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 755542610   1 MIMDRFGSDLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNPDQVYLVDYGLAYRYCPDG 80
Cdd:cd14122  104 MIMDRFGSDLQKIYEANAKRFSRKTVLQLGLRILDILEYIHEHEYVHGDIKASNLLLSYKNPDQVYLVDYGLAYRYCPEG 183

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  81 VHKEYKEDPKRCHDGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWEDNLKDPNYVRDSKIRYRDNVAALMEK 160
Cdd:cd14122  184 VHKEYKEDPKRCHDGTIEFTSIDAHKGVAPSRRGDLEILGYCMIQWLCGHLPWEDNLKDPNYVRDSKIRYRDNISELMEK 263

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 755542610 161 CFPEKNKPGEIAKYMESVKLLEYTEKPLYQNLRDILLQ 198
Cdd:cd14122  264 CFPGKNKPGEIRKYMETVKLLGYTEKPLYPHLREILLQ 301

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. Vertebrates contain three VRK proteins. Human VRK1 is implicated in the regulation of many cellular processes including cell cycle progression and proliferation, stress responses, nuclear envelope assembly and chromatin condensation. It regulates cell cycle progression during the DNA replication period by inducing cyclin D1 expression. VRK1 also phosphorylates and regulates some transcription factors including p53, c-Jun, ATF2, and nuclear factor BAF. VRK1 stabilizes p53 by interfering with its mdm2-mediated degradation. Accumulation of p53, which blocks cell growth and division, is modulated by an autoregulatory loop between p53 and VRK1 (accumulated p53 downregulates VRK1). This autoregulatory loop has been found to be nonfunctional in some lung carcinomas. The VRK1 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRFGSDLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNPDQVYLVDYGLAYRYCPDG 80
Cdd:cd14122  104 MIMDRFGSDLQKIYEANAKRFSRKTVLQLGLRILDILEYIHEHEYVHGDIKASNLLLSYKNPDQVYLVDYGLAYRYCPEG 183

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  81 VHKEYKEDPKRCHDGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWEDNLKDPNYVRDSKIRYRDNVAALMEK 160
Cdd:cd14122  184 VHKEYKEDPKRCHDGTIEFTSIDAHKGVAPSRRGDLEILGYCMIQWLCGHLPWEDNLKDPNYVRDSKIRYRDNISELMEK 263

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 755542610 161 CFPEKNKPGEIAKYMESVKLLEYTEKPLYQNLRDILLQ 198
Cdd:cd14122  264 CFPGKNKPGEIRKYMETVKLLGYTEKPLYPHLREILLQ 301

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRF-GSDLQKIYEANaKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNpdQVYLVDYGLAYRycPD 79
Cdd:COG0515   84 LVMEYVeGESLADLLRRR-GPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDG--RVKLIDFGIARA--LG 158

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 755542610  80 GVHKEYKEDPKrchdGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWE 134
Cdd:COG0515  159 GATLTQTGTVV----GTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFD 209

Kae1-associated kinase Bud32; Members of this protein family are the Bud32 protein associated with Kae1 (kinase-associated endopeptidase 1) in the Archaea. In many Archaeal genomes, Kae1 and Bud32 are fused. The complex is homologous to the Kae1 and Bud32 subunits of the eukaryotic KEOPS complex, an apparently ancient protein kinase-containing molecular machine. [Unknown function, General]

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755542610   10 LQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHknpDQVYLVDYGLAYR 75
Cdd:TIGR03724  76 MEYIEGKPLKDVIEENGDELAREIGRLVGKLHKAGIVHGDLTTSNIIVRD---DKVYLIDFGLGKY 138

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. Vertebrates contain three VRK proteins. Human VRK1 is implicated in the regulation of many cellular processes including cell cycle progression and proliferation, stress responses, nuclear envelope assembly and chromatin condensation. It regulates cell cycle progression during the DNA replication period by inducing cyclin D1 expression. VRK1 also phosphorylates and regulates some transcription factors including p53, c-Jun, ATF2, and nuclear factor BAF. VRK1 stabilizes p53 by interfering with its mdm2-mediated degradation. Accumulation of p53, which blocks cell growth and division, is modulated by an autoregulatory loop between p53 and VRK1 (accumulated p53 downregulates VRK1). This autoregulatory loop has been found to be nonfunctional in some lung carcinomas. The VRK1 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRFGSDLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNPDQVYLVDYGLAYRYCPDG 80
Cdd:cd14122  104 MIMDRFGSDLQKIYEANAKRFSRKTVLQLGLRILDILEYIHEHEYVHGDIKASNLLLSYKNPDQVYLVDYGLAYRYCPEG 183

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  81 VHKEYKEDPKRCHDGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWEDNLKDPNYVRDSKIRYRDNVAALMEK 160
Cdd:cd14122  184 VHKEYKEDPKRCHDGTIEFTSIDAHKGVAPSRRGDLEILGYCMIQWLCGHLPWEDNLKDPNYVRDSKIRYRDNISELMEK 263

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 755542610 161 CFPEKNKPGEIAKYMESVKLLEYTEKPLYQNLRDILLQ 198
Cdd:cd14122  264 CFPGKNKPGEIRKYMETVKLLGYTEKPLYPHLREILLQ 301

Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. VRKs were initially discovered due to its similarity to vaccinia virus B1R STK, which is important for viral replication. They play important roles in cell signaling, nuclear envelope dynamics, apoptosis, and stress responses. Vertebrates contain three VRK proteins. VRK2 exists as two alternative splice forms, A and B, which differ in their C-terminal regions. VRK2A, the predominant isoform, contains a hydrophobic tail and is anchored to the ER and mitochondria. It is expressed in all cell types. VRK2B lacks a membrane-anchor tail and is detected in the cytosol and the nucleus. Like VRK1, it can stabilize p53. VRK2B functionally replaces VRK1 in the nucleus of cell types where VRK1 is absent. VRK2 modulates hypoxia-induced stress responses by interacting with TAK1, an atypical MAPK kinase kinase which triggers cascades that activate JNK following oxidative stress. VRK2 also interacts with JIP1, a scaffold protein that assembles three consecutive members of a MAPK pathway. This interaction prevents the association of JNK with the signaling complex, leading to reduced phosphorylation and AP1-dependent transcription. The VRK2 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRFGSDLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNPDQVYLVDYGLAYRYCPDG 80
Cdd:cd14123  106 MVMDRLGTDLQKILIDNGGQFKKTTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLGYRNPNEVYLADYGLSYRYCPNG 185

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  81 VHKEYKEDPKRCHDGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWEDNLKDPNYVRDSKIRYRDNVAALMEK 160
Cdd:cd14123  186 NHKEYKENPRKGHNGTIEFTSLDAHKGVAPSRRGDLEILGYCMLHWLCGKLPWEQNLKNPVAVQEAKAKLLSNLPDSVLK 265

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 755542610 161 CFPEKNKPGEIAKYMESVKLLEYTEKPLYQNLRDILL 197
Cdd:cd14123  266 WSTGGSSSMEIAQFLSRVKDLAYDEKPDYQALKKILS 302

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRFGSDLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSH-KNPDQVYLVDYGLAYRYC-- 77
Cdd:cd14016   73 MVMDLLGPSLEDLFNKCGRKFSLKTVLMLADQMISRLEYLHSKGYIHRDIKPENFLMGLgKNSNKVYLIDFGLAKKYRdp 152

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  78 PDGVHKEYKEdpKRCHDGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWEdNLKDPNyvrdSKIRYRdnvaAL 157
Cdd:cd14016  153 RTGKHIPYRE--GKSLTGTARYASINAHLGIEQSRRDDLESLGYVLIYFLKGSLPWQ-GLKAQS----KKEKYE----KI 221

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 755542610 158 MEK---------CfpeKNKPGEIAKYMESVKLLEYTEKPLYQNLRDIL 196
Cdd:cd14016  222 GEKkmntspeelC---KGLPKEFAKYLEYVRSLKFEEEPDYDYLRQLF 266

Catalytic domain of the Serine/Threonine protein kinase, Fungal Casein Kinase 1 homolog 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. This subfamily is composed of fungal CK1 homolog 1 proteins, also called Yck1 in Saccharomyces cerevisiae and Cki1 in Schizosaccharomyces pombe. Yck1 (or Yck1p) and Cki1 are plasma membrane-anchored proteins. Yck1 phosphorylates and regulates Khd1p, a RNA-binding protein that represses translation of bud-localized mRNA. Cki1 phosphorylates and regulates phosphatidylinositol (PI)-(4)P-5-kinase, which catalyzes the last step in the sythesis of PI(4,5)P2, which is involved in actin cytoskeleton remodeling and membrane traffic. The fungal CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRFGSDLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLL---SHKNPDQVYLVDYGLA--YR 75
Cdd:cd14127   73 LVIDLLGPSLEDLFDLCGRKFSVKTVVMVAKQMLTRVQTIHEKNLIYRDIKPDNFLIgrpGTKNANVIHVVDFGMAkqYR 152

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  76 YCPDGVHKEYKEdpKRCHDGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWEdNLKDP-NYVRDSKIRYRDNV 154
Cdd:cd14127  153 DPKTKQHIPYRE--KKSLSGTARYMSINTHLGREQSRRDDLEALGHVFMYFLRGSLPWQ-GLKAAtNKQKYEKIGEKKQS 229

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 755542610 155 AALMEKC--FPEknkpgEIAKYMESVKLLEYTEKPLYQNLRDILLQGLKAIG 204
Cdd:cd14127  230 TPIRDLCegFPE-----EFAQYLEYVRNLGFDETPDYDYLRGLFSKALKDLG 276

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1 gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. CK1gamma proteins are unique within the CK1 subfamily in that they are palmitoylated at the C-termini and are anchored to the plasma membrane. CK1gamma is involved in transducing the signaling of LDL-receptor-related protein 6 (LRP6) through direct phosphorylation following Wnt stimulation, resulting in the recruitment of the scaffold protein Axin. In Xenopus embryos, CK1gamma is required during anterio-posterior patterning. In higher vertebrates, three CK1gamma (gamma1-3) isoforms exist. In mammalian cells, CK1gamma2 has been implicated in regulating the synthesis of sphingomyelin, a phospholipid that is found in the outer leaflet of the plasma membrane, by hyperphosphorylating and inactivating the ceramide transfer protein CERT. CK1gamma2 also phosphorylates the transcription factor Smad-3 resulting in its ubiquitination and degradation. It inhibits Smad-3 mediated responses of Transforming Growth Factor-beta (TGF-beta) including cell growth arrest. The CK1 gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRFGSDLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLL---SHKNPDQVYLVDYGLAYRYC 77
Cdd:cd14126   73 MVLELLGPSLEDLFDLCDRTFSLKTVLMIAIQLISRIEYVHSKHLIYRDVKPENFLIgrqSTKKQHVIHIIDFGLAKEYI 152

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  78 PDGVHKEYkedPKRCHD---GTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWE----DNLKDpnyvRDSKIRY 150
Cdd:cd14126  153 DPETNKHI---PYREHKsltGTARYMSINTHLGKEQSRRDDLEALGHMFMYFLRGSLPWQglkaDTLKE----RYQKIGD 225

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 755542610 151 RDNVAALMEKCfpeKNKPGEIAKYMESVKLLEYTEKPLYQNLRDILLQGLKAIGSKDDGKLDFS 214
Cdd:cd14126  226 TKRATPIEVLC---ENFPEEMATYLRYVRRLDFFETPDYDYLRKLFTDLFDRKGYTDDYEFDWT 286

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRFGSDLQKIY-EANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLL--SHKNPDQVYLVDYGLAYRYC 77
Cdd:cd14017   73 IVMTLLGPNLAELRrSQPRGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIgrGPSDERTVYILDFGLARQYT 152

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  78 -PDGVHKEykedPKRCHD---GTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWEdNLKDPNYVRDSKIRYRDN 153
Cdd:cd14017  153 nKDGEVER----PPRNAAgfrGTVRYASVNAHRNKEQGRRDDLWSWFYMLIEFVTGQLPWR-KLKDKEEVGKMKEKIDHE 227

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 755542610 154 VaaLMEKCfpeknkPGEIAKYMESVKLLEYTEKPLYQNLRDIL 196
Cdd:cd14017  228 E--LLKGL------PKEFFQILKHIRSLSYFDTPDYKKLHSLL 262

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. Mutations in TTBK2 is associated with the development of spinocerebellar ataxia type 11, belonging to a group of neurodegenerative disorders characterized by progressive incoordination, dysarthria and impairment of eye movements. Brain tissues of SCA11 patients show the presence of neurofibrillary tangles and tau deposition in the brain, similar to Alzheimer's disease (AD) patients. The TTBK2 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRFGSDLQKIYEANAK-RFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSH--KNPDQVYLVDYGLAYRY- 76
Cdd:cd14129   73 VVMQLQGRNLADLRRSQSRgTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAMGRfpSTCRKCYMLDFGLARQFt 152

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  77 --CPDgvhkeykEDPKRC---HDGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWEdNLKDPNYVRDSKIRYR 151
Cdd:cd14129  153 nsCGD-------VRPPRAvagFRGTVRYASINAHRNREMGRHDDLWSLFYMLVEFVVGQLPWR-KIKDKEQVGSIKERYE 224

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 755542610 152 DNVAAlmekcfpeKNKPGEIAKYMESVKLLEYTEKPLYQNLRDIL 196
Cdd:cd14129  225 HRLML--------KHLPPEFSVFLDHISGLDYFTKPDYQLLVSVF 261

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRF-GSDLQKIYEANaKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNpdQVYLVDYGLAYRycPD 79
Cdd:COG0515   84 LVMEYVeGESLADLLRRR-GPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDG--RVKLIDFGIARA--LG 158

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 755542610  80 GVHKEYKEDPKrchdGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWE 134
Cdd:COG0515  159 GATLTQTGTVV----GTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFD 209

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   2 IMDRFGsdlqKIYEANAKRFSRktvlqlslRILDILEYIHEHEYVHGDIKASNLLLSHKnpDQVYLVDYGLAYRycpdgV 81
Cdd:cd06606   89 LLKKFG----KLPEPVVRKYTR--------QILEGLEYLHSNGIVHRDIKGANILVDSD--GVVKLADFGCAKR-----L 149

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 755542610  82 HKEYKEDPKRCHDGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWEdNLKDP 140
Cdd:cd06606  150 AEIATGEGTKSLRGTPYWMAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPWS-ELGNP 207

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610     1 MIMDrF--GSDLQKIYEANaKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNpdQVYLVDYGLAYRYCP 78
Cdd:smart00220  74 LVME-YceGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDG--HVKLADFGLARQLDP 149

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610    79 DGVHKEYkedpkrChdGTLEFTSIDAHKGVAPSRRGD---LEILGYCMiqwLSGCLPWEDN----------LKDPNYVRD 145
Cdd:smart00220 150 GEKLTTF------V--GTPEYMAPEVLLGKGYGKAVDiwsLGVILYEL---LTGKPPFPGDdqllelfkkiGKPKPPFPP 218

                          170       180
                   ....*....|....*....|...
gi 755542610   146 SKIRYRDNVAALMEKCF---PEK 165
Cdd:smart00220 219 PEWDISPEAKDLIRKLLvkdPEK 241

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  33 ILDILEYIHEHEYVHGDIKASNLLLSHKNPDQVYLVDYGLAYRYCPDGVHKEYKedpkrchdGTLEFTSIDAHKGVAPSR 112
Cdd:cd14006   98 LLEGLQYLHNHHILHLDLKPENILLADRPSPQIKIIDFGLARKLNPGEELKEIF--------GTPEFVAPEIVNGEPVSL 169

                         90       100
                 ....*....|....*....|...
gi 755542610 113 RGD---LEILGYCMiqwLSGCLP 132
Cdd:cd14006  170 ATDmwsIGVLTYVL---LSGLSP 189

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755542610   1 MIMDRFGSDLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNpdQVYLVDYGLA 73
Cdd:cd07829   75 LVFEYCDQDLKKYLDKRPGPLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDG--VLKLADFGLA 145

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   1 MIMDRFGSDLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNpdQVYLVDYGLAYRYCPDG 80
Cdd:cd07840   81 MVFEYMDHDLTGLLDNPEVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDG--VLKLADFGLARPYTKEN 158

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  13 IYEANAKRfsrkTVLQLSLrildILEYIHEHEYVHGDIKASNLLLSHKNPDQVYLVDYGLAYR-------------YCPD 79
Cdd:cd13987   88 LPEERVKR----CAAQLAS----ALDFMHSKNLVHRDIKPENVLLFDKDCRRVKLCDFGLTRRvgstvkrvsgtipYTAP 159

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  80 GVHKEYKEDPKRCHdgtlefTSIDAHKgvapsrrgdLEILGYCMiqwLSGCLPWED-NLKDPNYVRDSKIRYRDNVAA-- 156
Cdd:cd13987  160 EVCEAKKNEGFVVD------PSIDVWA---------FGVLLFCC---LTGNFPWEKaDSDDQFYEEFVRWQKRKNTAVps 221

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 755542610 157 --------LMeKCF-----PEKNKPG---EIAKYM 175
Cdd:cd13987  222 qwrrftpkAL-RMFkkllaPEPERRCsikEVFKYL 255

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  31 LRILDILEYIHEHEYVHGDIKASNLLLSHKNPD-QVYLVDYGLAYR---YCPDGVHKEYKEdpkrchdgTLEFTSIDAHK 106
Cdd:cd14012  111 LQLLEALEYLHRNGVVHKSLHAGNVLLDRDAGTgIVKLTDYSLGKTlldMCSRGSLDEFKQ--------TYWLPPELAQG 182

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 755542610 107 GVAPSRRGDLEILGYCMIQWLSGCLPWEdNLKDPNYVRDSKI---RYRDnvaaLMEKCF 162
Cdd:cd14012  183 SKSPTRKTDVWDLGLLFLQMLFGLDVLE-KYTSPNPVLVSLDlsaSLQD----FLSKCL 236

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  19 KRFSRKTVLQLSLR-----ILDILEYIHEHEYVHGDIKASNLLLSHKNPDQVYLVDYGLAYRYCPDgvhkeykeDPKRCH 93
Cdd:cd14108   87 RITKRPTVCESEVRsymrqLLEGIEYLHQNDVLHLDLKPENLLMADQKTDQVRICDFGNAQELTPN--------EPQYCK 158

                 ....*.
gi 755542610  94 DGTLEF 99
Cdd:cd14108  159 YGTPEF 164

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755542610  11 QKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLShkNPDQVYLVDYGLA 73
Cdd:cd07830   86 QLMKDRKGKPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVS--GPEVVKIADFGLA 146

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610  27 LQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNPDqVYLVDYGLAYRYCPDGVHKEY--KEDPKrchdGTLEFTSIDA 104
Cdd:cd13991  101 LHYLGQALEGLEYLHSRKILHGDVKADNVLLSSDGSD-AFLCDFGHAECLDPDGLGKSLftGDYIP----GTETHMAPEV 175

                         90       100
                 ....*....|....*....|....*....
gi 755542610 105 HKGVAPSRRGDLEILGYCMIQWLSGCLPW 133
Cdd:cd13991  176 VLGKPCDAKVDVWSSCCMMLHMLNGCHPW 204

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755542610   1 MIMD--RFGSDLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNpdQVYLVDYGLAY 74
Cdd:cd14008   83 LVLEycEGGPVMELDSGDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADG--TVKISDFGVSE 156

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755542610   2 IMDRFGS-DLQK-IYEAnAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKnpDQVYLVDYGlayryCPD 79
Cdd:cd13979   80 IMEYCGNgTLQQlIYEG-SEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQ--GVCKLCDFG-----CSV 151

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 755542610  80 GVHKEYKEDPKRCH-DGTLEFTSIDAHKGVAPSRRGDLEILGYCMIQWLSGCLPWE 134
Cdd:cd13979  152 KLGEGNEVGTPRSHiGGTYTYRAPELLKGERVTPKADIYSFGITLWQMLTRELPYA 207

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 755542610   9 DLQKIYEANAKRFSRKTVLQLSLRILDILEYIHEHEYVHGDIKASNLLLSHKNpdQVYLVDYGLAYRYCPD 79
Cdd:cd07864  101 DLMGLLESGLVHFSEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNKG--QIKLADFGLARLYNSE 169