cyclin-dependent protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  12 KPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpfhHDQLDRIFSVMGFPAD 91
Cdd:PTZ00024  185 QRREEMTSKVVTLWYRAPELLMGAEKYHFAVDMWSVGCIFAELLTGKPLFPGENE---------IDQLGRIFELLGTPNE 255

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  92 KDWEDIRKMPEY----PTLQKDFRRT-TYANSSLIKymekhkvkpdskvflLLQKLLTMDPTKRITSEQALQDPYFQEDP 166
Cdd:PTZ00024  256 DNWPQAKKLPLYteftPRKPKDLKTIfPNASDDAID---------------LLQSLLKLNPLERISAKEALKHEYFKSDP 320

                  ..
gi 1034649373 167 LP 168
Cdd:PTZ00024  321 LP 322

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  11 LKPLADLDPVVVTFWYRAPELLlGARHYTKAIDIWAIGCIFAELLTSEPifhcrqediktsnPFHHDQLDRIFSVMGFpa 90
Cdd:pfam00069 111 LESGSSLTTFVGTPWYMAPEVL-GGNPYGPKVDVWSLGCILYELLTGKP-------------PFPGINGNEIYELIID-- 174

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034649373  91 dkdwEDIRKMPEYPTLQKDFRRttyansslikymekhkvkpdskvflLLQKLLTMDPTKRITSEQALQDPYF 162
Cdd:pfam00069 175 ----QPYAFPELPSNLSEEAKD-------------------------LLKKLLKKDPSKRLTATQALQHPWF 217

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   1 MGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPFHHDQLD 80
Cdd:cd07842   156 LGLARLFNAPLKPLADLDPVVVTIWYRAPELLLGARHYTKAIDIWAIGCIFAELLTLEPIFKGREAKIKKSNPFQRDQLE 235

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  81 RIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKvKPDSKVFLLLQKLLTMDPTKRITSEQALQDP 160
Cdd:cd07842   236 RIFEVLGTPTEKDWPDIKKMPEYDTLKSDTKASTYPNSLLAKWMHKHK-KPDSQGFDLLRKLLEYDPTKRITAEEALEHP 314

                  ..
gi 1034649373 161 YF 162
Cdd:cd07842   315 YF 316

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 1034649373   1 MGFARLFNSPLKPLadlDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpfhHDQLD 80
Cdd:cd07829   142 FGLARAFGIPLRTY---THEVVTLWYRAPEILLGSKHYSTAVDIWSVGCIFAELITGKPLFPGDSE---------IDQLF 209

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  81 RIFSVMGFPADKDWEDIRKMPEYptlQKDFRRttYANSSLIKYMEKHkvkpDSKVFLLLQKLLTMDPTKRITSEQALQDP 160
Cdd:cd07829   210 KIFQILGTPTEESWPGVTKLPDY---KPTFPK--WPKNDLEKVLPRL----DPEGIDLLSKMLQYNPAKRISAKEALKHP 280

                  ..
gi 1034649373 161 YF 162
Cdd:cd07829   281 YF 282

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   2 GFARLFNSPLKPLAdldPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpfhHDQLDR 81
Cdd:cd07843   151 GLAREYGSPLKPYT---QLVVTLWYRAPELLLGAKEYSTAIDMWSVGCIFAELLTKKPLFPGKSE---------IDQLNK 218

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  82 IFSVMGFPADKDWedirkmPEYPTLQ--KDFRRTTYANSSLikymeKHKVKPDS---KVFLLLQKLLTMDPTKRITSEQA 156
Cdd:cd07843   219 IFKLLGTPTEKIW------PGFSELPgaKKKTFTKYPYNQL-----RKKFPALSlsdNGFDLLNRLLTYDPAKRISAEDA 287

                  ....*.
gi 1034649373 157 LQDPYF 162
Cdd:cd07843   288 LKHPYF 293

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   2 GFARLFNSPLKPLAdldPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpfhHDQLDR 81
Cdd:cd07845   153 GLARTYGLPAKPMT---PKVVTLWYRAPELLLGCTTYTTAIDMWAVGCILAELLAHKPLLPGKSE---------IEQLDL 220

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  82 IFSVMGFPADKDWEDIRKMPEYPTLQkdFRRTTYANSslikymeKHKVKPDSKVFL-LLQKLLTMDPTKRITSEQALQDP 160
Cdd:cd07845   221 IIQLLGTPNESIWPGFSDLPLVGKFT--LPKQPYNNL-------KHKFPWLSEAGLrLLNFLLMYDPKKRATAEEALESS 291

                  ....*...
gi 1034649373 161 YFQEDPLP 168
Cdd:cd07845   292 YFKEKPLP 299

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   2 GFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdIktsnpfhhDQLDR 81
Cdd:cd07835   144 GLARAFGVPVRTYTH---EVVTLWYRAPEILLGSKHYSTPVDIWSVGCIFAEMVTRRPLFPGDSE-I--------DQLFR 211

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  82 IFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYanSSLIKYMEKHKVKpdskvflLLQKLLTMDPTKRITSEQALQDPY 161
Cdd:cd07835   212 IFRTLGTPDEDVWPGVTSLPDYKPTFPKWARQDL--SKVVPSLDEDGLD-------LLSQMLVYDPAKRISAKAALQHPY 282

                  .
gi 1034649373 162 F 162
Cdd:cd07835   283 F 283

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   2 GFARLFNSPLKPL--------ADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHcRQEDIktsnp 73
Cdd:cd07866   160 GLARPYDGPPPNPkggggggtRKYTNLVVTRWYRPPELLLGERRYTTAVDIWGIGCVFAEMFTRRPILQ-GKSDI----- 233

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  74 fhhDQLDRIFSVMGFPADKDWEDIRKMPEYPTLqkdFRRTTYANSslikyMEKHKVKPDSKVFLLLQKLLTMDPTKRITS 153
Cdd:cd07866   234 ---DQLHLIFKLCGTPTEETWPGWRSLPGCEGV---HSFTNYPRT-----LEERFGKLGPEGLDLLSKLLSLDPYKRLTA 302

                  ....*....
gi 1034649373 154 EQALQDPYF 162
Cdd:cd07866   303 SDALEHPYF 311

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  21 VVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFhcRQEDiktsnpfHHDQLDRIFSVMGFPADK-----DWE 95
Cdd:cd07851   176 VATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGKTLF--PGSD-------HIDQLKRIMNLVGTPDEEllkkiSSE 246

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034649373  96 D----IRKMPEYPtlQKDFRRT-TYANSSLIKymekhkvkpdskvflLLQKLLTMDPTKRITSEQALQDPYFQE--DP 166
Cdd:cd07851   247 SarnyIQSLPQMP--KKDFKEVfSGANPLAID---------------LLEKMLVLDPDKRITAAEALAHPYLAEyhDP 307

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  26 YRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRqedikTSNpfhhDQLDRIFSVMGFPADkdwEDIRKM-PEYP 104
Cdd:cd14137   172 YRAPELIFGATDYTTAIDIWSAGCVLAELLLGQPLFPGE-----SSV----DQLVEIIKVLGTPTR---EQIKAMnPNYT 239

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373 105 tlqkDFRRTTYANSSLIKYMEKHkvkPDSKVFLLLQKLLTMDPTKRITSEQALQDPYFQE 164
Cdd:cd14137   240 ----EFKFPQIKPHPWEKVFPKR---TPPDAIDLLSKILVYNPSKRLTALEALAHPFFDE 292

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   2 GFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQediktsnpfHHDQLDR 81
Cdd:cd07849   151 GLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKAIDIWSVGCILAEMLSNRPLFPGKD---------YLHQLNL 221

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  82 IFSVMGFPADKDWEDI---------RKMPEYPTLqkdfrrttyansSLIKYMEKHkvkpDSKVFLLLQKLLTMDPTKRIT 152
Cdd:cd07849   222 ILGILGTPSQEDLNCIislkarnyiKSLPFKPKV------------PWNKLFPNA----DPKALDLLDKMLTFNPHKRIT 285

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1034649373 153 SEQALQDPYFQE--DPL--PTLDVfagcqiPYPKREFLNEDDPEEK 194
Cdd:cd07849   286 VEEALAHPYLEQyhDPSdePVAEE------PFPFDMELFDDLPKEK 325

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   2 GFARLFNSPLKpladLDPVVVTFWYRAPELLLGArHYTKAIDIWAIGCIFAELLTSEPIFhCRQEDIktsnpfhhDQLDR 81
Cdd:cd07838   152 GLARIYSFEMA----LTSVVVTLWYRAPEVLLQS-SYATPVDMWSVGCIFAELFNRRPLF-RGSSEA--------DQLGK 217

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  82 IFSVMGFPADKDWedirkmPEYPTLQKD-FRRTTYAN-SSLIKYMEKHKVKpdskvflLLQKLLTMDPTKRITSEQALQD 159
Cdd:cd07838   218 IFDVIGLPSEEEW------PRNSALPRSsFPSYTPRPfKSFVPEIDEEGLD-------LLKKMLTFNPHKRISAFEALQH 284

                  ...
gi 1034649373 160 PYF 162
Cdd:cd07838   285 PYF 287

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   2 GFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDiktsnpfhhDQLDR 81
Cdd:cd07861   146 GLARAFGIPVRVYTH---EVVTLWYRAPEVLLGSPRYSTPVDIWSIGTIFAEMATKKPLFHGDSEI---------DQLFR 213

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  82 IFSVMGFPADKDWEDIRKMPEY----PTLQKDFRRTTYANSslikymekhkvkpDSKVFLLLQKLLTMDPTKRITSEQAL 157
Cdd:cd07861   214 IFRILGTPTEDIWPGVTSLPDYkntfPKWKKGSLRTAVKNL-------------DEDGLDLLEKMLIYDPAKRISAKKAL 280

                  ....*
gi 1034649373 158 QDPYF 162
Cdd:cd07861   281 VHPYF 285

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  21 VVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpfhHDQLDRIFSVMGFPADKDWedirkm 100
Cdd:cd07830   159 VSTRWYRAPEILLRSTSYSSPVDIWALGCIMAELYTLRPLFPGSSE---------IDQLYKICSVLGTPTKQDW------ 223

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034649373 101 PEYPTL--QKDFRRTTYANSSLikymekHKVKPDSKVFL--LLQKLLTMDPTKRITSEQALQDPYF 162
Cdd:cd07830   224 PEGYKLasKLGFRFPQFAPTSL------HQLIPNASPEAidLIKDMLRWDPKKRPTASQALQHPYF 283

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   2 GFARLFNSPLKPLAdldPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTS-EPIFHCRQEDiktsnpfhhDQLD 80
Cdd:cd07839   144 GLARAFGIPVRCYS---AEVVTLWYRPPDVLFGAKLYSTSIDMWSAGCIFAELANAgRPLFPGNDVD---------DQLK 211

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  81 RIFSVMGFPADKDWEDIRKMPEYPTLqkdfrrtTYANSSLIKYMEKHKVKPDSKVflLLQKLLTMDPTKRITSEQALQDP 160
Cdd:cd07839   212 RIFRLLGTPTEESWPGVSKLPDYKPY-------PMYPATTSLVNVVPKLNSTGRD--LLQNLLVCNPVQRISAEEALQHP 282

                  ..
gi 1034649373 161 YF 162
Cdd:cd07839   283 YF 284

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   1 MGFARLFNSPLkpladLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFhcrqediktSNPFHHDQLD 80
Cdd:cd05118   146 FGLARSFTSPP-----YTPYVATRWYRAPEVLLGAKPYGSSIDIWSLGCILAELLTGRPLF---------PGDSEVDQLA 211

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  81 RIFSVMGFPADKDwedirkmpeyptlqkdfrrttyansslikymekhkvkpdskvflLLQKLLTMDPTKRITSEQALQDP 160
Cdd:cd05118   212 KIVRLLGTPEALD--------------------------------------------LLSKMLKYDPAKRITASQALAHP 247

                  ..
gi 1034649373 161 YF 162
Cdd:cd05118   248 YF 249

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  21 VVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFhcrqEDIKTSNpfhhDQLDRIFSVMGFPADKDWEDIRKM 100
Cdd:cd07844   159 VVTLWYRPPDVLLGSTEYSTSLDMWGVGCIFYEMATGRPLF----PGSTDVE----DQLHKIFRVLGTPTEETWPGVSSN 230

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034649373 101 PEYptlqKDFRRTTYANSSLIKYMEKHKVKPDSkvFLLLQKLLTMDPTKRITSEQALQDPYF 162
Cdd:cd07844   231 PEF----KPYSFPFYPPRPLINHAPRLDRIPHG--EELALKFLQYEPKKRISAAEAMKHPYF 286

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   1 MGFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpfhHDQLD 80
Cdd:cd07837   154 LGLGRAFTIPIKSYTH---EIVTLWYRAPEVLLGSTHYSTPVDMWSVGCIFAEMSRKQPLFPGDSE---------LQQLL 221

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  81 RIFSVMGFPADKDWEDIRKMP---EYPTLQ-KDFrrttyanSSLIKYMEKHKVKpdskvflLLQKLLTMDPTKRITSEQA 156
Cdd:cd07837   222 HIFRLLGTPNEEVWPGVSKLRdwhEYPQWKpQDL-------SRAVPDLEPEGVD-------LLTKMLAYDPAKRISAKAA 287

                  ....*.
gi 1034649373 157 LQDPYF 162
Cdd:cd07837   288 LQHPYF 293

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373   2 GFARLFNSPLKPLADL-DPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpfhHDQLD 80
Cdd:cd07865   164 GLARAFSLAKNSQPNRyTNRVVTLWYRPPELLLGERDYGPPIDMWGAGCIMAEMWTRSPIMQGNTE---------QHQLT 234

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  81 RIFSVMGFPADKDWEDIRKMPEYPT--LQKDFRRTtyansslIKYMEKHKVKpDSKVFLLLQKLLTMDPTKRITSEQALQ 158
Cdd:cd07865   235 LISQLCGSITPEVWPGVDKLELFKKmeLPQGQKRK-------VKERLKPYVK-DPYALDLIDKLLVLDPAKRIDADTALN 306

                  ....
gi 1034649373 159 DPYF 162
Cdd:cd07865   307 HDFF 310

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034649373  21 VVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFhcrqediKTSNpfHHDQLDRIFSVMGFP---------AD 91
Cdd:cd07880   176 VVTRWYRAPEVILNWMHYTQTVDIWSVGCIMAEMLTGKPLF-------KGHD--HLDQLMEIMKVTGTPskefvqklqSE 246

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034649373  92 KDWEDIRKMPEYPtlQKDFRrttyansSLIKYMEKHKVKpdskvflLLQKLLTMDPTKRITSEQALQDPYFQE 164
Cdd:cd07880   247 DAKNYVKKLPRFR--KKDFR-------SLLPNANPLAVN-------VLEKMLVLDAESRITAAEALAHPYFEE 303