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Conserved domains on  [gi|392922083|ref|NP_506728|]
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Protein kinase domain-containing protein [Caenorhabditis elegans]

Protein Classification

protein kinase family protein( domain architecture ID 229378)

protein kinase family protein may catalyze the transfer of the gamma-phosphoryl group from ATP to substrates such as serine/threonine and/or tyrosine residues on proteins, or may be a pseudokinase

CATH:  1.10.510.10
PubMed:  16244704
SCOP:  4003661

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
138-427 8.07e-59

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member smart00221:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 258  Bit Score: 193.92  E-value: 8.07e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   138 IIEEKEIEH-YYSRIRLGKMKSMGAHKNSPTLsIKCALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLI 216
Cdd:smart00221   1 LTLGKKLGEgAFGEVYKGTLKGKGDGKEVEVA-VKTLKEDASEQQIEEFLREARIMRKLD-HPNIVKLLGVCTEEEPLMI 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   217 VSEHAEHGRLDQFLIDRKLNFnnqltcsdgsnqkvynfnngeqerisddmqaLCTLDLLSYGYQIAIAMKFLADSRCLHR 296
Cdd:smart00221  79 VMEYMPGGDLLDYLRKNRPKE-------------------------------LSLSDLLSFALQIARGMEYLESKNFIHR 127
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   297 ALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLApeVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPH 376
Cdd:smart00221 128 DLAARNCLVGENLVVKISDFGLSRDLYDDDYYKVKGGKLPIR--WMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPY 205
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 392922083   377 EAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFF 427
Cdd:smart00221 206 PGMSNAEVLEYLKKgyRLPKPPNCPPELYKLMLQCWAEDPEDRPTFSELVEIL 258
 
Name Accession Description Interval E-value
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
138-427 8.07e-59

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: 193.92  E-value: 8.07e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   138 IIEEKEIEH-YYSRIRLGKMKSMGAHKNSPTLsIKCALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLI 216
Cdd:smart00221   1 LTLGKKLGEgAFGEVYKGTLKGKGDGKEVEVA-VKTLKEDASEQQIEEFLREARIMRKLD-HPNIVKLLGVCTEEEPLMI 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   217 VSEHAEHGRLDQFLIDRKLNFnnqltcsdgsnqkvynfnngeqerisddmqaLCTLDLLSYGYQIAIAMKFLADSRCLHR 296
Cdd:smart00221  79 VMEYMPGGDLLDYLRKNRPKE-------------------------------LSLSDLLSFALQIARGMEYLESKNFIHR 127
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   297 ALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLApeVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPH 376
Cdd:smart00221 128 DLAARNCLVGENLVVKISDFGLSRDLYDDDYYKVKGGKLPIR--WMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPY 205
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 392922083   377 EAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFF 427
Cdd:smart00221 206 PGMSNAEVLEYLKKgyRLPKPPNCPPELYKLMLQCWAEDPEDRPTFSELVEIL 258
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
147-428 1.20e-58

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: 193.52  E-value: 1.20e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 147 YYSRIRLGKMKSMGahkNSPTL-SIKCALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGR 225
Cdd:cd00192    7 AFGEVYKGKLKGGD---GKTVDvAVKTLKEDASESERKDFLKEARVMKKLG-HPNVVRLLGVCTEEEPLYLVMEYMEGGD 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 226 LDQFLIDRKLNFNnqltcsdgsnqkvynfnngeqeriSDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFV 305
Cdd:cd00192   83 LLDFLRKSRPVFP------------------------SPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLV 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 306 TRNKTIRIGEFGLARINARKEYYIMKSPQ-LPLApeVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYC 384
Cdd:cd00192  139 GEDLVVKISDFGLSRDIYDDDYYRKKTGGkLPIR--WMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEV 216
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 392922083 385 GQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd00192  217 LEYLRKgyRLPKPENCPDELYELMLSCWQLDPEDRPTFSELVERLE 262
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
170-427 7.94e-47

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: 162.67  E-value: 7.94e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083  170 IKCALLRNDITHQKMIQDELVTLSSLrSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcsdgsnq 249
Cdd:pfam07714  33 VKTLKEGADEEEREDFLEEASIMKKL-DHPNIVKLLGVCTQGEPLYIVTEYMPGGDLLDFLRKHK--------------- 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083  250 kvynfnngeqerisddmQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYI 329
Cdd:pfam07714  97 -----------------RKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDYYR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083  330 MKSpQLPLAPEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLG------VPPHEAVNAVYCGQdierKLPELQYCHPDMY 403
Cdd:pfam07714 160 KRG-GGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGeqpypgMSNEEVLEFLEDGY----RLPQPENCPDELY 234
                         250       260
                  ....*....|....*....|....
gi 392922083  404 SFLSSCWNFDPEARPTYSKCVEFF 427
Cdd:pfam07714 235 DLMKQCWAYDPEDRPTFSELVEDL 258
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
175-429 1.52e-06

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 50.40  E-value: 1.52e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 175 LRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcsdgsnqkvynf 254
Cdd:COG0515   44 LAADPEARERFRREARALARLN-HPNIVRVYDVGEEDGRPYLVMEYVEGESLADLLRRRG-------------------- 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 255 nngeqeRISDDmqalctlDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEyyIMKSPQ 334
Cdd:COG0515  103 ------PLPPA-------EALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGAT--LTQTGT 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 335 LPLAPEVMAPESSEDKKFTEKSEVRSFAVCLtgiFQL--GVPPHEAVNAV-YCGQDIERKLPELQYCHPD----MYSFLS 407
Cdd:COG0515  168 VVGTPGYMAPEQARGEPVDPRSDVYSLGVTL---YELltGRPPFDGDSPAeLLRAHLREPPPPPSELRPDlppaLDAIVL 244
                        250       260
                 ....*....|....*....|..
gi 392922083 408 SCWNFDPEARptYSKCVEFFDD 429
Cdd:COG0515  245 RALAKDPEER--YQSAAELAAA 264
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
279-374 3.02e-05

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 46.16  E-value: 3.02e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLArinarKEYyiMKSPQLPLA------PEVMAPESSEDKKF 352
Cdd:PTZ00267 176 YQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFS-----KQY--SDSVSLDVAssfcgtPYYLAPELWERKRY 248
                         90       100
                 ....*....|....*....|..
gi 392922083 353 TEKSEVRSFAVCLTGIFQLGVP 374
Cdd:PTZ00267 249 SKKADMWSLGVILYELLTLHRP 270
 
Name Accession Description Interval E-value
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
138-427 8.07e-59

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: 193.92  E-value: 8.07e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   138 IIEEKEIEH-YYSRIRLGKMKSMGAHKNSPTLsIKCALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLI 216
Cdd:smart00221   1 LTLGKKLGEgAFGEVYKGTLKGKGDGKEVEVA-VKTLKEDASEQQIEEFLREARIMRKLD-HPNIVKLLGVCTEEEPLMI 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   217 VSEHAEHGRLDQFLIDRKLNFnnqltcsdgsnqkvynfnngeqerisddmqaLCTLDLLSYGYQIAIAMKFLADSRCLHR 296
Cdd:smart00221  79 VMEYMPGGDLLDYLRKNRPKE-------------------------------LSLSDLLSFALQIARGMEYLESKNFIHR 127
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   297 ALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLApeVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPH 376
Cdd:smart00221 128 DLAARNCLVGENLVVKISDFGLSRDLYDDDYYKVKGGKLPIR--WMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPY 205
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 392922083   377 EAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFF 427
Cdd:smart00221 206 PGMSNAEVLEYLKKgyRLPKPPNCPPELYKLMLQCWAEDPEDRPTFSELVEIL 258
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
147-428 1.20e-58

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: 193.52  E-value: 1.20e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 147 YYSRIRLGKMKSMGahkNSPTL-SIKCALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGR 225
Cdd:cd00192    7 AFGEVYKGKLKGGD---GKTVDvAVKTLKEDASESERKDFLKEARVMKKLG-HPNVVRLLGVCTEEEPLYLVMEYMEGGD 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 226 LDQFLIDRKLNFNnqltcsdgsnqkvynfnngeqeriSDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFV 305
Cdd:cd00192   83 LLDFLRKSRPVFP------------------------SPEPSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLV 138
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 306 TRNKTIRIGEFGLARINARKEYYIMKSPQ-LPLApeVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYC 384
Cdd:cd00192  139 GEDLVVKISDFGLSRDIYDDDYYRKKTGGkLPIR--WMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEV 216
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 392922083 385 GQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd00192  217 LEYLRKgyRLPKPENCPDELYELMLSCWQLDPEDRPTFSELVERLE 262
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
138-427 1.48e-57

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 190.82  E-value: 1.48e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   138 IIEEKEIEH-YYSRIRLGKMKsMGAHKNSPTLSIKCALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLI 216
Cdd:smart00219   1 LTLGKKLGEgAFGEVYKGKLK-GKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLD-HPNVVKLLGVCTEEEPLYI 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   217 VSEHAEHGRLDQFLIDRKLNfnnqltcsdgsnqkvynfnngeqerisddmqaLCTLDLLSYGYQIAIAMKFLADSRCLHR 296
Cdd:smart00219  79 VMEYMEGGDLLSYLRKNRPK--------------------------------LSLSDLLSFALQIARGMEYLESKNFIHR 126
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   297 ALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLApeVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPH 376
Cdd:smart00219 127 DLAARNCLVGENLVVKISDFGLSRDLYDDDYYRKRGGKLPIR--WMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPY 204
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 392922083   377 EAVNAVYCGQDIERK--LPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFF 427
Cdd:smart00219 205 PGMSNEEVLEYLKNGyrLPQPPNCPPELYDLMLQCWAEDPEDRPTFSELVEIL 257
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
170-427 7.94e-47

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: 162.67  E-value: 7.94e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083  170 IKCALLRNDITHQKMIQDELVTLSSLrSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcsdgsnq 249
Cdd:pfam07714  33 VKTLKEGADEEEREDFLEEASIMKKL-DHPNIVKLLGVCTQGEPLYIVTEYMPGGDLLDFLRKHK--------------- 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083  250 kvynfnngeqerisddmQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYI 329
Cdd:pfam07714  97 -----------------RKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDYYR 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083  330 MKSpQLPLAPEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLG------VPPHEAVNAVYCGQdierKLPELQYCHPDMY 403
Cdd:pfam07714 160 KRG-GGKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGeqpypgMSNEEVLEFLEDGY----RLPQPENCPDELY 234
                         250       260
                  ....*....|....*....|....
gi 392922083  404 SFLSSCWNFDPEARPTYSKCVEFF 427
Cdd:pfam07714 235 DLMKQCWAYDPEDRPTFSELVEDL 258
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
150-429 3.93e-39

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: 143.40  E-value: 3.93e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 150 RIRLGKMKSMGAH-----------KNSPTL-SIKCALLRNDITH--QKMIQDELVTLSSLRSHSCILALVGYVREPNM-L 214
Cdd:cd05054    8 RLKLGKPLGRGAFgkviqasafgiDKSATCrTVAVKMLKEGATAseHKALMTELKILIHIGHHLNVVNLLGACTKPGGpL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 215 LIVSEHAEHGRLDQFLIDRKLNFNNQLTCSDGSNQkvynfnngEQERISDDMQALCTL-DLLSYGYQIAIAMKFLADSRC 293
Cdd:cd05054   88 MVIVEFCKFGNLSNYLRSKREEFVPYRDKGARDVE--------EEEDDDELYKEPLTLeDLICYSFQVARGMEFLASRKC 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 294 LHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLG 372
Cdd:cd05054  160 IHRDLAARNILLSENNVVKICDFGLARdIYKDPDYVRKGDARLPL--KWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLG 237
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392922083 373 VPPHEAVNAvycGQDIERKLPE------LQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFDD 429
Cdd:cd05054  238 ASPYPGVQM---DEEFCRRLKEgtrmraPEYTTPEIYQIMLDCWHGEPKERPTFSELVEKLGD 297
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
150-434 7.71e-39

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: 143.58  E-value: 7.71e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 150 RIRLGKMKSMGA------------HKNSPTLSIKCALLRNDIT--HQKMIQDELVTLSSLRSHSCILALVGYVREPN-ML 214
Cdd:cd05102    8 RLRLGKVLGHGAfgkvveasafgiDKSSSCETVAVKMLKEGATasEHKALMSELKILIHIGNHLNVVNLLGACTKPNgPL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 215 LIVSEHAEHGRLDQFLIDRKLNFnnqLTCSD-----------------------GSNQKVYNFNNGEQERISDDMQA--- 268
Cdd:cd05102   88 MVIVEFCKYGNLSNFLRAKREGF---SPYRErsprtrsqvrsmveavradrrsrQGSDRVASFTESTSSTNQPRQEVddl 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 269 ----LCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMK-SPQLPLapEVMA 343
Cdd:cd05102  165 wqspLTMEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKgSARLPL--KWMA 242
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 344 PESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAV--NAVYCG--QDIER-KLPElqYCHPDMYSFLSSCWNFDPEARP 418
Cdd:cd05102  243 PESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVqiNEEFCQrlKDGTRmRAPE--YATPEIYRIMLSCWHGDPKERP 320
                        330
                 ....*....|....*.
gi 392922083 419 TYSKCVEFFDDHFSEN 434
Cdd:cd05102  321 TFSDLVEILGDLLQEN 336
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
124-428 1.27e-34

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They 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, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. 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. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR 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: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 131.00  E-value: 1.27e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 124 VQLDPSLKINLSYLIIEEKEIEHYYSRIRLGKMKSM-GAHKNSPTLSIKcaLLRNDITHQKMIQ--DELVTLSSLRSHSC 200
Cdd:cd05053    1 LPLDPEWELPRDRLTLGKPLGEGAFGQVVKAEAVGLdNKPNEVVTVAVK--MLKDDATEKDLSDlvSEMEMMKMIGKHKN 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 201 ILALVGYVREPNMLLIVSEHAEHGRLDQFLIDR-----KLNFNNQLTCSDGSNQKvynfnngeqerisddmqalctlDLL 275
Cdd:cd05053   79 IINLLGACTQDGPLYVVVEYASKGNLREFLRARrppgeEASPDDPRVPEEQLTQK----------------------DLV 136
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 276 SYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYiMKSPQLPLAPEVMAPESSEDKKFTEK 355
Cdd:cd05053  137 SFAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYY-RKTTNGRLPVKWMAPEALFDRVYTHQ 215
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392922083 356 SEVRSFAVCLTGIFQLG------VPPHEAVNAVYCGQDIERKlpelQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05053  216 SDVWSFGVLLWEIFTLGgspypgIPVEELFKLLKEGHRMEKP----QNCTQELYMLMRDCWHEVPSQRPTFKQLVEDLD 290
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
150-434 2.72e-34

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: 131.26  E-value: 2.72e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 150 RIRLGKMKSMGA------------HKNSPTLSIKCALLRNDITH--QKMIQDELVTLSSLRSHSCILALVGYVREPN-ML 214
Cdd:cd05103    8 RLKLGKPLGRGAfgqvieadafgiDKTATCRTVAVKMLKEGATHseHRALMSELKILIHIGHHLNVVNLLGACTKPGgPL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 215 LIVSEHAEHGRLDQFLIDRKLNF--------------------------------NNQLTCSDGSNQKVYNFNNGEQERI 262
Cdd:cd05103   88 MVIVEFCKFGNLSAYLRSKRSEFvpyktkgarfrqgkdyvgdisvdlkrrldsitSSQSSASSGFVEEKSLSDVEEEEAG 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 263 SDDM--QALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMK-SPQLPLap 339
Cdd:cd05103  168 QEDLykDFLTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKgDARLPL-- 245
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 340 EVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNavyCGQDIERKLPE------LQYCHPDMYSFLSSCWNFD 413
Cdd:cd05103  246 KWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVK---IDEEFCRRLKEgtrmraPDYTTPEMYQTMLDCWHGE 322
                        330       340
                 ....*....|....*....|.
gi 392922083 414 PEARPTYSKCVEFFDDHFSEN 434
Cdd:cd05103  323 PSQRPTFSELVEHLGNLLQAN 343
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
150-429 3.00e-32

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: 125.50  E-value: 3.00e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 150 RIRLGKMKSMGAH-----------KNSPTLSI-KCALLRNDIT--HQKMIQDELVTLSSLRSHSCILALVGY-VREPNML 214
Cdd:cd14207    8 RLKLGKSLGRGAFgkvvqasafgiKKSPTCRVvAVKMLKEGATasEYKALMTELKILIHIGHHLNVVNLLGAcTKSGGPL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 215 LIVSEHAEHGRLDQFLID-RKLNFNNQLTC--------------SDGSNQKVYNFNNGE------------------QER 261
Cdd:cd14207   88 MVIVEYCKYGNLSNYLKSkRDFFVTNKDTSlqeelikekkeaepTGGKKKRLESVTSSEsfassgfqedkslsdveeEEE 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 262 ISDDM--QALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMK-SPQLPLa 338
Cdd:cd14207  168 DSGDFykRPLTMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIYKNPDYVRKgDARLPL- 246
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 339 pEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAV--NAVYCG---QDIERKLPElqYCHPDMYSFLSSCWNFD 413
Cdd:cd14207  247 -KWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVqiDEDFCSklkEGIRMRAPE--FATSEIYQIMLDCWQGD 323
                        330
                 ....*....|....*.
gi 392922083 414 PEARPTYSKCVEFFDD 429
Cdd:cd14207  324 PNERPRFSELVERLGD 339
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
159-422 2.00e-31

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R 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: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 124.19  E-value: 2.00e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 159 MGAHKNSPTLSIKCALLRNDITHQKMIQDELVTLSSLRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFN 238
Cdd:cd05106   62 LGKEDNVLRVAVKMLKASAHTDEREALMSELKILSHLGQHKNIVNLLGACTHGGPVLVITEYCCYGDLLNFLRKKAETFL 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 239 NQL-------------------------------TCSDG------SNQKVYNFNNGEQERISDDMQALCTLDLLSYGYQI 281
Cdd:cd05106  142 NFVmalpeisetssdyknitlekkyirsdsgfssQGSDTyvemrpVSSSSSQSSDSKDEEDTEDSWPLDLDDLLRFSSQV 221
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 282 AIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKSEVRS 360
Cdd:cd05106  222 AQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLARdIMNDSNYVVKGNARLPV--KWMAPESIFDCVYTVQSDVWS 299
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392922083 361 FAVCLTGIFQLGVPPHEAV-------NAVYCGQDIERklPElqYCHPDMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd05106  300 YGILLWEIFSLGKSPYPGIlvnskfyKMVKRGYQMSR--PD--FAPPEIYSIMKMCWNLEPTERPTFSQ 364
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
123-428 5.10e-31

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: 121.27  E-value: 5.10e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 123 EVQLDPSLKINLSYLIIEEKEIEHYYSRIRLGKmkSMGAHKNSPTLSIKCA--LLRNDITHQKM--IQDELVTLSSLRSH 198
Cdd:cd05098    1 ELPEDPRWELPRDRLVLGKPLGEGCFGQVVLAE--AIGLDKDKPNRVTKVAvkMLKSDATEKDLsdLISEMEMMKMIGKH 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 199 SCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcsDGSNQKVYNFNNGEQERISddmqalcTLDLLSYG 278
Cdd:cd05098   79 KNIINLLGACTQDGPLYVIVEYASKGNLREYLQARR----------PPGMEYCYNPSHNPEEQLS-------SKDLVSCA 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYiMKSPQLPLAPEVMAPESSEDKKFTEKSEV 358
Cdd:cd05098  142 YQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYY-KKTTNGRLPVKWMAPEALFDRIYTHQSDV 220
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392922083 359 RSFAVCLTGIFQL------GVPPHEAVNAVYCGQDIERKlpelQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05098  221 WSFGVLLWEIFTLggspypGVPVEELFKLLKEGHRMDKP----SNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLD 292
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
160-429 1.23e-30

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR 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: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 120.28  E-value: 1.23e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 160 GAHKNSPTLSIKCALLRN--DITHQKMIQDELVTLSSLRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNF 237
Cdd:cd05055   58 GLSKSDAVMKVAVKMLKPtaHSSEREALMSELKIMSHLGNHENIVNLLGACTIGGPILVITEYCCYGDLLNFLRRKRESF 137
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 238 nnqltcsdgsnqkvynfnngeqerisddmqaLCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFG 317
Cdd:cd05055  138 -------------------------------LTLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLTHGKIVKICDFG 186
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 318 LARINARKEYYIMK-SPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEA--VNAVYCgQDIER--KL 392
Cdd:cd05055  187 LARDIMNDSNYVVKgNARLPV--KWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGmpVDSKFY-KLIKEgyRM 263
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 392922083 393 PELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFDD 429
Cdd:cd05055  264 AQPEHAPAEIYDIMKTCWDADPLKRPTFKQIVQLIGK 300
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
119-428 1.59e-30

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: 120.12  E-value: 1.59e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 119 ISNNEVQLDPSLKINLSYLIIEEKEIEHYYSRIRLGKmkSMGAHKNSPTLSIKCA--LLRNDITHQKM--IQDELVTLSS 194
Cdd:cd05101    8 VSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAE--AVGIDKDKPKEAVTVAvkMLKDDATEKDLsdLVSEMEMMKM 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 195 LRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcsdgSNQKVYNFnngEQERISDdmQALCTLDL 274
Cdd:cd05101   86 IGKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLRARR------------PPGMEYSY---DINRVPE--EQMTFKDL 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 275 LSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYiMKSPQLPLAPEVMAPESSEDKKFTE 354
Cdd:cd05101  149 VSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYY-KKTTNGRLPVKWMAPEALFDRVYTH 227
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392922083 355 KSEVRSFAVCLTGIFQLGVPPHEA--VNAVYCGQDIERKLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05101  228 QSDVWSFGVLMWEIFTLGGSPYPGipVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLD 303
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
170-429 1.84e-30

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: 118.60  E-value: 1.84e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 170 IKCalLRNDITHQKMIQDELV----TLSSLRsHSCILALVGYVREPNMLLiVSEHAEHGRLdqflidrklnfnnqltcsd 245
Cdd:cd05040   28 VKC--LKSDVLSQPNAMDDFLkevnAMHSLD-HPNLIRLYGVVLSSPLMM-VTELAPLGSL------------------- 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 246 gsnqkvynfnngeQERISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-INAR 324
Cdd:cd05040   85 -------------LDRLRKDQGHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRaLPQN 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 325 KEYYIMkSPQLPLAPEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIERK---LPELQYCHPD 401
Cdd:cd05040  152 EDHYVM-QEHRKVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQILEKIDKEgerLERPDDCPQD 230
                        250       260
                 ....*....|....*....|....*...
gi 392922083 402 MYSFLSSCWNFDPEARPTYSKCVEFFDD 429
Cdd:cd05040  231 IYNVMLQCWAHKPADRPTFVALRDFLPE 258
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
273-424 2.64e-30

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron 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: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 118.35  E-value: 2.64e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 273 DLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYY-IMKSPQLPLAPEVMAPESSEDKK 351
Cdd:cd05058   99 DLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLARDIYDKEYYsVHNHTGAKLPVKWMALESLQTQK 178
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 352 FTEKSEVRSFAVCLTGIFQLGVPPHEAVNA----VYCGQDieRKLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCV 424
Cdd:cd05058  179 FTTKSDVWSFGVLLWELMTRGAPPYPDVDSfditVYLLQG--RRLLQPEYCPDPLYEVMLSCWHPKPEMRPTFSELV 253
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
182-429 6.13e-30

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: 117.52  E-value: 6.13e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 182 QKMIQdELVTLSSLRsHSCILALVGYVREPNMLlIVSEHAEHGRLDQFLIDRKlnfnnqltcsdgsnqkvynfnngeqer 261
Cdd:cd05056   52 EKFLQ-EAYIMRQFD-HPHIVKLIGVITENPVW-IVMELAPLGELRSYLQVNK--------------------------- 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 262 isddmQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEV 341
Cdd:cd05056  102 -----YSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYMEDESYYKASKGKLPI--KW 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 342 MAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAV-NAVYCGQdIER--KLPELQYCHPDMYSFLSSCWNFDPEARP 418
Cdd:cd05056  175 MAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVkNNDVIGR-IENgeRLPMPPNCPPTLYSLMTKCWAYDPSKRP 253
                        250
                 ....*....|.
gi 392922083 419 TYSKCVEFFDD 429
Cdd:cd05056  254 RFTELKAQLSD 264
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
127-428 1.77e-29

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: 117.81  E-value: 1.77e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 127 DPSLKINLSYLIIEEKEIEHYYSRIRLGKMKSMGAHKNSPTLSIKCALLRNDITHQKM--IQDELVTLSSLRSHSCILAL 204
Cdd:cd05100    4 DPKWELSRTRLTLGKPLGEGCFGQVVMAEAIGIDKDKPNKPVTVAVKMLKDDATDKDLsdLVSEMEMMKMIGKHKNIINL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 205 VGYVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcSDGSNqkvYNFNNGeqeRISDdmQALCTLDLLSYGYQIAIA 284
Cdd:cd05100   84 LGACTQDGPLYVLVEYASKGNLREYLRARR---------PPGMD---YSFDTC---KLPE--EQLTFKDLVSCAYQVARG 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 285 MKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYiMKSPQLPLAPEVMAPESSEDKKFTEKSEVRSFAVC 364
Cdd:cd05100  147 MEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNIDYY-KKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVL 225
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392922083 365 LTGIFQLGVPPHEA--VNAVYCGQDIERKLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05100  226 LWEIFTLGGSPYPGipVEELFKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLD 291
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
121-425 1.90e-29

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit 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: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 118.47  E-value: 1.90e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 121 NNEVQLDPSlkiNLSYliieEKEIEHYYSRIRLGKMKSMGAH------------KNSPTLSIKCALLRND--ITHQKMIQ 186
Cdd:cd05104   14 NNYVYIDPT---QLPY----DHKWEFPRDRLRFGKTLGAGAFgkvveatayglaKADSAMTVAVKMLKPSahSTEREALM 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 187 DELVTLSSLRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNF------------------NNQLTCSDGSN 248
Cdd:cd05104   87 SELKVLSYLGNHINIVNLLGACTVGGPTLVITEYCCYGDLLNFLRRKRDSFicpkfedlaeaalyrnllHQREMACDSLN 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 249 QKV------------------------YNFNNGEQERISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIF 304
Cdd:cd05104  167 EYMdmkpsvsyvvptkadkrrgvrsgsYVDQDVTSEILEEDELALDTEDLLSFSYQVAKGMEFLASKNCIHRDLAARNIL 246
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 305 VTRNKTIRIGEFGLAR-INARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPheavnavY 383
Cdd:cd05104  247 LTHGRITKICDFGLARdIRNDSNYVVKGNARLPV--KWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSP-------Y 317
                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|..
gi 392922083 384 CGQDIERKLPEL----------QYCHPDMYSFLSSCWNFDPEARPTYSKCVE 425
Cdd:cd05104  318 PGMPVDSKFYKMikegyrmdspEFAPSEMYDIMRSCWDADPLKRPTFKQIVQ 369
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
197-421 7.34e-29

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: 115.06  E-value: 7.34e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 197 SHSCILALVGYVREPNMLLIVSEHAEHGRLDQFL-IDRKLNFNNqlTCSDGSNQKVYNFNngeqerisDDMQALCTLDLL 275
Cdd:cd05045   61 NHPHVIKLYGACSQDGPLLLIVEYAKYGSLRSFLrESRKVGPSY--LGSDGNRNSSYLDN--------PDERALTMGDLI 130
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 276 SYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSP-QLPLapEVMAPESSEDKKFTE 354
Cdd:cd05045  131 SFAWQISRGMQYLAEMKLVHRDLAARNVLVAEGRKMKISDFGLSRDVYEEDSYVKRSKgRIPV--KWMAIESLFDHIYTT 208
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392922083 355 KSEVRSFAVCLTGIFQL------GVPPHEAVNAVYCGQDIERklPElqYCHPDMYSFLSSCWNFDPEARPTYS 421
Cdd:cd05045  209 QSDVWSFGVLLWEIVTLggnpypGIAPERLFNLLKTGYRMER--PE--NCSEEMYNLMLTCWKQEPDKRPTFA 277
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
155-428 2.42e-28

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: 114.29  E-value: 2.42e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 155 KMKSMGAHKNSP--TLSIKCALLRNDITHQKM--IQDELVTLSSLRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFL 230
Cdd:cd05099   30 RAEAYGIDKSRPdqTVTVAVKMLKDNATDKDLadLISEMELMKLIGKHKNIINLLGVCTQEGPLYVIVEYAAKGNLREFL 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 231 IDRKlnfnnqltcSDGSNqkvYNFNNGEQERisddmQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKT 310
Cdd:cd05099  110 RARR---------PPGPD---YTFDITKVPE-----EQLSFKDLVSCAYQVARGMEYLESRRCIHRDLAARNVLVTEDNV 172
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 311 IRIGEFGLARINARKEYYIMKSP-QLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLG------VPPHEAVNAVY 383
Cdd:cd05099  173 MKIADFGLARGVHDIDYYKKTSNgRLPV--KWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGgspypgIPVEELFKLLR 250
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 392922083 384 CGQDIERKlpelQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05099  251 EGHRMDKP----SNCTHELYMLMRECWHAVPTQRPTFKQLVEALD 291
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
268-427 8.10e-28

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR 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: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 111.74  E-value: 8.10e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 268 ALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKE-YYIMKSPQLPLapEVMAPES 346
Cdd:cd05057  105 NIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKLLDVDEkEYHAEGGKVPI--KWMALES 182
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 347 SEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCV 424
Cdd:cd05057  183 IQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVEIPDLLEKgeRLPQPPICTIDVYMVLVKCWMIDAESRPTFKELA 262

                 ...
gi 392922083 425 EFF 427
Cdd:cd05057  263 NEF 265
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
181-425 3.83e-27

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: 109.16  E-value: 3.83e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 181 HQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNNQLtcsdgsnqkvynfnngeqe 260
Cdd:cd13999   33 LLKEFRREVSILSKLR-HPNIVQFIGACLSPPPLCIVTEYMPGGSLYDLLHKKKIPLSWSL------------------- 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 261 risddmqalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARInarKEYYIMKSPQLPLAPE 340
Cdd:cd13999   93 -------------RLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRI---KNSTTEKMTGVVGTPR 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 341 VMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHE----AVNAVYCGQDIERKLPElqYCHPDMYSFLSSCWNFDPEA 416
Cdd:cd13999  157 WMAPEVLRGEPYTEKADVYSFGIVLWELLTGEVPFKElspiQIAAAVVQKGLRPPIPP--DCPPELSKLIKRCWNEDPEK 234

                 ....*....
gi 392922083 417 RPTYSKCVE 425
Cdd:cd13999  235 RPSFSEIVK 243
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
181-428 5.60e-27

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: 109.78  E-value: 5.60e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 181 HQKMIQDELVTLSSLrSHSCILALVGYVREP--NMLLIVSEHAEHGRLDQFLIDRKLNFNNQLtcsdgsnqkvynfnnge 258
Cdd:cd05038   49 HMSDFKREIEILRTL-DHEYIVKYKGVCESPgrRSLRLIMEYLPSGSLRDYLQRHRDQIDLKR----------------- 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 259 qerisddmqalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARI-NARKEYYIMKSP-QLP 336
Cdd:cd05038  111 ---------------LLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVlPEDKEYYYVKEPgESP 175
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 337 LapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLG----VPPHEAVNAVYCGQD-------IER-----KLPELQYCHP 400
Cdd:cd05038  176 I--FWYAPECLRESRFSSASDVWSFGVTLYELFTYGdpsqSPPALFLRMIGIAQGqmivtrlLELlksgeRLPRPPSCPD 253
                        250       260
                 ....*....|....*....|....*...
gi 392922083 401 DMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05038  254 EVYDLMKECWEYEPQDRPSFSDLILIID 281
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
255-420 6.35e-27

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha 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: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 112.04  E-value: 6.35e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 255 NNGEQERI-SDDM-QALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMK- 331
Cdd:cd05105  218 NDSEVKNLlSDDGsEGLTTLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLARDIMHDSNYVSKg 297
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 332 SPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAV-------NAVYCGQDIERklPElqYCHPDMYS 404
Cdd:cd05105  298 STFLPV--KWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGMivdstfyNKIKSGYRMAK--PD--HATQEVYD 371
                        170
                 ....*....|....*.
gi 392922083 405 FLSSCWNFDPEARPTY 420
Cdd:cd05105  372 IMVKCWNSEPEKRPSF 387
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
169-429 1.24e-26

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: 107.82  E-value: 1.24e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 169 SIKCAL--LRNDitHQKMIQDELV----TLSSLrSHSCILALVGYVREPNMLLiVSEHAEHGRLDQFLIDRKlnfnnqlt 242
Cdd:cd05060   23 EVEVAVktLKQE--HEKAGKKEFLreasVMAQL-DHPCIVRLIGVCKGEPLML-VMELAPLGPLLKYLKKRR-------- 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 243 csdgsnqkvyNFNNgeqerisddmqalctLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-I 321
Cdd:cd05060   91 ----------EIPV---------------SDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRaL 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 322 NARKEYYIMKSP-QLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPH------EAVNAVYCGQDIERklPE 394
Cdd:cd05060  146 GAGSDYYRATTAgRWPL--KWYAPECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYgemkgpEVIAMLESGERLPR--PE 221
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 392922083 395 LqyCHPDMYSFLSSCWNFDPEARPTYSKCVEFFDD 429
Cdd:cd05060  222 E--CPQEIYSIMLSCWKYRPEDRPTFSELESTFRR 254
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
160-420 3.45e-26

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: 106.75  E-value: 3.45e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 160 GAHKNSPTLSIKcALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDrklnfnn 239
Cdd:cd05148   25 GLWKNRVRVAIK-ILKSDDLLKQQDFQKEVQALKRLR-HKHLISLFAVCSVGEPVYIITELMEKGSLLAFLRS------- 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 240 qltcSDGsnqkvynfnngeqerisddmQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLA 319
Cdd:cd05148   96 ----PEG--------------------QVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLA 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 320 RInARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQY 397
Cdd:cd05148  152 RL-IKEDVYLSSDKKIPY--KWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNNHEVYDQITAgyRMPCPAK 228
                        250       260
                 ....*....|....*....|...
gi 392922083 398 CHPDMYSFLSSCWNFDPEARPTY 420
Cdd:cd05148  229 CPQEIYKIMLECWAAEPEDRPSF 251
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
182-421 4.32e-26

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. 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. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror 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: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 107.08  E-value: 4.32e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 182 QKMIQDELVTLSSLRsHSCILALVGYV--REPNMLLIvsEHAEHGRLDQFLIDRKLNfnnqltcSDGSNQkvynfNNGEQ 259
Cdd:cd05048   52 QQDFRREAELMSDLQ-HPNIVCLLGVCtkEQPQCMLF--EYMAHGDLHEFLVRHSPH-------SDVGVS-----SDDDG 116
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 260 ERISddmqaLCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSpQLPLAP 339
Cdd:cd05048  117 TASS-----LDQSDFLHIAIQIAAGMEYLSSHHYVHRDLAARNCLVGDGLTVKISDFGLSRDIYSSDYYRVQS-KSLLPV 190
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 340 EVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAvnavYCGQDI-----ERK-LPELQYCHPDMYSFLSSCWNFD 413
Cdd:cd05048  191 RWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYG----YSNQEViemirSRQlLPCPEDCPARVYSLMVECWHEI 266

                 ....*...
gi 392922083 414 PEARPTYS 421
Cdd:cd05048  267 PSRRPRFK 274
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
197-424 1.78e-25

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: 105.24  E-value: 1.78e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 197 SHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNNQLTCSDGSNQKVynfnngeqerisddmqALCTldlls 276
Cdd:cd05046   66 SHKNVVRLLGLCREAEPHYMILEYTDLGDLKQFLRATKSKDEKLKPPPLSTKQKV----------------ALCT----- 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 ygyQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKS 356
Cdd:cd05046  125 ---QIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSLSKDVYNSEYYKLRNALIPL--RWLAPEAVQEDDFSTKS 199
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392922083 357 EVRSFAVCLTGIFQLGVPPH------EAVNAVYCGqDIERKLPElqYCHPDMYSFLSSCWNFDPEARPTYSKCV 424
Cdd:cd05046  200 DVWSFGVLMWEVFTQGELPFyglsdeEVLNRLQAG-KLELPVPE--GCPSRLYKLMTRCWAVNPKDRPSFSELV 270
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
209-428 4.24e-24

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: 100.82  E-value: 4.24e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 209 REPnmLLIVSEHAEHGRLDQFLID---RKLNFNNQLtcsdgsnqkvynfnngeqerisdDMQAlctldllsygyQIAIAM 285
Cdd:cd05034   62 EEP--IYIVTELMSKGSLLDYLRTgegRALRLPQLI-----------------------DMAA-----------QIASGM 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 286 KFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCL 365
Cdd:cd05034  106 AYLESRNYIHRDLAARNILVGENNVCKVADFGLARLIEDDEYTAREGAKFPI--KWTAPEAALYGRFTIKSDVWSFGILL 183
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392922083 366 TGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05034  184 YEIVTYGRVPYPGMTNREVLEQVERgyRMPKPPGCPDELYDIMLQCWKKEPEERPTFEYLQSFLE 248
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
258-429 9.66e-24

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: 100.50  E-value: 9.66e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 258 EQERISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYiMKSPQLPL 337
Cdd:cd05032  105 PEAENNPGLGPPTLQKFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIGDFGMTRDIYETDYY-RKGGKGLL 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 338 APEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPP-----HEAVNAVYCGQDIeRKLPElqyCHPD-MYSFLSSCWN 411
Cdd:cd05032  184 PVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPyqglsNEEVLKFVIDGGH-LDLPE---NCPDkLLELMRMCWQ 259
                        170
                 ....*....|....*...
gi 392922083 412 FDPEARPTYSKCVEFFDD 429
Cdd:cd05032  260 YNPKMRPTFLEIVSSLKD 277
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
170-425 1.40e-23

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: 99.56  E-value: 1.40e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 170 IKCallrnDITHQKMIqDELVTLSSLRsHSCILALVGYVREpNMLLIVSEHAEHGRLDQFLIDRklnfnnqltcsdgsnq 249
Cdd:cd05083   37 IKC-----DVTAQAFL-EETAVMTKLQ-HKNLVRLLGVILH-NGLYIVMELMSKGNLVNFLRSR---------------- 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 250 kvynfnngeqerisdDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKeyyi 329
Cdd:cd05083   93 ---------------GRALVPVIQLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKVGSMG---- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 330 MKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPH------EAVNAVYCGQDIERklPElqYCHPDMY 403
Cdd:cd05083  154 VDNSRLPV--KWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYpkmsvkEVKEAVEKGYRMEP--PE--GCPPDVY 227
                        250       260
                 ....*....|....*....|..
gi 392922083 404 SFLSSCWNFDPEARPTYSKCVE 425
Cdd:cd05083  228 SIMTSCWEAEPGKRPSFKKLRE 249
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
186-417 2.89e-23

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: 99.27  E-value: 2.89e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 186 QDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIdrklnfnnqltcSDGSNQKVynFNNGEqerisdd 265
Cdd:cd05092   55 QREAELLTVLQ-HQHIVRFYGVCTEGEPLIMVFEYMRHGDLNRFLR------------SHGPDAKI--LDGGE------- 112
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 266 MQALCTLDL---LSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYY-IMKSPQLPLapEV 341
Cdd:cd05092  113 GQAPGQLTLgqmLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDYYrVGGRTMLPI--RW 190
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 342 MAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPP------HEAVNAVYCGQDIERKlpelQYCHPDMYSFLSSCWNFDPE 415
Cdd:cd05092  191 MPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPwyqlsnTEAIECITQGRELERP----RTCPPEVYAIMQGCWQREPQ 266

                 ..
gi 392922083 416 AR 417
Cdd:cd05092  267 QR 268
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
167-422 4.39e-23

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: 97.81  E-value: 4.39e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 167 TLSIKCalLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRklnfnnqltcsdg 246
Cdd:cd05039   31 KVAVKC--LKDDSTAAQAFLAEASVMTTLR-HPNLVQLLGVVLEGNGLYIVTEYMAKGSLVDYLRSR------------- 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 247 snqkvynfnngeqERisddmQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLarinARKE 326
Cdd:cd05039   95 -------------GR-----AVITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGL----AKEA 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 327 YYIMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLG------VPPHEAVNAVYCGQDIERklPElqYCHP 400
Cdd:cd05039  153 SSNQDGGKLPI--KWTAPEALREKKFSTKSDVWSFGILLWEIYSFGrvpyprIPLKDVVPHVEKGYRMEA--PE--GCPP 226
                        250       260
                 ....*....|....*....|..
gi 392922083 401 DMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd05039  227 EVYKVMKNCWELDPAKRPTFKQ 248
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
274-421 8.03e-23

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: 98.04  E-value: 8.03e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINAR-KEYYIMKSP-QLPLApeVMAPESSEDKK 351
Cdd:cd05081  110 LLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLdKDYYVVREPgQSPIF--WYAPESLSDNI 187
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 352 FTEKSEVRSFAVCLTGIFQLG----VPPHEAVNAVYCGQDIE------------RKLPELQYCHPDMYSFLSSCWNFDPE 415
Cdd:cd05081  188 FSRQSDVWSFGVVLYELFTYCdkscSPSAEFLRMMGCERDVPalcrllelleegQRLPAPPACPAEVHELMKLCWAPSPQ 267

                 ....*.
gi 392922083 416 ARPTYS 421
Cdd:cd05081  268 DRPSFS 273
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
253-429 9.54e-23

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta 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: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 99.70  E-value: 9.54e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 253 NFNNGEQER-----ISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEY 327
Cdd:cd05107  215 QYLPSAPERtrrdtLINESPALSYMDLVGFSYQVANGMEFLASKNCVHRDLAARNVLICEGKLVKICDFGLARDIMRDSN 294
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 328 YIMK-SPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAV-------NAVYCGQdierKLPELQYCH 399
Cdd:cd05107  295 YISKgSTFLPL--KWMAPESIFNNLYTTLSDVWSFGILLWEIFTLGGTPYPELpmneqfyNAIKRGY----RMAKPAHAS 368
                        170       180       190
                 ....*....|....*....|....*....|
gi 392922083 400 PDMYSFLSSCWNFDPEARPTYSKCVEFFDD 429
Cdd:cd05107  369 DEIYEIMQKCWEEKFEIRPDFSQLVHLVGD 398
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
181-428 8.90e-22

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: 94.40  E-value: 8.90e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 181 HQKMIQdelvtlsslrshsciLALVGYVREPnmLLIVSEHAEHGRLDQFL--IDRKLNFNNQLtcsdgsnqkvynfnnge 258
Cdd:cd05068   62 HPKLIQ---------------LYAVCTLEEP--IYIITELMKHGSLLEYLqgKGRSLQLPQLI----------------- 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 259 qerisdDMQAlctldllsygyQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMKSPQLPL 337
Cdd:cd05068  108 ------DMAA-----------QVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARvIKVEDEYEAREGAKFPI 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 338 apEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPE 415
Cdd:cd05068  171 --KWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERgyRMPCPPNCPPQLYDIMLECWKADPM 248
                        250
                 ....*....|....*..
gi 392922083 416 ARPTYS----KCVEFFD 428
Cdd:cd05068  249 ERPTFEtlqwKLEDFFV 265
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
273-427 3.01e-21

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 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: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 93.17  E-value: 3.01e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 273 DLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMKSPQLPLapEVMAPESSEDKK 351
Cdd:cd05109  110 DLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARlLDIDETEYHADGGKVPI--KWMALESILHRR 187
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392922083 352 FTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFF 427
Cdd:cd05109  188 FTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKgeRLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVDEF 265
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
186-420 3.10e-21

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. 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 Ror1 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: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 93.54  E-value: 3.10e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 186 QDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRklNFNNQLTCSDGSNQKVYN-FNNGeqerisd 264
Cdd:cd05090   55 QQEASLMTELH-HPNIVCLLGVVTQEQPVCMLFEFMNQGDLHEFLIMR--SPHSDVGCSSDEDGTVKSsLDHG------- 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 265 dmqalctlDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLpLAPEVMAP 344
Cdd:cd05090  125 --------DFLHIAIQIAAGMEYLSSHFFVHKDLAARNILVGEQLHVKISDLGLSREIYSSDYYRVQNKSL-LPIRWMPP 195
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392922083 345 ESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIERK--LPELQYCHPDMYSFLSSCWNFDPEARPTY 420
Cdd:cd05090  196 EAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIEMVRKRqlLPCSEDCPPRMYSLMTECWQEIPSRRPRF 273
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
170-427 4.61e-21

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: 91.18  E-value: 4.61e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 170 IKCALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNNQLtcsdgsnq 249
Cdd:cd00180   23 VKVIPKEKLKKLLEELLREIEILKKLN-HPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKENKGPLSEEE-------- 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 250 kvynfnngeqerisddmqalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYI 329
Cdd:cd00180   94 ------------------------ALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLL 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 330 MKSPQlPLAPEVMAPESSEDKKFTEKSEVRSFAVCLtgifqlgvppheavnavycgqdierklpelqYCHPDMYSFLSSC 409
Cdd:cd00180  150 KTTGG-TTPPYYAPPELLGGRYYGPKVDIWSLGVIL-------------------------------YELEELKDLIRRM 197
                        250
                 ....*....|....*...
gi 392922083 410 WNFDPEARPTYSKCVEFF 427
Cdd:cd00180  198 LQYDPKKRPSAKELLEHL 215
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
269-425 1.35e-20

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, 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. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros 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: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 91.32  E-value: 1.35e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 269 LCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVT----RNKTIRIGEFGLARINARKEYYiMKSPQLPLAPEVMAP 344
Cdd:cd05044  103 LTLKDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSskdyRERVVKIGDFGLARDIYKNDYY-RKEGEGLLPVRWMAP 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 345 ESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd05044  182 ESLVDGVFTTQSDVWAFGVLMWEILTLGQQPYPARNNLEVLHFVRAggRLDQPDNCPDDLYELMLRCWSTDPEERPSFAR 261

                 ...
gi 392922083 423 CVE 425
Cdd:cd05044  262 ILE 264
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
182-421 1.37e-20

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk 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: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 91.43  E-value: 1.37e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 182 QKMIQDELVTLSSLrSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNNQLTCSDGSNQKVynfnngeqer 261
Cdd:cd05050   52 QADFQREAALMAEF-DHPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRHRSPRAQCSLSHSTSSARKC---------- 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 262 iSDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYimKSPQLPLAP-E 340
Cdd:cd05050  121 -GLNPLPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYY--KASENDAIPiR 197
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 341 VMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPP-----HEAV-------NAVYCgqdierklPElqYCHPDMYSFLSS 408
Cdd:cd05050  198 WMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPyygmaHEEViyyvrdgNVLSC--------PD--NCPLELYNLMRL 267
                        250
                 ....*....|...
gi 392922083 409 CWNFDPEARPTYS 421
Cdd:cd05050  268 CWSKLPSDRPSFA 280
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
269-422 2.78e-20

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: 90.07  E-value: 2.78e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 269 LCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPESSE 348
Cdd:cd05085   91 LKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSRQEDDGVYSSSGLKQIPI--KWTAPEALN 168
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392922083 349 DKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd05085  169 YGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVEKgyRMSAPQRCPEDIYKIMQRCWDYNPENRPKFSE 244
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
188-422 3.31e-20

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie 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: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 90.10  E-value: 3.31e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 188 ELVTLSSLRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFL-IDRKLNFNNQLTCSDGSnqkvynfnngeqerisddM 266
Cdd:cd05047   45 ELEVLCKLGHHPNIINLLGACEHRGYLYLAIEYAPHGNLLDFLrKSRVLETDPAFAIANST------------------A 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 267 QALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARinaRKEYYIMKS-PQLPLapEVMAPE 345
Cdd:cd05047  107 STLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSR---GQEVYVKKTmGRLPV--RWMAIE 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 346 SSEDKKFTEKSEVRSFAVCLTGIFQLGVPPheavnavYCGQ---DIERKLPE------LQYCHPDMYSFLSSCWNFDPEA 416
Cdd:cd05047  182 SLNYSVYTTNSDVWSYGVLLWEIVSLGGTP-------YCGMtcaELYEKLPQgyrlekPLNCDDEVYDLMRQCWREKPYE 254

                 ....*.
gi 392922083 417 RPTYSK 422
Cdd:cd05047  255 RPSFAQ 260
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
131-420 3.61e-20

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: 90.46  E-value: 3.61e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 131 KINLSYLIIEEKEIEHYYSRIRLGKMKSMGAHKNSPTLSIKC------ALLRNDITHQKMIQDELvtlsslrSHSCILAL 204
Cdd:cd05091    2 EINLSAVRFMEELGEDRFGKVYKGHLFGTAPGEQTQAVAIKTlkdkaeGPLREEFRHEAMLRSRL-------QHPNIVCL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 205 VGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNfnnqltcSD-GSNqkvynfnngeqeriSDDMQALCTL---DLLSYGYQ 280
Cdd:cd05091   75 LGVVTKEQPMSMIFSYCSHGDLHEFLVMRSPH-------SDvGST--------------DDDKTVKSTLepaDFLHIVTQ 133
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 281 IAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYY-IMKSPQLPLapEVMAPESSEDKKFTEKSEVR 359
Cdd:cd05091  134 IAAGMEYLSSHHVVHKDLATRNVLVFDKLNVKISDLGLFREVYAADYYkLMGNSLLPI--RWMSPEAIMYGKFSIDSDIW 211
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 360 SFAVCLTGIFQLGVPPheavnavYCG---QDI------ERKLPELQYCHPDMYSFLSSCWNFDPEARPTY 420
Cdd:cd05091  212 SYGVVLWEVFSYGLQP-------YCGysnQDViemirnRQVLPCPDDCPAWVYTLMLECWNEFPSRRPRF 274
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
197-422 3.66e-20

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: 89.81  E-value: 3.66e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 197 SHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNNQLtcsdgsnqkvynfnngeqerisddmqalctldLLS 276
Cdd:cd05059   57 SHPKLVQLYGVCTKQRPIFIVTEYMANGCLLNYLRERRGKFQTEQ--------------------------------LLE 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPL---APEVMapessEDKKFT 353
Cdd:cd05059  105 MCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARYVLDDEYTSSVGTKFPVkwsPPEVF-----MYSKFS 179
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392922083 354 EKSEVRSFAVCLTGIFQLGVPPH------EAVNAVYCGQDIERklPELqyCHPDMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd05059  180 SKSDVWSFGVLMWEVFSEGKMPYerfsnsEVVEHISQGYRLYR--PHL--APTEVYTIMYSCWHEKPEERPTFKI 250
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
182-429 5.04e-20

Catalytic domain of a subset 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. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. 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. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-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: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 89.21  E-value: 5.04e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 182 QKMIQDELVTLSSLRSHscilalvgyvrEPnmLLIVSEHAEHGRLDQFLIDrklnfnnqltcSDGSNQKVYNFNngeqer 261
Cdd:cd14203   45 KKLRHDKLVQLYAVVSE-----------EP--IYIVTEFMSKGSLLDFLKD-----------GEGKYLKLPQLV------ 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 262 isdDMQAlctldllsygyQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEV 341
Cdd:cd14203   95 ---DMAA-----------QIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIEDNEYTARQGAKFPI--KW 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 342 MAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPT 419
Cdd:cd14203  159 TAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERgyRMPCPPGCPESLHELMCQCWRKDPEERPT 238
                        250
                 ....*....|
gi 392922083 420 YSKCVEFFDD 429
Cdd:cd14203  239 FEYLQSFLED 248
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
147-432 6.62e-20

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: 89.18  E-value: 6.62e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 147 YYSRIRLGKMKSMGAHKNSPTLSIKCALLRNDITHQKMIqdelvtlsslRSHSCIlalvgyVREPnmLLIVSEHAEHGRL 226
Cdd:cd05067   27 YYNGHTKVAIKSLKQGSMSPDAFLAEANLMKQLQHQRLV----------RLYAVV------TQEP--IYIITEYMENGSL 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 227 DQFLidrklnfnnqlTCSDGSNQKVYNFNngeqerisdDMQAlctldllsygyQIAIAMKFLADSRCLHRALALRSIFVT 306
Cdd:cd05067   89 VDFL-----------KTPSGIKLTINKLL---------DMAA-----------QIAEGMAFIEERNYIHRDLRAANILVS 137
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 307 RNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQ 386
Cdd:cd05067  138 DTLSCKIADFGLARLIEDNEYTAREGAKFPI--KWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQ 215
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 392922083 387 DIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFDDHFS 432
Cdd:cd05067  216 NLERgyRMPRPDNCPEELYQLMRLCWKERPEDRPTFEYLRSVLEDFFT 263
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
282-422 7.39e-20

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: 88.66  E-value: 7.39e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 282 AIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYI---MKspQLPLapEVMAPESSEDKKFTEKSEV 358
Cdd:cd05041  104 AAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSREEEDGEYTVsdgLK--QIPI--KWTAPEALNYGRYTSESDV 179
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392922083 359 RSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd05041  180 WSFGILLWEIFSLGATPYPGMSNQQTREQIESgyRMPAPELCPEAVYRLMLQCWAYDPENRPSFSE 245
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
198-417 8.14e-20

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: 89.06  E-value: 8.14e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 198 HSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidRKLNFNNQLTCSDGSNQKvynfnngeqerisddmqALCTLDLLSY 277
Cdd:cd05049   67 HENIVKFYGVCTEGDPLLMVFEYMEHGDLNKFL--RSHGPDAAFLASEDSAPG-----------------ELTLSQLLHI 127
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 278 GYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYY-IMKSPQLPLapEVMAPESSEDKKFTEKS 356
Cdd:cd05049  128 AVQIASGMVYLASQHFVHRDLATRNCLVGTNLVVKIGDFGMSRDIYSTDYYrVGGHTMLPI--RWMPPESILYRKFTTES 205
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 357 EVRSFAVCLTGIFQLGVPP------HEAVNAVYCGQDIERklPELqyCHPDMYSFLSSCWNFDPEAR 417
Cdd:cd05049  206 DVWSFGVVLWEIFTYGKQPwfqlsnTEVIECITQGRLLQR--PRT--CPSEVYAVMLGCWKREPQQR 268
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
168-429 1.18e-19

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: 88.11  E-value: 1.18e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 168 LSIKCalLRNDITHQKMIQDELVtLSSLRsHSCILALVGY-VREPNMLLIVSEHAEHGRLDQFLIDRKLnfnnqlTCSDG 246
Cdd:cd05082   32 VAVKC--IKNDATAQAFLAEASV-MTQLR-HSNLVQLLGViVEEKGGLYIVTEYMAKGSLVDYLRSRGR------SVLGG 101
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 247 SNqkvynfnngeqerisddmqalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARinarKE 326
Cdd:cd05082  102 DC-------------------------LLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTK----EA 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 327 YYIMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLG------VPPHEAVNAVYCGQdierKLPELQYCHP 400
Cdd:cd05082  153 SSTQDTGKLPV--KWTAPEALREKKFSTKSDVWSFGILLWEIYSFGrvpyprIPLKDVVPRVEKGY----KMDAPDGCPP 226
                        250       260
                 ....*....|....*....|....*....
gi 392922083 401 DMYSFLSSCWNFDPEARPTYSKCVEFFDD 429
Cdd:cd05082  227 AVYDVMKNCWHLDAAMRPSFLQLREQLEH 255
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
197-428 1.64e-19

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR 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: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 88.20  E-value: 1.64e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 197 SHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidRKlnfnnqltcsdgsnqkvynfNNGEqerisddmqaLCTLDLLS 276
Cdd:cd05033   63 DHPNVIRLEGVVTKSRPVMIVTEYMENGSLDKFL--RE--------------------NDGK----------FTVTQLVG 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKE-YYIMKSPQLPLapEVMAPESSEDKKFTEK 355
Cdd:cd05033  111 MLRGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLEDSEaTYTTKGGKIPI--RWTAPEAIAYRKFTSA 188
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392922083 356 SEVRSFAVCLTGIFQLGVPP------HEAVNAVYCGQdierKLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05033  189 SDVWSFGIVMWEVMSYGERPywdmsnQDVIKAVEDGY----RLPPPMDCPSALYQLMLDCWQKDRNERPTFSQIVSTLD 263
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
193-429 2.59e-19

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand 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 signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR 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: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 88.10  E-value: 2.59e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 193 SSLRSHSC--ILALVGYVREPNMLLIVSEHAEHGRLDQFLidRKLNfnnqltcSDGSNqkvynfNNGeqeRISDDMQalc 270
Cdd:cd05061   61 SVMKGFTChhVVRLLGVVSKGQPTLVVMELMAHGDLKSYL--RSLR-------PEAEN------NPG---RPPPTLQ--- 119
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 271 tlDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYiMKSPQLPLAPEVMAPESSEDK 350
Cdd:cd05061  120 --EMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYY-RKGGKGLLPVRWMAPESLKDG 196
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 351 KFTEKSEVRSFAVCLTGIFQLGVPPHEAVNA------VYCGQDIERklPElqYCHPDMYSFLSSCWNFDPEARPTYSKCV 424
Cdd:cd05061  197 VFTTSSDMWSFGVVLWEITSLAEQPYQGLSNeqvlkfVMDGGYLDQ--PD--NCPERVTDLMRMCWQFNPKMRPTFLEIV 272

                 ....*
gi 392922083 425 EFFDD 429
Cdd:cd05061  273 NLLKD 277
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
267-435 3.60e-19

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. 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 Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 87.43  E-value: 3.60e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 267 QALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPES 346
Cdd:cd05070  100 RALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEYTARQGAKFPI--KWTAPEA 177
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 347 SEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCV 424
Cdd:cd05070  178 ALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERgyRMPCPQDCPISLHELMIHCWKKDPEERPTFEYLQ 257
                        170
                 ....*....|.
gi 392922083 425 EFFDDHFSENQ 435
Cdd:cd05070  258 GFLEDYFTATE 268
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
274-422 3.80e-19

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: 86.52  E-value: 3.80e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYI---MKspQLPLapEVMAPESSEDK 350
Cdd:cd05084   97 LIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSREEEDGVYAAtggMK--QIPV--KWTAPEALNYG 172
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392922083 351 KFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd05084  173 RYSSESDVWSFGILLWETFSLGAVPYANLSNQQTREAVEQgvRLPCPENCPDEVYRLMEQCWEYDPRKRPSFST 246
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
197-428 4.22e-19

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily 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).


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 86.95  E-value: 4.22e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 197 SHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDrklnfnnqltcsdgsnqkvynfNNGEqerisddmqaLCTLDLLS 276
Cdd:cd05063   64 SHHNIIRLEGVVTKFKPAMIITEYMENGALDKYLRD----------------------HDGE----------FSSYQLVG 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARI--NARKEYYIMKSPQLPLapEVMAPESSEDKKFTE 354
Cdd:cd05063  112 MLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVleDDPEGTYTTSGGKIPI--RWTAPEAIAYRKFTS 189
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 355 KSEVRSFAVCLTGIFQLGVPP------HEAVNAVYCGqdieRKLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05063  190 ASDVWSFGIVMWEVMSFGERPywdmsnHEVMKAINDG----FRLPAPMDCPSAVYQLMLQCWQQDRARRPRFVDIVNLLD 265
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
274-420 4.30e-19

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: 87.38  E-value: 4.30e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINAR-KEYYIMKSP-QLPLApeVMAPESSEDKK 351
Cdd:cd14205  110 LLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQdKEYYKVKEPgESPIF--WYAPESLTESK 187
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 352 FTEKSEVRSFAVCLTGIFQLG----VPPHEAVNAVycGQD----------IE-----RKLPELQYCHPDMYSFLSSCWNF 412
Cdd:cd14205  188 FSVASDVWSFGVVLYELFTYIekskSPPAEFMRMI--GNDkqgqmivfhlIEllknnGRLPRPDGCPDEIYMIMTECWNN 265

                 ....*...
gi 392922083 413 DPEARPTY 420
Cdd:cd14205  266 NVNQRPSF 273
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
274-435 4.85e-19

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. 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 Yes 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 (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 87.05  E-value: 4.85e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPESSEDKKFT 353
Cdd:cd05069  110 LVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIEDNEYTARQGAKFPI--KWTAPEAALYGRFT 187
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 354 EKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFDDHF 431
Cdd:cd05069  188 IKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERgyRMPCPQGCPESLHELMKLCWKKDPDERPTFEYIQSFLEDYF 267

                 ....
gi 392922083 432 SENQ 435
Cdd:cd05069  268 TATE 271
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
269-426 4.90e-19

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. The EGFR 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: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 87.77  E-value: 4.90e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 269 LCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMKSPQLPLapEVMAPESS 347
Cdd:cd05108  106 IGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKlLGAEEKEYHAEGGKVPI--KWMALESI 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 348 EDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCV- 424
Cdd:cd05108  184 LHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKgeRLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIi 263

                 ..
gi 392922083 425 EF 426
Cdd:cd05108  264 EF 265
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
163-421 6.50e-19

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk 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: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 86.17  E-value: 6.50e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 163 KNSPTLSIKcaLLRNDiTHQKMIQDELV---TLSSLRSHSCILALVGyVREPNMLLIVSEHAEHGRLDQFLidrklnfnn 239
Cdd:cd05116   20 KVVKTVAVK--ILKNE-ANDPALKDELLreaNVMQQLDNPYIVRMIG-ICEAESWMLVMEMAELGPLNKFL--------- 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 240 qltcsdGSNQKVYNFNngeqerisddmqalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLA 319
Cdd:cd05116   87 ------QKNRHVTEKN------------------ITELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLS 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 320 R-INARKEYYIMKSP-QLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPEL 395
Cdd:cd05116  143 KaLRADENYYKAQTHgKWPV--KWYAPECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKgeRMECP 220
                        250       260
                 ....*....|....*....|....*.
gi 392922083 396 QYCHPDMYSFLSSCWNFDPEARPTYS 421
Cdd:cd05116  221 AGCPPEMYDLMKLCWTYDVDERPGFA 246
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
138-417 6.94e-19

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC 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 TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC 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: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 86.60  E-value: 6.94e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 138 IIEEKEI-EHYYSRIRLGKMKSMGAHKNSPTLSIKcALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLI 216
Cdd:cd05094    7 IVLKRELgEGAFGKVFLAECYNLSPTKDKMLVAVK-TLKDPTLAARKDFQREAELLTNLQ-HDHIVKFYGVCGDGDPLIM 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 217 VSEHAEHGRLDQFLidrKLNFNNQLTCSDGSNQKvynfNNGEqerisddmqaLCTLDLLSYGYQIAIAMKFLADSRCLHR 296
Cdd:cd05094   85 VFEYMKHGDLNKFL---RAHGPDAMILVDGQPRQ----AKGE----------LGLSQMLHIATQIASGMVYLASQHFVHR 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 297 ALALRSIFVTRNKTIRIGEFGLARINARKEYY-IMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLG--- 372
Cdd:cd05094  148 DLATRNCLVGANLLVKIGDFGMSRDVYSTDYYrVGGHTMLPI--RWMPPESIMYRKFTTESDVWSFGVILWEIFTYGkqp 225
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 392922083 373 ---VPPHEAVNAVYCGQDIERKlpelQYCHPDMYSFLSSCWNFDPEAR 417
Cdd:cd05094  226 wfqLSNTEVIECITQGRVLERP----RVCPKEVYDIMLGCWQREPQQR 269
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
149-420 1.11e-18

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR 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: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 86.24  E-value: 1.11e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 149 SRIRLGKMKSMGAHKNSPTLsIKCALLRNDITH--QKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRL 226
Cdd:cd05051   29 LSDLTSDDFIGNDNKDEPVL-VAVKMLRPDASKnaREDFLKEVKIMSQLK-DPNIVRLLGVCTRDEPLCMIVEYMENGDL 106
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 227 DQFLIDRKLNFNNQLTCsdgsNQKVYNFNNgeqerisddmqalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFVT 306
Cdd:cd05051  107 NQFLQKHEAETQGASAT----NSKTLSYGT-----------------LLYMATQIASGMKYLESLNFVHRDLATRNCLVG 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 307 RNKTIRIGEFGLARINARKEYY-IMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLG-VPPHEAV----- 379
Cdd:cd05051  166 PNYTIKIADFGMSRNLYSGDYYrIEGRAVLPI--RWMAWESILLGKFTTKSDVWAFGVTLWEILTLCkEQPYEHLtdeqv 243
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 392922083 380 --NA--VYCGQDIERKLPELQYCHPDMYSFLSSCWNFDPEARPTY 420
Cdd:cd05051  244 ieNAgeFFRDDGMEVYLSRPPNCPKEIYELMLECWRRDEEDRPTF 288
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
174-427 1.78e-18

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-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: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 85.80  E-value: 1.78e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 174 LLRNDITH--QKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNfnNQLTcsdgsnqkv 251
Cdd:cd05097   51 MLRADVTKtaRNDFLKEIKIMSRLK-NPNIIRLLGVCVSDDPLCMITEYMENGDLNQFLSQREIE--STFT--------- 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 252 ynfnngeqerISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYY-IM 330
Cdd:cd05097  119 ----------HANNIPSVSIANLLYMAVQIASGMKYLASLNFVHRDLATRNCLVGNHYTIKIADFGMSRNLYSGDYYrIQ 188
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 331 KSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQL-GVPPH---------EAVNAVYCGQDIERKLPELQYCHP 400
Cdd:cd05097  189 GRAVLPI--RWMAWESILLGKFTTASDVWAFGVTLWEMFTLcKEQPYsllsdeqviENTGEFFRNQGRQIYLSQTPLCPS 266
                        250       260
                 ....*....|....*....|....*..
gi 392922083 401 DMYSFLSSCWNFDPEARPTYSKCVEFF 427
Cdd:cd05097  267 PVFKLMMRCWSRDIKDRPTFNKIHHFL 293
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
274-429 1.79e-18

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: 85.08  E-value: 1.79e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPESSEDKKFT 353
Cdd:cd05073  109 LIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPI--KWTAPEAINFGSFT 186
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392922083 354 EKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFDD 429
Cdd:cd05073  187 IKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERgyRMPRPENCPEELYNIMMRCWKNRPEERPTFEYIQSVLDD 264
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
159-435 3.97e-18

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: 84.32  E-value: 3.97e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 159 MGAHKNSPTLSIKcALLRNDITHQKMIQDelVTLSSLRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIdrklnfn 238
Cdd:cd05072   25 MGYYNNSTKVAVK-TLKPGTMSVQAFLEE--ANLMKTLQHDKLVRLYAVVTKEEPIYIITEYMAKGSLLDFLK------- 94
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 239 nqltcsdgsnqkvynfnngeqeriSDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGL 318
Cdd:cd05072   95 ------------------------SDEGGKVLLPKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGL 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 319 ARINARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQ 396
Cdd:cd05072  151 ARVIEDNEYTAREGAKFPI--KWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMSNSDVMSALQRgyRMPRME 228
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 392922083 397 YCHPDMYSFLSSCWNFDPEARPTYSKCVEFFDDHFSENQ 435
Cdd:cd05072  229 NCPDELYDIMKTCWKEKAEERPTFDYLQSVLDDFYTATE 267
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
267-425 4.51e-18

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK 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: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 83.98  E-value: 4.51e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 267 QALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTR---NKTIRIGEFGLARINARKEYYiMKSPQLPLAPEVMA 343
Cdd:cd05036  111 SSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLTCkgpGRVAKIGDFGMARDIYRADYY-RKGGKAMLPVKWMP 189
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 344 PESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPH------EAVNAVYCGqdiERKLPElQYCHPDMYSFLSSCWNFDPEAR 417
Cdd:cd05036  190 PEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYpgksnqEVMEFVTSG---GRMDPP-KNCPGPVYRIMTQCWQHIPEDR 265

                 ....*...
gi 392922083 418 PTYSKCVE 425
Cdd:cd05036  266 PNFSTILE 273
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
170-427 4.83e-18

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 83.35  E-value: 4.83e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   170 IKCALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcsdgsnq 249
Cdd:smart00220  29 IKVIKKKKIKKDRERILREIKILKKLK-HPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLLKKRG--------------- 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   250 kvynfnngeqeRISDDmqalctlDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYI 329
Cdd:smart00220  93 -----------RLSED-------EARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDPGEKLT 154
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083   330 mkspqlPLA--PEVMAPESSEDKKFTEKSEVRSFAVCLtGIFQLGVPPHEAVNAVY-----CGQDIERKLPELQYCHPDM 402
Cdd:smart00220 155 ------TFVgtPEYMAPEVLLGKGYGKAVDIWSLGVIL-YELLTGKPPFPGDDQLLelfkkIGKPKPPFPPPEWDISPEA 227
                          250       260
                   ....*....|....*....|....*..
gi 392922083   403 YSFLSSCWNFDPEARPTYSKCVE--FF 427
Cdd:smart00220 228 KDLIRKLLVKDPEKRLTAEEALQhpFF 254
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
188-422 8.88e-18

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; 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. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 83.51  E-value: 8.88e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 188 ELVTLSSLRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidRKlnfnNQLTCSDGSNQKVYNfnngeqerisdDMQ 267
Cdd:cd05089   52 ELEVLCKLGHHPNIINLLGACENRGYLYIAIEYAPYGNLLDFL--RK----SRVLETDPAFAKEHG-----------TAS 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 268 ALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARinaRKEYYIMKS-PQLPLapEVMAPES 346
Cdd:cd05089  115 TLTSQQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKIADFGLSR---GEEVYVKKTmGRLPV--RWMAIES 189
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 347 SEDKKFTEKSEVRSFAVCLTGIFQLGVPPheavnavYCGQ---DIERKLPE------LQYCHPDMYSFLSSCWNFDPEAR 417
Cdd:cd05089  190 LNYSVYTTKSDVWSFGVLLWEIVSLGGTP-------YCGMtcaELYEKLPQgyrmekPRNCDDEVYELMRQCWRDRPYER 262

                 ....*
gi 392922083 418 PTYSK 422
Cdd:cd05089  263 PPFSQ 267
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
187-447 2.74e-17

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 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: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 82.42  E-value: 2.74e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 187 DELVTLSSLrSHSCILALVGYVREPNMLLiVSEHAEHGRLDQFLIDRKLNFNNQLtcsdgsnqkvynfnngeqerisddm 266
Cdd:cd05110   58 DEALIMASM-DHPHLVRLLGVCLSPTIQL-VTQLMPHGCLLDYVHEHKDNIGSQL------------------------- 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 267 qalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMKSPQLPLapEVMAPE 345
Cdd:cd05110  111 -------LLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARlLEGDEKEYNADGGKMPI--KWMALE 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 346 SSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKC 423
Cdd:cd05110  182 CIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKgeRLPQPPICTIDVYMVMVKCWMIDADSRPKFKEL 261
                        250       260
                 ....*....|....*....|....
gi 392922083 424 VEFFDDHFSENQIMIGKQITEKLK 447
Cdd:cd05110  262 AAEFSRMARDPQRYLVIQGDDRMK 285
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
274-431 4.27e-17

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl 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: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 80.93  E-value: 4.27e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPESSEDKKFT 353
Cdd:cd05052  106 LLYMATQIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHAGAKFPI--KWTAPESLAYNKFS 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 354 EKSEVRSFAVCLTGIFQLGVPPHEAVN--AVYCGQDIERKLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFDDHF 431
Cdd:cd05052  184 IKSDVWAFGVLLWEIATYGMSPYPGIDlsQVYELLEKGYRMERPEGCPPKVYELMRACWQWNPSDRPSFAEIHQALETMF 263
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
135-421 1.22e-16

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 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: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 80.36  E-value: 1.22e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 135 SYLIIEEKEIEHYYSRIRLGKMKS----------MGAHKNSPTLsIKCALLRNDITHQKM--IQDELVTLSSLRSHScIL 202
Cdd:cd05096    5 GHLLFKEKLGEGQFGEVHLCEVVNpqdlptlqfpFNVRKGRPLL-VAVKILRPDANKNARndFLKEVKILSRLKDPN-II 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 203 ALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNfnnqltcsdgsnqkvynfnNGEQERISDDMQALCTL-----DLLSY 277
Cdd:cd05096   83 RLLGVCVDEDPLCMITEYMENGDLNQFLSSHHLD-------------------DKEENGNDAVPPAHCLPaisysSLLHV 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 278 GYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYY-IMKSPQLPLapEVMAPESSEDKKFTEKS 356
Cdd:cd05096  144 ALQIASGMKYLSSLNFVHRDLATRNCLVGENLTIKIADFGMSRNLYAGDYYrIQGRAVLPI--RWMAWECILMGKFTTAS 221
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392922083 357 EVRSFAVCLTGIFQL------GVPPHEAV--NAVYCGQDIERK--LPELQYCHPDMYSFLSSCWNFDPEARPTYS 421
Cdd:cd05096  222 DVWAFGVTLWEILMLckeqpyGELTDEQVieNAGEFFRDQGRQvyLFRPPPCPQGLYELMLQCWSRDCRERPSFS 296
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
274-435 1.26e-16

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing 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 with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src 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: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 79.73  E-value: 1.26e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPESSEDKKFT 353
Cdd:cd05071  107 LVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYTARQGAKFPI--KWTAPEAALYGRFT 184
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 354 EKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFDDHF 431
Cdd:cd05071  185 IKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERgyRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDYF 264

                 ....
gi 392922083 432 SENQ 435
Cdd:cd05071  265 TSTE 268
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
182-422 1.80e-16

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 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: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 79.22  E-value: 1.80e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 182 QKMIQDELVTLSSLR---SHSCILALVGyVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnNQLTCSDgsnqkvynfnnge 258
Cdd:cd05115   44 EKAVRDEMMREAQIMhqlDNPYIVRMIG-VCEAEALMLVMEMASGGPLNKFLSGKK----DEITVSN------------- 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 259 qerisddmqalcTLDLLsygYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMKSP-QLP 336
Cdd:cd05115  106 ------------VVELM---HQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKaLGADDSYYKARSAgKWP 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 337 LapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDP 414
Cdd:cd05115  171 L--KWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQgkRMDCPAECPPEMYALMSDCWIYKW 248

                 ....*...
gi 392922083 415 EARPTYSK 422
Cdd:cd05115  249 EDRPNFLT 256
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
185-427 1.93e-16

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 79.23  E-value: 1.93e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 185 IQDELVTLSSLrSHSCILALVGYVREPNMLLiVSEHAEHGRLDQFLIDRKLNFNNQLtcsdgsnqkvynfnngeqerisd 264
Cdd:cd05111   56 VTDHMLAIGSL-DHAYIVRLLGICPGASLQL-VTQLLPLGSLLDHVRQHRGSLGPQL----------------------- 110
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 265 dmqalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMKSPQLPLapEVMA 343
Cdd:cd05111  111 ---------LLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVADlLYPDDKKYFYSEAKTPI--KWMA 179
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 344 PESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYS 421
Cdd:cd05111  180 LESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKgeRLAQPQICTIDVYMVMVKCWMIDENIRPTFK 259

                 ....*.
gi 392922083 422 KCVEFF 427
Cdd:cd05111  260 ELANEF 265
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
261-425 2.77e-16

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM 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: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 78.73  E-value: 2.77e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 261 RISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYY----IMKSPQlp 336
Cdd:cd05035  102 RLGGLPEKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLSRKIYSGDYYrqgrISKMPV-- 179
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 337 lapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPP------HEAVNAVYCGQdierKLPELQYCHPDMYSFLSSCW 410
Cdd:cd05035  180 ---KWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPypgvenHEIYDYLRNGN----RLKQPEDCLDEVYFLMYFCW 252
                        170
                 ....*....|....*
gi 392922083 411 NFDPEARPTYSKCVE 425
Cdd:cd05035  253 TVDPKDRPTFTKLRE 267
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
261-421 2.84e-16

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer 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: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 78.82  E-value: 2.84e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 261 RISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYY----IMKSPQlp 336
Cdd:cd14204  109 RLGSGPQHVPLQTLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVADFGLSKKIYSGDYYrqgrIAKMPV-- 186
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 337 lapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPP------HEAVNAVYCGQdierKLPELQYCHPDMYSFLSSCW 410
Cdd:cd14204  187 ---KWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPypgvqnHEIYDYLLHGH----RLKQPEDCLDELYDIMYSCW 259
                        170
                 ....*....|.
gi 392922083 411 NFDPEARPTYS 421
Cdd:cd14204  260 RSDPTDRPTFT 270
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
168-423 1.18e-15

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: 76.72  E-value: 1.18e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 168 LSIKCA-LLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidrklnfnnqltcsdg 246
Cdd:cd13978   21 VAIKCLhSSPNCIEERKALLKEAEKMERAR-HSYVLPLLGVCVERRSLGLVMEYMENGSLKSLL---------------- 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 247 snqkvynfnngeqERISDDMQALCTLDLLSygyQIAIAMKFL--ADSRCLHRALALRSIFVTRNKTIRIGEFGLARIN-- 322
Cdd:cd13978   84 -------------EREIQDVPWSLRFRIIH---EIALGMNFLhnMDPPLLHHDLKPENILLDNHFHVKISDFGLSKLGmk 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 323 ARKEYYIMKSPQLPLAPEVMAPESSED--KKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER----KLPEL- 395
Cdd:cd13978  148 SISANRRRGTENLGGTPIYMAPEAFDDfnKKPTSKSDVYSFAIVIWAVLTRKEPFENAINPLLIMQIVSKgdrpSLDDIg 227
                        250       260       270
                 ....*....|....*....|....*....|..
gi 392922083 396 QYCH----PDMYSFLSSCWNFDPEARPTYSKC 423
Cdd:cd13978  228 RLKQienvQELISLMIRCWDGNPDARPTFLEC 259
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
198-417 1.51e-15

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB 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 TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB 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: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 77.00  E-value: 1.51e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 198 HSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidrKLNFNNQLTCSDGsnqkvynfnngeqerisDDMQALCTLDLLSY 277
Cdd:cd05093   66 HEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFL---RAHGPDAVLMAEG-----------------NRPAELTQSQMLHI 125
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 278 GYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYY-IMKSPQLPLapEVMAPESSEDKKFTEKS 356
Cdd:cd05093  126 AQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDYYrVGGHTMLPI--RWMPPESIMYRKFTTES 203
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 357 EVRSFAVCLTGIFQLGVPP------HEAVNAVYCGQDIERKlpelQYCHPDMYSFLSSCWNFDPEAR 417
Cdd:cd05093  204 DVWSLGVVLWEIFTYGKQPwyqlsnNEVIECITQGRVLQRP----RTCPKEVYDLMLGCWQREPHMR 266
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
153-420 2.02e-15

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 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 (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 76.57  E-value: 2.02e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 153 LGKMKSMGAHKNSPTLsIKCALLRNDITHQKM--IQDELVTLSSLRSHSCI-LALVGYVREPnmLLIVSEHAEHGRLDQF 229
Cdd:cd05095   33 MDKDFALEVSENQPVL-VAVKMLRADANKNARndFLKEIKIMSRLKDPNIIrLLAVCITDDP--LCMITEYMENGDLNQF 109
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 230 LidrklnfnnqltcsdgSNQKVYNfnngeQERISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNK 309
Cdd:cd05095  110 L----------------SRQQPEG-----QLALPSNALTVSYSDLRFMAAQIASGMKYLSSLNFVHRDLATRNCLVGKNY 168
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 310 TIRIGEFGLARINARKEYY-IMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQL-GVPPH---------EA 378
Cdd:cd05095  169 TIKIADFGMSRNLYSGDYYrIQGRAVLPI--RWMSWESILLGKFTTASDVWAFGVTLWETLTFcREQPYsqlsdeqviEN 246
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 392922083 379 VNAVYCGQDIERKLPELQYCHPDMYSFLSSCWNFDPEARPTY 420
Cdd:cd05095  247 TGEFFRDQGRQTYLPQPALCPDSVYKLMLSCWRRDTKDRPSF 288
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
198-428 2.18e-15

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA 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: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 76.06  E-value: 2.18e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 198 HSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidRKlnfnnqltcsdgsnqkvynfNNGEqerisddmqaLCTLDLLSY 277
Cdd:cd05066   64 HPNIIHLEGVVTRSKPVMIVTEYMENGSLDAFL--RK--------------------HDGQ----------FTVIQLVGM 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 278 GYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARI--NARKEYYIMKSPQLPLapEVMAPESSEDKKFTEK 355
Cdd:cd05066  112 LRGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVleDDPEAAYTTRGGKIPI--RWTAPEAIAYRKFTSA 189
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392922083 356 SEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05066  190 SDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEgyRLPAPMDCPAALHQLMLDCWQKDRNERPKFEQIVSILD 264
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
188-449 4.11e-15

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 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: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 75.80  E-value: 4.11e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 188 ELVTLSSLRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFL-IDRKLNFNNQLTCSDGSnqkvynfnngeqerisddM 266
Cdd:cd05088   57 ELEVLCKLGHHPNIINLLGACEHRGYLYLAIEYAPHGNLLDFLrKSRVLETDPAFAIANST------------------A 118
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 267 QALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARinaRKEYYIMKS-PQLPLapEVMAPE 345
Cdd:cd05088  119 STLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSR---GQEVYVKKTmGRLPV--RWMAIE 193
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 346 SSEDKKFTEKSEVRSFAVCLTGIFQLGVPPheavnavYCGQ---DIERKLPE---LQY---CHPDMYSFLSSCWNFDPEA 416
Cdd:cd05088  194 SLNYSVYTTNSDVWSYGVLLWEIVSLGGTP-------YCGMtcaELYEKLPQgyrLEKplnCDDEVYDLMRQCWREKPYE 266
                        250       260       270
                 ....*....|....*....|....*....|...
gi 392922083 417 RPTYSKCVEFFDDHFSENQIMIGKQITEKLKSA 449
Cdd:cd05088  267 RPSFAQILVSLNRMLEERKTYVNTTLYEKFTYA 299
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
274-428 5.37e-15

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: 75.35  E-value: 5.37e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMK----SPQLPLAPEVMApesse 348
Cdd:cd05079  111 QLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKaIETDKEYYTVKddldSPVFWYAPECLI----- 185
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 349 DKKFTEKSEVRSFAVCL--------------TGIFQLGVPPHEAVNAVYCGQDIE--RKLPELQYCHPDMYSFLSSCWNF 412
Cdd:cd05079  186 QSKFYIASDVWSFGVTLyelltycdsesspmTLFLKMIGPTHGQMTVTRLVRVLEegKRLPRPPNCPEEVYQLMRKCWEF 265
                        170
                 ....*....|....*.
gi 392922083 413 DPEARPTYSKCVEFFD 428
Cdd:cd05079  266 QPSKRTTFQNLIEGFE 281
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
261-421 5.60e-15

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl 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: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 75.04  E-value: 5.60e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 261 RISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYY----IMKSPQlp 336
Cdd:cd05075  102 RLGDCPVYLPTQMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGLSKKIYNGDYYrqgrISKMPV-- 179
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 337 lapEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAV--NAVYCGQDIERKLPELQYCHPDMYSFLSSCWNFDP 414
Cdd:cd05075  180 ---KWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVenSEIYDYLRQGNRLKQPPDCLDGLYELMSSCWLLNP 256

                 ....*..
gi 392922083 415 EARPTYS 421
Cdd:cd05075  257 KDRPSFE 263
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
132-428 7.06e-15

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB 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: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 74.52  E-value: 7.06e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 132 INLSYLIIEEKEIEHYYSRIRLGKMKSMGahKNSPTLSIKCalLRNDITHQKmiQDELVTLSSLR---SHSCILALVGYV 208
Cdd:cd05065    1 IDVSCVKIEEVIGAGEFGEVCRGRLKLPG--KREIFVAIKT--LKSGYTEKQ--RRDFLSEASIMgqfDHPNIIHLEGVV 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 209 REPNMLLIVSEHAEHGRLDQFLidrKLNfNNQLTcsdgsnqkvynfnngeqerisddmqalcTLDLLSYGYQIAIAMKFL 288
Cdd:cd05065   75 TKSRPVMIITEFMENGALDSFL---RQN-DGQFT----------------------------VIQLVGMLRGIAAGMKYL 122
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 289 ADSRCLHRALALRSIFVTRNKTIRIGEFGLARI----NARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKSEVRSFAVC 364
Cdd:cd05065  123 SEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFleddTSDPTYTSSLGGKIPI--RWTAPEAIAYRKFTSASDVWSYGIV 200
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 365 LTGIFQLGVPPH------EAVNAVycGQDIerKLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd05065  201 MWEVMSYGERPYwdmsnqDVINAI--EQDY--RLPPPMDCPTALHQLMLDCWQKDRNLRPKFGQIVNTLD 266
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
197-421 7.22e-15

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: 74.22  E-value: 7.22e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 197 SHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNNQltcsdgsnqkvynfnngeqerisddmqalctlDLLS 276
Cdd:cd05112   57 SHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFSAE--------------------------------TLLG 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKS 356
Cdd:cd05112  105 MCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFVLDDQYTSSTGTKFPV--KWSSPEVFSFSRYSSKS 182
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 357 EVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIER--KLPELQYCHPDMYSFLSSCWNFDPEARPTYS 421
Cdd:cd05112  183 DVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAgfRLYKPRLASTHVYEIMNHCWKERPEDRPSFS 249
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
198-422 1.05e-14

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 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: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 74.19  E-value: 1.05e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 198 HSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidRKlnFNNQLTCSDgsnqkvynfnngeqerisddmqalcTLDLLSy 277
Cdd:cd05064   65 HSNIVRLEGVITRGNTMMIVTEYMSNGALDSFL--RK--HEGQLVAGQ-------------------------LMGMLP- 114
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 278 gyQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFG-LARINARKEYYIM--KSPQLPLAPEVMapessEDKKFTE 354
Cdd:cd05064  115 --GLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRrLQEDKSEAIYTTMsgKSPVLWAAPEAI-----QYHHFSS 187
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392922083 355 KSEVRSFAVCLTGIFQLGVPPHEAVNavycGQDIER------KLPELQYCHPDMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd05064  188 ASDVWSFGIVMWEVMSYGERPYWDMS----GQDVIKavedgfRLPAPRNCPNLLHQLMLDCWQKERGERPRFSQ 257
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
271-424 1.35e-14

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: 73.38  E-value: 1.35e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 271 TLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPL---APEVMAPess 347
Cdd:cd05113   99 TQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFPVrwsPPEVLMY--- 175
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392922083 348 edKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIE--RKLPELQYCHPDMYSFLSSCWNFDPEARPTYSKCV 424
Cdd:cd05113  176 --SKFSSKSDVWAFGVLMWEVYSLGKMPYERFTNSETVEHVSqgLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILL 252
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
198-422 1.98e-14

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily 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).


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 73.45  E-value: 1.98e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 198 HSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidrklnfnnqltcsdgsnqkvynfnngEQERISDDMQA-LCTLDLLS 276
Cdd:cd14206   56 HPNILQCLGLCTETIPFLLIMEFCQLGDLKRYL---------------------------RAQRKADGMTPdLPTRDLRT 108
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 ---YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYImkSPQ---LPL---APEVMAPESS 347
Cdd:cd14206  109 lqrMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSHNNYKEDYYL--TPDrlwIPLrwvAPELLDELHG 186
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 348 E----DKkfTEKSEVRSFAVCLTGIFQLGVPPH------EAVNAVYCGQDIERKLPELQYCHPDM-YSFLSSCWnFDPEA 416
Cdd:cd14206  187 NlivvDQ--SKESNVWSLGVTIWELFEFGAQPYrhlsdeEVLTFVVREQQMKLAKPRLKLPYADYwYEIMQSCW-LPPSQ 263

                 ....*.
gi 392922083 417 RPTYSK 422
Cdd:cd14206  264 RPSVEE 269
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
197-429 6.13e-14

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: 71.82  E-value: 6.13e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 197 SHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFnnqltcsdgsnqkvynfnngeqeriSDDMqalctldLLS 276
Cdd:cd05114   57 THPKLVQLYGVCTQQKPIYIVTEFMENGCLLNYLRQRRGKL-------------------------SRDM-------LLS 104
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapEVMAPESSEDKKFTEKS 356
Cdd:cd05114  105 MCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLDDQYTSSSGAKFPV--KWSPPEVFNYSKFSSKS 182
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392922083 357 EVRSFAVCLTGIFQLGVPP------HEAVNAVYCGQDIERklPELQyCHpDMYSFLSSCWNFDPEARPTYSKCVEFFDD 429
Cdd:cd05114  183 DVWSFGVLMWEVFTEGKMPfesksnYEVVEMVSRGHRLYR--PKLA-SK-SVYEVMYSCWHEKPEGRPTFADLLRTITE 257
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
261-420 2.42e-13

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 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: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 70.33  E-value: 2.42e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 261 RISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKS-PQLPLap 339
Cdd:cd05074  112 RIGEEPFTLPLQTLVRFMIDIASGMEYLSSKNFIHRDLAARNCMLNENMTVCVADFGLSKKIYSGDYYRQGCaSKLPV-- 189
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 340 EVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAV-NA-VYCGQDIERKLPELQYCHPDMYSFLSSCWNFDPEAR 417
Cdd:cd05074  190 KWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVeNSeIYNYLIKGNRLKQPPDCLEDVYELMCQCWSPEPKCR 269

                 ...
gi 392922083 418 PTY 420
Cdd:cd05074  270 PSF 272
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
263-420 4.30e-13

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (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, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R 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: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 69.29  E-value: 4.30e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 263 SDDMQALCTLD-LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYiMKSPQLPLAPEV 341
Cdd:cd05062  109 NNPVQAPPSLKkMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYY-RKGGKGLLPVRW 187
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 342 MAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAV-NAVYCGQDIERKLPELQYCHPDM-YSFLSSCWNFDPEARPT 419
Cdd:cd05062  188 MSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMsNEQVLRFVMEGGLLDKPDNCPDMlFELMRMCWQYNPKMRPS 267

                 .
gi 392922083 420 Y 420
Cdd:cd05062  268 F 268
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
274-427 6.31e-13

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: 69.16  E-value: 6.31e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMK----SPQLPLAPEVMapessE 348
Cdd:cd05080  109 LLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKaVPEGHEYYRVRedgdSPVFWYAPECL-----K 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 349 DKKFTEKSEVRSFAVCL--------------TGIFQLGVPPHEAVNAVYCGQDIERK--LPELQYCHPDMYSFLSSCWNF 412
Cdd:cd05080  184 EYKFYYASDVWSFGVTLyellthcdssqsppTKFLEMIGIAQGQMTVVRLIELLERGerLPCPDKCPQEVYHLMKNCWET 263
                        170
                 ....*....|....*
gi 392922083 413 DPEARPTYSKCVEFF 427
Cdd:cd05080  264 EASFRPTFENLIPIL 278
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
167-419 1.48e-12

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: 67.25  E-value: 1.48e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 167 TLSIKCaLLRNDITHQKM--IQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidRKL-NFNNQLTC 243
Cdd:cd06627   27 FVAIKQ-ISLEKIPKSDLksVMGEIDLLKKLN-HPNIVKYIGSVKTKDSLYIILEYVENGSLASII--KKFgKFPESLVA 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 244 SdgsnqkvynfnngeqerisddmqalctldllsYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLA-RIN 322
Cdd:cd06627  103 V--------------------------------YIYQVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVAtKLN 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 323 ARKeyyimKSPQLPL-APEVMAPESSEDKKFTEKSEVRSFAvCLtgIFQL--GVPPH---EAVNAVYC-GQDIERKLPEl 395
Cdd:cd06627  151 EVE-----KDENSVVgTPYWMAPEVIEMSGVTTASDIWSVG-CT--VIELltGNPPYydlQPMAALFRiVQDDHPPLPE- 221
                        250       260
                 ....*....|....*....|....
gi 392922083 396 qYCHPDMYSFLSSCWNFDPEARPT 419
Cdd:cd06627  222 -NISPELRDFLLQCFQKDPTLRPS 244
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
267-429 3.69e-12

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: 66.71  E-value: 3.69e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 267 QALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIM-KSPQLPLapEVMAPE 345
Cdd:cd05043  111 QALSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDNALSRDLFPMDYHCLgDNENRPI--KWMSLE 188
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 346 SSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVN----AVYCgQDIERkLPELQYCHPDMYSFLSSCWNFDPEARPTYS 421
Cdd:cd05043  189 SLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDpfemAAYL-KDGYR-LAQPINCPDELFAVMACCWALDPEERPSFQ 266

                 ....*...
gi 392922083 422 KCVEFFDD 429
Cdd:cd05043  267 QLVQCLTD 274
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
182-419 4.35e-12

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: 65.95  E-value: 4.35e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 182 QKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNfnnqltcsdgsnqkvynfnngeQER 261
Cdd:cd08215   43 REEALNEVKLLSKLK-HPNIVKYYESFEENGKLCIVMEYADGGDLAQKIKKQKKK----------------------GQP 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 262 ISDDMqalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARInarkeyyimKSPQLPLA--- 338
Cdd:cd08215  100 FPEEQ-------ILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISKV---------LESTTDLAktv 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 339 ---PEVMAPESSEDKKFTEKSEVRSFAVCLtgiFQL--GVPPHEAVNavycgqdierkLPEL-------QYC-HPDMYS- 404
Cdd:cd08215  164 vgtPYYLSPELCENKPYNYKSDIWALGCVL---YELctLKHPFEANN-----------LPALvykivkgQYPpIPSQYSs 229
                        250
                 ....*....|....*....
gi 392922083 405 ----FLSSCWNFDPEARPT 419
Cdd:cd08215  230 elrdLVNSMLQKDPEKRPS 248
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
280-427 8.05e-12

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: 65.60  E-value: 8.05e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 280 QIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARIN---------ARKEYYIMKSPQLPLAPEV-MAPE--SS 347
Cdd:cd14027   98 EIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFKmwskltkeeHNEQREVDGTAKKNAGTLYyMAPEhlND 177
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 348 EDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNA---VYCGQDIERKLPEL--QYCHPDMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd14027  178 VNAKPTEKSDVYSFAIVLWAIFANKEPYENAINEdqiIMCIKSGNRPDVDDitEYCPREIIDLMKLCWEANPEARPTFPG 257

                 ....*
gi 392922083 423 CVEFF 427
Cdd:cd14027  258 IEEKF 262
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
278-421 1.24e-11

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk 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: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 64.92  E-value: 1.24e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 278 GYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQ-LPL---APEVMAPESSE----D 349
Cdd:cd05042  106 ACEVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLAHSRYKEDYIETDDKLwFPLrwtAPELVTEFHDRllvvD 185
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392922083 350 KkfTEKSEVRSFAVCLTGIFQLGVPPH------EAVNAVYCGQDIERKLPELQYCHPDM-YSFLSSCWnFDPEARPTYS 421
Cdd:cd05042  186 Q--TKYSNIWSLGVTLWELFENGAQPYsnlsdlDVLAQVVREQDTKLPKPQLELPYSDRwYEVLQFCW-LSPEQRPAAE 261
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
192-425 3.58e-11

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: 63.52  E-value: 3.58e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 192 LSSLRSHSCILALVGY-VREPNMLLIVsEHAEHGRLdqflidrklnfNNQLTCSDGSNQKvynfnnGEQERISDDMqalc 270
Cdd:cd14146   46 LFSMLRHPNIIKLEGVcLEEPNLCLVM-EFARGGTL-----------NRALAAANAAPGP------RRARRIPPHI---- 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 271 tldLLSYGYQIAIAMKFLADSR---CLHRALALRSIFVTR--------NKTIRIGEFGLARinarkEYYimKSPQLPLAP 339
Cdd:cd14146  104 ---LVNWAVQIARGMLYLHEEAvvpILHRDLKSSNILLLEkiehddicNKTLKITDFGLAR-----EWH--RTTKMSAAG 173
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 340 EV--MAPESSEDKKFTEKSEVRSFAVCLTGIFQlGVPPHEAVN--AVYCGQDIER-KLPELQYCHPDMYSFLSSCWNFDP 414
Cdd:cd14146  174 TYawMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDglAVAYGVAVNKlTLPIPSTCPEPFAKLMKECWEQDP 252
                        250
                 ....*....|.
gi 392922083 415 EARPTYSKCVE 425
Cdd:cd14146  253 HIRPSFALILE 263
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
198-422 5.38e-11

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: 63.14  E-value: 5.38e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 198 HSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNnqltcsdgsnqkvynfnngeQERIsddmqalctldlLSY 277
Cdd:cd14063   55 HDNLVLFMGACMDPPHLAIVTSLCKGRTLYSLIHERKEKFD--------------------FNKT------------VQI 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 278 GYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIrIGEFGLARINA-----RKEYYIMKSPQ-LP-LAPEV---MAPESS 347
Cdd:cd14063  103 AQQICQGMGYLHAKGIIHKDLKSKNIFLENGRVV-ITDFGLFSLSGllqpgRREDTLVIPNGwLCyLAPEIiraLSPDLD 181
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 348 --EDKKFTEKSEVRSFAVC----LTGIFQLGVPPHEA-VNAVYCGQ-------DIERKLPELqychpdmysfLSSCWNFD 413
Cdd:cd14063  182 feESLPFTKASDVYAFGTVwyelLAGRWPFKEQPAESiIWQVGCGKkqslsqlDIGREVKDI----------LMQCWAYD 251

                 ....*....
gi 392922083 414 PEARPTYSK 422
Cdd:cd14063  252 PEKRPTFSD 260
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
278-435 6.49e-11

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: 62.84  E-value: 6.49e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 278 GYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINAR---KEYYIMKSPQLpLAPEVMAPESSEDKKFTE 354
Cdd:cd06611  109 CRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVSAKNKStlqKRDTFIGTPYW-MAPEVVACETFKDNPYDY 187
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 355 KSEVRSFAVCLTGIFQlGVPPHEAVNAVycgqdieRKLPELQYCHP-----------DMYSFLSSCWNFDPEARPTyskC 423
Cdd:cd06611  188 KADIWSLGITLIELAQ-MEPPHHELNPM-------RVLLKILKSEPptldqpskwssSFNDFLKSCLVKDPDDRPT---A 256
                        170
                 ....*....|..
gi 392922083 424 VEFFDDHFSENQ 435
Cdd:cd06611  257 AELLKHPFVSDQ 268
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
280-419 6.58e-11

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: 62.45  E-value: 6.58e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 280 QIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARInaRKEYYIMKSpQLPLAPEVMAPESSEDKKFTEKSEVR 359
Cdd:cd08223  110 QIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARV--LESSSDMAT-TLIGTPYYMSPELFSNKPYNHKSDVW 186
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392922083 360 SFAVCLTGIFQLgvppHEAVNA------VYcgQDIERKLPEL--QYcHPDMYSFLSSCWNFDPEARPT 419
Cdd:cd08223  187 ALGCCVYEMATL----KHAFNAkdmnslVY--KILEGKLPPMpkQY-SPELGELIKAMLHQDPEKRPS 247
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
192-421 6.59e-11

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: 62.75  E-value: 6.59e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 192 LSSLRSHSCILALVGY-VREPNMLLIVsEHAEHGRLDQFLIDRklnfnnqltcsdgsnqkvynfnngeqeRISDDMqalc 270
Cdd:cd14145   58 LFAMLKHPNIIALRGVcLKEPNLCLVM-EFARGGPLNRVLSGK---------------------------RIPPDI---- 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 271 tldLLSYGYQIAIAMKFLADSR---CLHRALALRSIFVTR--------NKTIRIGEFGLARinarkEYYIMKSPQLPLAP 339
Cdd:cd14145  106 ---LVNWAVQIARGMNYLHCEAivpVIHRDLKSSNILILEkvengdlsNKILKITDFGLAR-----EWHRTTKMSAAGTY 177
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 340 EVMAPESSEDKKFTEKSEVRSFAVCLTGIFQlGVPPHEAVN--AVYCGQDIER-KLPELQYCHPDMYSFLSSCWNFDPEA 416
Cdd:cd14145  178 AWMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDglAVAYGVAMNKlSLPIPSTCPEPFARLMEDCWNPDPHS 256

                 ....*
gi 392922083 417 RPTYS 421
Cdd:cd14145  257 RPPFT 261
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
162-428 1.13e-10

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: 62.27  E-value: 1.13e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 162 HKNSPTLSIKCALLRNDITHQKMIQDELVTLSSLrSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDrklnfnnql 241
Cdd:cd14222   14 HKATGKVMVMKELIRCDEETQKTFLTEVKVMRSL-DHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDFLRA--------- 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 242 TCSDGSNQKVynfnngeqerisddmqalctldllSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR- 320
Cdd:cd14222   84 DDPFPWQQKV------------------------SFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGLSRl 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 321 ----------------------INARKEYYIMKSPQLplapevMAPESSEDKKFTEKSEVRSFAVCLTGIF-QLGVPPHE 377
Cdd:cd14222  140 iveekkkpppdkpttkkrtlrkNDRKKRYTVVGNPYW------MAPEMLNGKSYDEKVDIFSFGIVLCEIIgQVYADPDC 213
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 392922083 378 AVNAVYCGQDI----ERKLPElqYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd14222  214 LPRTLDFGLNVrlfwEKFVPK--DCPPAFFPLAAICCRLEPDSRPAFSKLEDSFE 266
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
192-419 1.22e-10

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 62.02  E-value: 1.22e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 192 LSSLR--SHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFnnqltcsdgsnqkvynfnngeqerisDDMQAL 269
Cdd:cd13992   47 LNQLKelVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVLLNREIKM--------------------------DWMFKS 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 270 CTLdllsygYQIAIAMKFLADSRC-LHRALALRSIFVTRNKTIRIGEFGLARI-----NARKEYYIMKSPQLPLAPEVMA 343
Cdd:cd13992  101 SFI------KDIVKGMNYLHSSSIgYHGRLKSSNCLVDSRWVVKLTDFGLRNLleeqtNHQLDEDAQHKKLLWTAPELLR 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 344 pESSEDKKFTEKSEVRSFAVCLTGIF--QLGVPPHEAVNAVYCGQDIERK--LPELQY----CHPDMYSFLSSCWNFDPE 415
Cdd:cd13992  175 -GSLLEVRGTQKGDVYSFAIILYEILfrSDPFALEREVAIVEKVISGGNKpfRPELAVlldeFPPRLVLLVKQCWAENPE 253

                 ....
gi 392922083 416 ARPT 419
Cdd:cd13992  254 KRPS 257
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
280-425 2.84e-10

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: 61.20  E-value: 2.84e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 280 QIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINA----RKEYYImKSPQLpLAPEVMAPESSEDKKFTEK 355
Cdd:cd06644  118 QMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVSAKNVktlqRRDSFI-GTPYW-MAPEVVMCETMKDTPYDYK 195
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392922083 356 SEVRSFAVCLTGIFQLGvPPHEAVNAVYCGQDIERKLPELQYC----HPDMYSFLSSCWNFDPEARPTYSKCVE 425
Cdd:cd06644  196 ADIWSLGITLIEMAQIE-PPHHELNPMRVLLKIAKSEPPTLSQpskwSMEFRDFLKTALDKHPETRPSAAQLLE 268
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
175-419 3.95e-10

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: 60.29  E-value: 3.95e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 175 LRNDITHQKMIQDELVTLSSLrSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidrklnfnnqltcsdgsnqkvynf 254
Cdd:cd14014   37 LAEDEEFRERFLREARALARL-SHPNIVRVYDVGEDDGRPYIVMEYVEGGSLADLL------------------------ 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 255 nnGEQERISDDMqalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARinARKEYYIMKSPQ 334
Cdd:cd14014   92 --RERGPLPPRE-------ALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIAR--ALGDSGLTQTGS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 335 LPLAPEVMAPESSEDKKFTEKSEVRSFAV----CLTGIFQLGVPPHEAVNAVYCGQDIERKLPELQYCHPDMYSFLSSCW 410
Cdd:cd14014  161 VLGTPAYMAPEQARGGPVDPRSDIYSLGVvlyeLLTGRPPFDGDSPAAVLAKHLQEAPPPPSPLNPDVPPALDAIILRAL 240

                 ....*....
gi 392922083 411 NFDPEARPT 419
Cdd:cd14014  241 AKDPEERPQ 249
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
275-429 5.88e-10

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: 59.97  E-value: 5.88e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 275 LSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARI-----------------NARKEYYIMKSPQLpl 337
Cdd:cd14221   94 VSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLARLmvdektqpeglrslkkpDRKKRYTVVGNPYW-- 171
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 338 apevMAPESSEDKKFTEKSEVRSFAVCLTGIF-QLGVPPHEAVNAVYCGQDI----ERKLPElqYCHPDMYSFLSSCWNF 412
Cdd:cd14221  172 ----MAPEMINGRSYDEKVDVFSFGIVLCEIIgRVNADPDYLPRTMDFGLNVrgflDRYCPP--NCPPSFFPIAVLCCDL 245
                        170
                 ....*....|....*..
gi 392922083 413 DPEARPTYSKCVEFFDD 429
Cdd:cd14221  246 DPEKRPSFSKLEHWLET 262
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
198-425 7.75e-10

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: 59.23  E-value: 7.75e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 198 HSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLnfnnqltcsdgsnqkvynfnngeQERIsddmqalctldLLSY 277
Cdd:cd14148   52 HPNIIALRGVCLNPPHLCLVMEYARGGALNRALAGKKV-----------------------PPHV-----------LVNW 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 278 GYQIAIAMKFLADSR---CLHRALALRSIFVTR--------NKTIRIGEFGLARinarkEYYimKSPQLPLAPEV--MAP 344
Cdd:cd14148   98 AVQIARGMNYLHNEAivpIIHRDLKSSNILILEpienddlsGKTLKITDFGLAR-----EWH--KTTKMSAAGTYawMAP 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 345 ESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHE--AVNAVYCGQDIERKLPELQYCHPDMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd14148  171 EVIRLSLFSKSSDVWSFGVLLWELLTGEVPYREidALAVAYGVAMNKLTLPIPSTCPEPFARLLEECWDPDPHGRPDFGS 250

                 ...
gi 392922083 423 CVE 425
Cdd:cd14148  251 ILK 253
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
167-420 1.29e-09

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: 58.56  E-value: 1.29e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 167 TLSIKCALLRNDITHQKMIQDEL--VTLSSLRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNNqltcs 244
Cdd:cd14061   19 EVAVKAARQDPDEDISVTLENVRqeARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGGALNRVLAGRKIPPHV----- 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 245 dgsnqkvynfnngeqerisddmqalctldLLSYGYQIAIAMKFLADSR---CLHRALALRSIFVTR--------NKTIRI 313
Cdd:cd14061   94 -----------------------------LVDWAIQIARGMNYLHNEApvpIIHRDLKSSNILILEaienedleNKTLKI 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 314 GEFGLARinarkEYYimKSPQLPLAPEV--MAPESSEDKKFTEKSEVRSFAVCLTGIFQlGVPPHEAVN--AVYCGQDIE 389
Cdd:cd14061  145 TDFGLAR-----EWH--KTTRMSAAGTYawMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKGIDglAVAYGVAVN 216
                        250       260       270
                 ....*....|....*....|....*....|...
gi 392922083 390 R-KLPELQYChPDMYS-FLSSCWNFDPEARPTY 420
Cdd:cd14061  217 KlTLPIPSTC-PEPFAqLMKDCWQPDPHDRPSF 248
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
284-425 1.43e-09

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: 58.88  E-value: 1.43e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 284 AMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINA----RKEYYImKSPQLpLAPEVMAPESSEDKKFTEKSEVR 359
Cdd:cd06643  115 ALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGVSAKNTrtlqRRDSFI-GTPYW-MAPEVVMCETSKDRPYDYKADVW 192
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 360 SFAVCLTGIFQLGvPPHEAVNAVYCGQDIERKLP----ELQYCHPDMYSFLSSCWNFDPEARPTYSKCVE 425
Cdd:cd06643  193 SLGVTLIEMAQIE-PPHHELNPMRVLLKIAKSEPptlaQPSRWSPEFKDFLRKCLEKNVDARWTTSQLLQ 261
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
272-421 1.67e-09

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: 58.17  E-value: 1.67e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 272 LDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEyYIMKSPQ-----LPLAPEVMAPEs 346
Cdd:cd14062   89 LQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLATVKTRWS-GSQQFEQptgsiLWMAPEVIRMQ- 166
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 347 sEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNA----VYCGQDIERklPELQYCHPD----MYSFLSSCWNFDPEARP 418
Cdd:cd14062  167 -DENPYSFQSDVYAFGIVLYELLTGQLPYSHINNRdqilFMVGRGYLR--PDLSKVRSDtpkaLRRLMEDCIKFQRDERP 243

                 ...
gi 392922083 419 TYS 421
Cdd:cd14062  244 LFP 246
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
154-421 1.99e-09

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: 58.12  E-value: 1.99e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 154 GKMKSMGAHKNSPTLSIKcallrndITHQKMIQDelVTLSSLRSHSCILALVGY-VREPNMLLIVsEHAEHGRLDQFLID 232
Cdd:cd14147   26 GELVAVKAARQDPDEDIS-------VTAESVRQE--ARLFAMLAHPNIIALKAVcLEEPNLCLVM-EYAAGGPLSRALAG 95
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 233 RklnfnnqltcsdgsnqkvynfnngeqeRISDDMqalctldLLSYGYQIAIAMKFL---ADSRCLHRALALRSIFVTRN- 308
Cdd:cd14147   96 R---------------------------RVPPHV-------LVNWAVQIARGMHYLhceALVPVIHRDLKSNNILLLQPi 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 309 -------KTIRIGEFGLARinarkEYYimKSPQLPLAPEV--MAPESSEDKKFTEKSEVRSFAVCLTGIFQlGVPPHEAV 379
Cdd:cd14147  142 enddmehKTLKITDFGLAR-----EWH--KTTQMSAAGTYawMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGI 213
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 392922083 380 N--AVYCGQDIER-KLPELQYCHPDMYSFLSSCWNFDPEARPTYS 421
Cdd:cd14147  214 DclAVAYGVAVNKlTLPIPSTCPEPFAQLMADCWAQDPHRRPDFA 258
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
280-419 3.87e-09

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: 57.43  E-value: 3.87e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 280 QIAIAMKFLADSRCLHRALALRSIFVtRNKTIRIGEFGLARInarkeyyIMKSPQLPL----APEVMAPESSEDKKFTEK 355
Cdd:cd08222  114 QLLLAVQYMHERRILHRDLKAKNIFL-KNNVIKVGDFGISRI-------LMGTSDLATtftgTPYYMSPEVLKHEGYNSK 185
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392922083 356 SEVRSFAV------CLTGIFQlgvpPHEAVNAVYcgQDIERKLPELqychPDMYS-----FLSSCWNFDPEARPT 419
Cdd:cd08222  186 SDIWSLGCilyemcCLKHAFD----GQNLLSVMY--KIVEGETPSL----PDKYSkelnaIYSRMLNKDPALRPS 250
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
280-419 4.90e-09

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 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: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 57.31  E-value: 4.90e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 280 QIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYImKSPQLPLAPEVMAPESSED-------KKF 352
Cdd:cd05087  110 EVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSHCKYKEDYFV-TADQLWVPLRWIAPELVDEvhgnllvVDQ 188
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392922083 353 TEKSEVRSFAVCLTGIFQLGVPPHEAVN----AVYCGQDIERKLPELQYCHP---DMYSFLSSCWnFDPEARPT 419
Cdd:cd05087  189 TKQSNVWSLGVTIWELFELGNQPYRHYSdrqvLTYTVREQQLKLPKPQLKLSlaeRWYEVMQFCW-LQPEQRPT 261
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
180-426 9.70e-09

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: 55.91  E-value: 9.70e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 180 THQKMIQDELVTLSSLrSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcsdgsNQKVYNFNNGeq 259
Cdd:cd14058   28 SEKKAFEVEVRQLSRV-DHPNIIKLYGACSNQKPVCLVMEYAEGGSLYNVLHGKE-------------PKPIYTAAHA-- 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 260 erisddmqalctldlLSYGYQIAIAMKFL---ADSRCLHRALALRSIFVTRNKT-IRIGEFGLArinARKEYYiMKSPQL 335
Cdd:cd14058   92 ---------------MSWALQCAKGVAYLhsmKPKALIHRDLKPPNLLLTNGGTvLKICDFGTA---CDISTH-MTNNKG 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 336 PLApeVMAPESSEDKKFTEKSEVRSFAVCLTGIF-------QLGVPPHEAVNAVYCGqdieRKLPELQYCHPDMYSFLSS 408
Cdd:cd14058  153 SAA--WMAPEVFEGSKYSEKCDVFSWGIILWEVItrrkpfdHIGGPAFRIMWAVHNG----ERPPLIKNCPKPIESLMTR 226
                        250
                 ....*....|....*...
gi 392922083 409 CWNFDPEARPTYSKCVEF 426
Cdd:cd14058  227 CWSKDPEKRPSMKEIVKI 244
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
187-419 1.14e-08

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: 55.88  E-value: 1.14e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 187 DELVTLSSLRSHSCILALVGYVrEPNMLLIVSEHAEHGRLDQFLidrKLNFNNQLTcsdgsNQKVYNFNngeqerisddm 266
Cdd:cd08529   48 DEARVLSKLNSPYVIKYYDSFV-DKGKLNIVMEYAENGDLHSLI---KSQRGRPLP-----EDQIWKFF----------- 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 267 qalctldllsygYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARInarkeyyimKSPQLPLA------PE 340
Cdd:cd08529  108 ------------IQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKI---------LSDTTNFAqtivgtPY 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 341 VMAPESSEDKKFTEKSEVRSFAVCLtgiFQL--GVPPHEAVNAVYCGQDIERK--LPELQYCHPDMYSFLSSCWNFDPEA 416
Cdd:cd08529  167 YLSPELCEDKPYNEKSDVWALGCVL---YELctGKHPFEAQNQGALILKIVRGkyPPISASYSQDLSQLIDSCLTKDYRQ 243

                 ...
gi 392922083 417 RPT 419
Cdd:cd08529  244 RPD 246
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
162-428 1.38e-08

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: 55.98  E-value: 1.38e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 162 HKNSPTLSIKCALLRNDITHQKMIQDELVTLSSLrSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNNQl 241
Cdd:cd14154   14 HRETGEVMVMKELIRFDEEAQRNFLKEVKVMRSL-DHPNVLKFIGVLYKDKKLNLITEYIPGGTLKDVLKDMARPLPWA- 91
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 242 tcsdgsnQKVynfnngeqeRISDDmqalctldllsygyqIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR- 320
Cdd:cd14154   92 -------QRV---------RFAKD---------------IASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLARl 140
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 321 INARKEYYIMKSPQLPLA----------------PEVMAPESSEDKKFTEKSEVRSFAVCLTGIF-QLGVPPHEAVNAVY 383
Cdd:cd14154  141 IVEERLPSGNMSPSETLRhlkspdrkkrytvvgnPYWMAPEMLNGRSYDEKVDIFSFGIVLCEIIgRVEADPDYLPRTKD 220
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 392922083 384 CGQDIERKLPEL-QYCHPDMYSFLSSCWNFDPEARPTYSKCVEFFD 428
Cdd:cd14154  221 FGLNVDSFREKFcAGCPPPFFKLAFLCCDLDPEKRPPFETLEEWLE 266
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
274-420 2.78e-08

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: 54.42  E-value: 2.78e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARInarkeyYIMKSPQLPLAPEV--MAPESSEDKK 351
Cdd:cd14059   83 LVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDVLKISDFGTSKE------LSEKSTKMSFAGTVawMAPEVIRNEP 156
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392922083 352 FTEKSEVRSFAVCLTGIFQlGVPPHEAVN--AVYCGQDIER-KLPELQYChPDMYSFL-SSCWNFDPEARPTY 420
Cdd:cd14059  157 CSEKVDIWSFGVVLWELLT-GEIPYKDVDssAIIWGVGSNSlQLPVPSTC-PDGFKLLmKQCWNSKPRNRPSF 227
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
184-430 3.28e-08

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting 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. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K 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: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 54.46  E-value: 3.28e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 184 MIQDELVTLSSLrSHSCILALVGY-VREPNMLLIVSEHAEHGRLDQFLidrklnfnnqltcsdgsnqkvynfnnGEQERI 262
Cdd:cd14064   37 MFCREVSILCRL-NHPCVIQFVGAcLDDPSQFAIVTQYVSGGSLFSLL--------------------------HEQKRV 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 263 SDdMQALCTLDLlsygyQIAIAMKFLADSR--CLHRALALRSIFVTRNKTIRIGEFGLAR-INARKEYYIMKSPQ--LPL 337
Cdd:cd14064   90 ID-LQSKLIIAV-----DVAKGMEYLHNLTqpIIHRDLNSHNILLYEDGHAVVADFGESRfLQSLDEDNMTKQPGnlRWM 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 338 APEVMapesSEDKKFTEKSEVRSFAVCLTGIFQLGVP-PHEAVNAVYCGQDIERKLPELQYCHPD-MYSFLSSCWNFDPE 415
Cdd:cd14064  164 APEVF----TQCTRYSIKADVFSYALCLWELLTGEIPfAHLKPAAAAADMAYHHIRPPIGYSIPKpISSLLMRGWNAEPE 239
                        250
                 ....*....|....*
gi 392922083 416 ARPTYSKCVEFFDDH 430
Cdd:cd14064  240 SRPSFVEIVALLEPC 254
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
226-426 5.61e-08

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: 53.88  E-value: 5.61e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 226 LDQFLIDRKLNFNNQLTCSDGSNQKVYNFNngEQERISDDMQalctldLLSYGYQIAIAMKFLADSRCLHRALALRSIFV 305
Cdd:cd08228   68 LDSFIEDNELNIVLELADAGDLSQMIKYFK--KQKRLIPERT------VWKYFVQLCSAVEHMHSRRVMHRDIKPANVFI 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 306 TRNKTIRIGEFGLARINARKeyyIMKSPQLPLAPEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPH-EAVNAVYC 384
Cdd:cd08228  140 TATGVVKLGDLGLGRFFSSK---TTAAHSLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYgDKMNLFSL 216
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 392922083 385 GQDIER----KLPELQYCHpDMYSFLSSCWNFDPEARPTYSKCVEF 426
Cdd:cd08228  217 CQKIEQcdypPLPTEHYSE-KLRELVSMCIYPDPDQRPDIGYVHQI 261
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
198-419 6.25e-08

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 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: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 53.72  E-value: 6.25e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 198 HSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDrklnfnnqltcsdgsnqkvynfnngEQERISDDMQalcTLDLLSY 277
Cdd:cd05086   56 HPNILQCVGQCVEAIPYLLVFEFCDLGDLKTYLAN-------------------------QQEKLRGDSQ---IMLLQRM 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 278 GYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQL-PL---APEVMApeSSEDKKF- 352
Cdd:cd05086  108 ACEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIGFSRYKEDYIETDDKKYaPLrwtAPELVT--SFQDGLLa 185
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 353 ---TEKSEVRSFAVCLTGIFQLGVPPH------EAVNAVYCGQDIERKLPELQYCHPDM-YSFLSSCWnFDPEARPT 419
Cdd:cd05086  186 aeqTKYSNIWSLGVTLWELFENAAQPYsdlsdrEVLNHVIKERQVKLFKPHLEQPYSDRwYEVLQFCW-LSPEKRPT 261
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
274-425 7.62e-08

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: 53.28  E-value: 7.62e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARI-NARKEyyimkspqlpLA------PEVMAPES 346
Cdd:cd08218  103 ILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVlNSTVE----------LArtcigtPYYLSPEI 172
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 347 SEDKKFTEKSEVRSFAVCLTGIFQLGvPPHEAVNAVYCGQDIER-KLP--ELQYCHpDMYSFLSSCWNFDPEARPTYSKC 423
Cdd:cd08218  173 CENKPYNNKSDIWALGCVLYEMCTLK-HAFEAGNMKNLVLKIIRgSYPpvPSRYSY-DLRSLVSQLFKRNPRDRPSINSI 250

                 ..
gi 392922083 424 VE 425
Cdd:cd08218  251 LE 252
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
145-419 9.57e-08

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: 53.04  E-value: 9.57e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 145 EHYYSRIRLGKMKSmgahKNSPTLSIKCALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHG 224
Cdd:cd08225   10 EGSFGKIYLAKAKS----DSEHCVIKEIDLTKMPVKEKEASKKEVILLAKMK-HPNIVTFFASFQENGRLFIVMEYCDGG 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 225 RLdqflidrklnfnnqltcsdgsnqkvynfnngeQERISDDMQALCTLD-LLSYGYQIAIAMKFLADSRCLHRALALRSI 303
Cdd:cd08225   85 DL--------------------------------MKRINRQRGVLFSEDqILSWFVQISLGLKHIHDRKILHRDIKSQNI 132
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 304 FVTRN-KTIRIGEFGLAR-INARKEYyimkSPQLPLAPEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVP-----PH 376
Cdd:cd08225  133 FLSKNgMVAKLGDFGIARqLNDSMEL----AYTCVGTPYYLSPEICQNRPYNNKTDIWSLGCVLYELCTLKHPfegnnLH 208
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 392922083 377 EAVNAVyCGQDIERKLPELQYchpDMYSFLSSCWNFDPEARPT 419
Cdd:cd08225  209 QLVLKI-CQGYFAPISPNFSR---DLRSLISQLFKVSPRDRPS 247
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
185-420 1.00e-07

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: 53.04  E-value: 1.00e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 185 IQDELVTLSSLrSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLidrklnfnnqltcsdgsnqkvynfNNGEQERISD 264
Cdd:cd14060   29 IEKEAEILSVL-SHRNIIQFYGAILEAPNYGIVTEYASYGSLFDYL------------------------NSNESEEMDM 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 265 DmqalctlDLLSYGYQIAIAMKFL---ADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSpQLPLapev 341
Cdd:cd14060   84 D-------QIMTWATDIAKGMHYLhmeAPVKVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHMSLVG-TFPW---- 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 342 MAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPH--EAVNAVYCGQDIERKLPELQYCHPDMYSFLSSCWNFDPEARPT 419
Cdd:cd14060  152 MAPEVIQSLPVSETCDTYSYGVVLWEMLTREVPFKglEGLQVAWLVVEKNERPTIPSSCPRSFAELMRRCWEADVKERPS 231

                 .
gi 392922083 420 Y 420
Cdd:cd14060  232 F 232
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
259-425 1.01e-07

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: 52.88  E-value: 1.01e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 259 QERISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFV---TRNKTIRIGEFGLARI--------NARKEY 327
Cdd:cd14065   76 EELLKSMDEQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLVreaNRGRNAVVADFGLAREmpdektkkPDRKKR 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 328 YIMKSPQLPLAPEVMAPESsedkkFTEKSEVRSFAVCLTGIF-QLGVPPHEAVNAVYCGQDIeRKLPEL--QYCHPDMYS 404
Cdd:cd14065  156 LTVVGSPYWMAPEMLRGES-----YDEKVDVFSFGIVLCEIIgRVPADPDYLPRTMDFGLDV-RAFRTLyvPDCPPSFLP 229
                        170       180
                 ....*....|....*....|.
gi 392922083 405 FLSSCWNFDPEARPTYSKCVE 425
Cdd:cd14065  230 LAIRCCQLDPEKRPSFVELEH 250
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
188-420 1.29e-07

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They 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. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. 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 serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 52.87  E-value: 1.29e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 188 ELVTLSSLRSHSCILALVGY-VREPNMllIVSEHAEHGRLDQFLIDRKLNFNnqltcsdgsnqkvynfnngeqerisddm 266
Cdd:cd05037   51 ETASLMSQISHKHLVKLYGVcVADENI--MVQEYVRYGPLDKYLRRMGNNVP---------------------------- 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 267 qALCTLDLLsygYQIAIAMKFLADSRCLHRALALRSIFVTRNKT------IRIGEFGLARINARKEYYIMKSPQLPlaPE 340
Cdd:cd05037  101 -LSWKLQVA---KQLASALHYLEDKKLIHGNVRGRNILLAREGLdgyppfIKLSDPGVPITVLSREERVDRIPWIA--PE 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 341 VMAPESSEDKKFTEKsevRSFAVCLTGIFQLGVPPHEAvnavYCGQDIERK------LPELQYchPDMYSFLSSCWNFDP 414
Cdd:cd05037  175 CLRNLQANLTIAADK---WSFGTTLWEICSGGEEPLSA----LSSQEKLQFyedqhqLPAPDC--AELAELIMQCWTYEP 245

                 ....*.
gi 392922083 415 EARPTY 420
Cdd:cd05037  246 TKRPSF 251
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
255-425 1.70e-07

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: 52.09  E-value: 1.70e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 255 NNGEQERISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNK---TIRIGEFGLArinARKEYYIMK 331
Cdd:cd14155   71 NGGNLEQLLDSNEPLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSKNCLIKRDEngyTAVVGDFGLA---EKIPDYSDG 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 332 SPQLPL--APEVMAPESSEDKKFTEKSEVRSFAVCLTGIF-QLGVPPHEAVNAVYCGQDIERKLPELQYCHPDMYSFLSS 408
Cdd:cd14155  148 KEKLAVvgSPYWMAPEVLRGEPYNEKADVFSYGIILCEIIaRIQADPDYLPRTEDFGLDYDAFQHMVGDCPPDFLQLAFN 227
                        170
                 ....*....|....*..
gi 392922083 409 CWNFDPEARPTYSKCVE 425
Cdd:cd14155  228 CCNMDPKSRPSFHDIVK 244
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
277-431 2.09e-07

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: 52.17  E-value: 2.09e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLArinARKEYYIMKSPQLPLAPEVMAPESSEDKK-FTEK 355
Cdd:cd14099  106 FMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLA---ARLEYDGERKKTLCGTPNYIAPEVLEKKKgHSFE 182
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 356 SEVRSFAVCL-TGIFqlGVPPHEA--VNAVYcgqdieRKLPELQYCHPD--MYS-----FLSSCWNFDPEARPTyskCVE 425
Cdd:cd14099  183 VDIWSLGVILyTLLV--GKPPFETsdVKETY------KRIKKNEYSFPShlSISdeakdLIRSMLQPDPTKRPS---LDE 251

                 ....*.
gi 392922083 426 FFDDHF 431
Cdd:cd14099  252 ILSHPF 257
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
183-419 2.96e-07

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: 51.77  E-value: 2.96e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 183 KMIQDELVTLSSLRsHSCIlalVGY-----VREPNMLLIVSEHAEHGRLDQFLIDRKLNFnnqltcsdgsnqkvynfnng 257
Cdd:cd08217   44 QQLVSEVNILRELK-HPNI---VRYydrivDRANTTLYIVMEYCEGGDLAQLIKKCKKEN-------------------- 99
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 258 eqERISDDMqalctldLLSYGYQIAIAMKF-----LADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKE------ 326
Cdd:cd08217  100 --QYIPEEF-------IWKIFTQLLLALYEchnrsVGGGKILHRDLKPANIFLDSDNNVKLGDFGLARVLSHDSsfakty 170
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 327 ----YYimkspqlplapevMAPESSEDKKFTEKSEVRSFAvCLtgIFQL--GVPPHEAVNAVYCGQDIER-KLPELqych 399
Cdd:cd08217  171 vgtpYY-------------MSPELLNEQSYDEKSDIWSLG-CL--IYELcaLHPPFQAANQLELAKKIKEgKFPRI---- 230
                        250       260
                 ....*....|....*....|....*
gi 392922083 400 PDMYS-----FLSSCWNFDPEARPT 419
Cdd:cd08217  231 PSRYSselneVIKSMLNVDPDKRPS 255
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
276-429 3.24e-07

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: 51.55  E-value: 3.24e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 276 SYG-YQIAIAMKFLADS-RCLHRALALRSIFVTRNKTIRIGEFGLA-------RINARKEYYIMKSPQLP-LAPEVMAPE 345
Cdd:cd14011  117 KYGlLQISEALSFLHNDvKLVHGNICPESVVINSNGEWKLAGFDFCisseqatDQFPYFREYDPNLPPLAqPNLNYLAPE 196
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 346 SSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAvycgQDIERKLPElQYCHPDM----------YSFLSSCWNFDPE 415
Cdd:cd14011  197 YILSKTCDPASDMFSLGVLIYAIYNKGKPLFDCVNN----LLSYKKNSN-QLRQLSLsllekvpeelRDHVKTLLNVTPE 271
                        170
                 ....*....|....*..
gi 392922083 416 ARP---TYSKcVEFFDD 429
Cdd:cd14011  272 VRPdaeQLSK-IPFFDD 287
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
180-419 3.46e-07

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: 51.43  E-value: 3.46e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 180 THQKMIQDELVTLSSLrSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNnqltcsdgsnqkvynfnngEQ 259
Cdd:cd05122   39 EKKESILNEIAILKKC-KHPNIVKYYGSYLKKDELWIVMEFCSGGSLKDLLKNTNKTLT-------------------EQ 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 260 ER--ISDDM-QALCTLDllsyGYQIaiamkfladsrcLHRALALRSIFVTRNKTIRIGEFGLA----RINARKEyyIMKS 332
Cdd:cd05122   99 QIayVCKEVlKGLEYLH----SHGI------------IHRDIKAANILLTSDGEVKLIDFGLSaqlsDGKTRNT--FVGT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 333 PQLplapevMAPESSEDKKFTEKSEVRSFAVCLTGIFQlGVPPHEAVNAV----YCGQDIERKLPELQYCHPDMYSFLSS 408
Cdd:cd05122  161 PYW------MAPEVIQGKPYGFKADIWSLGITAIEMAE-GKPPYSELPPMkalfLIATNGPPGLRNPKKWSKEFKDFLKK 233
                        250
                 ....*....|.
gi 392922083 409 CWNFDPEARPT 419
Cdd:cd05122  234 CLQKDPEKRPT 244
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
280-418 4.53e-07

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: 51.35  E-value: 4.53e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 280 QIAIAMKFL-ADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLapeVMAPESSEDKKFTEKSEV 358
Cdd:cd08528  121 QMVLALRYLhKEKQIVHRDLKPNNIMLGEDDKVTITDFGLAKQKGPESSKMTSVVGTIL---YSCPEIVQNEPYGEKADI 197
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 392922083 359 RSFAVCLTGIFQLGVPPH---------EAVNAVYcgqdieRKLPELQYCHpDMYSFLSSCWNFDPEARP 418
Cdd:cd08528  198 WALGCILYQMCTLQPPFYstnmltlatKIVEAEY------EPLPEGMYSD-DITFVIRSCLTPDPEARP 259
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
146-424 5.78e-07

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 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: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 51.07  E-value: 5.78e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 146 HYYSRIRLGKMKSMGAHKNSPTLSIKC---ALLRNDITHQKMIQDELVTLSSLRSHscILALVGYVREPNMLLIVSEHAE 222
Cdd:cd14026    3 RYLSRGAFGTVSRARHADWRVTVAIKClklDSPVGDSERNCLLKEAEILHKARFSY--ILPILGICNEPEFLGIVTEYMT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 223 HGRLDQFLidrklnfnnqltcsdgsnqkvynfnngEQERISDDMQALCTLDLLsygYQIAIAMKFLADSR--CLHRALAL 300
Cdd:cd14026   81 NGSLNELL---------------------------HEKDIYPDVAWPLRLRIL---YEIALGVNYLHNMSppLLHHDLKT 130
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 301 RSIFVTRNKTIRIGEFGLARInarKEYYIMKSPQLPLAPE-----VMAPESSEDKKFTE---KSEVRSFAVCLTGIFQLG 372
Cdd:cd14026  131 QNILLDGEFHVKIADFGLSKW---RQLSISQSRSSKSAPEggtiiYMPPEEYEPSQKRRasvKHDIYSYAIIMWEVLSRK 207
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 392922083 373 VPPHEAVN------AVYCGQDIERKLPELQYCHPD---MYSFLSSCWNFDPEARPTYSKCV 424
Cdd:cd14026  208 IPFEEVTNplqimySVSQGHRPDTGEDSLPVDIPHratLINLIESGWAQNPDERPSFLKCL 268
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
277-419 6.43e-07

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: 50.40  E-value: 6.43e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLArinARKEYYIMKSPQLPLAPEVMAPESSEDKKFTEKS 356
Cdd:cd14188  106 YLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLA---ARLEPLEHRRRTICGTPNYLSPEVLNKQGHGCES 182
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392922083 357 EVRSFAvCLTGIFQLGVPPHEAVNAvycgQDIERKLPELQYCHPDMYS-----FLSSCWNFDPEARPT 419
Cdd:cd14188  183 DIWALG-CVMYTMLLGRPPFETTNL----KETYRCIREARYSLPSSLLapakhLIASMLSKNPEDRPS 245
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
277-427 6.70e-07

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: 50.70  E-value: 6.70e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLArinARKEYYIMKSPQLPLAPEVMAPESSEDKKFTEKS 356
Cdd:cd14189  106 YLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLA---ARLEPPEQRKKTICGTPNYLAPEVLLRQGHGPES 182
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392922083 357 EVRSFAvCLTGIFQLGVPPHEAVNAvycgQDIERKLPELQYCHPDMYS-----FLSSCWNFDPEARPTYSKCV--EFF 427
Cdd:cd14189  183 DVWSLG-CVMYTLLCGNPPFETLDL----KETYRCIKQVKYTLPASLSlparhLLAGILKRNPGDRLTLDQILehEFF 255
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
277-427 7.39e-07

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: 50.32  E-value: 7.39e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLArinARKEYYIMKSPQLPLAPEVMAPESSEDKKFTEKS 356
Cdd:cd14187  112 YLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLA---TKVEYDGERKKTLCGTPNYIAPEVLSKKGHSFEV 188
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392922083 357 EVRSFAvCLTGIFQLGVPPHEAVnavyCGQDIERKLPELQYC-----HPDMYSFLSSCWNFDPEARPTYSKCV--EFF 427
Cdd:cd14187  189 DIWSIG-CIMYTLLVGKPPFETS----CLKETYLRIKKNEYSipkhiNPVAASLIQKMLQTDPTARPTINELLndEFF 261
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
258-419 1.04e-06

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: 49.98  E-value: 1.04e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 258 EQERISDDMQALCTLDLLsygYQIAIAMKFLADSRCLHRALALRSIFVT-RNKTIRIGEFGLAR--INARKEYYIMKSPQ 334
Cdd:cd13996   96 DRRNSSSKNDRKLALELF---KQILKGVSYIHSKGIVHRDLKPSNIFLDnDDLQVKIGDFGLATsiGNQKRELNNLNNNN 172
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 335 LPLAPEV---------MAPESSEDKKFTEKSEVRSFAVCLtgiFQLGVPP---HEAVNAVycgQDIER-KLPE-LQYCHP 400
Cdd:cd13996  173 NGNTSNNsvgigtplyASPEQLDGENYNEKADIYSLGIIL---FEMLHPFktaMERSTIL---TDLRNgILPEsFKAKHP 246
                        170
                 ....*....|....*....
gi 392922083 401 DMYSFLSSCWNFDPEARPT 419
Cdd:cd13996  247 KEADLIQSLLSKNPEERPS 265
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
271-422 1.09e-06

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: 50.02  E-value: 1.09e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 271 TLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINAR-KEYYIMKSPQ---LPLAPEVMapES 346
Cdd:cd14150   95 TMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLATVKTRwSGSQQVEQPSgsiLWMAPEVI--RM 172
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 347 SEDKKFTEKSEVRSFAVCLTGIFQlGVPPHEAVNAV----------YCGQDIERKLPElqyCHPDMYSFLSSCWNFDPEA 416
Cdd:cd14150  173 QDTNPYSFQSDVYAYGVVLYELMS-GTLPYSNINNRdqiifmvgrgYLSPDLSKLSSN---CPKAMKRLLIDCLKFKREE 248

                 ....*.
gi 392922083 417 RPTYSK 422
Cdd:cd14150  249 RPLFPQ 254
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
175-429 1.52e-06

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 50.40  E-value: 1.52e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 175 LRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcsdgsnqkvynf 254
Cdd:COG0515   44 LAADPEARERFRREARALARLN-HPNIVRVYDVGEEDGRPYLVMEYVEGESLADLLRRRG-------------------- 102
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 255 nngeqeRISDDmqalctlDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEyyIMKSPQ 334
Cdd:COG0515  103 ------PLPPA-------EALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGAT--LTQTGT 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 335 LPLAPEVMAPESSEDKKFTEKSEVRSFAVCLtgiFQL--GVPPHEAVNAV-YCGQDIERKLPELQYCHPD----MYSFLS 407
Cdd:COG0515  168 VVGTPGYMAPEQARGEPVDPRSDVYSLGVTL---YELltGRPPFDGDSPAeLLRAHLREPPPPPSELRPDlppaLDAIVL 244
                        250       260
                 ....*....|....*....|..
gi 392922083 408 SCWNFDPEARptYSKCVEFFDD 429
Cdd:COG0515  245 RALAKDPEER--YQSAAELAAA 264
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
294-431 2.28e-06

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: 48.76  E-value: 2.28e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 294 LHRALALRSIFVTRNK-TIRIGEFGLARI-NARKEYYIMKSpqlplaPEVMAPESSEDkKFTEKSEVRSFAVCLTGIFQL 371
Cdd:cd13983  126 IHRDLKCDNIFINGNTgEVKIGDLGLATLlRQSFAKSVIGT------PEFMAPEMYEE-HYDEKVDIYAFGMCLLEMATG 198
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 372 GVPPHEAVNAVycgqDIERKL-----PE-LQYC-HPDMYSFLSSCWNfDPEARPTyskCVEFFDDHF 431
Cdd:cd13983  199 EYPYSECTNAA----QIYKKVtsgikPEsLSKVkDPELKDFIEKCLK-PPDERPS---ARELLEHPF 257
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
260-365 2.41e-06

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: 48.82  E-value: 2.41e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 260 ERISDDMQALCTLD-LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQlplA 338
Cdd:cd08219   87 QKIKLQRGKLFPEDtILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLTSPGAYACTYVG---T 163
                         90       100
                 ....*....|....*....|....*..
gi 392922083 339 PEVMAPESSEDKKFTEKSEVRSFAVCL 365
Cdd:cd08219  164 PYYVPPEIWENMPYNNKSDIWSLGCIL 190
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
279-441 2.52e-06

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: 49.06  E-value: 2.52e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARI---NARKE---------YYimkspqlpLAPEVMApes 346
Cdd:cd07834  110 YQILRGLKYLHSAGVIHRDLKPSNILVNSNCDLKICDFGLARGvdpDEDKGflteyvvtrWY--------RAPELLL--- 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 347 sEDKKFTEKSEVRS----FAVCLTG---------------IF-QLGVPPHEAVNAV--------------YCGQDIERKL 392
Cdd:cd07834  179 -SSKKYTKAIDIWSvgciFAELLTRkplfpgrdyidqlnlIVeVLGTPSEEDLKFIssekarnylkslpkKPKKPLSEVF 257
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 392922083 393 PElqyCHPDMYSFLSSCWNFDPEARPTYSKCVE--FFDDHFSENQIMIGKQ 441
Cdd:cd07834  258 PG---ASPEAIDLLEKMLVFNPKKRITADEALAhpYLAQLHDPEDEPVAKP 305
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
274-409 4.73e-06

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: 48.13  E-value: 4.73e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINAR----KEYYIMKSPQLPLAPEVMAPESSED 349
Cdd:cd14151  106 LIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRwsgsHQFEQLSGSILWMAPEVIRMQDKNP 185
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 350 KKFteKSEVRSFAVCLTGIFQlGVPPHEAVNavycGQDIERKLPELQYCHPDMYSFLSSC 409
Cdd:cd14151  186 YSF--QSDVYAFGIVLYELMT-GQLPYSNIN----NRDQIIFMVGRGYLSPDLSKVRSNC 238
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
276-419 5.48e-06

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: 47.61  E-value: 5.48e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 276 SYGYQIAIAMKFLADSRCLHRALALRSIFVT-RNKTIRIGEFGLARINARKEYYIMKSPQLPLAPEVMApessEDKKFTE 354
Cdd:cd05118  105 SYLYQLLQALDFLHSNGIIHRDLKPENILINlELGQLKLADFGLARSFTSPPYTPYVATRWYRAPEVLL----GAKPYGS 180
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392922083 355 KSEVRSFAVCLTGIFQlGVP---PHEAVNAVYCgqdIERKLPElqychPDMYSFLSSCWNFDPEARPT 419
Cdd:cd05118  181 SIDIWSLGCILAELLT-GRPlfpGDSEVDQLAK---IVRLLGT-----PEALDLLSKMLKYDPAKRIT 239
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
152-429 5.78e-06

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: 47.99  E-value: 5.78e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 152 RLGKMKSMGAHKNSPTLSIKCALLRNDITHQKMIQDELVTLSSLRsHSCILALVGYVREPNMLliVSEHAEHGRLDQFLI 231
Cdd:cd14000   24 IFNKHTSSNFANVPADTMLRHLRATDAMKNFRLLRQELTVLSHLH-HPSIVYLLGIGIHPLML--VLELAPLGSLDHLLQ 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 232 DRKLNFnnqltcsdgsnqkvYNFNNGEQERISddmqalctldllsygYQIAIAMKFLADSRCLHRALA-----LRSIFVT 306
Cdd:cd14000  101 QDSRSF--------------ASLGRTLQQRIA---------------LQVADGLRYLHSAMIIYRDLKshnvlVWTLYPN 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 307 RNKTIRIGEFGLARINARkeyyiMKSPQLPLAPEVMAPE-SSEDKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCG 385
Cdd:cd14000  152 SAIIIKIADYGISRQCCR-----MGAKGSEGTPGFRAPEiARGNVIYNEKVDVFSFGMLLYEILSGGAPMVGHLKFPNEF 226
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 392922083 386 QDIERKLPEL-QY-CH--PDMYSFLSSCWNFDPEARPTYSKCVEFFDD 429
Cdd:cd14000  227 DIHGGLRPPLkQYeCApwPEVEVLMKKCWKENPQQRPTAVTVVSILNS 274
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
160-431 7.45e-06

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: 47.22  E-value: 7.45e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 160 GAHKNSPTL-SIKCALLRndiTHQKMIQD----ELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRK 234
Cdd:cd14009   12 GRHKQTGEVvAIKEISRK---KLNKKLQEnlesEIAILKSIK-HPNIVRLYDVQKTEDFIYLVLEYCAGGDLSQYIRKRG 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 235 lnfnnqltcsdgsnqkvynfnngeqeRISDD-----MQalctldllsygyQIAIAMKFLADSRCLHRALALRSIFVTRNK 309
Cdd:cd14009   88 --------------------------RLPEAvarhfMQ------------QLASGLKFLRSKNIIHRDLKPQNLLLSTSG 129
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 310 ---TIRIGEFGLARinarkeyYImksPQLPLA------PEVMAPESSEDKKFTEKSEVRSFAVCLtgiFQL--GVPPHEA 378
Cdd:cd14009  130 ddpVLKIADFGFAR-------SL---QPASMAetlcgsPLYMAPEILQFQKYDAKADLWSVGAIL---FEMlvGKPPFRG 196
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 392922083 379 VNAVYCGQDIER-----KLPELQYCHPDMYSFLSSCWNFDPEARPTYSkcvEFFDDHF 431
Cdd:cd14009  197 SNHVQLLRNIERsdaviPFPIAAQLSPDCKDLLRRLLRRDPAERISFE---EFFAHPF 251
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
274-381 8.72e-06

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: 47.31  E-value: 8.72e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLaDSRC---LHRALALRSIFVT-RNKTIRIGEFGLARInarKEYYIMKSpqLPLAPEVMAPESSED 349
Cdd:cd14033  106 LQRWSRQILKGLHFL-HSRCppiLHRDLKCDNIFITgPTGSVKIGDLGLATL---KRASFAKS--VIGTPEFMAPEMYEE 179
                         90       100       110
                 ....*....|....*....|....*....|..
gi 392922083 350 kKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNA 381
Cdd:cd14033  180 -KYDEAVDVYAFGMCILEMATSEYPYSECQNA 210
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
259-425 1.10e-05

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: 47.18  E-value: 1.10e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 259 QERISDDMQALCTLDLLSYGY------QIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLA-RINARKEYYIMK 331
Cdd:cd14048   99 KENLKDWMNRRCTMESRELFVclnifkQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLVtAMDQGEPEQTVL 178
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 332 SPQLPLAPEV--------MAPESSEDKKFTEKSEVrsFAVCLTgIFQLGVPPHEAVNAVYCGQDIeRKL---PELQYCHP 400
Cdd:cd14048  179 TPMPAYAKHTgqvgtrlyMSPEQIHGNQYSEKVDI--FALGLI-LFELIYSFSTQMERIRTLTDV-RKLkfpALFTNKYP 254
                        170       180
                 ....*....|....*....|....*
gi 392922083 401 DMYSFLSSCWNFDPEARPTYSKCVE 425
Cdd:cd14048  255 EERDMVQQMLSPSPSERPEAHEVIE 279
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
277-418 1.14e-05

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: 46.95  E-value: 1.14e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKeyyIMKSPQLPLAPEVMAPESSEDKKFTEKS 356
Cdd:cd08229  133 YFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSK---TTAAHSLVGTPYYMSPERIHENGYNFKS 209
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 357 EVRSFAVCLTGIFQLGVPPH-EAVNAVYCGQDIER----KLPELQYCHpDMYSFLSSCWNFDPEARP 418
Cdd:cd08229  210 DIWSLGCLLYEMAALQSPFYgDKMNLYSLCKKIEQcdypPLPSDHYSE-ELRQLVNMCINPDPEKRP 275
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
283-417 1.28e-05

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: 46.70  E-value: 1.28e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 283 IAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLA---RINARKEYYIMKSPQLpLAPEVMapesSEDKKFTEKSEVR 359
Cdd:cd06917  112 VALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAaslNQNSSKRSTFVGTPYW-MAPEVI----TEGKYYDTKADIW 186
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 392922083 360 SFAVCLTGIfQLGVPPHEAVNAVYCGQDIERKLP---ELQYCHPDMYSFLSSCWNFDPEAR 417
Cdd:cd06917  187 SLGITTYEM-ATGNPPYSDVDALRAVMLIPKSKPprlEGNGYSPLLKEFVAACLDEEPKDR 246
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
186-431 1.94e-05

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 46.25  E-value: 1.94e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 186 QDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDR--KLN--FNNQLTcsdgsnqkvynfnngeqer 261
Cdd:cd14043   44 KNVFSKLRELR-HENVNLFLGLFVDCGILAIVSEHCSRGSLEDLLRNDdmKLDwmFKSSLL------------------- 103
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 262 isddmqalctLDLLSygyqiaiAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARInarkeYYIMKSPQLPLAPEV 341
Cdd:cd14043  104 ----------LDLIK-------GMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYNEI-----LEAQNLPLPEPAPEE 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 342 M---APESSED----KKFTEKSEVRSFA------VCLTGIF-QLGVPPHEAVNAVycgqdieRKLPELqyCHP------- 400
Cdd:cd14043  162 LlwtAPELLRDprleRRGTFPGDVFSFAiimqevIVRGAPYcMLGLSPEEIIEKV-------RSPPPL--CRPsvsmdqa 232
                        250       260       270
                 ....*....|....*....|....*....|...
gi 392922083 401 --DMYSFLSSCWNFDPEARPTyskcvefFDDHF 431
Cdd:cd14043  233 plECIQLMKQCWSEAPERRPT-------FDQIF 258
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
273-419 2.56e-05

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: 45.50  E-value: 2.56e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 273 DLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARInARKEYYIMKSpqLPLAPEVMAPESSEDKKF 352
Cdd:cd08221  102 VVLWYLYQIVSAVSHIHKAGILHRDIKTLNIFLTKADLVKLGDFGISKV-LDSESSMAES--IVGTPYYMSPELVQGVKY 178
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 353 TEKSEVRSFAVCLTGIFQLGvPPHEAVNAVYCGQDI---ERKLPELQYCHpDMYSFLSSCWNFDPEARPT 419
Cdd:cd08221  179 NFKSDIWAVGCVLYELLTLK-RTFDATNPLRLAVKIvqgEYEDIDEQYSE-EIIQLVHDCLHQDPEDRPT 246
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
279-374 3.02e-05

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 46.16  E-value: 3.02e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLArinarKEYyiMKSPQLPLA------PEVMAPESSEDKKF 352
Cdd:PTZ00267 176 YQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFS-----KQY--SDSVSLDVAssfcgtPYYLAPELWERKRY 248
                         90       100
                 ....*....|....*....|..
gi 392922083 353 TEKSEVRSFAVCLTGIFQLGVP 374
Cdd:PTZ00267 249 SKKADMWSLGVILYELLTLHRP 270
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
175-419 4.13e-05

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: 45.07  E-value: 4.13e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 175 LRNDITHQKMIQdELVTLSSLRSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDrklnfnnqltcsdgsnqkvynf 254
Cdd:cd13997   37 FRGPKERARALR-EVEAHAALGQHPNIVRYYSSWEEGGHLYIQMELCENGSLQDALEE---------------------- 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 255 nNGEQERISDdmqalctLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLArinarkeYYIMKSPQ 334
Cdd:cd13997   94 -LSPISKLSE-------AEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLA-------TRLETSGD 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 335 LP------LAPEVMApessEDKKFTEKSEvrsfavcltgIFQLGVPPHEAV-------NAVYCGQDIERKLP-ELQYCHP 400
Cdd:cd13997  159 VEegdsryLAPELLN----ENYTHLPKAD----------IFSLGVTVYEAAtgeplprNGQQWQQLRQGKLPlPPGLVLS 224
                        250       260
                 ....*....|....*....|
gi 392922083 401 -DMYSFLSSCWNFDPEARPT 419
Cdd:cd13997  225 qELTRLLKVMLDPDPTRRPT 244
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
280-428 5.62e-05

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: 44.61  E-value: 5.62e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 280 QIAIAMKFLADSRCLHRALALRSIFVTRNKTIrIGEFGLARINA------RKEYYIMKSPQL-PLAPEV---MAPESSED 349
Cdd:cd14153  105 EIVKGMGYLHAKGILHKDLKSKNVFYDNGKVV-ITDFGLFTISGvlqagrREDKLRIQSGWLcHLAPEIirqLSPETEED 183
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 350 K-KFTEKSEVRSFAVCLTGIFQLGVP----PHEAVnAVYCGQDIERKLPELQYcHPDMYSFLSSCWNFDPEARPTYSKCV 424
Cdd:cd14153  184 KlPFSKHSDVFAFGTIWYELHAREWPfktqPAEAI-IWQVGSGMKPNLSQIGM-GKEISDILLFCWAYEQEERPTFSKLM 261

                 ....
gi 392922083 425 EFFD 428
Cdd:cd14153  262 EMLE 265
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
279-419 6.75e-05

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: 44.87  E-value: 6.75e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARI-NARKEYYImkSPQLPLAPEVMAPESSEDKK------ 351
Cdd:cd07856  115 YQILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLARIqDPQMTGYV--STRYYRAPEIMLTWQKYDVEvdiwsa 192
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 352 -------------FTEKSEVRSFAVcLTGIfqLGVPPHEAVNAVyCGQDIER---KLPE---------LQYCHPDMYSFL 406
Cdd:cd07856  193 gcifaemlegkplFPGKDHVNQFSI-ITEL--LGTPPDDVINTI-CSENTLRfvqSLPKrervpfsekFKNADPDAIDLL 268
                        170
                 ....*....|...
gi 392922083 407 SSCWNFDPEARPT 419
Cdd:cd07856  269 EKMLVFDPKKRIS 281
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
276-345 7.30e-05

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: 44.40  E-value: 7.30e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392922083 276 SYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARinarkeyyIMKSPQLPLAPEVM-----APE 345
Cdd:cd07829  102 SIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLAR--------AFGIPLRTYTHEVVtlwyrAPE 168
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
284-419 8.63e-05

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: 44.12  E-value: 8.63e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 284 AMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGL-ARINARKEyyimKSPQLPLAPEVMAPESSEDKKFTEKSEVRSFa 362
Cdd:cd06614  109 GLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFaAQLTKEKS----KRNSVVGTPYWMAPEVIKRKDYGPKVDIWSL- 183
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392922083 363 vcltGIFQL----GVPPH---EAVNAVYCgqdIERK-LPELQYCH---PDMYSFLSSCWNFDPEARPT 419
Cdd:cd06614  184 ----GIMCIemaeGEPPYleePPLRALFL---ITTKgIPPLKNPEkwsPEFKDFLNKCLVKDPEKRPS 244
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
279-421 1.19e-04

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-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: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 43.64  E-value: 1.19e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 279 YQIAIAMKFL--ADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLAPEVMAPES--SEDKKFTE 354
Cdd:cd14025   99 HETAVGMNFLhcMKPPLLHLDLKPANILLDAHYHVKISDFGLAKWNGLSHSHDLSRDGLRGTIAYLPPERfkEKNRCPDT 178
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392922083 355 KSEVRSFAVCLTGIFQLGVPPHEAVNA----VYCGQDIERKLPELQYCHP----DMYSFLSSCWNFDPEARPTYS 421
Cdd:cd14025  179 KHDVYSFAIVIWGILTQKKPFAGENNIlhimVKVVKGHRPSLSPIPRQRPsecqQMICLMKRCWDQDPRKRPTFQ 253
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
280-428 1.43e-04

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 43.42  E-value: 1.43e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 280 QIAIAMKFLADSRCLHRALALRSIFVTRNKTIrIGEFGLARINA-----RKEYYImkspQLP------LAPEV---MAPE 345
Cdd:cd14152  105 EIIKGMGYLHAKGIVHKDLKSKNVFYDNGKVV-ITDFGLFGISGvvqegRRENEL----KLPhdwlcyLAPEIvreMTPG 179
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 346 SSEDK-KFTEKSEVRSFAVCLTGIFQLGVP----PHEA-VNAVYCGQDIERKLPELQYcHPDMYSFLSSCWNFDPEARPT 419
Cdd:cd14152  180 KDEDClPFSKAADVYAFGTIWYELQARDWPlknqPAEAlIWQIGSGEGMKQVLTTISL-GKEVTEILSACWAFDLEERPS 258

                 ....*....
gi 392922083 420 YSKCVEFFD 428
Cdd:cd14152  259 FTLLMDMLE 267
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
185-377 2.01e-04

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: 42.93  E-value: 2.01e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 185 IQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLNFNNqltcsdgsnqkvynfnngEQERisd 264
Cdd:cd14186   48 VRNEVEIHCQLK-HPSILELYNYFEDSNYVYLVLEMCHNGEMSRYLKNRKKPFTE------------------DEAR--- 105
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 265 dmqalctldllSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLA---RINARKEYYIMKSPQLplapev 341
Cdd:cd14186  106 -----------HFMHQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLAtqlKMPHEKHFTMCGTPNY------ 168
                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 392922083 342 MAPESSEDKKFTEKSEVRSFAvCLTGIFQLGVPPHE 377
Cdd:cd14186  169 ISPEIATRSAHGLESDVWSLG-CMFYTLLVGRPPFD 203
Pkinase pfam00069
Protein kinase domain;
170-419 2.27e-04

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 42.23  E-value: 2.27e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083  170 IKCALLRNDITHQKM-IQDELVTLSSLRsHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcsdgsn 248
Cdd:pfam00069  29 IKKIKKEKIKKKKDKnILREIKILKKLN-HPNIVRLYDAFEDKDNLYLVLEYVEGGSLFDLLSEKG-------------- 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083  249 qkvynfnngeqeRISDDmqalctlDLLSYGYQIAIAMKfladsrclhRALALRSIFVTRnktirigefglarinarkeYY 328
Cdd:pfam00069  94 ------------AFSER-------EAKFIMKQILEGLE---------SGSSLTTFVGTP-------------------WY 126
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083  329 imkspqlplapevMAPESSEDKKFTEKSEVRS----FAVCLTG--IFQLGVPPHEAVNAVYCGQDIERKLPElqyCHPDM 402
Cdd:pfam00069 127 -------------MAPEVLGGNPYGPKVDVWSlgciLYELLTGkpPFPGINGNEIYELIIDQPYAFPELPSN---LSEEA 190
                         250
                  ....*....|....*..
gi 392922083  403 YSFLSSCWNFDPEARPT 419
Cdd:pfam00069 191 KDLLKKLLKKDPSKRLT 207
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
210-425 2.34e-04

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: 43.08  E-value: 2.34e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 210 EPNMLLIVSEHAEHGRLDQFLIDRKLNFNNQL-----TCSDGSnqkVYNFNNGEQERiSDDMQALCTLDLLsygYQIAIA 284
Cdd:cd06638   64 EYNILKALSDHPNVVKFYGMYYKKDVKNGDQLwlvleLCNGGS---VTDLVKGFLKR-GERMEEPIIAYIL---HEALMG 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 285 MKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR--INARKEYYIMKSPQLPLAPEVMAPESSEDKKFTEKSEVRSFA 362
Cdd:cd06638  137 LQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGVSAqlTSTRLRRNTSVGTPFWMAPEVIACEQQLDSTYDARCDVWSLG 216
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 363 VclTGI-FQLGVPPHEAVNAVYCGQDIERK-LPELQycHPDMYS-----FLSSCWNFDPEARPTYSKCVE 425
Cdd:cd06638  217 I--TAIeLGDGDPPLADLHPMRALFKIPRNpPPTLH--QPELWSnefndFIRKCLTKDYEKRPTVSDLLQ 282
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
274-365 2.80e-04

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: 42.71  E-value: 2.80e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 274 LLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINAR----KEYYIMKSPQLPLAPEVMapESSED 349
Cdd:cd14149  110 LIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATVKSRwsgsQQVEQPTGSILWMAPEVI--RMQDN 187
                         90
                 ....*....|....*.
gi 392922083 350 KKFTEKSEVRSFAVCL 365
Cdd:cd14149  188 NPFSFQSDVYSYGIVL 203
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
251-417 3.16e-04

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: 42.24  E-value: 3.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 251 VYNFNNGEQERISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARinarkeyyIM 330
Cdd:cd14002   78 VTEYAQGELFQILEDDGTLPEEEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFAR--------AM 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 331 KSPQLPL-----APEVMAPESSEDKKFTEKSEVRSFAVCLTGIFqLGVPPHEAVNAVYCGQDIER---KLPELQYchPDM 402
Cdd:cd14002  150 SCNTLVLtsikgTPLYMAPELVQEQPYDHTADLWSLGCILYELF-VGQPPFYTNSIYQLVQMIVKdpvKWPSNMS--PEF 226
                        170
                 ....*....|....*
gi 392922083 403 YSFLSSCWNFDPEAR 417
Cdd:cd14002  227 KSFLQGLLNKDPSKR 241
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
279-419 5.42e-04

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: 41.90  E-value: 5.42e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFG----LARINARKEYYImKSPQLpLAPEVMAPESSEDKKFTE 354
Cdd:cd06608  120 RETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGvsaqLDSTLGRRNTFI-GTPYW-MAPEVIACDQQPDASYDA 197
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392922083 355 KSEVRSFAVclTGIfQL--GVPP----HeAVNAVYcgQDIERKLPELQycHPDMYS-----FLSSCWNFDPEARPT 419
Cdd:cd06608  198 RCDVWSLGI--TAI-ELadGKPPlcdmH-PMRALF--KIPRNPPPTLK--SPEKWSkefndFISECLIKNYEQRPF 265
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
251-378 6.10e-04

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: 41.53  E-value: 6.10e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 251 VYNFNNGEQerISDDMQALCTLD---LLSYGYQIAIAMKFLADSRCLHRALALRSI---FVTRNKT------IRIGEFGL 318
Cdd:cd14201   83 VMEYCNGGD--LADYLQAKGTLSedtIRVFLQQIAAAMRILHSKGIIHRDLKPQNIllsYASRKKSsvsgirIKIADFGF 160
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392922083 319 ARINARKeyyiMKSPQLPLAPEVMAPESSEDKKFTEKSEVRSFAvclTGIFQ--LGVPPHEA 378
Cdd:cd14201  161 ARYLQSN----MMAATLCGSPMYMAPEVIMSQHYDAKADLWSIG---TVIYQclVGKPPFQA 215
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
279-425 7.16e-04

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: 41.52  E-value: 7.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR--INARKEYYIMKSPQLPLAPEVMAPESSEDKKFTEKS 356
Cdd:cd06639  135 YGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAqlTSARLRRNTSVGTPFWMAPEVIACEQQYDYSYDARC 214
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392922083 357 EVRSFAVclTGI-FQLGVPPHEAVNAVYCGQDIERKlPELQYCHPDMY-----SFLSSCWNFDPEARPTYSKCVE 425
Cdd:cd06639  215 DVWSLGI--TAIeLADGDPPLFDMHPVKALFKIPRN-PPPTLLNPEKWcrgfsHFISQCLIKDFEKRPSVTHLLE 286
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
251-428 8.21e-04

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: 41.38  E-value: 8.21e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 251 VYNFNNGEQ--ERISDDMQALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSI--FVTRNKTIRIGEFGLARINARKE 326
Cdd:cd14104   74 IFEFISGVDifERITTARFELNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIiyCTRRGSYIKIIEFGQSRQLKPGD 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 327 YYIMKSpqlpLAPEVMAPESSEDKKFTEKSEVRSFAvCLTGIFQLGVPPHEAVNavycGQDIERKLPELQychpdmysfl 406
Cdd:cd14104  154 KFRLQY----TSAEFYAPEVHQHESVSTATDMWSLG-CLVYVLLSGINPFEAET----NQQTIENIRNAE---------- 214
                        170       180
                 ....*....|....*....|...
gi 392922083 407 sscWNFDPEARPTYS-KCVEFFD 428
Cdd:cd14104  215 ---YAFDDEAFKNISiEALDFVD 234
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
279-321 9.72e-04

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: 40.82  E-value: 9.72e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARI 321
Cdd:cd07847  107 WQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARI 149
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
258-339 1.02e-03

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: 41.30  E-value: 1.02e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 258 EQERISDDMQALctldllsYGYQIAIAMKFLADSRCLHRALALRSIFV-TRNKTIRIGEFGLARI----NARKEYYIM-- 330
Cdd:cd07854  107 EQGPLSEEHARL-------FMYQLLRGLKYIHSANVLHRDLKPANVFInTEDLVLKIGDFGLARIvdphYSHKGYLSEgl 179
                         90
                 ....*....|....
gi 392922083 331 -----KSPQLPLAP 339
Cdd:cd07854  180 vtkwyRSPRLLLSP 193
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
276-425 1.05e-03

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: 40.85  E-value: 1.05e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 276 SYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARInaRKEYYIMKSpqLPLAPEVMAPESSEDKKFTEK 355
Cdd:cd06632  106 LYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKH--VEAFSFAKS--FKGSPYWMAPEVIMQKNSGYG 181
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 356 SEVRSFAVCLTGI-FQLGVPP---HEAVNAVYcgqDIERK--LPEL-QYCHPDMYSFLSSCWNFDPEARPTYSKCVE 425
Cdd:cd06632  182 LAVDIWSLGCTVLeMATGKPPwsqYEGVAAIF---KIGNSgeLPPIpDHLSPDAKDFIRLCLQRDPEDRPTASQLLE 255
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
178-421 1.25e-03

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: 40.72  E-value: 1.25e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 178 DITHQKMIQD---ELVTLSSLRSHSCILALVGYVrEPNMLLIVSEHAEHGRLDQFLIDRKlnfnnqltcsdgsNQKVYnf 254
Cdd:cd08224   37 EMMDAKARQDclkEIDLLQQLNHPNIIKYLASFI-ENNELNIVLELADAGDLSRLIKHFK-------------KQKRL-- 100
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 255 nngEQERisddmqalctlDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEyyiMKSPQ 334
Cdd:cd08224  101 ---IPER-----------TIWKYFVQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFSSKT---TAAHS 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 335 LPLAPEVMAPESSEDKKFTEKSEVRSFAVCLTGIFQLGVPPH-EAVNAVYCGQDIER----KLPELQYCHPdMYSFLSSC 409
Cdd:cd08224  164 LVGTPYYMSPERIREQGYDFKSDIWSLGCLLYEMAALQSPFYgEKMNLYSLCKKIEKceypPLPADLYSQE-LRDLVAAC 242
                        250
                 ....*....|..
gi 392922083 410 WNFDPEARPTYS 421
Cdd:cd08224  243 IQPDPEKRPDIS 254
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
260-345 1.29e-03

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: 40.72  E-value: 1.29e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 260 ERISDDM-QALCTLDllsygyqiaiamkFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARInarkeyyimKSPQLPLA 338
Cdd:cd07863  108 ETIKDLMrQFLRGLD-------------FLHANCIVHRDLKPENILVTSGGQVKLADFGLARI---------YSCQMALT 165
                         90
                 ....*....|..
gi 392922083 339 PEVM-----APE 345
Cdd:cd07863  166 PVVVtlwyrAPE 177
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
197-420 1.40e-03

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 40.16  E-value: 1.40e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 197 SHSCILALVGYVREPNMLLIVSEHAEHGRLdqflidrklnfnnqltcsdgsnqkvYNFNNGEQERISDDMQALctldllS 276
Cdd:cd14057   50 SHPNVLPVLGACNSPPNLVVISQYMPYGSL-------------------------YNVLHEGTGVVVDQSQAV------K 98
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLadsrclHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKSPQLPLAPEVMAPES---SEDKKFT 353
Cdd:cd14057   99 FALDIARGMAFL------HTLEPLIPRHHLNSKHVMIDEDMTARINMADVKFSFQEPGKMYNPAWMAPEAlqkKPEDINR 172
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392922083 354 EKSEVRSFAVCLTGIFQLGVPPHEAVNaVYCGQDIerKLPELQY-----CHPDMYSFLSSCWNFDPEARPTY 420
Cdd:cd14057  173 RSADMWSFAILLWELVTREVPFADLSN-MEIGMKI--ALEGLRVtippgISPHMCKLMKICMNEDPGKRPKF 241
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
280-419 1.52e-03

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: 40.43  E-value: 1.52e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 280 QIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEyyiMKSPQLPLAPEVMAPESSEDKKFTEKSEVR 359
Cdd:cd06642  109 EILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQ---IKRNTFVGTPFWMAPEVIKQSAYDFKADIW 185
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392922083 360 SFAVCLTGIFQlGVPPHEAVNAVYCGQDIERKLP---ELQYCHPdMYSFLSSCWNFDPEARPT 419
Cdd:cd06642  186 SLGITAIELAK-GEPPNSDLHPMRVLFLIPKNSPptlEGQHSKP-FKEFVEACLNKDPRFRPT 246
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
276-320 1.84e-03

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: 40.10  E-value: 1.84e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 392922083 276 SYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR 320
Cdd:cd07861  105 SYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLAR 149
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
279-321 1.88e-03

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: 40.02  E-value: 1.88e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARI 321
Cdd:cd07862  117 FQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARI 159
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
275-420 2.13e-03

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It 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 cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 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: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 39.93  E-value: 2.13e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 275 LSYGYQIAIAMKFLADSRCLHRALALRSIFVTRN---KT-----IRIGEFGLARINARKEYYIMKSPQLPlapevmaPES 346
Cdd:cd05078  107 LEVAKQLAWAMHFLEEKTLVHGNVCAKNILLIREedrKTgnppfIKLSDPGISITVLPKDILLERIPWVP-------PEC 179
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 347 SED-KKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIERK--LPELQYChpDMYSFLSSCWNFDPEARPTY 420
Cdd:cd05078  180 IENpKNLSLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRhqLPAPKWT--ELANLINNCMDYEPDHRPSF 254
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
279-380 2.23e-03

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: 39.63  E-value: 2.23e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTR----NKTIRIGEFGLARINARKEYYIMKSPQLpLAPEVMApesseDKKFTE 354
Cdd:cd14184  106 YNLASALKYLHGLCIVHRDIKPENLLVCEypdgTKSLKLGDFGLATVVEGPLYTVCGTPTY-VAPEIIA-----ETGYGL 179
                         90       100
                 ....*....|....*....|....*.
gi 392922083 355 KSEVRSFAVcLTGIFQLGVPPHEAVN 380
Cdd:cd14184  180 KVDIWAAGV-ITYILLCGFPPFRSEN 204
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
279-321 2.61e-03

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: 39.57  E-value: 2.61e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARI 321
Cdd:cd07838  114 RQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLADFGLARI 156
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
176-429 2.85e-03

Catalytic domain of an unknown subfamily of 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. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). 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: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 39.42  E-value: 2.85e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 176 RNDITHQKMIQdELVTLSSLrSHSCILALVGYVREPNMLLIVSEHAEHGRLDQFLIDRKLnfnnqltcsdgsnqkvynfn 255
Cdd:cd14156   27 KNDVDQHKIVR-EISLLQKL-SHPNIVRYLGICVKDEKLHPILEYVSGGCLEELLAREEL-------------------- 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 256 ngeqerisddmqALCTLDLLSYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIR---IGEFGLARINARKEyyiMKS 332
Cdd:cd14156   85 ------------PLSWREKVELACDISRGMVYLHSKNIYHRDLNSKNCLIRVTPRGReavVTDFGLAREVGEMP---AND 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 333 PQLPLA----PEVMAPESSEDKKFTEKSEVRSFAVCLTGIF-QLGVPPHEAVNAVYCGQDIERKLPELQYCHPDMYSFLS 407
Cdd:cd14156  150 PERKLSlvgsAFWMAPEMLRGEPYDRKVDVFSFGIVLCEILaRIPADPEVLPRTGDFGLDVQAFKEMVPGCPEPFLDLAA 229
                        250       260
                 ....*....|....*....|..
gi 392922083 408 SCWNFDPEARPTYSKCVEFFDD 429
Cdd:cd14156  230 SCCRMDAFKRPSFAELLDELED 251
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
277-419 3.20e-03

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: 39.34  E-value: 3.20e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR-----INARKEYYIMKSpqLPLAPEVMAPESSEDKK 351
Cdd:cd06631  108 YTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKrlcinLSSGSQSQLLKS--MRGTPYWMAPEVINETG 185
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 392922083 352 FTEKSEVRSFAvCLtgIFQLG--------VPPHEAVNAVYCGQDIERKLPElqYCHPDMYSFLSSCWNFDPEARPT 419
Cdd:cd06631  186 HGRKSDIWSIG-CT--VFEMAtgkppwadMNPMAAIFAIGSGRKPVPRLPD--KFSPEARDFVHACLTRDQDERPS 256
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
280-438 3.54e-03

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: 39.32  E-value: 3.54e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 280 QIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFG----LARINARKEYYImKSPQLpLAPEVMAPESSEDKKFTEK 355
Cdd:cd06637  119 EILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGvsaqLDRTVGRRNTFI-GTPYW-MAPEVIACDENPDATYDFK 196
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 356 SEVRSFAVCLTGIFQlGVPPHEAVNAVYCGQDIERK-LPELQY--CHPDMYSFLSSCWNFDPEARPTYSKCVE--FFDDH 430
Cdd:cd06637  197 SDLWSLGITAIEMAE-GAPPLCDMHPMRALFLIPRNpAPRLKSkkWSKKFQSFIESCLVKNHSQRPSTEQLMKhpFIRDQ 275

                 ....*...
gi 392922083 431 FSENQIMI 438
Cdd:cd06637  276 PNERQVRI 283
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
279-342 3.76e-03

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: 39.34  E-value: 3.76e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 279 YQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEYYIMKS---PQLPLAPEVM 342
Cdd:cd07853  110 YQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEEPDESKHMTQevvTQYYRAPEIL 176
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
276-422 3.91e-03

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 39.07  E-value: 3.91e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 276 SYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARInaRKE-------YYIMKSPQLPLAPEVmapESSE 348
Cdd:cd14045  107 SFATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLTTY--RKEdgsenasGYQQRLMQVYLPPEN---HSNT 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 349 DKKFTEKSEVRSFAVCLTGIFQLGVPPHEAVNAVYCGQDIerKLPELQY--------CHPDMYSFLSSCWNFDPEARPTY 420
Cdd:cd14045  182 DTEPTQATDVYSYAIILLEIATRNDPVPEDDYSLDEAWCP--PLPELISgktenscpCPADYVELIRRCRKNNPAQRPTF 259

                 ..
gi 392922083 421 SK 422
Cdd:cd14045  260 EQ 261
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
277-365 4.13e-03

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: 39.29  E-value: 4.13e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEyyiMKSPQLPLAPEVMAPESSEDKKFTEKS 356
Cdd:cd05592  101 YGAEIICGLQFLHSRGIIYRDLKLDNVLLDREGHIKIADFGMCKENIYGE---NKASTFCGTPDYIAPEILKGQKYNQSV 177

                 ....*....
gi 392922083 357 EVRSFAVCL 365
Cdd:cd05592  178 DWWSFGVLL 186
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
284-417 4.73e-03

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: 38.94  E-value: 4.73e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 284 AMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGL-ARINARKEyyimKSPQLPLAPEVMAPESSEDKKFTEKSEVRSFA 362
Cdd:cd06654  128 ALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFcAQITPEQS----KRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLG 203
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 392922083 363 VCLTGIFQlGVPPHEAVNAVYCGQDIERK-LPELQycHPDMYS-----FLSSCWNFDPEAR 417
Cdd:cd06654  204 IMAIEMIE-GEPPYLNENPLRALYLIATNgTPELQ--NPEKLSaifrdFLNRCLEMDVEKR 261
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
277-365 5.16e-03

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: 38.77  E-value: 5.16e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEyyiMKSPQLPLAPEVMAPESSEDKKFTEKS 356
Cdd:cd05620  101 YAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENVFGD---NRASTFCGTPDYIAPEILQGLKYTFSV 177

                 ....*....
gi 392922083 357 EVRSFAVCL 365
Cdd:cd05620  178 DWWSFGVLL 186
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
206-422 7.09e-03

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 38.33  E-value: 7.09e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 206 GYVREPNMLLIVSEHAEHGRLDQFLidrklnfNNQLTCSDGSnqkvynFNNGEQErisddmqalctldlLSYGYQIAIAM 285
Cdd:cd14044   70 GTVKLDTMIFGVIEYCERGSLRDVL-------NDKISYPDGT------FMDWEFK--------------ISVMYDIAKGM 122
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 286 KFLADSRC-LHRALALRSIFVTRNKTIRIGEFGLARI-NARKEYYimkspqlplapevMAPESSEDKKFTEKSEVRSFAV 363
Cdd:cd14044  123 SYLHSSKTeVHGRLKSTNCVVDSRMVVKITDFGCNSIlPPSKDLW-------------TAPEHLRQAGTSQKGDVYSYGI 189
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392922083 364 cltgIFQLGVPPHEAVNAVYCgQDIERKLPELQY---CHP---------------DMYSFLSSCWNFDPEARPTYSK 422
Cdd:cd14044  190 ----IAQEIILRKETFYTAAC-SDRKEKIYRVQNpkgMKPfrpdlnlesagererEVYGLVKNCWEEDPEKRPDFKK 261
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
277-391 8.73e-03

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: 37.85  E-value: 8.73e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392922083 277 YGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLARINARKEyyimKSPQLPLAPEVMAPESSEDKKFTEKS 356
Cdd:cd05611  102 YIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLEKR----HNKKFVGTPDYLAPETILGVGDDKMS 177
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 392922083 357 EVRSFAvCLTGIFQLGVPPHEA--VNAVYcgQDIERK 391
Cdd:cd05611  178 DWWSLG-CVIFEFLFGYPPFHAetPDAVF--DNILSR 211
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
276-320 9.84e-03

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: 38.04  E-value: 9.84e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 392922083 276 SYGYQIAIAMKFLADSRCLHRALALRSIFVTRNKTIRIGEFGLAR 320
Cdd:cd07835  103 SYLYQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLAR 147
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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