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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 116 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQ 195
Cdd:cd14217     1 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRESDPEDPNKDMVVQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 196 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 275
Cdd:cd14217    81 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 160

                         170       180
                  ....*....|....*....|....*....
gi 1370510836 276 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 304
Cdd:cd14217   161 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 189

K+-dependent Na+/Ca+ exchanger; [Transport and binding proteins, Cations and iron carrying compounds]

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1370510836  389 DNGEAEDQEEKEDAEKENIEKDEDDVDQELANIDPTWIESPKT 431
Cdd:TIGR00927  859 DGGDSEEEEEEEEEEEEEEEEEEEEEEEEEENEEPLSLEWPET 901

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK2 mediates neuronal cell cycle and cell death through regulation of nuclear cyclin D1. It has also been found to promote leukemia cell proliferation by regulating cyclin A1. SRPK2 also plays a role in regulating pre-mRNA splicing and is required for spliceosomal B complex formation. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 116 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQ 195
Cdd:cd14217     1 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRESDPEDPNKDMVVQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 196 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 275
Cdd:cd14217    81 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 160

                         170       180
                  ....*....|....*....|....*....
gi 1370510836 276 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 304
Cdd:cd14217   161 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 189

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836  129 YHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVK--SAQHYTETALDEIKLLKCVREsdpsdPNkdmVVQLIDDFKisgmN 206
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKkkKIKKDRERILREIKILKKLKH-----PN---IVRLYDVFE----D 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370510836  207 GIHVCMVFEVLGHHLLKWIIKSNyQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVD 273
Cdd:smart00220  69 EDKLYLVMEYCEGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLHSK-GIVHRDLKPENILLDED 133

protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 123 DLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQ--LIDDf 200
Cdd:PTZ00284  125 DVSTQRFKILSLLGEGTFGKVVEAWDRKRKEYCAVKIVRNVPKYTRDAKIEIQFMEKVRQADPADRFPLMKIQryFQNE- 203

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 201 kiSGmngiHVCMVFEVLGHHLLKWIIKsnYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRM 280
Cdd:PTZ00284  204 --TG----HMCIVMPKYGPCLLDWIMK--HGPFSHRHLAQIIFQTGVALDYFHTELHLMHTDLKPENILMETSDTVVDPV 275

                  ....*
gi 1370510836 281 AAEAT 285
Cdd:PTZ00284  276 TNRAL 280

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 121 IGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKsaqhyTETALDEIKLLKCVRE----SDPSDPNkdmVVQL 196
Cdd:NF033483    1 IGKLLGGRYEIGERIGRGGMAEVYLAKDTRLDRDVAVKVLR-----PDLARDPEFVARFRREaqsaASLSHPN---IVSV 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370510836 197 IDdfkiSGMNGIHVCMVFE-VLGhHLLKWIIKSNYQgLPVRCVKSIIRQVLQGLDYLHsKCKIIHTDIKPENILM 270
Cdd:NF033483   73 YD----VGEDGGIPYIVMEyVDG-RTLKDYIREHGP-LSPEEAVEIMIQILSALEHAH-RNGIVHRDIKPQNILI 140

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 595 TRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGedysrDEDHIALIIELLGKVPRKYAmlgkYSKEfftr 674
Cdd:pfam00069 123 TPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGING-----NEIYELIIDQPYAFPELPSN----LSEE---- 189

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 675 kgelrhitklkpwslfdvlvekygwphedaaqFTDFLIPMLEMVPEKRASAGECLRHPWL 734
Cdd:pfam00069 190 --------------------------------AKDLLKKLLKKDPSKRLTATQALQHPWF 217

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370510836 573 RVKIADLGNACWVHK-HFTED---IQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGED 639
Cdd:COG0515   145 RVKLIDFGIARALGGaTLTQTgtvVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAE 215

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK2 mediates neuronal cell cycle and cell death through regulation of nuclear cyclin D1. It has also been found to promote leukemia cell proliferation by regulating cyclin A1. SRPK2 also plays a role in regulating pre-mRNA splicing and is required for spliceosomal B complex formation. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 116 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQ 195
Cdd:cd14217     1 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRESDPEDPNKDMVVQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 196 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 275
Cdd:cd14217    81 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 160

                         170       180
                  ....*....|....*....|....*....
gi 1370510836 276 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 304
Cdd:cd14217   161 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 189

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK2 mediates neuronal cell cycle and cell death through regulation of nuclear cyclin D1. It has also been found to promote leukemia cell proliferation by regulating cyclin A1. SRPK2 also plays a role in regulating pre-mRNA splicing and is required for spliceosomal B complex formation. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 552 AKTRAADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYL 631
Cdd:cd14217   184 AVSTAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYL 263

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 632 FEPHSGEDYSRDEDHIALIIELLGKVPRKYAMLGKYSKEFFTRKGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFL 711
Cdd:cd14217   264 FEPHSGEDYSRDEDHIAHIIELLGCIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFL 343

                         170       180
                  ....*....|....*....|...
gi 1370510836 712 IPMLEMVPEKRASAGECLRHPWL 734
Cdd:cd14217   344 IPMLEMVPEKRASAGECLRHPWL 366

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK3 is highly expressed in the heart and skeletal muscles, and is controlled by a muscle-specific enhancer that is regulated by MEF2. It may play an important role in muscle development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 556 AADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPH 635
Cdd:cd14218   187 ASDFLVNPLEPQNADKIRVKIADLGNACWVHKHFTEDIQTRQYRALEVLIGAEYGTPADIWSTACMAFELATGDYLFEPH 266

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 636 SGEDYSRDEDHIALIIELLGKVPRKYAMLGKYSKEFFTRKGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPML 715
Cdd:cd14218   267 SGEDYTRDEDHIAHIVELLGDIPPHFALSGRYSREYFNRRGELRHIKNLKHWGLYEVLVEKYEWPLEQAAQFTDFLLPMM 346

                         170
                  ....*....|....*....
gi 1370510836 716 EMVPEKRASAGECLRHPWL 734
Cdd:cd14218   347 EFLPEKRATAAQCLQHPWL 365

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 564 LDPRN----ADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGED 639
Cdd:cd14136   146 IKPENvllcISKIEVKIADLGNACWTDKHFTEDIQTRQYRSPEVILGAGYGTPADIWSTACMAFELATGDYLFDPHSGED 225

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 640 YSRDEDHIALIIELLGKVPRKYAMLGKYSKEFFTRKGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVP 719
Cdd:cd14136   226 YSRDEDHLALIIELLGRIPRSIILSGKYSREFFNRKGELRHISKLKPWPLEDVLVEKYKWSKEEAKEFASFLLPMLEYDP 305

                         170
                  ....*....|....*
gi 1370510836 720 EKRASAGECLRHPWL 734
Cdd:cd14136   306 EKRATAAQCLQHPWL 320

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 119 VKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSdpNKDMVVQLID 198
Cdd:cd14134     4 YKPGDLLTNRYKILRLLGEGTFGKVLECWDRKRKRYVAVKIIRNVEKYREAAKIEIDVLETLAEKDPN--GKSHCVQLRD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 199 DFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHsKCKIIHTDIKPENILMcVDDAYVR 278
Cdd:cd14134    82 WFDYRG----HMCIVFELLGPSLYDFLKKNNYGPFPLEHVQHIAKQLLEAVAFLH-DLKLTHTDLKPENILL-VDSDYVK 155

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 115 GYHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDpnKDMVV 194
Cdd:cd14210     1 GDYKVVLGDHIAYRYEVLSVLGKGSFGQVVKCLDHKTGQLVAIKIIRNKKRFHQQALVEVKILKHLNDNDPDD--KHNIV 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370510836 195 QLIDDFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMC 271
Cdd:cd14210    79 RYKDSFIFRG----HLCIVFELLSINLYELLKSNNFQGLSLSLIRKFAKQILQALQFLHKL-NIIHCDLKPENILLK 150

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 559 LLVNPldprnaDKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGE 638
Cdd:cd14210   148 LLKQP------SKSSIKVIDFGSSCFEGEKVYTYIQSRFYRAPEVILGLPYDTAIDMWSLGCILAELYTGYPLF---PGE 218

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 639 DysrDEDHIALIIELLGKVPRKYAMLGKYSKEFFTRKGELRHITklkpwslfdVLVEKYGWP---------HEDAAQFTD 709
Cdd:cd14210   219 N---EEEQLACIMEVLGVPPKSLIDKASRRKKFFDSNGKPRPTT---------NSKGKKRRPgskslaqvlKCDDPSFLD 286

                         170       180
                  ....*....|....*....|....*
gi 1370510836 710 FLIPMLEMVPEKRASAGECLRHPWL 734
Cdd:cd14210   287 FLKKCLRWDPSERMTPEEALQHPWI 311

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 129 YHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDpSDPNKDMVVQLIDDFkisgMNGI 208
Cdd:cd14212     1 YLVLDLLGQGTFGQVVKCQDLKTNKLVAVKVLKNKPAYFRQAMLEIAILTLLNTKY-DPEDKHHIVRLLDHF----MHHG 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370510836 209 HVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHsKCKIIHTDIKPENILMCVDDA 275
Cdd:cd14212    76 HLCIVFELLGVNLYELLKQNQFRGLSLQLIRKFLQQLLDALSVLK-DARIIHCDLKPENILLVNLDS 141

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 573 RVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSgedysrDEDHIALIIE 652
Cdd:cd14134   172 DIKLIDFGSATFDDEYHSSIVSTRHYRAPEVILGLGWSYPCDVWSIGCILVELYTGELLFQTHD------NLEHLAMMER 245

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 653 LLGKVPRKYAMLGKY-SKEFFTRKGEL---------RHITKL-KPWSLFDVLVekygwpHEDAAQFTDFLIPMLEMVPEK 721
Cdd:cd14134   246 ILGPLPKRMIRRAKKgAKYFYFYHGRLdwpegsssgRSIKRVcKPLKRLMLLV------DPEHRLLFDLIRKMLEYDPSK 319

                         170
                  ....*....|...
gi 1370510836 722 RASAGECLRHPWL 734
Cdd:cd14134   320 RITAKEALKHPFF 332

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 129 YHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQH---YTETALDEIKLLKcvresDPSDPNkdmVVQLIDdfKISGM 205
Cdd:cd07829     1 YEKLEKLGEGTYGVVYKAKDKKTGEIVALKKIRLDNEeegIPSTALREISLLK-----ELKHPN---IVKLLD--VIHTE 70

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370510836 206 NGIHvcMVFEVLgHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILM 270
Cdd:cd07829    71 NKLY--LVFEYC-DQDLKKYLDKRPGPLPPNLIKSIMYQLLRGLAYCHSH-RILHRDLKPQNLLI 131

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 559 LLVNPldprnaDKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFePHSGE 638
Cdd:cd14133   134 LLASY------SRCQIKIIDFGSSCFLTQRLYSYIQSRYYRAPEVILGLPYDEKIDMWSLGCILAELYTGEPLF-PGASE 206

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 639 dysrdEDHIALIIELLGKVPRKyaMLGKYSkefftrkgelrhitklkpwslfdvlvekygwphEDAAQFTDFLIPMLEMV 718
Cdd:cd14133   207 -----VDQLARIIGTIGIPPAH--MLDQGK---------------------------------ADDELFVDFLKKLLEID 246

                         170
                  ....*....|....*.
gi 1370510836 719 PEKRASAGECLRHPWL 734
Cdd:cd14133   247 PKERPTASQALSHPWL 262

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK2 plays a role in hepatic insulin signaling and glucose metabolism. It is induced by the insulin/Akt pathway as part of the hepatic refeeding reponse, and it directly phosphorylates the SR domain of PGC-1alpha, which results in decreased gluconeogenic gene expression and glucose output. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 120 KIGDLFNGRYHVIRKLGWGHFSTVWLCWD-MQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSdpNKDMVVQLID 198
Cdd:cd14215     5 RSGDWLQERYEIVSTLGEGTFGRVVQCIDhRRGGARVALKIIKNVEKYKEAARLEINVLEKINEKDPE--NKNLCVQMFD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 199 DFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVDDAYVR 278
Cdd:cd14215    83 WFDYHG----HMCISFELLGLSTFDFLKENNYLPYPIHQVRHMAFQVCQAVKFLHDN-KLTHTDLKPENILFVNSDYELT 157

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 128 RYHVIRKLGWGHFSTVWLCWDMQ-GKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDpnKDMVVQLIDDFKISGmn 206
Cdd:cd14135     1 RYRVYGYLGKGVFSNVVRARDLArGNQEVAIKIIRNNELMHKAGLKELEILKKLNDADPDD--KKHCIRLLRHFEHKN-- 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370510836 207 giHVCMVFEVLgHHLLKWIIK--SNYQGLPVRCVKSIIRQVLQGLDYLhSKCKIIHTDIKPENIL 269
Cdd:cd14135    77 --HLCLVFESL-SMNLREVLKkyGKNVGLNIKAVRSYAQQLFLALKHL-KKCNILHADIKPDNIL 137

Catalytic domain of the protein kinases, Dual-specificity tYrosine-phosphorylated and -Regulated Kinases 2 and 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of DYRK2 and DYRK3, and similar proteins. Drosophila DYRK2 interacts and phosphorylates the chromatin remodelling factor, SNR1 (Snf5-related 1), and also interacts with the essential chromatin component, trithorax. It may play a role in chromatin remodelling. Vertebrate DYRK2 phosphorylates and regulates the tumor suppressor p53 to induce apoptosis in response to DNA damage. It can also phosphorylate the transcription factor, nuclear factor of activated T cells (NFAT). DYRK2 is overexpressed in lung adenocarcinoma and esophageal carcinomas, and is a predictor for favorable prognosis in lung adenocarcinoma. DYRK3, also called regulatory erythroid kinase (REDK), is highly expressed in erythroid cells and the testis, and is also present in adult kidney and liver. It promotes cell survival by phosphorylating and activating SIRT1, an NAD(+)-dependent protein deacetylase, which promotes p53 deacetylation, resulting in the inhibition of apoptosis. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other S/T kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 574 VKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGEDysrDEDHIALIIEL 653
Cdd:cd14224   209 IKVIDFGSSCYEHQRIYTYIQSRFYRAPEVILGARYGMPIDMWSFGCILAELLTGYPLF---PGED---EGDQLACMIEL 282

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 654 LGKVPRKYAMLGKYSKEFFTRKGELRHITKLkpwSLFDVLV----------EKYGWPHE----------DAAQFTDFLIP 713
Cdd:cd14224   283 LGMPPQKLLETSKRAKNFISSKGYPRYCTVT---TLPDGSVvlnggrsrrgKMRGPPGSkdwvtalkgcDDPLFLDFLKR 359

                         170       180
                  ....*....|....*....|.
gi 1370510836 714 MLEMVPEKRASAGECLRHPWL 734
Cdd:cd14224   360 CLEWDPAARMTPSQALRHPWL 380

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510836 123 DLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALD----EIKLLKCVResdpsDPNkdmVVQLID 198
Cdd:COG0515     3 ALLLGRYRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAADPEARErfrrEARALARLN-----HPN---IVRVYD 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370510836 199 DFKISGmngiHVCMVFE-VLGHHLLKWIikSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVD 273
Cdd:COG0515    75 VGEEDG----RPYLVMEyVEGESLADLL--RRRGPLPPAEALRILAQLAEALAAAHAA-GIVHRDIKPANILLTPD 143

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