008 RICDFGNAQELTPGEPQYcqfgTPEFV-----APEI-VNQSPVSGVTDIWPVGVVaFLCLTGISP-FVGENDRTTLMNI- 1079
Cdd:cd07837   150 KIADLGLGRAFTIPIKSY----THEIVtlwyrAPEVlLGSTHYSTPVDMWSVGCI-FAEMSRKQPlFPGDSELQQLLHIf 224

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 1080 RNYNVAFEET-----------------------TFLSLSREARGFLIKVLVQDRL-RPTAEETLEHPWF 1124
Cdd:cd07837   225 RLLGTPNEEVwpgvsklrdwheypqwkpqdlsrAVPDLEPEGVDLLTKMLAYDPAkRISAKAALQHPYF 293

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 52.74 E-value: 5.57e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  755 PRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKDE--VLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNL 832
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGqvISTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|..
gi 564369110  833 AGEVSCKAELSV 844
Cdd:cd20974    81 SGQATSTAELLV 92

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270685 [Multi-domain] Cd Length: 260 Bit Score: 56.41 E-value: 5.62e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSgLEFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEE-LLE 953
Cdd:cd05114    10 KELGSGLFGVVRLGKWRAQ-YKVAIKAIREGAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEFMENGcLLN 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  954 RMARKPTVCESETRTYMRQ-VLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTpgEPQYCQFGTPE 1032
Cdd:cd05114    89 YLRQRRGKLSRDMLLSMCQdVCEGMEYLERNNFIHRDLAARNCLVND----TGVVKVSDFGMTRYVL--DDQYTSSSGAK 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 564369110 1033 F----VAPEIVNQSPVSGVTDIWPVGVVAFLCLT-GISPF 1067
Cdd:cd05114   163 FpvkwSPPEVFNYSKFSSKSDVWSFGVLMWEVFTeGKMPF 202

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 52.20 E-value: 5.65e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110  152 EGQDVIMSIRVQGEPKPVVSWLRNRQPVRP-DQRRFAEEAEgglcrLRILAAERGDAGFYTCKAVNEYGARQCEARL 227
Cdd:cd05723    11 ESMDIVFECEVTGKPTPTVKWVKNGDVVIPsDYFKIVKEHN-----LQVLGLVKSDEGFYQCIAENDVGNAQASAQL 82

glycogen synthase kinase; Provisional

Pssm-ID: 173333 [Multi-domain] Cd Length: 440 Bit Score: 57.74 E-value: 5.83e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  865 RRLSDYYDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKasaRREARLLARLQHDCVL-----YFHEAF---ER 936
Cdd:PTZ00036   62 RSPNKSYKLGNIIGNGSFGVVYEAICIDTSEKVAIKKVLQDPQYK---NRELLIMKNLNHINIIflkdyYYTECFkknEK 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  937 RRGLVIVTELCTEELLERM---ARK----PTVCeseTRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgAGGEEQVRI 1009
Cdd:PTZ00036  139 NIFLNVVMEFIPQTVHKYMkhyARNnhalPLFL---VKLYSYQLCRALAYIHSKFICHRDLKPQNLLI---DPNTHTLKL 212

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1010 CDFGNAQELTPGEPQYCQFGTPEFVAPEI-VNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNI 1079
Cdd:PTZ00036  213 CDFGSAKNLLAGQRSVSYICSRFYRAPELmLGATNYTTHIDLWSLGCIIAEMILGYPIFSGQSSVDQLVRI 283

Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB1 interacts directly with the mitogen activated protein kinase (MAPK) kinase MKK4, an activator of JNK. It regulates vascular smooth muscle cell proliferation and chemotaxis through the JNK signaling pathway. It is found to be down-regulated in human acute myeloid leukaemia (AML) and may play a role in the pathogenesis of the disease. It has also been identified as a potential biomarker for antibody-mediated allograft failure. TRB1 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB1 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270925 [Multi-domain] Cd Length: 242 Bit Score: 56.21 E-value: 6.42e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2375 LGHRTGTLEFMAPEMVR--GDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIVGGRfdaFQLYPNTSQSATLFL 2452
Cdd:cd14023   143 LSDKHGCPAYVSPEILNttGTYSGKSADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQ---FCIPDHVSPKARCLI 219

                          90       100
                  ....*....|....*....|...
gi 564369110 2453 RKVLSVHPWSRPSLQDCLAHPWL 2475
Cdd:cd14023   220 RSLLRREPSERLTAPEILLHPWF 242

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 52.12 E-value: 6.49e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    465 QDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDR-RMTQYRDIHRLVFPAVGPQHAGVYKSVIANKLGKAACYA 543
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRfSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 564369110    544 HLYV 547
Cdd:smart00410   82 TLTV 85

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 52.13 E-value: 6.55e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  144 SLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLcrLRILAAERGDAGFYTCKAVNE-YGARQ 222
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTT--LTIRNIRRSDMGIYLCIASNGvPGSVE 85


                  ....*..
gi 564369110  223 CEARLEV 229
Cdd:cd20970    86 KRITLQV 92

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270969 [Multi-domain] Cd Length: 276 Bit Score: 56.51 E-value: 7.05e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  913 RREARLLARLQHDCVLYFheaferrRGLVIvTELCTEELLERMARKPTVCESETR--TYM-----------RQVLEGIGY 979
Cdd:cd14067    58 RQEASMLHSLQHPCIVYL-------IGISI-HPLCFALELAPLGSLNTVLEENHKgsSFMplghmltfkiaYQIAAGLAY 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  980 LHQSHVLHLDVKPENLLVWDGAGGEE-QVRICDFGNAQElTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAF 1058
Cdd:cd14067   130 LHKKNIIFCDLKSDNILVWSLDVQEHiNIKLSDYGISRQ-SFHEGALGVEGTPGYQAPEIRPRIVYDEKVDMFSYGMVLY 208

                         170
                  ....*....|...
gi 564369110 1059 LCLTGISPFVGEN 1071
Cdd:cd14067   209 ELLSGQRPSLGHH 221

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 52.02 E-value: 7.22e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  755 PRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKD-EVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLA 833
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDgKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 564369110  834 GEVSCKAELSV 844
Cdd:cd20990    81 GQNSFNLELVV 91

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 52.09 E-value: 7.74e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAE-RGDAGFYTCKAVNE 217
Cdd:cd20971     2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEFKGGYHQLIIASVtDDDATVYQVRATNQ 81


                  ..
gi 564369110  218 YG 219
Cdd:cd20971    82 GG 83

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271114 [Multi-domain] Cd Length: 330 Bit Score: 56.87 E-value: 7.90e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  940 LVIVTELCTEELLErMARK------PTvceSETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEeqVRICDFG 1013
Cdd:cd14212    77 LCIVFELLGVNLYE-LLKQnqfrglSL---QLIRKFLQQLLDALSVLKDARIIHCDLKPENILLVNLDSPE--IKLIDFG 150

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 1014 NAQELTPGEPQYCQfgTPEFVAPEIVNQSPVSGVTDIWPVG-VVAFLCLtGISPFVGEN 1071
Cdd:cd14212   151 SACFENYTLYTYIQ--SRFYRSPEVLLGLPYSTAIDMWSLGcIAAELFL-GLPLFPGNS 206

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS1 functions as a tumor suppressor and is implicated in cell cycle regulation. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. Promoter methylation, loss of heterozygosity, and missense mutations targeting the LATS1 gene have also been found in human sarcomas and ovarian cancers. In addition, decreased expression of LATS1 is associated with an aggressive phenotype and poor prognosis. LATS1 induces G2 arrest and promotes cytokinesis. It may be a component of the mitotic exit network in higher eukaryotes. The LATS1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270775 [Multi-domain] Cd Length: 382 Bit Score: 56.98 E-value: 8.09e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2314 YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG---------------------------SAQP 2366
Cdd:cd05625    98 FPEDLARFYIAELTCAVESVHKMGFIHRDIKPDNILIDRDGHIKLTDFGlctgfrwthdskyyqsgdhlrqdsmdfSNEW 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2367 YNPQA------LKPLGHRT-------------GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETE 2427
Cdd:cd05625   178 GDPENcrcgdrLKPLERRAarqhqrclahslvGTPNYIAPEVLLRTGYTQLCDWWSVGVILFEMLVGQPPFLAQTPLETQ 257


                  ....
gi 564369110 2428 ARIV 2431
Cdd:cd05625   258 MKVI 261

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 51.87 E-value: 8.40e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1848 PPVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVviVSCKDGRQLLSIPRASKRHAGLYECSATNV 1927
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADR--STCEAGVGELHIQDVLPEDHGTYTCLAKNA 78

                          90
                  ....*....|..
gi 564369110 1928 LGSITSSCTVAV 1939
Cdd:cd20976    79 AGQVSCSAWVTV 90

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 51.95 E-value: 9.22e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110  343 VEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDGGLHSLHIARVGSEDEGLYEVSATNTHGQA 415
Cdd:cd20949     9 TTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSIA 81

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK1 plays a role in neuronal differentiation. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271115 [Multi-domain] Cd Length: 330 Bit Score: 56.40 E-value: 9.61e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  862 HRGRRLSDYYDIHQEIGRGAFSylrRVVE----RSSGLEFAAKFIPSQAKPKASARREARLLARLQH-DCVLYFH----- 931
Cdd:cd14213     5 QSGDVLRARYEIVDTLGEGAFG---KVVEcidhKMGGMHVAVKIVKNVDRYREAARSEIQVLEHLNTtDPNSTFRcvqml 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  932 EAFERRRGLVIVTEL---CTEELLERMARKPTVCEsETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEE--- 1005
Cdd:cd14213    82 EWFDHHGHVCIVFELlglSTYDFIKENSFLPFPID-HIRNMAYQICKSVNFLHHNKLTHTDLKPENILFVQSDYVVKynp 160

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110 1006 ------------QVRICDFGNAQelTPGEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVV 1056
Cdd:cd14213   161 kmkrdertlknpDIKVVDFGSAT--YDDEHHSTLVSTRHYRAPEVILALGWSQPCDVWSIGCI 221

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271053 [Multi-domain] Cd Length: 274 Bit Score: 55.84 E-value: 9.92e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  913 RREARLLARLQHDCVLYFHeAFERRRGLVIVTELCTEELLERMARKptvceSETRTYM-------RQVLEGIGYLHQSHV 985
Cdd:cd14151    52 KNEVGVLRKTRHVNILLFM-GYSTKPQLAIVTQWCEGSSLYHHLHI-----IETKFEMiklidiaRQTAQGMDYLHAKSI 125

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  986 LHLDVKPENLLVWDgaggEEQVRICDFGNA--QELTPGEPQYCQF-GTPEFVAPEIV---NQSPVSGVTDIWPVGVVAFL 1059
Cdd:cd14151   126 IHRDLKSNNIFLHE----DLTVKIGDFGLAtvKSRWSGSHQFEQLsGSILWMAPEVIrmqDKNPYSFQSDVYAFGIVLYE 201

                         170
                  ....*....|....*...
gi 564369110 1060 CLTGISPFVGENDRTTLM 1077
Cdd:cd14151   202 LMTGQLPYSNINNRDQII 219

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270964 [Multi-domain] Cd Length: 253 Bit Score: 55.48 E-value: 9.99e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  903 PSQAKpkaSARREARLLARLQHDCVLYFHeAFERRRGLVIVTELCTEELLERMarkptVCESETRTYM-------RQVLE 975
Cdd:cd14062    30 PSQLQ---AFKNEVAVLRKTRHVNILLFM-GYMTKPQLAIVTQWCEGSSLYKH-----LHVLETKFEMlqlidiaRQTAQ 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  976 GIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQELT--PGEPQYCQ-FGTPEFVAPEIV---NQSPVSGVTD 1049
Cdd:cd14062   101 GMDYLHAKNIIHRDLKSNNIFLHEDL----TVKIGDFGLATVKTrwSGSQQFEQpTGSILWMAPEVIrmqDENPYSFQSD 176

                         170       180
                  ....*....|....*....|....
gi 564369110 1050 IWPVGVVAFLCLTGISPFVGENDR 1073
Cdd:cd14062   177 VYAFGIVLYELLTGQLPYSHINNR 200

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 51.97 E-value: 1.01e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  321 TCSARLTVRPslaplftrllEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDGGLHSLHIARVGSED 400
Cdd:cd05747     1 TLPATILTKP----------RSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSD 70

                          90
                  ....*....|....
gi 564369110  401 EGLYEVSATNTHGQ 414
Cdd:cd05747    71 EGNYTVVVENSEGK 84

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 51.64 E-value: 1.03e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 218
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80


                  .
gi 564369110  219 G 219
Cdd:cd20990    81 G 81

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 51.81 E-value: 1.07e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  754 APRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLA 833
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                          90
                  ....*....|.
gi 564369110  834 GEVSCKAELSV 844
Cdd:cd20972    81 GSDTTSAEIFV 91

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 51.62 E-value: 1.08e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLHSE-GRLLIraegERHTLLLREAQAADAGSYTATATNELG 71
Cdd:cd20978    11 VVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPmERATV----EDGTLTIINVQPEDTGYYGCVATNEIG 78

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 51.34 E-value: 1.10e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  763 DVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEENecSLVVLSAGSQDGGVYTCTARNLAGEVSCKAEL 842
Cdd:cd20952     8 NQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENG--SLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85


                  ..
gi 564369110  843 SV 844
Cdd:cd20952    86 DV 87

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270918 [Multi-domain] Cd Length: 266 Bit Score: 55.54 E-value: 1.14e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKaSARREARLLARLQhDCV----LYFHEAFERRRglVIVTEL 946
Cdd:cd14016     2 YKLVKKIGSGSFGEVYLGIDLKTGEEVAIKIEKKDSKHP-QLEYEAKVYKLLQ-GGPgiprLYWFGQEGDYN--VMVMDL 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110  947 C---TEELLERMARK---PTVCesetrtyM--RQVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGEE-QVRICDFG 1013
Cdd:cd14016    78 LgpsLEDLFNKCGRKfslKTVL-------MlaDQMISRLEYLHSKGYIHRDIKPENFLM--GLGKNSnKVYLIDFG 144

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 51.78 E-value: 1.15e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  146 MDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVR-----PDQRRFAEEAeGGLCRLRILAAERG--DAGFYTCKAVNEY 218
Cdd:cd07693     8 SDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLEtdkddPRSHRIVLPS-GSLFFLRVVHGRKGrsDEGVYVCVAHNSL 86

                          90
                  ....*....|..
gi 564369110  219 G-ARQCEARLEV 229
Cdd:cd07693    87 GeAVSRNASLEV 98

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271056 [Multi-domain] Cd Length: 272 Bit Score: 55.59 E-value: 1.18e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAK-FIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL----CTEEL 951
Cdd:cd14154     1 LGKGFFGQAIKVTHRETGEVMVMKeLIRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYipggTLKDV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  952 LERMARkPTVCESETRtYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFG-----NAQELTPGEP--- 1023
Cdd:cd14154    81 LKDMAR-PLPWAQRVR-FAKDIASGMAYLHSMNIIHRDLNSHNCLVRE----DKTVVVADFGlarliVEERLPSGNMsps 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 1024 -------------QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVafLC 1060
Cdd:cd14154   155 etlrhlkspdrkkRYTVVGNPYWMAPEMLNGRSYDEKVDIFSFGIV--LC 202

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 51.25 E-value: 1.18e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 1856 KDQVLLEGEAATLLCLPA-ACPTPRISWMKDKQSLR-SEPSVVIVscKDGRqlLSIPRASKRHAGLYECSATNVLG 1929
Cdd:cd05724     5 SDTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNlDNERVRIV--DDGN--LLIAEARKSDEGTYKCVATNMVG 76

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270790 [Multi-domain] Cd Length: 291 Bit Score: 55.83 E-value: 1.19e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTF-------LEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGK--RRVLQEYEVLR-------------TLHHE--- 2277
Cdd:cd06616     1 YEFtaedlkdLGEIGRGAFGTVNKMLHKPSGTIMAVKRIRSTVDEKeqKRLLMDLDVVMrssdcpyivkfygALFREgdc 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2278 ----RLM--SLHEAYitpRYLVLIAESCGNRELLCGLSdrfryseddVATyvvqlLQGLDYLHGR-HVLHLDIKPDNLLL 2350
Cdd:cd06616    81 wicmELMdiSLDKFY---KYVYEVLDSVIPEEILGKIA---------VAT-----VKALNYLKEElKIIHRDVKPSNILL 143

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2351 AADNALKIVDFG-SAQPYNPQALKplgHRTGTLEFMAPEmvRGDPIGSA------TDIWGAGVLTYIMLSGYSPFYEPDP 2423
Cdd:cd06616   144 DRNGNIKLCDFGiSGQLVDSIAKT---RDAGCRPYMAPE--RIDPSASRdgydvrSDVWSLGITLYEVATGKFPYPKWNS 218

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2424 Q-ETEARIVGGrfDAFQLYPNT----SQSATLFLRKVLSVHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd06616   219 VfDQLTQVVKG--DPPILSNSEerefSPSFVNFVNLCLIKDESKRPKYKELLKHPFIKM 275

serine/threonine kinase US3; Provisional

Pssm-ID: 165478 [Multi-domain] Cd Length: 391 Bit Score: 56.54 E-value: 1.22e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAA------KFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEE 950
Cdd:PHA03212   89 IEKAGFSILETFTPGAEGFAFACidnktcEHVVIKAGQRGGTATEAHILRAINHPSIIQLKGTFTYNKFTCLILPRYKTD 168

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  951 LLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwDGAGgeeQVRICDFGNA---QELTPGEpQYCQ 1027
Cdd:PHA03212  169 LYCYLAAKRNIAICDILAIERSVLRAIQYLHENRIIHRDIKAENIFI-NHPG---DVCLGDFGAAcfpVDINANK-YYGW 243

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 564369110 1028 FGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTG 1063
Cdd:PHA03212  244 AGTIATNAPELLARDPYGPAVDIWSAGIVLFEMATC 279

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270623 [Multi-domain] Cd Length: 262 Bit Score: 55.24 E-value: 1.26e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFS-----YLRRVVERSsgLEFAAKFIPSQAKPKASA--RREARLLARLQHDCVLYFHEAFERRRGLVIVTELC- 947
Cdd:cd00192     2 KLGEGAFGevykgKLKGGDGKT--VDVAVKTLKEDASESERKdfLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMe 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 ---------TEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQEL 1018
Cdd:cd00192    80 ggdlldflrKSRPVFPSPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLV----GEDLVVKISDFGLSRDI 155

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 1019 TPGEPQYCQFGTPEFV---APEIVNQSPVSGVTDIWPVGVVAFLCLT-GISPFVG 1069
Cdd:cd00192   156 YDDDYYRKKTGGKLPIrwmAPESLKDGIFTSKSDVWSFGVLLWEIFTlGATPYPG 210

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270653 [Multi-domain] Cd Length: 267 Bit Score: 55.49 E-value: 1.28e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  914 REARLLARLQHDCVLYFHEAFERRRGLVIVTEL-CTEELLERMARKPTVCESETRTYMR-QVLEGIGYLHQSHVLHLDVK 991
Cdd:cd05068    52 REAQIMKKLRHPKLIQLYAVCTLEEPIYIITELmKHGSLLEYLQGKGRSLQLPQLIDMAaQVASGMAYLESQNYIHRDLA 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  992 PENLLVwdgaGGEEQVRICDFGNAQeLTPGEPQY-CQFGTP---EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLT-GISP 1066
Cdd:cd05068   132 ARNVLV----GENNICKVADFGLAR-VIKVEDEYeAREGAKfpiKWTAPEAANYNRFSIKSDVWSFGILLTEIVTyGRIP 206

                         170
                  ....*....|....*..
gi 564369110 1067 FVGENDRTTLMNI-RNY 1082
Cdd:cd05068   207 YPGMTNAEVLQQVeRGY 223

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133248 [Multi-domain] Cd Length: 261 Bit Score: 55.52 E-value: 1.33e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFSYLRRVverssglefAAKFIPSQAKPKASA-RREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLER 954
Cdd:cd05148    21 EVWEGLWKNRVRV---------AIKILKSDDLLKQQDfQKEVQALKRLRHKHLISLFAVCSVGEPVYIITELMEKGSLLA 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  955 MARKP--TVCESETRTYMR-QVLEGIGYLHQSHVLHLDVKPENLLVwdgagGEEQV-RICDFGNAQELTpgEPQYCQFGT 1030
Cdd:cd05148    92 FLRSPegQVLPVASLIDMAcQVAEGMAYLEEQNSIHRDLAARNILV-----GEDLVcKVADFGLARLIK--EDVYLSSDK 164

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 1031 P---EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLT-GISPFVGENDRTTLMNI-RNY 1082
Cdd:cd05148   165 KipyKWTAPEAASHGTFSTKSDVWSFGILLYEMFTyGQVPYPGMNNHEVYDQItAGY 221

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133213 [Multi-domain] Cd Length: 256 Bit Score: 55.37 E-value: 1.33e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAkivpyaaegkrrvlqEYEVLRTLHHERLMSLHEAYITPR-YLVLIAESCGNRELLCGLS 2309
Cdd:cd05082    28 RGNKVAVKCIKNDATAQAFLA---------------EASVMTQLRHSNLVQLLGVIVEEKgGLYIVTEYMAKGSLVDYLR 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRFR--YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPLghrtgTLEFMA 2386
Cdd:cd05082    93 SRGRsvLGGDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGlTKEASSTQDTGKL-----PVKWTA 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2387 PEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPFYEPDPQETEARIVGG-RFDAfqlyPNTSQSATL-FLRKVLSVHPWSR 2463
Cdd:cd05082   168 PEALREKKFSTKSDVWSFGILLWEIYSfGRVPYPRIPLKDVVPRVEKGyKMDA----PDGCPPAVYdVMKNCWHLDAAMR 243

                         250
                  ....*....|....
gi 564369110 2464 PSLQDClaHPWLQD 2477
Cdd:cd05082   244 PSFLQL--REQLEH 255

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270673 [Multi-domain] Cd Length: 284 Bit Score: 55.79 E-value: 1.35e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  913 RREARLLARLQHDCVLYFHEAFERRRGLVIVTELCT-----EELLERMARKPTVCESETRTY------------MRQVLE 975
Cdd:cd05091    57 RHEAMLRSRLQHPNIVCLLGVVTKEQPMSMIFSYCShgdlhEFLVMRSPHSDVGSTDDDKTVkstlepadflhiVTQIAA 136

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  976 GIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEpQYCQFGTPEF----VAPEIVNQSPVSGVTDIW 1051
Cdd:cd05091   137 GMEYLSSHHVVHKDLATRNVLVFD----KLNVKISDLGLFREVYAAD-YYKLMGNSLLpirwMSPEAIMYGKFSIDSDIW 211

                         170       180       190
                  ....*....|....*....|....*....|....
gi 564369110 1052 PVGVVAFLCLT-GISPFVGENDRTTLMNIRNYNV 1084
Cdd:cd05091   212 SYGVVLWEVFSyGLQPYCGYSNQDVIEMIRNRQV 245

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1 gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. CK1gamma proteins are unique within the CK1 subfamily in that they are palmitoylated at the C-termini and are anchored to the plasma membrane. CK1gamma is involved in transducing the signaling of LDL-receptor-related protein 6 (LRP6) through direct phosphorylation following Wnt stimulation, resulting in the recruitment of the scaffold protein Axin. In Xenopus embryos, CK1gamma is required during anterio-posterior patterning. In higher vertebrates, three CK1gamma (gamma1-3) isoforms exist. In mammalian cells, CK1gamma2 has been implicated in regulating the synthesis of sphingomyelin, a phospholipid that is found in the outer leaflet of the plasma membrane, by hyperphosphorylating and inactivating the ceramide transfer protein CERT. CK1gamma2 also phosphorylates the transcription factor Smad-3 resulting in its ubiquitination and degradation. It inhibits Smad-3 mediated responses of Transforming Growth Factor-beta (TGF-beta) including cell growth arrest. The CK1 gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271028 [Multi-domain] Cd Length: 288 Bit Score: 55.51 E-value: 1.40e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTFVAKIVPYaaegKRRVLQ---EYEVLRTL-HHERLMSLHeaYITP--RYLVLIAESCG-NRE 2303
Cdd:cd14126    10 CGNFGELRLGKNLYNNEHVAIKLEPM----KSRAPQlhlEYRFYKLLgQAEGLPQVY--YFGPcgKYNAMVLELLGpSLE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2304 LLCGLSDRfRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA-----ADNALKIVDFGSAQPY-NPQALKPLGH 2377
Cdd:cd14126    84 DLFDLCDR-TFSLKTVLMIAIQLISRIEYVHSKHLIYRDVKPENFLIGrqstkKQHVIHIIDFGLAKEYiDPETNKHIPY 162

                         170
                  ....*....|....
gi 564369110 2378 R-----TGTLEFMA 2386
Cdd:cd14126   163 RehkslTGTARYMS 176

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173652 [Multi-domain] Cd Length: 334 Bit Score: 56.18 E-value: 1.43e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2318 DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQP-YNPQALKPLGHRTGTLEFMAPEMVRGDPIG 2396
Cdd:cd05100   135 DLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDvHNIDYYKKTTNGRLPVKWMAPEALFDRVYT 214

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2397 SATDIWGAGVLTY-IMLSGYSPfYEPDPQETEARIV--GGRFDAfqlYPNTSQSATLFLRKVLSVHPWSRPSLQ 2467
Cdd:cd05100   215 HQSDVWSFGVLLWeIFTLGGSP-YPGIPVEELFKLLkeGHRMDK---PANCTHELYMIMRECWHAVPSQRPTFK 284

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271107 [Multi-domain] Cd Length: 284 Bit Score: 55.41 E-value: 1.46e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRV----VERSSGLEFAAKFIP-SQAKPKASARREARLLARLQHDCVLYFHEAFER--RRGLVIVTE-L 946
Cdd:cd14205    10 QQLGKGNFGSVEMCrydpLQDNTGEVVAVKKLQhSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSagRRNLRLIMEyL 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 CTEELLERMAR-KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELtPGEPQY 1025
Cdd:cd14205    90 PYGSLRDYLQKhKERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVEN----ENRVKIGDFGLTKVL-PQDKEY 164

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 564369110 1026 CQFGTPE-----FVAPEIVNQSPVSGVTDIWPVGVVAFLCLT 1062
Cdd:cd14205   165 YKVKEPGespifWYAPESLTESKFSVASDVWSFGVVLYELFT 206

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270678 [Multi-domain] Cd Length: 302 Bit Score: 55.79 E-value: 1.46e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2315 SEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQP-YNPQALKPLGHRTGTLEFMAPEMVRGD 2393
Cdd:cd05098   133 SSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDiHHIDYYKKTTNGRLPVKWMAPEALFDR 212

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2394 PIGSATDIWGAGVLTY-IMLSGYSPfYEPDPQETEARIV--GGRFDAfqlYPNTSQSATLFLRKVLSVHPWSRPSLQ 2467
Cdd:cd05098   213 IYTHQSDVWSFGVLLWeIFTLGGSP-YPGVPVEELFKLLkeGHRMDK---PSNCTNELYMMMRDCWHAVPSQRPTFK 285

serine/threonine-protein kinase PknD;

Pssm-ID: 183880 [Multi-domain] Cd Length: 932 Bit Score: 57.09 E-value: 1.48e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  972 QVLEGIGYLHQSHVLHLDVKPENLLVwdGAGGEeqVRICDFG-----NAQE-----LTPGEPQYCQ---------FGTPE 1032
Cdd:PRK13184  121 KICATIEYVHSKGVLHRDLKPDNILL--GLFGE--VVILDWGaaifkKLEEedlldIDVDERNICYssmtipgkiVGTPD 196

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 564369110 1033 FVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:PRK13184  197 YMAPERLLGVPASESTDIYALGVILYQMLTLSFPY 231

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 51.31 E-value: 1.49e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQS--VREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEaEGGLcrlRILAAERGDAGFYTCKAVN 216
Cdd:cd04969     1 PDFELNPVKKKilAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILP-DGSL---KIKNVTKSDEGKYTCFAVN 76

                          90
                  ....*....|...
gi 564369110  217 EYGARQCEARLEV 229
Cdd:cd04969    77 FFGKANSTGSLSV 89

serine/threonine kinase US3; Provisional

Pssm-ID: 223009 [Multi-domain] Cd Length: 461 Bit Score: 56.44 E-value: 1.55e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2266 QEYEVLRTLHHERLMSLHEAYITPRY--LVLIAESCgnrELLCGLSDRFR-YSEDDVATYVVQLLQGLDYLHGRHVLHLD 2342
Cdd:PHA03211  209 HEARLLRRLSHPAVLALLDVRVVGGLtcLVLPKYRS---DLYTYLGARLRpLGLAQVTAVARQLLSAIDYIHGEGIIHRD 285

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2343 IKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHR-TGTLEFMAPEMVRGDPIGSATDIWGAGVLTY 2409
Cdd:PHA03211  286 IKTENVLVNGPEDICLGDFGAACFARGSWSTPFHYGiAGTVDTNAPEVLAGDPYTPSVDIWSAGLVIF 353

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270664 [Multi-domain] Cd Length: 283 Bit Score: 55.29 E-value: 1.61e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2266 QEYEVLRTLHHERLMSLHEAYITP--RYLVLIAESCGNRELLCGLSdRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDI 2343
Cdd:cd05080    55 QEIDILKTLYHENIVKYKGCCSEQggKSLQLIMEYVPLGSLRDYLP-KHSIGLAQLLLFAQQICEGMAYLHSQHYIHRDL 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2344 KPDNLLLAADNALKIVDFGSAQPYnpqalkPLGHR--------TGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGY 2415
Cdd:cd05080   134 AARNVLLDNDRLVKIGDFGLAKAV------PEGHEyyrvredgDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHC 207


                  ....*.
gi 564369110 2416 SPFYEP 2421
Cdd:cd05080   208 DSSQSP 213

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270929 [Multi-domain] Cd Length: 267 Bit Score: 55.20 E-value: 1.64e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  903 PSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQ 982
Cdd:cd14027    29 PNCIEHNEALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVLKKVSVPLSVKGRIILEIIEGMAYLHG 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  983 SHVLHLDVKPENLLVwdgaGGEEQVRICDFGNA-----QELTPGEPQY-------CQF--GTPEFVAPE---IVNQSPVS 1045
Cdd:cd14027   109 KGVIHKDLKPENILV----DNDFHIKIADLGLAsfkmwSKLTKEEHNEqrevdgtAKKnaGTLYYMAPEhlnDVNAKPTE 184

                         170       180
                  ....*....|....*....|..
gi 564369110 1046 GvTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd14027   185 K-SDVYSFAIVLWAIFANKEPY 205

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270673 [Multi-domain] Cd Length: 284 Bit Score: 55.41 E-value: 1.66e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2225 FLEEKARGRFGVVRSCRENATG-----RTFVAKIVPYAAEGKRRVLQEYE-VLRT-LHHERLMSLHEAYITPRYLVLIAE 2297
Cdd:cd05091    10 FMEELGEDRFGKVYKGHLFGTApgeqtQAVAIKTLKDKAEGPLREEFRHEaMLRSrLQHPNIVCLLGVVTKEQPMSMIFS 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSE----DDVATY------------VVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDF 2361
Cdd:cd05091    90 YCSHGDLHEFLVMRSPHSDvgstDDDKTVkstlepadflhiVTQIAAGMEYLSSHHVVHKDLATRNVLVFDKLNVKISDL 169

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 2362 G-SAQPYNPQALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPF 2418
Cdd:cd05091   170 GlFREVYAADYYKLMGNSLLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSyGLQPY 228

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270933 [Multi-domain] Cd Length: 275 Bit Score: 55.11 E-value: 1.67e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2261 KRRVLQEYEVLRTLHHERLMSLHEAYIT----PRYLVLIAESCGNRELLCGLSdRFRYSEDDV-ATYVVQLLQGLDYLHG 2335
Cdd:cd14031    53 QQRFKEEAEMLKGLQHPNIVRFYDSWESvlkgKKCIVLVTELMTSGTLKTYLK-RFKVMKPKVlRSWCRQILKGLQFLHT 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2336 RH--VLHLDIKPDNLLLAA-DNALKIVDFGSAQPYNPQALKPLghrTGTLEFMAPEMVRgDPIGSATDIWGAGVLTYIML 2412
Cdd:cd14031   132 RTppIIHRDLKCDNIFITGpTGSVKIGDLGLATLMRTSFAKSV---IGTPEFMAPEMYE-EHYDESVDVYAFGMCMLEMA 207


                  ....*...
gi 564369110 2413 SGYSPFYE 2420
Cdd:cd14031   208 TSEYPYSE 215

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133178 [Multi-domain] Cd Length: 275 Bit Score: 55.16 E-value: 1.94e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2325 QLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNP------QALKPlghrtgtLEFMAPEMVRGDPIGS 2397
Cdd:cd05046   125 QIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSlSKDVYNSeyyklrNALIP-------LRWLAPEAVQEDDFST 197

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 2398 ATDIWGAGVLTY-IMLSGYSPFYEPDPQETEARIVGGRFDaFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDCLA 2471
Cdd:cd05046   198 KSDVWSFGVLMWeVFTQGELPFYGLSDEEVLNRLQAGKLE-LPVPEGCPSRLYKLMTRCWAVNPKDRPSFSELVS 271

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270665 [Multi-domain] Cd Length: 283 Bit Score: 54.90 E-value: 2.02e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVRSCRENATGRTF-----VAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITP--RYLVLIAESCGN-- 2301
Cdd:cd05081    14 KGNFGSVELCRYDPLGDNTgalvaVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPgrRSLRLVMEYLPSgc 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2302 -RELLcgLSDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ--PYNPQALKPLGHR 2378
Cdd:cd05081    94 lRDFL--QRHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKllPLDKDYYVVREPG 171

                         170       180       190
                  ....*....|....*....|....*....|.
gi 564369110 2379 TGTLEFMAPEMVRGDPIGSATDIWGAGVLTY 2409
Cdd:cd05081   172 QSPIFWYAPESLSDNIFSRQSDVWSFGVVLY 202

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.

Pssm-ID: 270870 [Multi-domain] Cd Length: 136 Bit Score: 52.06 E-value: 2.03e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASA-RREARLLARLQ-HDCVLYFHEAFERRRG-LVIVTELCTEELLE 953
Cdd:cd13968     1 MGEGASAKVFWAEGECTTIGVAVKIGDDVNNEEGEDlESEMDILRRLKgLELNIPKVLVTEDVDGpNILLMELVKGGTLI 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  954 RMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFG 1013
Cdd:cd13968    81 AYTQEEELDEKDVESIMYQLAECMRLLHSFHLIHRDLNNDNILLSEDG----NVKLIDFG 136

Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB3 binds and regulates ATF4, p65/RelA, and PKB (or Akt). It negatively regulates ATF4-mediated gene expression including that of CHOP (C/EBP homologous protein) and HO-1, which are both involved in modulating apoptosis. It also inhibits insulin-mediated phosphorylation of PKB and is a possible determinant of insulin resistance and related disorders. In osteoarthritic chondrocytes where it inhibits insulin-like growth factor 1-mediated cell survival, TRB3 is overexpressed, resulting in increased cell death. TRB3 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB3 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270926 [Multi-domain] Cd Length: 242 Bit Score: 54.50 E-value: 2.06e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2311 RFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIV--DFGSAQPYNPQAlKPLGHRTGTLEFMAPE 2388
Cdd:cd14024    78 RRRLSEDEARGLFTQMARAVAHCHQHGVILRDLKLRRFVFTDELRTKLVlvNLEDSCPLNGDD-DSLTDKHGCPAYVGPE 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2389 MV--RGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEARIvggRFDAFQLYPNTSQSATLFLRKVLSVHPWSRPSL 2466
Cdd:cd14024   157 ILssRRSYSGKAADVWSLGVCLYTMLLGRYPFQDTEPAALFAKI---RRGAFSLPAWLSPGARCLVSCMLRRSPAERLKA 233


                  ....*....
gi 564369110 2467 QDCLAHPWL 2475
Cdd:cd14024   234 SEILLHPWL 242

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 56.67 E-value: 2.10e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  866 RLSDYyDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQA---KPKASARREARLLARLQHDCVLYFHEAF--ERRRGL 940
Cdd:PTZ00266   11 RLNEY-EVIKKIGNGRFGEVFLVKHKRTQEFFCWKAISYRGlkeREKSQLVIEVNVMRELKHKNIVRYIDRFlnKANQKL 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  941 VIVTELCTEELLERMARK-----PTVCESETRTYMRQVLEGIGYLHQ-------SHVLHLDVKPENLLVWDGA------- 1001
Cdd:PTZ00266   90 YILMEFCDAGDLSRNIQKcykmfGKIEEHAIVDITRQLLHALAYCHNlkdgpngERVLHRDLKPQNIFLSTGIrhigkit 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1002 ------GGEEQVRICDFGNAQELTPGEPQYCQFGTPEFVAPEIVNQSPVS--GVTDIWPVGVVAFLCLTGISPFVGENDR 1073
Cdd:PTZ00266  170 aqannlNGRPIAKIGDFGLSKNIGIESMAHSCVGTPYYWSPELLLHETKSydDKSDMWALGCIIYELCSGKTPFHKANNF 249


                  ....*
gi 564369110 1074 TTLMN 1078
Cdd:PTZ00266  250 SQLIS 254

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270967 [Multi-domain] Cd Length: 252 Bit Score: 54.42 E-value: 2.15e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEgKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE--SCGN-RELLC 2306
Cdd:cd14065     2 GKGFFGEVYKVTHRETGKVMVMKELKRFDE-QRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEyvNGGTlEELLK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2307 GLSDRFRYSED-----DVAtyvvqllQGLDYLHGRHVLHLDIKPDNLLLAADNALK---IVDFGSAQ-----PYNPQALK 2373
Cdd:cd14065    81 SMDEQLPWSQRvslakDIA-------SGMAYLHSKNIIHRDLNSKNCLVREANRGRnavVADFGLARempdeKTKKPDRK 153

                         170       180       190
                  ....*....|....*....|....*....|....
gi 564369110 2374 PLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVL 2407
Cdd:cd14065   154 KRLTVVGSPYWMAPEMLRGESYDEKVDVFSFGIV 187

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270888 [Multi-domain] Cd Length: 282 Bit Score: 54.99 E-value: 2.16e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--PSQaKPKASARREARLLARLQHDCVL--YFHEAFERRRGLVIVTEL 946
Cdd:cd13986     2 YRIQRLLGEGGFSFVYLVEDLSTGRLYALKKIlcHSK-EDVKEAMREIENYRLFNHPNILrlLDSQIVKEAGGKKEVYLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 -------CTEELLERMARKPT-VCESETRTYMRQVLEGIGYLHQSH---VLHLDVKPENLLVWDgaggEEQVRICDFGN- 1014
Cdd:cd13986    81 lpyykrgSLQDEIERRLVKGTfFPEDRILHIFLGICRGLKAMHEPElvpYAHRDIKPGNVLLSE----DDEPILMDLGSm 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 1015 ------------AQELTPGEPQYCqfgTPEFVAPEIVN---QSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd13986   157 nparieiegrreALALQDWAAEHC---TMPYRAPELFDvksHCTIDEKTDIWSLGCTLYALMYGESPF 221

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133243 [Multi-domain] Cd Length: 256 Bit Score: 54.57 E-value: 2.17e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSylrrVVERSSGL---EFAAKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTEL----C 947
Cdd:cd05112    10 QEIGSGQFG----LVHLGYWLnkdKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFmehgC 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  948 TEELLErmARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgagGEEQV-RICDFGNAQELTpgEPQYC 1026
Cdd:cd05112    86 LSDYLR--TQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLV-----GENQVvKVSDFGMTRFVL--DDQYT 156

                         170       180       190
                  ....*....|....*....|....*....|...
gi 564369110 1027 QFGTPEF----VAPEIVNQSPVSGVTDIWPVGV 1055
Cdd:cd05112   157 SSTGTKFpvkwSSPEVFSFSRYSSKSDVWSFGV 189

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 50.68 E-value: 2.23e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110  153 GQDVIMSIRVQGEPKPVVSWLRNRQPVrPDQRRFaeEAEGGLCRLRILAAErgDAGFYTCKAVNEYGARQCEARLEV 229
Cdd:cd05728    14 GSSLRWECKASGNPRPAYRWLKNGQPL-ASENRI--EVEAGDLRITKLSLS--DSGMYQCVAENKHGTIYASAELAV 85

Catalytic domain of the Serine/Threonine kinases, Spindle assembly checkpoint proteins Bub1 and BubR1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Bub1 (Budding uninhibited by benzimidazoles 1), BubR1, and similar proteins. They contain an N-terminal Bub1/Mad3 homology domain essential for Cdc20 binding and a C-terminal kinase domain. Bub1 and BubR1 are involved in SAC, a surveillance system that delays metaphase to anaphase transition by blocking the activity of APC/C (the anaphase promoting complex) until all chromosomes achieve proper attachments to the mitotic spindle, to avoid chromosome missegregation. Impaired SAC leads to genomic instabilities and tumor development. Bub1 and BubR1 facilitate the localization of SAC proteins to kinetochores and regulate kinetochore-microtubule (K-MT) attachments. Repression studies of Bub1 and BubR1 show that they exert an additive effect in misalignment phenotypes and may function cooperatively or in parallel pathways in regulating K-MT attachments. The Bub1/BubR1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270883 [Multi-domain] Cd Length: 298 Bit Score: 55.05 E-value: 2.25e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2231 RGRFGVVR---SCRENATGRTFVAKIVpyaaegKRRVLQEYEVLRTLHhERLMS--LHEAYITPRYL-------VLIAE- 2297
Cdd:cd13981    10 EGGYASVYlakDDDEQSDGSLVALKVE------KPPSIWEFYICDQLH-SRLKNsrLRESISGAHSAhlfqdesILVMDy 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 -SCGN-RELLCGLSDRFRYSEDDVAT--YVVQLLQGLDYLHGRHVLHLDIKPDNLLL------------AADN---ALKI 2358
Cdd:cd13981    83 sSQGTlLDVVNKMKNKTGGGMDEPLAmfFTIELLKVVEALHEVGIIHGDIKPDNFLLrleicadwpgegENGWlskGLKL 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2359 VDFG-----SAQPYNpQALKPLGHrtgTLEFMAPEMVRGDPIGSATDIWG-AGVLtYIMLSGyspfyepdpQETEARIVG 2432
Cdd:cd13981   163 IDFGrsidmSLFPKN-QSFKADWH---TDSFDCIEMREGRPWTYQIDYFGiAATI-HVMLFG---------KYMELTQES 228

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 564369110 2433 GRFDAFQLYPNTSQSA--TLFLRKVLSVHPWSrPSLQDC 2469
Cdd:cd13981   229 GRWKINQNLKRYWQRDiwNKFFDTLLNPEPSC-NTLPLL 266

serine/threonine protein kinase; Provisional

Pssm-ID: 240344 [Multi-domain] Cd Length: 496 Bit Score: 56.03 E-value: 2.36e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFS---YLRRVverSSGLEFAAKFIPSQAKPKASARRearllARLQHDCVL---YF-----HEAF----E 935
Cdd:PTZ00283   34 YWISRVLGSGATGtvlCAKRV---SDGEPFAVKVVDMEGMSEADKNR-----AQAEVCCLLncdFFsivkcHEDFakkdP 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  936 RRRGLVIVTELC---------TEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQ 1006
Cdd:PTZ00283  106 RNPENVLMIALVldyanagdlRQEIKSRAKTNRTFREHEAGLLFIQVLLAVHHVHSKHMIHRDIKSANILLCSNG----L 181

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1007 VRICDFGNAQELTP------GEpQYCqfGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEN 1071
Cdd:PTZ00283  182 VKLGDFGFSKMYAAtvsddvGR-TFC--GTPYYVAPEIWRRKPYSKKADMFSLGVLLYELLTLKRPFDGEN 249

serine/threonine kinase US3; Provisional

Pssm-ID: 165476 [Multi-domain] Cd Length: 501 Bit Score: 55.86 E-value: 2.75e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  899 AKFIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMAR-----KPTVCESETRTYMRQV 973
Cdd:PHA03210  197 AKRVKAGSRAAIQLENEILALGRLNHENILKIEEILRSEANTYMITQKYDFDLYSFMYDeafdwKDRPLLKQTRAIMKQL 276

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  974 LEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQEL-TPGEP-QYCQFGTPEFVAPEIVNQSPVSGVTDIW 1051
Cdd:PHA03210  277 LCAVEYIHDKKLIHRDIKLENIFL----NCDGKIVLGDFGTAMPFeKEREAfDYGWVGTVATNSPEILAGDGYCEITDIW 352

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1052 PVGVVAFLCLTG----ISPFVGENDRTTLMNIRNYNVAFEE---------------------------TTFLSLSREARG 1100
Cdd:PHA03210  353 SCGLILLDMLSHdfcpIGDGGGKPGKQLLKIIDSLSVCDEEfpdppcklfdyidsaeidhaghsvpplIRNLGLPADFEY 432

                         250       260
                  ....*....|....*....|....*...
gi 564369110 1101 FLIKVLVQD-RLRPTAEETLEHPWFKTE 1127
Cdd:PHA03210  433 PLVKMLTFDwHLRPGAAELLALPLFSAE 460

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK3 is highly expressed in the heart and skeletal muscles, and is controlled by a muscle-specific enhancer that is regulated by MEF2. It may play an important role in muscle development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271120 [Multi-domain] Cd Length: 365 Bit Score: 55.41 E-value: 2.97e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2319 VATYVVQLLQGLDYLHGR-HVLHLDIKPDNLLLAADNAL---------------------KIVDFGSAQ----PYNPQ-- 2370
Cdd:cd14218   121 VKSILRQVLQGLDYLHTKcKIIHTDIKPENILMCVDEGYvrrlaaeatiwqqagapppsgSSVSFGASDflvnPLEPQna 200

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2371 -----ALKPLG-------HRT---GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGySPFYEPDPQETEAR------ 2429
Cdd:cd14218   201 dkirvKIADLGnacwvhkHFTediQTRQYRALEVLIGAEYGTPADIWSTACMAFELATG-DYLFEPHSGEDYTRdedhia 279

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2430 -------------IVGGRF---------------------------DAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQDC 2469
Cdd:cd14218   280 hivellgdipphfALSGRYsreyfnrrgelrhiknlkhwglyevlvEKYEWPLEQAAQFTDFLLPMMEFLPEKRATAAQC 359


                  ....*.
gi 564369110 2470 LAHPWL 2475
Cdd:cd14218   360 LQHPWL 365

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 50.27 E-value: 2.99e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  462 RPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRRMTQYRD-IHRLVFPAVGPQHAGVYKSVIANKLGKAA 540
Cdd:cd20973     2 QTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDgLCSLIISDVCGDDSGKYTCKAVNSLGEAT 81


                  ....*..
gi 564369110  541 CYAHLYV 547
Cdd:cd20973    82 CSAELTV 88

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 50.09 E-value: 3.08e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  763 DVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNhvSFVYEENecSLVVLSAGSQDGGVYTCTARNLAGEVSCKAEL 842
Cdd:cd05725     6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGR--YEILDDH--SLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81


                  ..
gi 564369110  843 SV 844
Cdd:cd05725    82 TV 83

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 50.22 E-value: 3.11e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  334 PLFTRLLEDVEVLE-GRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDgglHSLHIARVGSEDEGLYEVSATNTH 412
Cdd:cd20957     1 PLSATIDPPVQTVDfGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSE---DVLVIPSVKREDKGMYQCFVRNDG 77


                  ....*....
gi 564369110  413 GQAHCSAQL 421
Cdd:cd20957    78 DSAQATAEL 86

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 50.20 E-value: 3.12e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLHSEG-RLLIRAEGErhTLLLREAQAADAGSYTATATNEL-GQASCASS 78
Cdd:cd20970    12 VTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNtRYIVRENGT--TLTIRNIRRSDMGIYLCIASNGVpGSVEKRIT 89


                  ...
gi 564369110   79 LAV 81
Cdd:cd20970    90 LQV 92

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270643 [Multi-domain] Cd Length: 280 Bit Score: 54.39 E-value: 3.22e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2224 TFLEEKARGRFGVV------RSCRENATGRTFVAKIVPYAAEGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIA 2296
Cdd:cd05049     8 VLKRELGEGAFGKVflgecyNLEPEQDKMLVAVKTLKDASSPDARKDFErEAELLTNLQHENIVKFYGVCTEGDPLLMVF 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2297 ESCGNRELLCGL--------------SDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG 2362
Cdd:cd05049    88 EYMEHGDLNKFLrshgpdaaflasedSAPGELTLSQLLHIAVQIASGMVYLASQHFVHRDLATRNCLVGTNLVVKIGDFG 167

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2363 -SAQPYNPQALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTY-IMLSGYSPFYEPDPQETEARIVGGR 2434
Cdd:cd05049   168 mSRDIYSTDYYRVGGHTMLPIRWMPPESILYRKFTTESDVWSFGVVLWeIFTYGKQPWFQLSNTEVIECITQGR 241

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132950 [Multi-domain] Cd Length: 279 Bit Score: 54.50 E-value: 3.31e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  874 HQEI-GRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASAR--REARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEE 950
Cdd:cd06619     5 YQEIlGHGNGGTVYKAYHLLTRRILAVKVIPLDITVELQKQimSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDGG 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  951 LLERMARKPtvcESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQyCQFGT 1030
Cdd:cd06619    85 SLDVYRKIP---EHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLV----NTRGQVKLCDFGVSTQLVNSIAK-TYVGT 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1031 PEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVG-ENDRTTLMNIRNYN-VAFEETTFLSLSREARGFLIKVLV- 1107
Cdd:cd06619   157 NAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPYPQiQKNQGSLMPLQLLQcIVDEDPPVLPVGQFSEKFVHFITQc 236

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 1108 ---QDRLRPTAEETLEHPWFKTEAKGaevSTDHLKLFLSRRRWQR 1149
Cdd:cd06619   237 mrkQPKERPAPENLMDHPFIVQYNDG---NAEVVSMWVCRALEER 278

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173631 [Multi-domain] Cd Length: 290 Bit Score: 54.58 E-value: 3.38e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2262 RRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG----------NRELLCG--LSDRFRYSED------------ 2317
Cdd:cd05045    48 RDLLSEFNLLKQVNHPHVIKLYGACSQDGPLLLIVEYAKygslrsflreSRKVGPSylGSDGNRNSSYldnpderaltmg 127

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2318 DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG-SAQPYNPQALKPLGHRTGTLEFMAPEMVRGDPIG 2396
Cdd:cd05045   128 DLISFAWQISRGMQYLAEMKLVHRDLAARNVLVAEGRKMKISDFGlSRDVYEEDSYVKRSKGRIPVKWMAIESLFDHIYT 207

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2397 SATDIWGAGVLTY-IMLSGYSPFYEPDPQETEARI-VGGRFDAFQlypNTSQSATLFLRKVLSVHPWSRPSLQD 2468
Cdd:cd05045   208 TQSDVWSFGVLLWeIVTLGGNPYPGIAPERLFNLLkTGYRMERPE---NCSEEMYNLMLTCWKQEPDKRPTFAD 278

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173625 [Multi-domain] Cd Length: 277 Bit Score: 54.27 E-value: 3.39e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2325 QLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQP-YNPQALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWG 2403
Cdd:cd05032   127 EIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIGDFGMTRDiYETDYYRKGGKGLLPVRWMAPESLKDGVFTTKSDVWS 206

                          90
                  ....*....|
gi 564369110 2404 AGVLTYIMLS 2413
Cdd:cd05032   207 FGVVLWEMAT 216

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270652 [Multi-domain] Cd Length: 264 Bit Score: 54.12 E-value: 3.41e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2265 LQEYEVLRTLHHERLMSLHeAYITPRYLVLIAESCGNRELLCGL--SDRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLD 2342
Cdd:cd05067    50 LAEANLMKQLQHQRLVRLY-AVVTQEPIYIITEYMENGSLVDFLktPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRD 128

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2343 IKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGV-LTYIMLSGYSPF 2418
Cdd:cd05067   129 LRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGIlLTEIVTHGRIPY 205

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK2 plays a role in hepatic insulin signaling and glucose metabolism. It is induced by the insulin/Akt pathway as part of the hepatic refeeding reponse, and it directly phosphorylates the SR domain of PGC-1alpha, which results in decreased gluconeogenic gene expression and glucose output. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271117 [Multi-domain] Cd Length: 330 Bit Score: 54.64 E-value: 3.48e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2220 QKPYTFLEEKARGRFGVVRSCRENATGRTFVA-KIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd14215    11 QERYEIVSTLGEGTFGRVVQCIDHRRGGARVAlKIIKNVEKYKEAARLEINVLEKINEKDPENKNLCVQMFDWFDYHGHM 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLcGLS--------DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADN---------------- 2354
Cdd:cd14215    91 CISFELL-GLStfdflkenNYLPYPIHQVRHMAFQVCQAVKFLHDNKLTHTDLKPENILFVNSDyeltynlekkrdersv 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2355 ---ALKIVDFGSAqpynpqALKPLGHRT--GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEA- 2428
Cdd:cd14215   170 kstAIRVVDFGSA------TFDHEHHSTivSTRHYRAPEVILELGWSQPCDVWSIGCIIFEYYVGFTLFQTHDNREHLAm 243


                  ....*.
gi 564369110 2429 --RIVG 2432
Cdd:cd14215   244 meRILG 249

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 50.36 E-value: 3.50e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110    9 VLLKCIITANPPPQVSWKKDGSVLHSE-----GRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQASCASSLAV 81
Cdd:cd05869    20 ITLTCEASGDPIPSITWRTSTRNISSEektldGHIVVRSHARVSSLTLKYIQYTDAGEYLCTASNTIGQDSQSMYLEV 97

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270897 [Multi-domain] Cd Length: 256 Bit Score: 53.86 E-value: 3.54e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAKFIP-SQAKPKasarrEARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-ELLER 954
Cdd:cd13995    12 IPRGAFGKVYLAQDTKTKKRMACKLIPvEQFKPS-----DVEIQACFRHENIAELYGALLWEETVHLFMEAGEGgSVLEK 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  955 MARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWdgaggEEQVRICDFGNAQELT-----PGEPQycqfG 1029
Cdd:cd13995    87 LESCGPMREFEIIWVTKHVLKGLDFLHSKNIIHHDIKPSNIVFM-----STKAVLVDFGLSVQMTedvyvPKDLR----G 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 564369110 1030 TPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRT 1074
Cdd:cd13995   158 TEIYMSPEVILCRGHNTKADIYSLGATIIHMQTGSPPWVRRYPRS 202

Catalytic domain of the Serine/Threonine kinase, SINK-homologous inhibitory kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SHIK, also referred to as STK40 or LYK4, is a cytoplasmic and nuclear protein that is involved in the negative regulation of NF-kappaB- and p53-mediated transcription. It was identified as a protein related to SINK, a p65-interacting protein that inhibits p65 phosphorylation by the catalytic subunit of PKA, thereby inhibiting transcriptional competence of NF-kappaB. The SHIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270876 [Multi-domain] Cd Length: 290 Bit Score: 54.33 E-value: 3.64e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2333 LHGRHVLHLDIKPDNLLL-AADNALKIVDFGSAQPYNPQAlKPLGHRTGTLEFMAPEMVRGDP-IGSATDIWGAGVLTYI 2410
Cdd:cd13974   148 LHKKNIVHRDLKLGNMVLnKRTRKITITNFCLGKHLVSED-DLLKDQRGSPAYISPDVLSGKPyLGKPSDMWALGVVLFT 226

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 2411 MLSGYSPFYEPDPQETEARIVGGRF---DAFQLYPNTSQsatlFLRKVLSVHPWSRPSLQDCLAH 2472
Cdd:cd13974   227 MLYGQFPFYDSIPQELFRKIKAAEYtipEDGRVSENTVC----LIRKLLVLNPQKRLTASEVLDS 287

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 50.09 E-value: 3.84e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110  164 GEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCrlrILAAERGDAGFYTCKAVNEYGARQCE-ARLEV 229
Cdd:cd05724    24 GHPEPTVSWRKDGQPLNLDNERVRIVDDGNLL---IAEARKSDEGTYKCVATNMVGERESRaARLSV 87

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270679 [Multi-domain] Cd Length: 313 Bit Score: 54.64 E-value: 3.94e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2318 DVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQP-YNPQALKPLGHRTGTLEFMAPEMVRGDPIG 2396
Cdd:cd05101   147 DLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDiNNIDYYKKTTNGRLPVKWMAPEALFDRVYT 226

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2397 SATDIWGAGVLTY-IMLSGYSPfYEPDPQETEARIV--GGRFDAfqlYPNTSQSATLFLRKVLSVHPWSRPSLQDclahp 2473
Cdd:cd05101   227 HQSDVWSFGVLMWeIFTLGGSP-YPGIPVEELFKLLkeGHRMDK---PANCTNELYMMMRDCWHAVPSQRPTFKQ----- 297

                         170       180
                  ....*....|....*....|
gi 564369110 2474 wlqdayLMKLRRQTLTFTTN 2493
Cdd:cd05101   298 ------LVEDLDRILTLTTN 311

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 50.15 E-value: 4.20e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  755 PRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKD-EVLLAESNHVSfVYEEN--ECSLVVLSAGSQDGGVYTCTARN 831
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNnEMLQYNTDRIS-LYQDNcgRICLLIQNANKKDAGWYTVSAVN 79

                          90
                  ....*....|...
gi 564369110  832 LAGEVSCKAELSV 844
Cdd:cd05892    80 EAGVVSCNARLDV 92

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 50.10 E-value: 4.35e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  458 PDFLRPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRRM-TQYRDIHRLVFPAVGPQHAGVYKSVIANKL 536
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMlVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 564369110  537 GKAACYAHLYV 547
Cdd:cd20990    81 GQNSFNLELVV 91

serine/threonine kinase US3; Provisional

Pssm-ID: 223009 [Multi-domain] Cd Length: 461 Bit Score: 54.90 E-value: 4.63e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  910 ASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMARKPT-VCESETRTYMRQVLEGIGYLHQSHVLHL 988
Cdd:PHA03211  205 ASSVHEARLLRRLSHPAVLALLDVRVVGGLTCLVLPKYRSDLYTYLGARLRpLGLAQVTAVARQLLSAIDYIHGEGIIHR 284

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110  989 DVKPENLLVwdgaGGEEQVRICDFGNA-----QELTPGepQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAF 1058
Cdd:PHA03211  285 DIKTENVLV----NGPEDICLGDFGAAcfargSWSTPF--HYGIAGTVDTNAPEVLAGDPYTPSVDIWSAGLVIF 353

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173637 [Multi-domain] Cd Length: 256 Bit Score: 53.61 E-value: 4.66e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2224 TFLEEKARGRFGVVRSCRENatGRTFVA-KIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNR 2302
Cdd:cd05059     7 TFLKELGSGQFGVVHLGKWR--GKIDVAiKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEYMANG 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2303 ELLCGLSDR-FRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQ-PYNPQALKPLGHRTg 2380
Cdd:cd05059    85 CLLNYLRERrGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARyVLDDEYTSSVGTKF- 163

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2381 TLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS-GYSPFYEPDPQETEARIVGGrfdaFQLY 2441
Cdd:cd05059   164 PVKWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSeGKMPYERFSNSEVVEHISQG----YRLY 221

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271055 [Multi-domain] Cd Length: 270 Bit Score: 53.86 E-value: 4.77e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  913 RREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMAR--KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDV 990
Cdd:cd14153    44 KREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYSVVRdaKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDL 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  991 KPENLLVWDGaggeeQVRICDFG---NAQELTPGEPQ---YCQFGTPEFVAPEIV---------NQSPVSGVTDIWPVGV 1055
Cdd:cd14153   124 KSKNVFYDNG-----KVVITDFGlftISGVLQAGRREdklRIQSGWLCHLAPEIIrqlspeteeDKLPFSKHSDVFAFGT 198


                  ...
gi 564369110 1056 VAF 1058
Cdd:cd14153   199 IWY 201

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270674 [Multi-domain] Cd Length: 280 Bit Score: 53.82 E-value: 4.80e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2247 RTFVA-KIVPYAAEGKRRVLQ-EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCG----NRELLCGLSDRFRYSEDDVA 2320
Cdd:cd05092    35 KMLVAvKALKEATESARQDFQrEAELLTVLQHQHIVRFYGVCTEGEPLIMVFEYMRhgdlNRFLRSHGPDAKILDGGEGQ 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2321 TY----VVQLLQ-------GLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTG-TLEFMAPE 2388
Cdd:cd05092   115 APgqltLGQMLQiasqiasGMVYLASLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYRVGGRTMlPIRWMPPE 194

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 2389 MVRGDPIGSATDIWGAGVLTY-IMLSGYSPFYEPDPQETEARIVGGR 2434
Cdd:cd05092   195 SILYRKFTTESDIWSFGVVLWeIFTYGKQPWYQLSNTEAIECITQGR 241

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271134 [Multi-domain] Cd Length: 270 Bit Score: 53.65 E-value: 4.89e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2267 EYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRFRYSED-DVAT---YVVQLLQGLDYLHGR---HVL 2339
Cdd:cd14664    40 EIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGSLGELLHSRPESQPPlDWETrqrIALGSARGLAYLHHDcspLII 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2340 HLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFY 2419
Cdd:cd14664   120 HRDVKSNNILLDEEFEAHVADFGLAKLMDDKDSHVMSSVAGSYGYIAPEYAYTGKVSEKSDVYSYGVVLLELITGKRPFD 199


                  .
gi 564369110 2420 E 2420
Cdd:cd14664   200 E 200

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270934 [Multi-domain] Cd Length: 266 Bit Score: 53.54 E-value: 4.98e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2261 KRRVLQEYEVLRTLHHERLMSLHEAYITP----RYLVLIAESCGNRELLCGLSdRFRYSEDDV-ATYVVQLLQGLDYLHG 2335
Cdd:cd14032    44 RQRFKEEAEMLKGLQHPNIVRFYDFWESCakgkRCIVLVTELMTSGTLKTYLK-RFKVMKPKVlRSWCRQILKGLLFLHT 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2336 RH--VLHLDIKPDNLLLAA-DNALKIVDFGSAQPYNPQALKPLghrTGTLEFMAPEMVRgDPIGSATDIWGAGVLTYIML 2412
Cdd:cd14032   123 RTppIIHRDLKCDNIFITGpTGSVKIGDLGLATLKRASFAKSV---IGTPEFMAPEMYE-EHYDESVDVYAFGMCMLEMA 198


                  ....*...
gi 564369110 2413 SGYSPFYE 2420
Cdd:cd14032   199 TSEYPYSE 206

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 49.87 E-value: 5.05e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1848 PPVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVI---VScKDGRQL--LSIPRASKRHAGLYEC 1922
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVgdyVT-SDGDVVsyVNISSVRVEDGGEYTC 79

                          90
                  ....*....|..
gi 564369110 1923 SATNVLGSITSS 1934
Cdd:cd20956    80 TATNDVGSVSHS 91

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133187 [Multi-domain] Cd Length: 270 Bit Score: 53.58 E-value: 5.19e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2237 VRSCRENATGrtfvakivpyaaEGKRRVLQEYEVLRTLHHERLMSLhEAYIT--PRYLVLiaESCGNRELLCGLSDRfRY 2314
Cdd:cd05056    39 VKTCKNCTSP------------SVREKFLQEAYIMRQFDHPHIVKL-IGVITenPVWIVM--ELAPLGELRSYLQVN-KY 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2315 SEDDVA--TYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQALKPLGHRTGTLEFMAPEMVRG 2392
Cdd:cd05056   103 SLDLASliLYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYMEDESYYKASKGKLPIKWMAPESINF 182

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 2393 DPIGSATDIWGAGVLTY-IMLSGYSPFYEPDPQETEARIVGGrfDAFQLYPNTSQSATLFLRKVLSVHPWSRPSLQD 2468
Cdd:cd05056   183 RRFTSASDVWMFGVCMWeILMLGVKPFQGVKNNDVIGRIENG--ERLPMPPNCPPTLYSLMTKCWAYDPSKRPRFTE 257

Catalytic domain of the Serine/Threonine kinase, Plant SNT7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNT7 is a plant thylakoid-associated kinase that is essential in short- and long-term acclimation responses to cope with various light conditions in order to maintain photosynthetic redox poise for optimal photosynthetic performance. Short-term response involves state transitions over periods of minutes while the long-term response (LTR) occurs over hours to days and involves changing the relative amounts of photosystems I and II. SNT7 acts as a redox sensor and a signal transducer for both responses, which are triggered by the redox state of the plastoquinone (PQ) pool. It is positioned at the top of a phosphorylation cascade that induces state transitions by phosphorylating light-harvesting complex II (LHCII), and triggers the LTR through the phosphorylation of chloroplast proteins. The SNT7 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270915 [Multi-domain] Cd Length: 318 Bit Score: 53.98 E-value: 5.35e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110  967 RTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeeQVRICDFGNAQELTPG---EPQYCQFgTPEFVAPE 1037
Cdd:cd14013   123 KSIMRQILVALRKLHSTGIVHRDVKPQNIIVSEGDG---QFKIIDLGAAADLRIGinyIPKEFLL-DPRYAPPE 192

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 49.45 E-value: 5.37e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  465 QDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRRMTqyrDIHRLVFPAVGPQHAGVYKSVIAN 534
Cdd:cd20957     9 PVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQIL---SEDVLVIPSVKREDKGMYQCFVRN 75

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 49.51 E-value: 5.68e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110  348 GRAARLDCKISGTPPPSVTWTHFGHPVNESE-NLRLRQDGGlhSLHIARVGSEDEGLYEVSATNTHGQAHCSAQLYV 423
Cdd:cd05867    14 GETARLDCQVEGIPTPNITWSINGAPIEGTDpDPRRHVSSG--ALILTDVQPSDTAVYQCEARNRHGNLLANAHVHV 88

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270650 [Multi-domain] Cd Length: 257 Bit Score: 53.51 E-value: 5.78e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2260 GKRRVLQEYEVLRTLHHE---RLMSLHEAyitpRYLVLIAESCGNRELLCGLSDRFRYSEDDVATYVVQLLQGLDYLHGR 2336
Cdd:cd05060    39 GKKEFLREASVMAQLDHPcivRLIGVCKG----EPLMLVMELAPLGPLLKYLKKRREIPVSDLKELAHQVAMGMAYLESK 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2337 HVLHLDIKPDNLLLAADNALKIVDFGSAQPYNP-----QAlkplghRTG---TLEFMAPEMVRGDPIGSATDIWGAGVLT 2408
Cdd:cd05060   115 HFVHRDLAARNVLLVNRHQAKISDFGMSRALGAgsdyyRA------TTAgrwPLKWYAPECINYGKFSSKSDVWSYGVTL 188

                         170       180
                  ....*....|....*....|....*.
gi 564369110 2409 YIMLS-GYSPFYEPDPQETEARIVGG 2433
Cdd:cd05060   189 WEAFSyGAKPYGEMKGPEVIAMLESG 214

Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB2 binds and negatively regulates the mitogen activated protein kinase (MAPK) kinases, MKK7 and MEK1, which are activators of the MAPKs, ERK and JNK. It controls the activation of inflammatory monocytes, which is essential in innate immune responses and the pathogenesis of inflammatory diseases such as atherosclerosis. TRB2 expression is down-regulated in human acute myeloid leukaemia (AML), which may lead to enhanced cell survival and pathogenesis of the disease. TRB2 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270924 [Multi-domain] Cd Length: 242 Bit Score: 53.12 E-value: 5.83e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAggEEQVRICDFGNAQELTPGEPQYC-QFGTPEFVAPEIVNQ 1041
Cdd:cd14022    83 EEEAARLFYQIASAVAHCHDGGLVLRDLKLRKFVFKDEE--RTRVKLESLEDAYILRGHDDSLSdKHGCPAYVSPEILNT 160

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1042 S-PVSG-VTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREARGFLIKVLVQD-RLRPTAEET 1118
Cdd:cd14022   161 SgSYSGkAADVWSLGVMLYTMLVGRYPFHDIEPSSLFSKIRRGQFNIPET----LSPKAKCLIRSILRREpSERLTSQEI 236


                  ....*.
gi 564369110 1119 LEHPWF 1124
Cdd:cd14022   237 LDHPWF 242

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270630 [Multi-domain] Cd Length: 248 Bit Score: 53.06 E-value: 5.99e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  903 PSQAKPKASARrEARLLARLQHDCVLYFHEAFERRRGLVIVTEL-CTEELLE--RMARKPTVCESETRTYMRQVLEGIGY 979
Cdd:cd05034    29 PGTMSPEAFLQ-EAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELmSKGSLLDylRTGEGRALRLPQLIDMAAQIASGMAY 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  980 LHQSHVLHLDVKPENLLVwdgagGEEQV-RICDFGNAQELTPGEpqYC-QFGT--P-EFVAPEIVNQSPVSGVTDIWPVG 1054
Cdd:cd05034   108 LESRNYIHRDLAARNILV-----GENNVcKVADFGLARLIEDDE--YTaREGAkfPiKWTAPEAALYGRFTIKSDVWSFG 180

                         170       180       190
                  ....*....|....*....|....*....|
gi 564369110 1055 VVAFLCLT-GISPFVGENDRTTLMNI-RNY 1082
Cdd:cd05034   181 ILLYEIVTyGRVPYPGMTNREVLEQVeRGY 210

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270657 [Multi-domain] Cd Length: 272 Bit Score: 53.51 E-value: 6.06e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  915 EARLLARLQHDCVLYFHEAFERRRGLVIVTE-LCTEELLERMARKP--TVCESETRTYMRQVLEGIGYLHQSHVLHLDVK 991
Cdd:cd05072    52 EANLMKTLQHDKLVRLYAVVTKEEPIYIITEyMAKGSLLDFLKSDEggKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLR 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  992 PENLLVWDGAggeeQVRICDFGNAQELTpgEPQYCQFGTPEF----VAPEIVNQSPVSGVTDIWPVGVVAFLCLT-GISP 1066
Cdd:cd05072   132 AANVLVSESL----MCKIADFGLARVIE--DNEYTAREGAKFpikwTAPEAINFGSFTIKSDVWSFGILLYEIVTyGKIP 205

                         170       180
                  ....*....|....*....|....
gi 564369110 1067 FVGENDRTTLMNI-RNYNVAFEET 1089
Cdd:cd05072   206 YPGMSNSDVMSALqRGYRMPRMEN 229

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 49.42 E-value: 6.08e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  342 DVEVLEGRAARLDCKISGTPPPSVTWTHFGHPV-NESENLRLRQDGglhSLHIARVGSEDEGLYEVSATNTHGQAHCSAQ 420
Cdd:cd20952     8 NQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLlGKDERITTLENG---SLQIKGAEKSDTGEYTCVALNLSGEATWSAV 84


                  ...
gi 564369110  421 LYV 423
Cdd:cd20952    85 LDV 87

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 49.39 E-value: 6.28e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1849 PVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVSCKDGRQLLSIPRASKRHAGLYECSATNVL 1928
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80


                  ..
gi 564369110 1929 GS 1930
Cdd:cd20975    81 GA 82

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 49.25 E-value: 6.34e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  340 LEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLrqDGGLhsLHIARVGSEDEGLYEVSATNTHGQAHCSA 419
Cdd:cd05851     8 FKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISM--SGAV--LKIFNIQPEDEGTYECEAENIKGKDKHQA 83


                  ....*
gi 564369110  420 QLYVE 424
Cdd:cd05851    84 RVYVQ 88

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 49.42 E-value: 6.45e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  465 QDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRRMTQyrDIHRLVFPAVGPQHAGVYKSVIANKLGKAACYAH 544
Cdd:cd20952     7 QNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTL--ENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAV 84


                  ...
gi 564369110  545 LYV 547
Cdd:cd20952    85 LDV 87

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 49.43 E-value: 6.75e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110  340 LEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNE-SENLRLRQDGGLhsLHIARVGSEDEGLYEVSATN 410
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGTT--LTIRNIRRSDMGIYLCIASN 78

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270664 [Multi-domain] Cd Length: 283 Bit Score: 53.36 E-value: 6.94e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  870 YYDIHQEIGRGAFS----YLRRVVERSSGLEFAAKFIPSQAKPK--ASARREARLLARLQHDCVLYFHEAFERR--RGLV 941
Cdd:cd05080     5 YLKKIRDLGEGHFGkvslYCYDPTNDGTGEMVAVKALKADCGPQhrSGWKQEIDILKTLYHENIVKYKGCCSEQggKSLQ 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPG 1021
Cdd:cd05080    85 LIMEYVPLGSLRDYLPKHSIGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLL----DNDRLVKIGDFGLAKAVPEG 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 564369110 1022 EPQY--CQFG-TPEF-VAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd05080   161 HEYYrvREDGdSPVFwYAPECLKEYKFYYASDVWSFGVTLYELLTHCDSS 210

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143381 [Multi-domain] Cd Length: 359 Bit Score: 53.88 E-value: 7.16e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFI--PSQAKPKAS-ARREARLLARLQHDCVLYFHEAF------ERRRGLV 941
Cdd:cd07876    23 YQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLsrPFQNQTHAKrAYRELVLLKCVNHKNIISLLNVFtpqkslEEFQDVY 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTEELLERMARKptvCESETRTYM-RQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTP 1020
Cdd:cd07876   103 LVMELMDANLCQVIHME---LDHERMSYLlYQMLCGIKHLHSAGIIHRDLKPSNIVV----KSDCTLKILDFGLARTACT 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1021 GEPQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEND--------------RTTLMN-----IRN 1081
Cdd:cd07876   176 NFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGSVIFQGTDHidqwnkvieqlgtpSAEFMNrlqptVRN 255

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1082 Y--------NVAFEET----TFLSLSR-------EARGFLIKVLVQD-RLRPTAEETLEHPWFKTEAKGAE 1132
Cdd:cd07876   256 YvenrpqypGISFEELfpdwIFPSESErdklktsQARDLLSKMLVIDpDKRISVDEALRHPYITVWYDPAE 326

Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1a, Xenopus laevis Wee1b (XeWee1b) and similar vertebrate proteins. Members of this subfamily show a wide expression pattern. XeWee1b functions after the first zygotic cell divisions. It is expressed in all tissues and is also present after the gastrulation stage of embryos. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1a subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271040 [Multi-domain] Cd Length: 276 Bit Score: 53.49 E-value: 7.27e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2226 LEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKrrvLQEYEVLRTLH-------HERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd14138    10 LEKIGSGEFGSVFKCVKRLDGCIYAIKRSKKPLAGS---VDEQNALREVYahavlgqHSHVVRYYSAWAEDDHMLIQNEY 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFR----YSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA---ADNALKIVDFGSAQPYNPQA 2371
Cdd:cd14138    87 CNGGSLADAISENYRimsyFTEPELKDLLLQVARGLKYIHSMSLVHMDIKPSNIFISrtsIPNAASEEGDEDEWASNKVI 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2372 LK--PLGHRT---------GTLEFMAPEMVRGDPIG-SATDIWgAGVLTYIMLSGYSPFyePDPQETEARIVGGRFDAFq 2439
Cdd:cd14138   167 FKigDLGHVTrvsspqveeGDSRFLANEVLQENYTHlPKADIF-ALALTVVCAAGAEPL--PTNGDQWHEIRQGKLPRI- 242

                         250       260       270
                  ....*....|....*....|....*....|....*
gi 564369110 2440 lyPNT-SQSATLFLRKVLSVHPWSRPSLQDCLAHP 2473
Cdd:cd14138   243 --PQVlSQEFLDLLKVMIHPDPERRPSAVALVKHS 275

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.

Pssm-ID: 270637 [Multi-domain] Cd Length: 251 Bit Score: 52.83 E-value: 8.20e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKP--KASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd05041     1 EKIGRGNFGDVYRGVLKPDNTEVAVKTCRETLPPdlKRKFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMELVPGGSL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARKPTVcESETRTYMRQVLE---GIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEpqY-CQF 1028
Cdd:cd05041    81 LTFLRKKGA-RLTVKQLLQMCLDaaaGMEYLESKNCIHRDLAARNCLV----GENNVLKISDFGMSREEEDGE--YtVSD 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 1029 GTPE----FVAPEIVNQSPVSGVTDIWPVGVVAFLCLT-GISPFVGENDRTT 1075
Cdd:cd05041   154 GLKQipikWTAPEALNYGRYTSESDVWSFGILLWEIFSlGATPYPGMSNQQT 205

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270790 [Multi-domain] Cd Length: 291 Bit Score: 53.14 E-value: 8.56e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFSYLRRVVERSSGLEFAAKFIPSQAkpkaSARREARLLARLQ-----HDCV-------LYFHEA---------- 933
Cdd:cd06616    13 EIGRGAFGTVNKMLHKPSGTIMAVKRIRSTV----DEKEQKRLLMDLDvvmrsSDCPyivkfygALFREGdcwicmelmd 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  934 -----FERrrglvIVTELCTEELLERMARKPTVCESETRTYMRQVLegigylhqsHVLHLDVKPENLLVwDGAGgeeQVR 1008
Cdd:cd06616    89 isldkFYK-----YVYEVLDSVIPEEILGKIAVATVKALNYLKEEL---------KIIHRDVKPSNILL-DRNG---NIK 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1009 ICDFGNAQELTPGEPQYCQFGTPEFVAPEIVNQSPVSGV----TDIWPVGVVAFLCLTGISPFvgendrttlmniRNYNV 1084
Cdd:cd06616   151 LCDFGISGQLVDSIAKTRDAGCRPYMAPERIDPSASRDGydvrSDVWSLGITLYEVATGKFPY------------PKWNS 218

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 1085 AFEE--------------TTFLSLSREARGFLIKVLVQDR-LRPTAEETLEHPWFKT 1126
Cdd:cd06616   219 VFDQltqvvkgdppilsnSEEREFSPSFVNFVNLCLIKDEsKRPKYKELLKHPFIKM 275

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 48.98 E-value: 9.70e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  345 VLEGRAARLDCKISGTPPPSVTWTHFGHPV-NESENLRLRQDGGlhSLHIARVGSEDEGLYEVSATNTHGQAHCSAQLYV 423
Cdd:cd04978    11 LSPGETGELICEAEGNPQPTITWRLNGVPIePAPEDMRRTVDGR--TLIFSNLQPNDTAVYQCNASNVHGYLLANAFLHV 88

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. DYRK4 is a testis-specific kinase with restricted expression to postmeiotic spermatids. It may function during spermiogenesis, however, it is not required for male fertility. DYRK4 has also been detected in a human teratocarcinoma cell line induced to produce postmitotic neurons. It may have a role in neuronal differentiation. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. The DYRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271127 [Multi-domain] Cd Length: 341 Bit Score: 53.55 E-value: 9.71e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKPKASARREARLLARL-------QHDcVLYFHEAFERRRGLVIV 943
Cdd:cd14225    45 YEILEVIGKGSFGQVVKALDHKTNEHVAIKIIRNKKRFHHQALVEVKILDALrrkdrdnSHN-VIHMKEYFYFRNHLCIT 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  944 TELCTEELLERMARK--PTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWdgAGGEEQVRICDFGNAQEltpg 1021
Cdd:cd14225   124 FELLGMNLYELIKKNnfQGFSLSLIRRFAISLLQCLRLLYRERIIHCDLKPENILLR--QRGQSSIKVIDFGSSCY---- 197

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 1022 EPQ--YCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPFVGEND 1072
Cdd:cd14225   198 EHQrvYTYIQSRFYRSPEVILGLPYSMAIDMWSLGCILAELYTGYPLFPGENE 250

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 48.94 E-value: 1.12e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  755 PRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKD-EVLLAESNHVSFVYE-ENECSLVVLSAGSQDGGVYTCTARNL 832
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDgKQISPKSDHYTIQRDlDGTCSLHTTASTLDDDGNYTIMAANP 80

                          90
                  ....*....|..
gi 564369110  833 AGEVSCKAELSV 844
Cdd:cd05893    81 QGRISCTGRLMV 92

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 48.55 E-value: 1.13e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  342 DVEVLEGRAARLDCKISGTPPPSVTWThfghpvnesenlrlRQDGGL----------HSLHIARVGSEDEGLYEVSATNT 411
Cdd:cd05725     6 NQVVLVDDSAEFQCEVGGDPVPTVRWR--------------KEDGELpkgryeilddHSLKIRKVTAGDMGSYTCVAENM 71

                          90
                  ....*....|..
gi 564369110  412 HGQAHCSAQLYV 423
Cdd:cd05725    72 VGKIEASATLTV 83

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270932 [Multi-domain] Cd Length: 289 Bit Score: 52.36 E-value: 1.46e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2261 KRRVLQEYEVLRTLHHERLMSLHEAYITP----RYLVLIAESCGNRELLCGLSdRFRYSEDDV-ATYVVQLLQGLDYLHG 2335
Cdd:cd14030    68 RQRFKEEAGMLKGLQHPNIVRFYDSWESTvkgkKCIVLVTELMTSGTLKTYLK-RFKVMKIKVlRSWCRQILKGLQFLHT 146

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2336 RH--VLHLDIKPDNLLLAA-DNALKIVDFGSAQPYNPQALKPLghrTGTLEFMAPEMVRgDPIGSATDIWGAGVLTYIML 2412
Cdd:cd14030   147 RTppIIHRDLKCDNIFITGpTGSVKIGDLGLATLKRASFAKSV---IGTPEFMAPEMYE-EKYDESVDVYAFGMCMLEMA 222

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2413 SGYSPFYE-PDPQETEARIVGG----RFDAFQLyPNTSQSATLFLRKvlsvHPWSRPSLQDCLAHPWLQD 2477
Cdd:cd14030   223 TSEYPYSEcQNAAQIYRRVTSGvkpaSFDKVAI-PEVKEIIEGCIRQ----NKDERYAIKDLLNHAFFQE 287

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 48.40 E-value: 1.65e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110    3 VAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLlIRAEGERHTLLLREAQAADAGSYTATATNELGQASCASSLAV 81
Cdd:cd20976    13 AVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADR-STCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PINK1 contains an N-terminal mitochondrial targeting sequence, a catalytic domain, and a C-terminal regulatory region. It plays an important role in maintaining mitochondrial homeostasis. It protects cells against oxidative stress-induced apoptosis by phosphorylating the chaperone TNFR-associated protein 1 (TRAP1), also called Hsp75. Phosphorylated TRAP1 prevents cytochrome c release and peroxide-induced apoptosis. PINK1 interacts with Omi/HtrA2, a serine protease, and Parkin, an E3 ubiquitin ligase, in different pathways to promote mitochondrial health. The parkin gene is the most commonly mutated gene in autosomal recessive familial parkinsonism. Mutations within the catalytic domain of PINK1 are also associated with Parkinson's disease. The PINK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270920 [Multi-domain] Cd Length: 313 Bit Score: 52.50 E-value: 1.66e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  972 QVLEGIGYLHQSHVLHLDVKPENLLVWDGAGGEEQVRICDFGN--AQELT----PGEPQYCQF-GTPEFVAPEIVNQSPV 1044
Cdd:cd14018   146 QLLEGVDHLVRHGIAHRDLKSDNILLELDFDGCPWLVIADFGCclADDSIglqlPFSSWYVDRgGNACLMAPEVSTAVPG 225

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110 1045 SGV------TDIWPVGVVAFLCLTGISPFVGENDrtTLMNIRNYnvafEETTFLSLSrEARGFLIKVLVQDRLRPTAEE 1117
Cdd:cd14018   226 PGVvinyskADAWAVGAIAYEIFGLSNPFYGLGD--TMLESRSY----QESQLPALP-SAVPPDVRQVVKDLLQRDPNK 297

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 48.17 E-value: 1.81e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  763 DVEVGPGETArfavVVE-----GKPLPDIMWYKDEVLLAESNhvSFVYEENECSLVVLSAGSQDGGVYTCTARNLAGE-V 836
Cdd:cd05724     6 DTQVAVGEMA----VLEcspprGHPEPTVSWRKDGQPLNLDN--ERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGErE 79


                  ....*...
gi 564369110  837 SCKAELSV 844
Cdd:cd05724    80 SRAARLSV 87

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270903 [Multi-domain] Cd Length: 292 Bit Score: 52.02 E-value: 1.99e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  970 MRQVLEGIGYLHQ-SHVLHLDVKPENLLVwdgAGGEEQVRICDFGNAQELT-----PGEPQYCQFGTPEFVAPEIVNQ-S 1042
Cdd:cd14001   116 ALSIARALEYLHNeKKILHGDIKSGNVLI---KGDFESVKLCDFGVSLPLTenlevDSDPKAQYVGTEPWKAKEALEEgG 192

                          90
                  ....*....|....
gi 564369110 1043 PVSGVTDIWPVGVV 1056
Cdd:cd14001   193 VITDKADIFAYGLV 206

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK3 is highly expressed in the heart and skeletal muscles, and is controlled by a muscle-specific enhancer that is regulated by MEF2. It may play an important role in muscle development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271120 [Multi-domain] Cd Length: 365 Bit Score: 52.71 E-value: 2.04e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTEELLERMARK-----PTVCeseTRTYMRQVLEGIGYLH-QSHVLHLDVKPENLL----------------VWD 999
Cdd:cd14218    95 MVLEVLGHQLLKWIIKSnyqglPLPC---VKSILRQVLQGLDYLHtKCKIIHTDIKPENILmcvdegyvrrlaaeatIWQ 171

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1000 GAGG--------------------------EEQVRICDFGNAQELTPGEPQYCQfgTPEFVAPEIVNQSPVSGVTDIWPV 1053
Cdd:cd14218   172 QAGApppsgssvsfgasdflvnplepqnadKIRVKIADLGNACWVHKHFTEDIQ--TRQYRALEVLIGAEYGTPADIWST 249

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1054 GVVAFLCLTG---ISPFVGE----------------------------------NDRTTLMNIRN------YNVAFEETT 1090
Cdd:cd14218   250 ACMAFELATGdylFEPHSGEdytrdedhiahivellgdipphfalsgrysreyfNRRGELRHIKNlkhwglYEVLVEKYE 329

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 1091 F-LSLSREARGFLIKVL-VQDRLRPTAEETLEHPWF 1124
Cdd:cd14218   330 WpLEQAAQFTDFLLPMMeFLPEKRATAAQCLQHPWL 365

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 47.58 E-value: 2.14e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110  353 LDCKISGTPPPSVTWTHFGHPVNESENLRLRQDgglHSLHIARVGSEDEGLYEVSATNTHGQAHCSAQLYV 423
Cdd:cd05723    17 FECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKE---HNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 48.12 E-value: 2.34e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQASCASSL 79
Cdd:cd05747    13 LTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEGKQEAQFTL 91

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271123 [Multi-domain] Cd Length: 267 Bit Score: 51.50 E-value: 2.77e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAK-FIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERM 955
Cdd:cd14221     1 LGKGCFGQAIKVTHRETGEVMVMKeLIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  956 ARK-PTVCESETR-TYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDGAGgeeqVRICDFGNAQeLTPGE----------- 1022
Cdd:cd14221    81 IKSmDSHYPWSQRvSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKS----VVVADFGLAR-LMVDEktqpeglrslk 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 564369110 1023 -----PQYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVafLC 1060
Cdd:cd14221   156 kpdrkKRYTVVGNPYWMAPEMINGRSYDEKVDVFSFGIV--LC 196

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270634 [Multi-domain] Cd Length: 284 Bit Score: 51.61 E-value: 2.90e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFS--YLRR--VVERSSGLEFAAKFIPSQAKPKASA--RREARLLARLQHDCVLYFHEAFER--RRGLVIVTEL 946
Cdd:cd05038    10 KQLGEGHFGsvELCRydPLGDNTGEQVAVKSLQPSGEEQHMSdfKREIEILRTLDHEYIVKYKGVCESpgRRSLRLIMEY 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  947 ----CTEELLERmaRKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELT--- 1019
Cdd:cd05038    90 lpsgSLRDYLQR--HRDQIDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILV----ESEDLVKISDFGLAKVLPedk 163

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 1020 -------PGEpqycqfgTPEF-VAPEIVNQSPVSGVTDIWPVGVVAFLCLTGISPF 1067
Cdd:cd05038   164 eyyyvkePGE-------SPIFwYAPECLRESRFSSASDVWSFGVTLYELFTYGDPS 212

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 47.40 E-value: 3.41e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLH--SEGRLLIRAEGErHTLLLREAQAADAGSYTATATNELGQASCASS 78
Cdd:cd20990    10 LTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRpdSAHKMLVRENGV-HSLIIEPVTSRDAGIYTCIATNRAGQNSFNLE 88


                  ...
gi 564369110   79 LAV 81
Cdd:cd20990    89 LVV 91

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 47.35 E-value: 4.04e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKKDGSV--LHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQASCASS 78
Cdd:cd20974    10 VVVLEGSTATFEAHVSGKPVPEVSWFRDGQVisTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNGSGQATSTAE 89


                  ...
gi 564369110   79 LAV 81
Cdd:cd20974    90 LLV 92

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 47.06 E-value: 4.54e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110  152 EGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILaaERGDAGFYTCKAVNEYGARQCEARLEVR 230
Cdd:cd04978    13 PGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNL--QPNDTAVYQCNASNVHGYLLANAFLHVL 89

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 46.94 E-value: 4.56e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1848 PPVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKdkqSLRSEPSVVIVSCKDGrqLLSIPRASKRHAGLYECSATNV 1927
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRK---ILEPMPATAEISMSGA--VLKIFNIQPEDEGTYECEAENI 75

                          90
                  ....*....|..
gi 564369110 1928 LGSITSSCTVAV 1939
Cdd:cd05851    76 KGKDKHQARVYV 87

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270840 [Multi-domain] Cd Length: 337 Bit Score: 51.26 E-value: 4.93e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  912 ARREARLLARLQHDCVLYFHEAF------ERRRGLVIVTELCTEELLERMARKptvCESETRTYM-RQVLEGIGYLHQSH 984
Cdd:cd07850    46 AYRELVLMKLVNHKNIIGLLNVFtpqkslEEFQDVYLVMELMDANLCQVIQMD---LDHERMSYLlYQMLCGIKHLHSAG 122

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  985 VLHLDVKPENLLVWDGAggeeQVRICDFGNAQelTPGEpqycQFG-TPEFV-----APEIVNQSPVSGVTDIWPVGVVAF 1058
Cdd:cd07850   123 IIHRDLKPSNIVVKSDC----TLKILDFGLAR--TAGT----SFMmTPYVVtryyrAPEVILGMGYKENVDIWSVGCIMG 192

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1059 LCLTGISPFVGeNDRTTLMN--------------------IRNY------------NVAFEETTFLSLSRE--------A 1098
Cdd:cd07850   193 EMIRGTVLFPG-TDHIDQWNkiieqlgtpsdefmsrlqptVRNYvenrpkyagysfEELFPDVLFPPDSEEhnklkasqA 271

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 564369110 1099 RGFLIKVLVQDRL-RPTAEETLEHPWFKTEAKGAEV 1133
Cdd:cd07850   272 RDLLSKMLVIDPEkRISVDDALQHPYINVWYDPSEV 307

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 46.63 E-value: 4.96e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110  342 DVEVLEGRAARLDCKIS-GTPPPSVTWTHFGHPVNESENLRLRQDGGlhSLHIARVGSEDEGLYEVSATNTHG 413
Cdd:cd05724     6 DTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNLDNERVRIVDDG--NLLIAEARKSDEGTYKCVATNMVG 76

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270630 [Multi-domain] Cd Length: 248 Bit Score: 50.36 E-value: 5.13e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2265 LQEYEVLRTLHHERLMSLHeAYIT---PRYLVliAESCGNRELLCGL-SDRFRYS-EDDVATYVVQLLQGLDYLHGRHVL 2339
Cdd:cd05034    38 LQEAQIMKKLRHDKLVQLY-AVCSdeePIYIV--TELMSKGSLLDYLrTGEGRALrLPQLIDMAAQIASGMAYLESRNYI 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2340 HLDIKPDNLLLAADNALKIVDFGSAQ-----PYNPqalkplghRTGT---LEFMAPEMVRGDPIGSATDIWGAGVLTY-I 2410
Cdd:cd05034   115 HRDLAARNILVGENNVCKVADFGLARlieddEYTA--------REGAkfpIKWTAPEAALYGRFTIKSDVWSFGILLYeI 186


                  ....*...
gi 564369110 2411 MLSGYSPF 2418
Cdd:cd05034   187 VTYGRVPY 194

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271060 [Multi-domain] Cd Length: 288 Bit Score: 50.58 E-value: 5.49e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  951 LLERMArkptvCESET-------RTYMRQ-VLEGIGYLHQSHVLHLDVKPENLLVWDGAggeeQVRICDFGnaqeLTPGE 1022
Cdd:cd14158   101 LLDRLA-----CLNDTpplswhmRCKIAQgTANGINYLHENNHIHRDIKSANILLDETF----VPKISDFG----LARAS 167

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 1023 PQYCQ-------FGTPEFVAPEIVnQSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIR 1080
Cdd:cd14158   168 EKFSQtimteriVGTTAYMAPEAL-RGEITPKSDIFSFGVVLLEIITGLPPVDENRDPQLLLDIK 231

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270665 [Multi-domain] Cd Length: 283 Bit Score: 50.66 E-value: 5.56e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  913 RREARLLARLQHD-CVLYFHEAFER-RRGLVIVTEL----CTEELLERMARKPTVCEseTRTYMRQVLEGIGYLHQSHVL 986
Cdd:cd05081    53 QREIQILKALHSDfIVKYRGVSYGPgRRSLRLVMEYlpsgCLRDFLQRHRARLDASR--LLLYSSQICKGMEYLGSRRCV 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  987 HLDVKPENLLVwdgaGGEEQVRICDFGNAQeLTPGEPQYCQFGTPE-----FVAPEIVNQSPVSGVTDIWPVGVVAFLCL 1061
Cdd:cd05081   131 HRDLAARNILV----ESEAHVKIADFGLAK-LLPLDKDYYVVREPGqspifWYAPESLSDNIFSRQSDVWSFGVVLYELF 205


                  .
gi 564369110 1062 T 1062
Cdd:cd05081   206 T 206

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 46.69 E-value: 6.29e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  755 PRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKD-EVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLA 833
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNrQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80

                          90
                  ....*....|.
gi 564369110  834 GEVSCKAELSV 844
Cdd:cd20975    81 GARQCEARLEV 91

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 46.81 E-value: 6.37e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  244 LQDVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPAlLKCKMHFDGRKCKLLLTSVHEDDSGVYTCKLSTVKDELTCS 323
Cdd:cd20972     8 LRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNS-PDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSVGSDTTS 86


                  ....*
gi 564369110  324 ARLTV 328
Cdd:cd20972    87 AEIFV 91

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271124 [Multi-domain] Cd Length: 272 Bit Score: 50.33 E-value: 6.72e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  877 IGRGAFSYLRRVVERSSGLEFAAK-FIPSQAKPKASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERM 955
Cdd:cd14222     1 LGKGFFGQAIKVTHKATGKVMVMKeLIRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDF 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  956 ARKPTVCESETR-TYMRQVLEGIGYLHQSHVLHLDVKPENLLV-WDGAggeeqVRICDFGNAQELTPGEP---------- 1023
Cdd:cd14222    81 LRADDPFPWQQKvSFAKGIASGMAYLHSMSIIHRDLNSHNCLIkLDKT-----VVVADFGLSRLIVEEKKkpppdkpttk 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 564369110 1024 -----------QYCQFGTPEFVAPEIVNQSPVSGVTDIWPVGVVafLC 1060
Cdd:cd14222   156 krtlrkndrkkRYTVVGNPYWMAPEMLNGKSYDEKVDIFSFGIV--LC 201

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 46.47 E-value: 7.35e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  458 PDFLRPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDrRMTQYRDIHRLVFPAVGPQHAGVYKSVIANKLG 537
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAAD-RSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAG 80

                          90
                  ....*....|
gi 564369110  538 KAACYAHLYV 547
Cdd:cd20976    81 QVSCSAWVTV 90

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 46.04 E-value: 7.74e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1876 PTPRISWMKDKQSLRsEPSVVIVSCKDGRQLLSIPRASKRHAGLYECSATNVLGSITSSCTVAV 1939
Cdd:cd05748    20 PTPTVTWSKDGQPLK-ETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 46.39 E-value: 8.37e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  466 DLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRRMTqyrdiHRLVFPA------------VGPQHAGVYKSVIA 533
Cdd:cd07693     9 DLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRS-----HRIVLPSgslfflrvvhgrKGRSDEGVYVCVAH 83


                  ....*.
gi 564369110  534 NKLGKA 539
Cdd:cd07693    84 NSLGEA 89

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 46.05 E-value: 8.97e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110    6 GADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGERHTLLLREaqaaDAGSYTATATNELGQASCASSLAV 81
Cdd:cd05728    14 GSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLRITKLSLS----DSGMYQCVAENKHGTIYASAELAV 85

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 45.85 E-value: 9.18e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110    1 MVVAPGADVLLKCiitaNPP-----PQVSWKKDGSVLHSEG-RLLIRAEGerhTLLLREAQAADAGSYTATATNELG 71
Cdd:cd05724     7 TQVAVGEMAVLEC----SPPrghpePTVSWRKDGQPLNLDNeRVRIVDDG---NLLIAEARKSDEGTYKCVATNMVG 76

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270939 [Multi-domain] Cd Length: 277 Bit Score: 49.97 E-value: 9.49e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLH--QSHVLHLDVKPENLLVWDGAggeeQVRICDFGNAQE--LTPGEPQYCQF--------GT 1030
Cdd:cd14037   107 ESEILKIFCDVCEAVAAMHylKPPLIHRDLKVENVLISDSG----NYKLCDFGSATTkiLPPQTKQGVTYveedikkyTT 182

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1031 PEFVAPEIVN---QSPVSGVTDIWPVGVVAF-LCLTgISPFvGENDRTTLMNIRnynvaFEETTFLSLSREARGFLIKVL 1106
Cdd:cd14037   183 LQYRAPEMIDlyrGKPITEKSDIWALGCLLYkLCFY-TTPF-EESGQLAILNGN-----FTFPDNSRYSKRLHKLIRYML 255

                         170
                  ....*....|....*.
gi 564369110 1107 VQD-RLRPTAEETLEH 1121
Cdd:cd14037   256 EEDpEKRPNIYQVSYE 271

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.

Pssm-ID: 270870 [Multi-domain] Cd Length: 136 Bit Score: 47.44 E-value: 9.64e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRR-VLQEYEVLRTL--HHERLMSLHEAYITPRYLVLIAESCGNRELLC 2306
Cdd:cd13968     2 GEGASAKVFWAEGECTTIGVAVKIGDDVNNEEGEdLESEMDILRRLkgLELNIPKVLVTEDVDGPNILLMELVKGGTLIA 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110 2307 GLSDRFRySEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFG 2362
Cdd:cd13968    82 YTQEEEL-DEKDVESIMYQLAECMRLLHSFHLIHRDLNNDNILLSEDGNVKLIDFG 136

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 46.19 E-value: 9.72e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  458 PDFLRPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRR--MTQYRDIHRLVFPAVGPQHAGVYKSVIANK 535
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLPGvqISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|...
gi 564369110  536 LGKAACYAHLYVT 548
Cdd:cd20974    81 SGQATSTAELLVL 93

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 45.99 E-value: 9.74e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  150 VREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEARLEV 229
Cdd:cd05894     7 VVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEGRVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHASLFVKV 86

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 45.85 E-value: 9.91e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  147 DQSVREGQDVIMSIRVQGEPKPVVSWLRN-------RQPVRPDQrrfaeeaegglcRLRILAAERGDAGFYTCKAVNEYG 219
Cdd:cd05725     6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEdgelpkgRYEILDDH------------SLKIRKVTAGDMGSYTCVAENMVG 73

                          90
                  ....*....|
gi 564369110  220 ARQCEARLEV 229
Cdd:cd05725    74 KIEASATLTV 83

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 45.67 E-value: 1.04e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  757 FESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEENECSLVVLSagsqDGGVYTCTARNLAGEV 836
Cdd:cd05728     2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLRITKLSLS----DSGMYQCVAENKHGTI 77


                  ....*...
gi 564369110  837 SCKAELSV 844
Cdd:cd05728    78 YASAELAV 85

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 45.25 E-value: 1.05e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110  779 EGKPLPDIMWYKDEVLLAESN--HVSfvyeeNECSLVVLSAGSQDGGVYTCTARNLAGEVSCKAELS 843
Cdd:cd05746     8 QGDPEPTITWNKDGVQVTESGkfHIS-----PEGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 51.09 E-value: 1.23e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1206 PRPLQPEF--SGSRVSLtdiPTEDEALGTPEAGAATPMDWQEQGRAP-------SKDQEAPSPEALPSPGQESPDGPSPR 1276
Cdd:PHA03247 2647 PPPERPRDdpAPGRVSR---PRRARRLGRAAQASSPPQRPRRRAARPtvgsltsLADPPPPPPTPEPAPHALVSATPLPP 2723

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1277 RPELRRGSS-------------AESALPRVGSREPGRSLHKAASVELPQRRSPSPGATRLTRGGLgegeyAQRLQALRQR 1343
Cdd:PHA03247 2724 GPAAARQASpalpaapappavpAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAV-----ASLSESRESL 2798

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1344 LLRGGPEDgkvsglrgPLLESLGGRARDPRMARAASSEAAP---HHQPPPESRGLQKSSSFSQGEAEPRGRHRRAG---- 1416
Cdd:PHA03247 2799 PSPWDPAD--------PPAAVLAPAAALPPAASPAGPLPPPtsaQPTAPPPPPGPPPPSLPLGGSVAPGGDVRRRPpsrs 2870

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1417 ------APLEIPVARLGARRLQESPSLSALSETQPPSPALPSAPKPSITKSPEPSAAtsrdsPQPPAPQPVPEKIPEPKP 1490
Cdd:PHA03247 2871 paakpaAPARPPVRRLARPAVSRSTESFALPPDQPERPPQPQAPPPPQPQPQPPPPP-----QPQPPPPPPPRPQPPLAP 2945

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1491 EPVRAAKPAQPPLALQMPAQSLTPYAQIMQSLQLSSPTLSPQVP-PSEPKPHAAVFARVAS 1550
Cdd:PHA03247 2946 TTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPaSSTPPLTGHSLSRVSS 3006

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 45.60 E-value: 1.24e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  762 EDVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEEnecSLVVLSAGSQDGGVYTCTARNLAGEVSCKAE 841
Cdd:cd20957     9 PVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSAQATAE 85


                  .
gi 564369110  842 L 842
Cdd:cd20957    86 L 86

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270965 [Multi-domain] Cd Length: 271 Bit Score: 49.27 E-value: 1.25e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2266 QEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLSDRF-RYSEDDVATYVVQLLQGLDYLHGRHVLHLDIK 2344
Cdd:cd14063    45 EEVAAYKNTRHDNLVLFMGACMDPPHLAIVTSLCKGRTLYSLIHERKeKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLK 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2345 PDNLLLaaDNAlKIV--DFGSaqpYNPQALKPLGHRTGTL-------EFMAPEMVRG----------DPIGSATDIWGAG 2405
Cdd:cd14063   125 SKNIFL--ENG-RVVitDFGL---FSLSGLLQPGRREDTLvipngwlCYLAPEIIRAlspdldfeesLPFTKASDVYAFG 198

                         170       180
                  ....*....|....*....|
gi 564369110 2406 VLTYIMLSGYSPFYEpDPQE 2425
Cdd:cd14063   199 TVWYELLAGRWPFKE-QPAE 217

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270667 [Multi-domain] Cd Length: 252 Bit Score: 49.16 E-value: 1.42e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  875 QEIGRGAFSYLRRVVERSSGLEFAAKFIPSQAKP--KASARREARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELL 952
Cdd:cd05084     2 ERIGRGNFGEVFSGRLRADNTPVAVKSCRETLPPdlKAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGDF 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  953 ERMARK--PTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGepQYCQFG- 1029
Cdd:cd05084    82 LTFLRTegPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCLV----TEKNVLKISDFGMSREEEDG--VYAATGg 155

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 1030 ---TP-EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLT-GISPFVGENDRTT 1075
Cdd:cd05084   156 mkqIPvKWTAPEALNYGRYSSESDVWSFGILLWETFSlGAVPYANLSNQQT 206

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.

Pssm-ID: 270668 [Multi-domain] Cd Length: 251 Bit Score: 48.85 E-value: 1.58e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  902 IPSQAKPKASArrEARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE-ELLERMARKPTvcESETRTYMRQVLE---GI 977
Cdd:cd05085    32 LPQELKIKFLS--EARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGgDFLSFLRKKKD--ELKTKQLVKFSLDaaaGM 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  978 GYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGepQYCQFGTPE----FVAPEIVNQSPVSGVTDIWPV 1053
Cdd:cd05085   108 AYLESKNCIHRDLAARNCLV----GENNALKISDFGMSRQEDDG--VYSSSGLKQipikWTAPEALNYGRYSSESDVWSF 181

                         170
                  ....*....|....*..
gi 564369110 1054 GVVAFLCLT-GISPFVG 1069
Cdd:cd05085   182 GILLWETFSlGVCPYPG 198

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 44.87 E-value: 1.60e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110    9 VLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNELGQASCASSLA 80
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEG---YLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 50.71 E-value: 1.77e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1248 RAPSKDQEAPSPEALPSPGQESPDGPSPRRPE-LRRGSSAESALPRV-------------GSREPGRSLHKAASVELPQR 1313
Cdd:PHA03247 2487 RFPFAAGAAPDPGGGGPPDPDAPPAPSRLAPAiLPDEPVGEPVHPRMltwirgleelasdDAGDPPPPLPPAAPPAAPDR 2566

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1314 RSPSPgatrltrgglgegEYAQRLQ--ALRQRLLRGG--PEDGKVSGLRGPlleslggRARDPRMARAASSEAAPHHQPP 1389
Cdd:PHA03247 2567 SVPPP-------------RPAPRPSepAVTSRARRPDapPQSARPRAPVDD-------RGDPRGPAPPSPLPPDTHAPDP 2626

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1390 PESRGLQKSSSFSQGE---AEPRGRHRRAGAPleiPVARLGARRLQESPSLSALSETQPPSPALPSAPKPSITKSPEPSA 1466
Cdd:PHA03247 2627 PPPSPSPAANEPDPHPpptVPPPERPRDDPAP---GRVSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTSLADPPP 2703

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1467 atsrdspqppapqpvPEKIPEPKPEPVRAAKPAQP------------PLALQMPAQSLTPYAQIMQSLQLSSPTLSPQVP 1534
Cdd:PHA03247 2704 ---------------PPPTPEPAPHALVSATPLPPgpaaarqaspalPAAPAPPAVPAGPATPGGPARPARPPTTAGPPA 2768

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1535 PSEPKPHAAVFARVASPPPGAS----EKRVPSARIPPVLAEKVRVPTVPPRPGSSLSGSIENLESEA-VFEAKFKRSRES 1609
Cdd:PHA03247 2769 PAPPAAPAAGPPRRLTRPAVASlsesRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQpTAPPPPPGPPPP 2848

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564369110 1610 PLSRGLRLLSRSRSEERGPFRGAEDDGIYRPSPagtPLELVRRPERSRSVQDL 1662
Cdd:PHA03247 2849 SLPLGGSVAPGGDVRRRPPSRSPAAKPAAPARP---PVRRLARPAVSRSTESF 2898

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271134 [Multi-domain] Cd Length: 270 Bit Score: 49.03 E-value: 1.81e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  976 GIGYLHQS---HVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQYCQF--GTPEFVAPEIVNQSPVSGVTDI 1050
Cdd:cd14664   106 GLAYLHHDcspLIIHRDVKSNNILL----DEEFEAHVADFGLAKLMDDKDSHVMSSvaGSYGYIAPEYAYTGKVSEKSDV 181

                          90
                  ....*....|....*..
gi 564369110 1051 WPVGVVAFLCLTGISPF 1067
Cdd:cd14664   182 YSYGVVLLELITGKRPF 198

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 45.30 E-value: 1.82e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  336 FTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFG---HPVNESENLRLRQDggLHSLHIARVGSEDEGLYEVSATNTH 412
Cdd:cd05763     2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGgtdFPAARERRMHVMPE--DDVFFIVDVKIEDTGVYSCTAQNSA 79

                          90
                  ....*....|.
gi 564369110  413 GQAHCSAQLYV 423
Cdd:cd05763    80 GSISANATLTV 90

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 45.13 E-value: 1.89e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    2 VVAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAeGERHTLLLREAQAADAGSYTATATNELG 71
Cdd:cd04978    10 VLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRT-VDGRTLIFSNLQPNDTAVYQCNASNVHG 78

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 45.14 E-value: 1.93e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110  345 VLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDGglhSLHIARVGSEDEGLYEVSATNTHGQAHCSAQLYV 423
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133213 [Multi-domain] Cd Length: 256 Bit Score: 48.82 E-value: 2.00e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  873 IHQEIGRGAFSYLrrVVERSSGLEFAAKFIPSQAKPKASARrEARLLARLQHD-CVLYFHEAFERRRGLVIVTE-LCTEE 950
Cdd:cd05082    10 LLQTIGKGEFGDV--MLGDYRGNKVAVKCIKNDATAQAFLA-EASVMTQLRHSnLVQLLGVIVEEKGGLYIVTEyMAKGS 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  951 LLERM-ARKPTVCESETR-TYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgagGEEQV-RICDFGNAQELTpgEPQYCQ 1027
Cdd:cd05082    87 LVDYLrSRGRSVLGGDCLlKFSLDVCEAMEYLEGNNFVHRDLAARNVLV-----SEDNVaKVSDFGLTKEAS--STQDTG 159

                         170       180
                  ....*....|....*....|....*....
gi 564369110 1028 FGTPEFVAPEIVNQSPVSGVTDIWPVGVV 1056
Cdd:cd05082   160 KLPVKWTAPEALREKKFSTKSDVWSFGIL 188

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 45.18 E-value: 2.05e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1857 DQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSvVIVSCKDGRqlLSIPRASKRHAGLYECSATNVLGSITSSCT 1936
Cdd:cd20952     8 NQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDE-RITTLENGS--LQIKGAEKSDTGEYTCVALNLSGEATWSAV 84


                  ...
gi 564369110 1937 VAV 1939
Cdd:cd20952    85 LDV 87

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 45.38 E-value: 2.10e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  138 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCR---LRILAAERGDAGFYTCKA 214
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEYKDLLYDPNVRILPngtLVFGHVQKENEGHYLCEA 80


                  ....*.
gi 564369110  215 VNEYGA 220
Cdd:cd20954    81 KNGIGS 86

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 44.86 E-value: 2.18e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110   240 VLAPLQDVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPALLKcKMHFDGRKCKLLLTSVHEDDSGVYTCKLS 314
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTR-SRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 45.14 E-value: 2.48e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  458 PDFLRPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDrRMTQYRD---IHRLVFPAVGPQHAGVYKSVIAN 534
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTD-RISLYQDncgRICLLIQNANKKDAGWYTVSAVN 79

                          90
                  ....*....|...
gi 564369110  535 KLGKAACYAHLYV 547
Cdd:cd05892    80 EAGVVSCNARLDV 92

cyclin-dependent protein kinase; Provisional

Pssm-ID: 240233 [Multi-domain] Cd Length: 335 Bit Score: 48.99 E-value: 2.50e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  914 REARLLARLQHDCVLYFHEAFERRRGLVIVTELCTEELLERMARKPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPE 993
Cdd:PTZ00024   69 RELKIMNEIKHENIMGLVDVYVEGDFINLVMDIMASDLKKVVDRKIRLTESQVKCILLQILNGLNVLHKWYFMHRDLSPA 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  994 NLLVWDgaggEEQVRICDFGNAQ---------ELTPGE-PQYCQFGTPEFV-----APEIVNQSP-VSGVTDIWPVGVVA 1057
Cdd:PTZ00024  149 NIFINS----KGICKIADFGLARrygyppysdTLSKDEtMQRREEMTSKVVtlwyrAPELLMGAEkYHFAVDMWSVGCIF 224

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1058 FLCLTGISPFVGENDRTTLMNIRNY-----NVAFEETTFLSL-------------------SREARGFLIKVLVQDRL-R 1112
Cdd:PTZ00024  225 AELLTGKPLFPGENEIDQLGRIFELlgtpnEDNWPQAKKLPLyteftprkpkdlktifpnaSDDAIDLLQSLLKLNPLeR 304

                         250
                  ....*....|....
gi 564369110 1113 PTAEETLEHPWFKT 1126
Cdd:PTZ00024  305 ISAKEALKHEYFKS 318

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271109 [Multi-domain] Cd Length: 340 Bit Score: 48.85 E-value: 2.55e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  902 IPSQAKPKASARREARLLARLQHDCvlYFHEAFERRRGLVIVTElcTEELLERMARKPTVCEsETRTYMRQVLEGIGYLH 981
Cdd:cd14207   123 IKEKKEAEPTGGKKKRLESVTSSES--FASSGFQEDKSLSDVEE--EEEDSGDFYKRPLTME-DLISYSFQVARGMEFLS 197

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  982 QSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPgEPQYCQFGTP----EFVAPEIVNQSPVSGVTDIWPVGVVA 1057
Cdd:cd14207   198 SRKCIHRDLAARNILLSE----NNVVKICDFGLARDIYK-NPDYVRKGDArlplKWMAPESIFDKIYSTKSDVWSYGVLL 272

                         170
                  ....*....|...
gi 564369110 1058 FLCLT-GISPFVG 1069
Cdd:cd14207   273 WEIFSlGASPYPG 285

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 45.15 E-value: 2.70e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  333 APLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENlRLRQDGGLHSLHIARVG---SEDEGLYEVSAT 409
Cdd:cd20971     1 APHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGL-KYRIQEFKGGYHQLIIAsvtDDDATVYQVRAT 79

                          90
                  ....*....|....
gi 564369110  410 NTHGQAHCSAQLYV 423
Cdd:cd20971    80 NQGGSVSGTASLEV 93

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 44.77 E-value: 3.00e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  334 PLFTRLLEDVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVN-ESENLRLRQDGGLHSLHIARVGSEDEGLYEVSATNTH 412
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRpDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80

                          90
                  ....*....|.
gi 564369110  413 GQAHCSAQLYV 423
Cdd:cd20975    81 GARQCEARLEV 91

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271128 [Multi-domain] Cd Length: 339 Bit Score: 48.47 E-value: 3.41e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2325 QLLQGLDYLHGR--HVLHLDIKPDNLLLAADN--ALKIVDFGSAQPYNPQALKPLGHRTgtleFMAPEMVRGDPIGSATD 2400
Cdd:cd14226   124 QLCTALLFLSTPelSIIHCDLKPENILLCNPKrsAIKIIDFGSSCQLGQRIYQYIQSRF----YRSPEVLLGLPYDLAID 199

                          90
                  ....*....|....
gi 564369110 2401 IWGAGVLTYIMLSG 2414
Cdd:cd14226   200 MWSLGCILVEMHTG 213

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK3 is a Fas-interacting protein that induces FADD (Fas-associated death domain) phosphorylation and mediates FasL-induced JNK activation. Overexpression of HIPK3 does not affect cell death, however its expression in prostate cancer cells contributes to increased resistance to Fas receptor-mediated apoptosis. HIPK3 also plays a role in regulating steroidogenic gene expression. In response to cAMP, HIPK3 activates the phosphorylation of JNK and c-Jun, leading to increased activity of the transcription factor SF-1 (Steroidogenic factor 1), a key regulator for steroid biosynthesis in the gonad and adrenal gland. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 271131 [Multi-domain] Cd Length: 330 Bit Score: 48.49 E-value: 3.42e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHER-----LMSLHEAYITPRYLVLIAE 2297
Cdd:cd14229     2 YEVLDFLGRGTFGQVVKCWKRGTNEIVAVKILKNHPSYARQGQIEVGILARLSNENadefnFVRAYECFQHRNHTCLVFE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCGNRELLCGLSDRFRYSEDDVATYVVQ-LLQGLDYLHGRHVLHLDIKPDNLLLA----ADNALKIVDFGSAQPYNPQAL 2372
Cdd:cd14229    82 MLEQNLYDFLKQNKFSPLPLKVIRPILQqVATALKKLKSLGLIHADLKPENIMLVdpvrQPYRVKVIDFGSASHVSKTVC 161

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 564369110 2373 KP-LGHRTgtleFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYsPFYePDPQE 2425
Cdd:cd14229   162 STyLQSRY----YRAPEIILGLPFCEAIDMWSLGCVIAELFLGW-PLY-PGALE 209

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 44.53 E-value: 3.90e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110    6 GADVLLKCIITANPPPQVSWKKDGSV---LHSEGRLLIRAEGErhTLLLREAQAADAGSYTATATNELGQASCASSLAV 81
Cdd:cd05763    14 GSTARLECAATGHPTPQIAWQKDGGTdfpAARERRMHVMPEDD--VFFIVDVKIEDTGVYSCTAQNSAGSISANATLTV 90

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 44.11 E-value: 4.32e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 564369110  774 FAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEENecsLVVLSAGSQDGGVYTCTARNLAGEVSCKAELSV 844
Cdd:cd05723    17 FECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHN---LQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 43.47 E-value: 4.37e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  255 ALFECLVAGPADVEVDWLcRGRLLQPALLKCKMHFDGRKCKLLLTSVHEDDSGVYTCKLS 314
Cdd:cd00096     1 VTLTCSASGNPPPTITWY-KNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVAS 59

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270681 [Multi-domain] Cd Length: 343 Bit Score: 48.05 E-value: 4.83e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  958 KPTVCESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPgEPQYCQFGTP----EF 1033
Cdd:cd05103   173 KDFLTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSE----NNVVKICDFGLARDIYK-DPDYVRKGDArlplKW 247

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 564369110 1034 VAPEIVNQSPVSGVTDIWPVGVVAFLCLT-GISPFVG 1069
Cdd:cd05103   248 MAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPG 284

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 43.99 E-value: 5.39e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110  779 EGKPLPDIMWYKDEVLLAESNHVSFVyeeNECSLVVLSAGSQDGGVYTCTARNLAGEVSCKAELSV 844
Cdd:cd04969    27 KASPKPTISWSKGTELLTNSSRICIL---PDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 43.67 E-value: 5.62e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564369110 1852 HIKLKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVSckdgRQLLSIPRASKRHAGLYECSATN 1926
Cdd:cd20957     5 TIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILS----EDVLVIPSVKREDKGMYQCFVRN 75

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 43.55 E-value: 7.12e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1857 DQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVSCKDGRQLLSIPRASKRHAGLYECSATNVLGSITSSCT 1936
Cdd:cd20990     9 DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRAGQNSFNLE 88


                  ...
gi 564369110 1937 VAV 1939
Cdd:cd20990    89 LVV 91

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 43.47 E-value: 7.21e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  764 VEVGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLAGEVSCKAELS 843
Cdd:cd20949     9 TTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSIASDMQERT 88


                  .
gi 564369110  844 V 844
Cdd:cd20949    89 V 89

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271055 [Multi-domain] Cd Length: 270 Bit Score: 46.93 E-value: 7.42e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2230 ARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNRELLCGLS 2309
Cdd:cd14153     9 GKGRFGQVYHGRWHGEVAIRLIDIERDNEEQLKAFKREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYSVVR 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRFRYSEDDVATYVVQ-LLQGLDYLHGRHVLHLDIKPDNLLLaaDNA-LKIVDFGSaqpYNPQALKPLGHR-------TG 2380
Cdd:cd14153    89 DAKVVLDVNKTRQIAQeIVKGMGYLHAKGILHKDLKSKNVFY--DNGkVVITDFGL---FTISGVLQAGRRedklriqSG 163

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110 2381 TLEFMAPEMVR---------GDPIGSATDIWGAGVLTYIMLSGYSPF 2418
Cdd:cd14153   164 WLCHLAPEIIRqlspeteedKLPFSKHSDVFAFGTIWYELHAREWPF 210

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270652 [Multi-domain] Cd Length: 264 Bit Score: 46.80 E-value: 8.18e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  915 EARLLARLQHDCVLYFHeAFERRRGLVIVTELCTEELLERMARKPTVCESETRTYM---RQVLEGIGYLHQSHVLHLDVK 991
Cdd:cd05067    52 EANLMKQLQHQRLVRLY-AVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLdmaAQIAEGMAFIEERNYIHRDLR 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  992 PENLLVWDgaggEEQVRICDFGNAQELTPGEpQYCQFGTP---EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLT-GISPF 1067
Cdd:cd05067   131 AANILVSD----TLSCKIADFGLARLIEDNE-YTAREGAKfpiKWTAPEAINYGTFTIKSDVWSFGILLTEIVThGRIPY 205

                         170
                  ....*....|....*.
gi 564369110 1068 VGENDRTTLMNI-RNY 1082
Cdd:cd05067   206 PGMTNPEVIQNLeRGY 221

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK3 is predominantly expressed in mature spermatozoa, and might play a role in the fertilization process. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271116 [Multi-domain] Cd Length: 331 Bit Score: 47.31 E-value: 8.37e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2220 QKPYTFLEEKARGRFGVVRSCRENATGRTFVA-KIVPYAAEGKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAES 2298
Cdd:cd14214    12 QERYEIVGDLGEGTFGKVVECLDHARGKSQVAlKIIRNVGKYREAARLEINVLKKIKEKDKENKFLCVLMSDWFNFHGHM 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2299 CGNRELLCGLSDRFRySEDDVATY--------VVQLLQGLDYLHGRHVLHLDIKPDNLLLA------------------- 2351
Cdd:cd14214    92 CIAFELLGKNTFEFL-KENNFQPYplphirhmAYQLCHALKFLHENQLTHTDLKPENILFVnsefdtlynesksceeksv 170

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2352 ADNALKIVDFGSAqpynpqALKPLGHRT--GTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQE---T 2426
Cdd:cd14214   171 KNTSIRVADFGSA------TFDHEHHTTivATRHYRPPEVILELGWAQPCDVWSLGCILFEYYRGFTLFQTHENREhlvM 244

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2427 EARIVG-----------------------------GRFDAFQLYP-------NTSQSATLF--LRKVLSVHPWSRPSLQD 2468
Cdd:cd14214   245 MEKILGpipshmihrtrkqkyfykgslvwdenssdGRYVSENCKPlmsymlgDSLEHTQLFdlLRRMLEFDPALRITLKE 324


                  ....*..
gi 564369110 2469 CLAHPWL 2475
Cdd:cd14214   325 ALLHPFF 331

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173657 [Multi-domain] Cd Length: 256 Bit Score: 46.80 E-value: 8.48e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  915 EARLLARLQHDCVLYFHEAFERRRGLVIVTEL----CTEELLERMARKPTVceSETRTYMRQVLEGIGYLHQSHVLHLDV 990
Cdd:cd05113    49 EAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYmangCLLNYLREMRKRFQT--QQLLEMCKDVCEAMEYLESKQFLHRDL 126

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  991 KPENLLVWDgaggEEQVRICDFGNAQELTpgEPQYCQFGTPEF----VAPEIVNQSPVSGVTDIWPVGVV 1056
Cdd:cd05113   127 AARNCLVND----QGVVKVSDFGLSRYVL--DDEYTSSVGSKFpvrwSPPEVLMYSKFSSKSDVWAFGVL 190

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 43.69 E-value: 8.68e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1856 KDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEP----SVVIVSCKDGRQLLSI--PRASKRHAGLYECSATNVLG 1929
Cdd:cd07693     8 SDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKddprSHRIVLPSGSLFFLRVvhGRKGRSDEGVYVCVAHNSLG 87


                  ....
gi 564369110 1930 SITS 1933
Cdd:cd07693    88 EAVS 91

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 43.47 E-value: 8.94e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110    1 MVVAPGADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQAS 74
Cdd:cd20949     9 TTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSIAS 82

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270658 [Multi-domain] Cd Length: 265 Bit Score: 46.94 E-value: 9.03e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  915 EARLLARLQHDCVLYFHeAFERRRGLVIVTELCTEELL------ERMARKPTvceSETRTYMRQVLEGIGYLHQSHVLHL 988
Cdd:cd05073    56 EANVMKTLQHDKLVKLH-AVVTKEPIYIITEFMAKGSLldflksDEGSKQPL---PKLIDFSAQIAEGMAFIEQRNYIHR 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  989 DVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEpqYCQFGTPEF----VAPEIVNQSPVSGVTDIWPVGVVAFLCLT-G 1063
Cdd:cd05073   132 DLRAANILV----SASLVCKIADFGLARVIEDNE--YTAREGAKFpikwTAPEAINFGSFTIKSDVWSFGILLMEIVTyG 205


                  ....*.
gi 564369110 1064 ISPFVG 1069
Cdd:cd05073   206 RIPYPG 211

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 43.31 E-value: 1.03e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  755 PRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKD------EVLLAESNHVSFvyeeNECSLVVLSA-----GSQDGG 823
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNgqpletDKDDPRSHRIVL----PSGSLFFLRVvhgrkGRSDEG 76

                          90       100
                  ....*....|....*....|..
gi 564369110  824 VYTCTARNLAGE-VSCKAELSV 844
Cdd:cd07693    77 VYVCVAHNSLGEaVSRNASLEV 98

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 42.99 E-value: 1.14e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  246 DVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPALLKCKMHFDGRKCKLLLTSVHEDDSGVYTCKLSTVKDELTCSAR 325
Cdd:cd05763     8 DITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANAT 87


                  ...
gi 564369110  326 LTV 328
Cdd:cd05763    88 LTV 90

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 42.97 E-value: 1.21e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1870 CLPAACPTPRISWMKDKQSLRSEPSVVIVSCKdgrqlLSIPRASKRHAGLYECSATNVLGSITSSCTVAV 1939
Cdd:cd05728    21 CKASGNPRPAYRWLKNGQPLASENRIEVEAGD-----LRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270639 [Multi-domain] Cd Length: 279 Bit Score: 46.29 E-value: 1.40e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  972 QVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEpqYCQFGTPE-----FVAPEIVNQSPVSG 1046
Cdd:cd05043   124 QIACGMSYLHRRGVIHKDIAARNCVIDD----ELQVKITDNALSRDLFPMD--YHCLGDNEnrpikWMSLESLVNKEYSS 197

                          90       100
                  ....*....|....*....|...
gi 564369110 1047 VTDIWPVGVVAF-LCLTGISPFV 1068
Cdd:cd05043   198 ASDVWSFGVLLWeLMTLGQTPYV 220

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 42.73 E-value: 1.59e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110  149 SVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGlCRLRILAAERGDAGFYTCKAVNEYGARQCEARL 227
Cdd:cd05747    14 TVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYK-STFEISKVQMSDEGNYTVVVENSEGKQEAQFTL 91

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 42.52 E-value: 1.61e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110  764 VEVGPGETARFAVVVEGKPLPDIMWYK-DEVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLAGE 835
Cdd:cd05894     5 IVVVAGNKLRLDVPISGEPAPTVTWSRgDKAFTATEGRVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGE 77

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors including homeodomain proteins (Nkx and HOX families), Smad1-4, Pax6, c-Myb, AML1, the histone acetyltransferase p300, and the tumor repressor p53, among others. It regulates gene transcription during development and in DNA damage response (DDR), and mediates cell processes such as apoptosis, survival, differentiation, and proliferation. HIPK2 mediates apoptosis by phosphorylating and activating p53 during DDR, resulting in the activation of apoptotic genes. In the absence of p53, HIPK2 targets the anti-apoptotic corepressor C-terminal binding protein (CtBP), leading to CtBP's degradation and the promotion of apoptosis. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271129 [Multi-domain] Cd Length: 355 Bit Score: 46.62 E-value: 1.63e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHE-----RLMSLHEAYITPRYLVLIAE 2297
Cdd:cd14227    17 YEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILARLSTEsaddyNFVRAYECFQHKNHTCLVFE 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCgnRELLCGLSDRFRYSEDDVaTYVVQLLQ----GLDYLHGRHVLHLDIKPDNLLLAADNA----LKIVDFGSAQPYNP 2369
Cdd:cd14227    97 ML--EQNLYDFLKQNKFSPLPL-KYIRPILQqvatALMKLKSLGLIHADLKPENIMLVDPSRqpyrVKVIDFGSASHVSK 173

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2370 QALKPLghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYsPFYEPDPQETEARIVGGR--FDAFQLYPNTSQS 2447
Cdd:cd14227   174 AVCSTY---LQSRYYRAPEIILGLPFCEAIDMWSLGCVIAELFLGW-PLYPGASEYDQIRYISQTqgLPAEYLLSAGTKT 249

                         250       260
                  ....*....|....*....|.
gi 564369110 2448 ATLFLRKVLSVHPWSRPSLQD 2468
Cdd:cd14227   250 TRFFNRDTDSPYPLWRLKTPE 270

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 42.19 E-value: 1.71e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110  345 VLEGRAARLDCKISGTPPPSVTWTHFGHPVNESENLRLRQDGGLHSLHIARVGSEDEGLYEVSATNTHGQAH 416
Cdd:cd05748     4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKS 75

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173644 [Multi-domain] Cd Length: 284 Bit Score: 46.08 E-value: 1.71e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  910 ASARREARLLARLQHDCVLYFHEAFERR--RGLVIVTE-LCTEELLERMAR-KPTVCESETRTYMRQVLEGIGYLHQSHV 985
Cdd:cd05079    51 ADLKKEIEILRNLYHENIVKYKGICTEDggNGIKLIMEfLPSGSLKEYLPRnKNKINLKQQLKYAVQICKGMDYLGSRQY 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  986 LHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPGEPQYC---QFGTPEF-VAPEIVNQSPVSGVTDIWPVGVVAFLCL 1061
Cdd:cd05079   131 VHRDLAARNVLVES----EHQVKIGDFGLTKAIETDKEYYTvkdDLDSPVFwYAPECLIQSKFYIASDVWSFGVTLYELL 206


                  .
gi 564369110 1062 T 1062
Cdd:cd05079   207 T 207

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 42.73 E-value: 1.71e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQR-RFAEEAEGGLCRLRILAAERGDAGFYTCKAVNE 217
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLpGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|..
gi 564369110  218 YGARQCEARLEV 229
Cdd:cd20974    81 SGQATSTAELLV 92

Catalytic domain of the Serine/Threonine kinase, Plant SNT7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNT7 is a plant thylakoid-associated kinase that is essential in short- and long-term acclimation responses to cope with various light conditions in order to maintain photosynthetic redox poise for optimal photosynthetic performance. Short-term response involves state transitions over periods of minutes while the long-term response (LTR) occurs over hours to days and involves changing the relative amounts of photosystems I and II. SNT7 acts as a redox sensor and a signal transducer for both responses, which are triggered by the redox state of the plastoquinone (PQ) pool. It is positioned at the top of a phosphorylation cascade that induces state transitions by phosphorylating light-harvesting complex II (LHCII), and triggers the LTR through the phosphorylation of chloroplast proteins. The SNT7 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270915 [Multi-domain] Cd Length: 318 Bit Score: 46.28 E-value: 1.83e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 564369110 2325 QLLQGLDYLHGRHVLHLDIKPDNLLLA-ADNALKIVDFGSA 2364
Cdd:cd14013   128 QILVALRKLHSTGIVHRDVKPQNIIVSeGDGQFKIIDLGAA 168

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270674 [Multi-domain] Cd Length: 280 Bit Score: 45.73 E-value: 1.86e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  876 EIGRGAFS--YLRRVVERSSGLEFAAKFIPSQAKPKASAR----REARLLARLQHDCVLYFHEAFERRRGLVIVTELCTE 949
Cdd:cd05092    12 ELGEGAFGkvFLAECHNLLPEQDKMLVAVKALKEATESARqdfqREAELLTVLQHQHIVRFYGVCTEGEPLIMVFEYMRH 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  950 ELLERMAR------------KPTVCESETRTYM----RQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFG 1013
Cdd:cd05092    92 GDLNRFLRshgpdakildggEGQAPGQLTLGQMlqiaSQIASGMVYLASLHFVHRDLATRNCLV----GQGLVVKIGDFG 167

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 564369110 1014 NAQELTPGEpqYCQFG----TP-EFVAPEIVNQSPVSGVTDIWPVGVV 1056
Cdd:cd05092   168 MSRDIYSTD--YYRVGgrtmLPiRWMPPESILYRKFTTESDIWSFGVV 213

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270653 [Multi-domain] Cd Length: 267 Bit Score: 45.86 E-value: 1.96e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2219 PQKPYTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRrVLQEYEVLRTLHHERLMSLHeAYIT---PRYLvlI 2295
Cdd:cd05068     6 DRKSLKLLRKLGSGQFGEVWEGLWNNTTPVAVKTLKPGTMDPED-FLREAQIMKKLRHPKLIQLY-AVCTleePIYI--I 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2296 AESCGNRELLCGLSDRFRY----SEDDVATyvvQLLQGLDYLHGRHVLHLDIKPDNLLLAADNALKIVDFGSAQPYNPQA 2371
Cdd:cd05068    82 TELMKHGSLLEYLQGKGRSlqlpQLIDMAA---QVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIKVED 158

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564369110 2372 LkpLGHRTGT---LEFMAPEMVRGDPIGSATDIWGAGVL-TYIMLSGYSPF 2418
Cdd:cd05068   159 E--YEAREGAkfpIKWTAPEAANYNRFSIKSDVWSFGILlTEIVTYGRIPY 207

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 42.18 E-value: 2.15e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110  472 AKEAM---LECQVTGLPYPTISWFHNGHRIQSSDDRRMTQYRDIHRLvfpAVGPQHAGVYKSVIANKLGKAACYAHLYV 547
Cdd:cd05723     9 AHESMdivFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVL---GLVKSDEGFYQCIAENDVGNAQASAQLII 84

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK1 has been implicated in regulating eye size, lens formation, and retinal morphogenesis during late embryogenesis. It also contributes to the regulation of haematopoiesis and leukaemogenesis by phosphorylating and repressing the transcription factor c-Myb, which is crucial in T- and B-cell development. In glucose-deprived conditions, HIPK1 phosphorylates Daxx, leading to its relocalization from the nucleus to the cytoplasm, where it binds and stabilizes ASK1 (apoptosis signal-regulating kinase 1), a mitogen-activated protein kinase (MAPK) kinase kinase that activates the JNK and p38 MAPK pathways. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271130 [Multi-domain] Cd Length: 355 Bit Score: 46.24 E-value: 2.20e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHER-----LMSLHEAYITPRYLVLIAE 2297
Cdd:cd14228    17 YEVLEFLGRGTFGQVAKCWKRSTKEIVAIKILKNHPSYARQGQIEVSILSRLSSENadeynFVRSYECFQHKNHTCLVFE 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 SCgnRELLCGLSDRFRYSEDDVaTYVVQLLQ----GLDYLHGRHVLHLDIKPDNLLLA----ADNALKIVDFGSAQPYNP 2369
Cdd:cd14228    97 ML--EQNLYDFLKQNKFSPLPL-KYIRPILQqvatALMKLKSLGLIHADLKPENIMLVdpvrQPYRVKVIDFGSASHVSK 173

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2370 QALKPLghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYsPFYEPDPQETEARIV 2431
Cdd:cd14228   174 AVCSTY---LQSRYYRAPEIILGLPFCEAIDMWSLGCVIAELFLGW-PLYPGASEYDQIRYI 231

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 41.75 E-value: 2.79e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  138 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEgglcRLRILAAERGDAGFYTCKAVNE 217
Cdd:cd20957     1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSED----VLVIPSVKREDKGMYQCFVRND 76

                          90
                  ....*....|..
gi 564369110  218 YGARQCEARLEV 229
Cdd:cd20957    77 GDSAQATAELKL 88

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 41.67 E-value: 3.12e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  245 QDVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPALLKCKMHFDGRkcKLLLTSVHEDDSGVYTCKLSTVKDELTCSA 324
Cdd:cd04978     7 PSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGR--TLIFSNLQPNDTAVYQCNASNVHGYLLANA 84


                  ....*
gi 564369110  325 RLTVR 329
Cdd:cd04978    85 FLHVL 89

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 41.55 E-value: 3.93e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  138 PPTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVrPDQrrfAEEAEGGLCrLRILAAERGDAGFYTCKAVNE 217
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPM-PAT---AEISMSGAV-LKIFNIQPEDEGTYECEAENI 75

                          90
                  ....*....|...
gi 564369110  218 YGARQCEARLEVR 230
Cdd:cd05851    76 KGKDKHQARVYVQ 88

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270647 [Multi-domain] Cd Length: 298 Bit Score: 44.79 E-value: 4.12e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  969 YMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPgEPQYCQFGTP----EFVAPEIVNQSPV 1044
Cdd:cd05054   143 YSFQVARGMEFLASRKCIHRDLAARNILLSE----NNVVKICDFGLARDIYK-DPDYVRKGDArlplKWMAPESIFDKVY 217

                          90       100
                  ....*....|....*....|....*.
gi 564369110 1045 SGVTDIWPVGVVAFLCLT-GISPFVG 1069
Cdd:cd05054   218 TTQSDVWSFGVLLWEIFSlGASPYPG 243

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270969 [Multi-domain] Cd Length: 276 Bit Score: 44.57 E-value: 4.33e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2266 QEYEVLRTLHHERLMSLHEAYITPRYLVLIAESCGNreLLCGLSDRFRYSE----DDVATYVV--QLLQGLDYLHGRHVL 2339
Cdd:cd14067    59 QEASMLHSLQHPCIVYLIGISIHPLCFALELAPLGS--LNTVLEENHKGSSfmplGHMLTFKIayQIAAGLAYLHKKNII 136

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2340 HLDIKPDNLLLAADNA-----LKIVDFG-SAQPYNPQALKPlghrTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLS 2413
Cdd:cd14067   137 FCDLKSDNILVWSLDVqehinIKLSDYGiSRQSFHEGALGV----EGTPGYQAPEIRPRIVYDEKVDMFSYGMVLYELLS 212


                  ....
gi 564369110 2414 GYSP 2417
Cdd:cd14067   213 GQRP 216

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 41.38 E-value: 4.75e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  139 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWL-----RNRQPVRPDQRRfAEEAEGGLCRLRILAAERGDAGFYTCK 213
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEkqvpgKENLIMRPNHVR-GNVVVTNIGQLVIYNAQPQDAGLYTCT 79

                          90
                  ....*....|....*.
gi 564369110  214 AVNEYGARQCEARLEV 229
Cdd:cd05765    80 ARNSGGLLRANFPLSV 95

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 40.84 E-value: 5.70e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1855 LKDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLRSEPSVVIVscKDGRqlLSIPRASKRHAGLYECSATNVLGSITSS 1934
Cdd:cd20978     8 EKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATV--EDGT--LTIINVQPEDTGYYGCVATNEIGDIYTE 83


                  ....*
gi 564369110 1935 CTVAV 1939
Cdd:cd20978    84 TLLHV 88

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 40.95 E-value: 6.39e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564369110  243 PLQDVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPALLKCKMHFDGRkcKLLLTSVHEDDSGVYTCKLS 314
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGT--TLTIRNIRRSDMGIYLCIAS 77

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 41.19 E-value: 6.48e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  766 VGPGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEENECSLVVLSAGSQDGGVYTCTARNLAGE 835
Cdd:cd05747    15 VSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEGK 84

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271057 [Multi-domain] Cd Length: 253 Bit Score: 44.00 E-value: 6.61e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2232 GRFGVVRSCRENATGRTFVAKIVPYAAEgKRRVLQEYEVLRTLHHERLMSLHEAYITPRYLVLIAE--SCGNRELLcgLS 2309
Cdd:cd14155     4 GFFSEVYKVRHRTSGQVMALKMNTLSSN-RANMLREVQLMNRLSHPNILRFMGVCVHQGQLHALTEyiNGGNLEQL--LD 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2310 DRFRYSEDDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLAAD-NALKIV--DFGSAQ--PYNPQALKPLGhRTGTLEF 2384
Cdd:cd14155    81 SNEPLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIKRDeNGYTAVvgDFGLAEkiPDYSDGKEKLA-VVGSPYW 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2385 MAPEMVRGDPIGSATDIWGAGvltyIMLSGYSPFYEPDPQ---ETEAriVGGRFDAFQ-LYPNTSQSatlFLRKVLS--- 2457
Cdd:cd14155   160 MAPEVLRGEPYNEKADVFSYG----IILCEIIARIQADPDylpRTED--FGLDYDAFQhMVGDCPPD---FLQLAFNccn 230

                         250
                  ....*....|.
gi 564369110 2458 VHPWSRPSLQD 2468
Cdd:cd14155   231 MDPKSRPSFHD 241

Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB3 binds and regulates ATF4, p65/RelA, and PKB (or Akt). It negatively regulates ATF4-mediated gene expression including that of CHOP (C/EBP homologous protein) and HO-1, which are both involved in modulating apoptosis. It also inhibits insulin-mediated phosphorylation of PKB and is a possible determinant of insulin resistance and related disorders. In osteoarthritic chondrocytes where it inhibits insulin-like growth factor 1-mediated cell survival, TRB3 is overexpressed, resulting in increased cell death. TRB3 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB3 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270926 [Multi-domain] Cd Length: 242 Bit Score: 43.71 E-value: 6.90e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRI-------CDFGNAqeltPGEPQYCQFGTPEFVA 1035
Cdd:cd14024    83 EDEARGLFTQMARAVAHCHQHGVILRDLKLRRFVFTD----ELRTKLvlvnledSCPLNG----DDDSLTDKHGCPAYVG 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1036 PEIVN--QSPVSGVTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETtflsLSREARGfLIKVLVQ----D 1109
Cdd:cd14024   155 PEILSsrRSYSGKAADVWSLGVCLYTMLLGRYPFQDTEPAALFAKIRRGAFSLPAW----LSPGARC-LVSCMLRrspaE 229

                         170
                  ....*....|....
gi 564369110 1110 RLrpTAEETLEHPW 1123
Cdd:cd14024   230 RL--KASEILLHPW 241

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271113 [Multi-domain] Cd Length: 329 Bit Score: 44.36 E-value: 7.03e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2223 YTFLEEKARGRFGVVRSCRENATGRTFVAKIVPYAAEGKRRVLQEYEVLRTLHHERLMSLH-----EAYITPRYLVLIAE 2297
Cdd:cd14211     1 YEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILSRLSQENADEFNfvrayECFQHKNHTCLVFE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2298 ScgnreLLCGLSDRFRYSE------DDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLaADNA-----LKIVDFGSAQP 2366
Cdd:cd14211    81 M-----LEQNLYDFLKQNKfsplplKYIRPILQQVLTALLKLKSLGLIHADLKPENIML-VDPVrqpyrVKVIDFGSASH 154

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 564369110 2367 YNPQALKP-LGHRTgtleFMAPEMVRGDPIGSATDIWGAG 2405
Cdd:cd14211   155 VSKAVCSTyLQSRY----YRAPEIILGLPFCEAIDMWSLG 190

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 40.95 E-value: 7.12e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564369110  463 PLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDRRMtqYRDIHR-LVFPAVGPQHAGVYKSVIANKLGKAA 540
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYI--VRENGTtLTIRNIRRSDMGIYLCIASNGVPGSV 84

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 40.61 E-value: 8.04e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110    3 VAPGADVLLKCIITANPPPQVSWKKDgsvLHSEGRLLIRAEGERHT--------LLLREAQAADAGSYTATATNELG 71
Cdd:cd05765    12 VKVGETASFHCDVTGRPQPEITWEKQ---VPGKENLIMRPNHVRGNvvvtnigqLVIYNAQPQDAGLYTCTARNSGG 85

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 40.65 E-value: 8.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  470 GLAKEAMLECQVTGLPYPTISWFHNGHRIQSSDDrrmTQYRDIHR--LVFPAVGPQHAGVYKSVIANKLGKAACYAHLYV 547
Cdd:cd05867    12 GPGETARLDCQVEGIPTPNITWSINGAPIEGTDP---DPRRHVSSgaLILTDVQPSDTAVYQCEARNRHGNLLANAHVHV 88

Catalytic domain of the Serine/Threonine kinases, Spindle assembly checkpoint proteins Bub1 and BubR1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Bub1 (Budding uninhibited by benzimidazoles 1), BubR1, and similar proteins. They contain an N-terminal Bub1/Mad3 homology domain essential for Cdc20 binding and a C-terminal kinase domain. Bub1 and BubR1 are involved in SAC, a surveillance system that delays metaphase to anaphase transition by blocking the activity of APC/C (the anaphase promoting complex) until all chromosomes achieve proper attachments to the mitotic spindle, to avoid chromosome missegregation. Impaired SAC leads to genomic instabilities and tumor development. Bub1 and BubR1 facilitate the localization of SAC proteins to kinetochores and regulate kinetochore-microtubule (K-MT) attachments. Repression studies of Bub1 and BubR1 show that they exert an additive effect in misalignment phenotypes and may function cooperatively or in parallel pathways in regulating K-MT attachments. The Bub1/BubR1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270883 [Multi-domain] Cd Length: 298 Bit Score: 43.88 E-value: 8.92e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  871 YDIHQEIGRGAFSYLRRVVERSSGLE---FAAKF----------IPSQAkpkasarrEARL-LARLQHDCVLYfHEAFER 936
Cdd:cd13981     2 YVISKELGEGGYASVYLAKDDDEQSDgslVALKVekppsiwefyICDQL--------HSRLkNSRLRESISGA-HSAHLF 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  937 RRGLVIVTELCTE-ELLErmarkpTVCESETRTYMR-----------QVLEGIGYLHQSHVLHLDVKPENLLV------- 997
Cdd:cd13981    73 QDESILVMDYSSQgTLLD------VVNKMKNKTGGGmdeplamfftiELLKVVEALHEVGIIHGDIKPDNFLLrleicad 146

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110  998 --WDGAGGEE--QVRICDFGNAQELTPgEPQYCQF----GTPEFVAPEIVNQSPVSGVTDIWPVGVVAFLCLTG 1063
Cdd:cd13981   147 wpGEGENGWLskGLKLIDFGRSIDMSL-FPKNQSFkadwHTDSFDCIEMREGRPWTYQIDYFGIAATIHVMLFG 219

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 40.65 E-value: 9.16e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110  767 GPGETARFAVVVEGKPLPDIMWYKDEVLLAESNhVSFVYEENECSLVVLSAGSQDGGVYTCTARNLAGEVSCKAELSV 844
Cdd:cd05867    12 GPGETARLDCQVEGIPTPNITWSINGAPIEGTD-PDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNLLANAHVHV 88

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 40.65 E-value: 9.28e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  755 PRFESIMEdvevgpGETARFAVVVEGKPLPDIMWYKDEVLLAESNHVSFVYEE-NECSLVVLSAGSQDGGVYTCTARNLA 833
Cdd:cd05737     8 PDVVTIME------GKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAgRTVYFTINGVSSEDSGKYGLVVKNKY 81

                          90
                  ....*....|.
gi 564369110  834 GEVSCKAELSV 844
Cdd:cd05737    82 GSETSDVTVSV 92

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270680 [Multi-domain] Cd Length: 336 Bit Score: 43.81 E-value: 9.61e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  969 YMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELTPgEPQYCQFGTP----EFVAPEIVNQSPV 1044
Cdd:cd05102   177 YSFQVARGMEFLASRKCIHRDLAARNILLSE----NNVVKICDFGLARDIYK-DPDYVRKGSArlplKWMAPESIFDKVY 251

                          90       100
                  ....*....|....*....|....*.
gi 564369110 1045 SGVTDIWPVGVVAFLCLT-GISPFVG 1069
Cdd:cd05102   252 TTQSDVWSFGVLLWEIFSlGASPYPG 277

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 40.47 E-value: 1.01e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1849 PVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMKD-KQSLRSEPSVVIVSCKDGRQLLSIPRASKRHAGLYECSATNV 1927
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDgKQISPKSDHYTIQRDLDGTCSLHTTASTLDDDGNYTIMAANP 80


                  ....*....
gi 564369110 1928 LGSItsSCT 1936
Cdd:cd05893    81 QGRI--SCT 87

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143379 [Multi-domain] Cd Length: 355 Bit Score: 43.92 E-value: 1.01e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  888 VVERSSGLEFAAKFIPSQAKPKaSARREARLLARLQHDCVLYFHEAF------ERRRGLVIVTELCTEELLERMARKptv 961
Cdd:cd07874    40 VLDRNVAIKKLSRPFQNQTHAK-RAYRELVLMKCVNHKNIISLLNVFtpqkslEEFQDVYLVMELMDANLCQVIQME--- 115

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  962 CESETRTYM-RQVLEGIGYLHQSHVLHLDVKPENLLVwdgaGGEEQVRICDFGNAQELTPGEPQYCQFGTPEFVAPEIVN 1040
Cdd:cd07874   116 LDHERMSYLlYQMLCGIKHLHSAGIIHRDLKPSNIVV----KSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVIL 191

                         170
                  ....*....|....*.
gi 564369110 1041 QSPVSGVTDIWPVGVV 1056
Cdd:cd07874   192 GMGYKENVDIWSVGCI 207

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 44.93 E-value: 1.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1923 SATNVLGSITSSCTVAVARTPGKLAPPEVPQTYCDTALVLwKPGDSRAPCTYTLERRVDGESvwHPVSSGIPDCYYNVTQ 2002
Cdd:PHA03247 2746 AGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTR-PAVASLSESRESLPSPWDPAD--PPAAVLAPAAALPPAA 2822

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2003 LPVGVtvrfrVACSNRAGQGPFSNPSEkvfirgtqdsPAQSAAAPRDAPVTSGPTRAPPPDSPTSLVPTPPLAPQVSQAS 2082
Cdd:PHA03247 2823 SPAGP-----LPPPTSAQPTAPPPPPG----------PPPPSLPLGGSVAPGGDVRRRPPSRSPAAKPAAPARPPVRRLA 2887

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2083 TLSPSTSSMSANQALSSLKAVgPPPATPPRKHRGLLATQQAEPSPPsiLVTPSEHKSFVPDTGTLTPTSSPQGVKPAPSS 2162
Cdd:PHA03247 2888 RPAVSRSTESFALPPDQPERP-PQPQAPPPPQPQPQPPPPPQPQPP--PPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWL 2964


                  ...
gi 564369110 2163 SSL 2165
Cdd:PHA03247 2965 GAL 2967

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 40.27 E-value: 1.06e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  149 SVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEARLE 228
Cdd:cd05737    12 TIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNKYGSETSDVTVS 91


                  .
gi 564369110  229 V 229
Cdd:cd05737    92 V 92

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 40.23 E-value: 1.35e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  342 DVEVLEGRAARLDCKISGTPPPSVTWTHFGHPVN-ESENLRLRQ----DGGLHSLHI--ARVGSEDEGLYEVSATNTHGQ 414
Cdd:cd07693     9 DLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLEtDKDDPRSHRivlpSGSLFFLRVvhGRKGRSDEGVYVCVAHNSLGE 88


                  .
gi 564369110  415 A 415
Cdd:cd07693    89 A 89

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK1 plays a role in neuronal differentiation. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271115 [Multi-domain] Cd Length: 330 Bit Score: 43.30 E-value: 1.36e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2317 DDVATYVVQLLQGLDYLHGRHVLHLDIKPDNLLLA-------------------ADNALKIVDFGSAQpYNPQALKPLgh 2377
Cdd:cd14213   116 DHIRNMAYQICKSVNFLHHNKLTHTDLKPENILFVqsdyvvkynpkmkrdertlKNPDIKVVDFGSAT-YDDEHHSTL-- 192

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110 2378 rTGTLEFMAPEMVRGDPIGSATDIWGAGVLTYIMLSGYSPFYEPDPQETEA---RIVG 2432
Cdd:cd14213   193 -VSTRHYRAPEVILALGWSQPCDVWSIGCILIEYYLGFTVFQTHDSKEHLAmmeRILG 249

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 39.70 E-value: 1.78e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564369110    6 GADVLLKCIITANPPPQVSWKKDGSVL--HSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQASCASSLAV 81
Cdd:cd05893    15 GMPVTFTCRVAGNPKPKIYWFKDGKQIspKSDHYTIQRDLDGTCSLHTTASTLDDDGNYTIMAANPQGRISCTGRLMV 92

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 39.62 E-value: 2.08e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110 1862 EGEAATLLCLPAACPTPRISWMKDKQSLRSepsvvivSCKDGRQL------LSIPRASKRHAGLYECSATNVLG 1929
Cdd:cd20949    13 EGQSATILCEVKGEPQPNVTWHFNGQPISA-------SVADMSKYriladgLLINKVTQDDTGEYTCRAYQVNS 79

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 39.76 E-value: 2.12e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  754 APRFESIMEDVEVGPGETARFAVVVEGKPLPDIMWYKDEVLLA-ESNHVSFVYEENECSLVVLSAG-SQDGGVYTCTARN 831
Cdd:cd20971     1 APHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIaDGLKYRIQEFKGGYHQLIIASVtDDDATVYQVRATN 80


                  ....*....
gi 564369110  832 LAGEVSCKA 840
Cdd:cd20971    81 QGGSVSGTA 89

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1 gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. CK1gamma proteins are unique within the CK1 subfamily in that they are palmitoylated at the C-termini and are anchored to the plasma membrane. CK1gamma is involved in transducing the signaling of LDL-receptor-related protein 6 (LRP6) through direct phosphorylation following Wnt stimulation, resulting in the recruitment of the scaffold protein Axin. In Xenopus embryos, CK1gamma is required during anterio-posterior patterning. In higher vertebrates, three CK1gamma (gamma1-3) isoforms exist. In mammalian cells, CK1gamma2 has been implicated in regulating the synthesis of sphingomyelin, a phospholipid that is found in the outer leaflet of the plasma membrane, by hyperphosphorylating and inactivating the ceramide transfer protein CERT. CK1gamma2 also phosphorylates the transcription factor Smad-3 resulting in its ubiquitination and degradation. It inhibits Smad-3 mediated responses of Transforming Growth Factor-beta (TGF-beta) including cell growth arrest. The CK1 gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271028 [Multi-domain] Cd Length: 288 Bit Score: 42.80 E-value: 2.15e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 564369110  972 QVLEGIGYLHQSHVLHLDVKPENLLVW-DGAGGEEQVRICDFGNAQE 1017
Cdd:cd14126   104 QLISRIEYVHSKHLIYRDVKPENFLIGrQSTKKQHVIHIIDFGLAKE 150

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 39.10 E-value: 2.32e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110    8 DVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRAEgerHTLLLREAQAADAGSYTATATNELGQASCASSLAV 81
Cdd:cd05723    14 DIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKE---HNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 39.38 E-value: 2.71e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110    3 VAPGADVLLKCIITANPPPQVSWKKDGS-VLHSEGRLLIRAEGERHTLLLREAQAADAGSYTATATNELGQASCASSLAV 81
Cdd:cd20975    12 VREGQDVIMSIRVQGEPKPVVSWLRNRQpVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEARLEV 91

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133187 [Multi-domain] Cd Length: 270 Bit Score: 42.02 E-value: 2.77e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  942 IVTELCTE-ELLERMARKPTVCESETRT-YMRQVLEGIGYLHQSHVLHLDVKPENLLVWDgaggEEQVRICDFGNAQELT 1019
Cdd:cd05056    83 IVMELAPLgELRSYLQVNKYSLDLASLIlYAYQLSTALAYLESKRFVHRDIAARNVLVSS----PDCVKLGDFGLSRYME 158

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 564369110 1020 pgEPQYCQFGT---P-EFVAPEIVNQSPVSGVTDIWPVGVVAFLCLT-GISPFVGENDRTTLMNIRN 1081
Cdd:cd05056   159 --DESYYKASKgklPiKWMAPESINFRRFTSASDVWMFGVCMWEILMlGVKPFQGVKNNDVIGRIEN 223

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 39.05 E-value: 2.98e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564369110    6 GADVLLKCIITANPPPQVSWKKDGSVLHSEGRLLIRaegERHTLLLREAQAADAGSYTATATNELGQASCASSL 79
Cdd:cd20957    16 GRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQIL---SEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

Catalytic domain of the Serine/Threonine kinase, SINK-homologous inhibitory kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SHIK, also referred to as STK40 or LYK4, is a cytoplasmic and nuclear protein that is involved in the negative regulation of NF-kappaB- and p53-mediated transcription. It was identified as a protein related to SINK, a p65-interacting protein that inhibits p65 phosphorylation by the catalytic subunit of PKA, thereby inhibiting transcriptional competence of NF-kappaB. The SHIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270876 [Multi-domain] Cd Length: 290 Bit Score: 42.01 E-value: 3.18e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  963 ESETRTYMRQVLEGIGYLHQSHVLHLDVKPENLLVwdgAGGEEQVRICDFGNAQEL-TPGEPQYCQFGTPEFVAPEIVNQ 1041
Cdd:cd13974   131 EREALVIFYDVVRVVEALHKKNIVHRDLKLGNMVL---NKRTRKITITNFCLGKHLvSEDDLLKDQRGSPAYISPDVLSG 207

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1042 SPVSG-VTDIWPVGVVAFLCLTGISPFVGENDRTTLMNIRNYNVAFEETTFLSlsrEARGFLI-KVLVQDRL-RPTAEET 1118
Cdd:cd13974   208 KPYLGkPSDMWALGVVLFTMLYGQFPFYDSIPQELFRKIKAAEYTIPEDGRVS---ENTVCLIrKLLVLNPQkRLTASEV 284


                  ...
gi 564369110 1119 LEH 1121
Cdd:cd13974   285 LDS 287

large tegument protein UL36; Provisional

Pssm-ID: 223021 [Multi-domain] Cd Length: 3151 Bit Score: 43.00 E-value: 3.61e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2040 PAQSAAAPRDAPVTS-------GPTRAPPPDSPTSLVPTPPLAPQVSQASTLSPSTSSMSANQALSSLKAVGPPPATPPr 2112
Cdd:PHA03247 2683 PRRRAARPTVGSLTSladppppPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPP- 2761

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 2113 khrglLATQQAEPSPPSILVTPSEHKSFVPDTGTLTPTSSPQGVKPAPSSSSLYMVTSFVSAPPDPQPPApeppPEPTKV 2192
Cdd:PHA03247 2762 -----TTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAG----PLPPPT 2832

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564369110 2193 TVRSLSPAKEvvSSPTPESTTL-----------RQGPPQKPYTFLEEKARGR 2233
Cdd:PHA03247 2833 SAQPTAPPPP--PGPPPPSLPLggsvapggdvrRRPPSRSPAAKPAAPARPP 2882

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 38.53 E-value: 3.91e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  243 PLQDVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPALLKCKMHfDGRkckLLLTSVHEDDSGVYTCK 312
Cdd:cd20978     7 PEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE-DGT---LTIINVQPEDTGYYGCV 72

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 38.54 E-value: 4.18e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564369110  466 DLEVGLAKEAMLECQV-TGLPYPTISWFHNGHRIQSSDDRRMTqyRDIHRLVFPAVGPQHAGVYKSVIANKLG 537
Cdd:cd05724     6 DTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRI--VDDGNLLIAEARKSDEGTYKCVATNMVG 76

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 38.49 E-value: 4.93e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  243 PLQDVDVGAGEMALFECLVAGPADVEVDWLCRGRLLQPALL-KCKMHFDGRKCKLLLTSVHEDDSGVYTCKLSTVKDELT 321
Cdd:cd20974     6 PLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLpGVQISFSDGRAKLSIPAVTKANSGRYSLTATNGSGQAT 85


                  ....*..
gi 564369110  322 CSARLTV 328
Cdd:cd20974    86 STAELLV 92

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 38.34 E-value: 5.28e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1860 LLEGEAATLLCLPAACPTPRISWMKDKQSLrSEPSVVIVSCKDGRQL-LSIPRASKRHAGLYECSATNVLGSITSSCTVA 1938
Cdd:cd05737    13 IMEGKTLNLTCNVWGDPPPEVSWLKNDQAL-AFLDHCNLKVEAGRTVyFTINGVSSEDSGKYGLVVKNKYGSETSDVTVS 91


                  .
gi 564369110 1939 V 1939
Cdd:cd05737    92 V 92

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 38.45 E-value: 5.95e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564369110    3 VAPGADVLLKCIITANPPPQVSWKKD-GSV------LHSEGRLLIRAEGerhTLLLREAQAADAGSYTATATNELG 71
Cdd:cd20954    13 VAAGQDVMLHCQADGFPTPTVTWKKAtGSTpgeykdLLYDPNVRILPNG---TLVFGHVQKENEGHYLCEAKNGIG 85

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 37.76 E-value: 7.64e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110  461 LRPLQDLEVGLAKEAMLECQVTGLPYPTISWFHNGHRIQssddRRMTQYRDIHRLVFPAVGPQHAGVYKSVIANKLGKAA 540
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELP----KGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIE 76


                  ....*..
gi 564369110  541 CYAHLYV 547
Cdd:cd05725    77 ASATLTV 83

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 37.91 E-value: 8.52e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1849 PVFHIKLKDQVLLEGEAATLLCLPAACPTPRISWMK---DKQSLRSEPSVV---IVSCKDGRqlLSIPRASKRHAGLYEC 1922
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKqvpGKENLIMRPNHVrgnVVVTNIGQ--LVIYNAQPQDAGLYTC 78


                  ....*....
gi 564369110 1923 SATNVLGSI 1931
Cdd:cd05765    79 TARNSGGLL 87

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 37.37 E-value: 8.76e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564369110 1856 KDQVLLEGEAATLLCLPAACPTPRISWMKDKQSLrsepsvvivscKDGR------QLLSIPRASKRHAGLYECSATNVLG 1929
Cdd:cd05725     5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-----------PKGRyeilddHSLKIRKVTAGDMGSYTCVAENMVG 73

                          90
                  ....*....|
gi 564369110 1930 SITSSCTVAV 1939
Cdd:cd05725    74 KIEASATLTV 83