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 2217360504   9 KPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07867   136 KPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 215

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLLL 168
Cdd:cd07867   216 IFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLLL 295

                         170       180
                  ....*....|....*....|...
gi 2217360504 169 QKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07867   296 QKLLTMDPTKRITSEQALQDPYF 318

Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L6 is also called CDK8-like and was previously referred to as CDK11. However, this is a confusing nomenclature as CDC2L6 is distinct from CDC2L1, which is represented by the two protein products from its gene, called CDK11(p110) and CDK11(p58), as well as the caspase-processed CDK11(p46). CDK11(p110), CDK11(p58), and CDK11(p46)do not belong to this subfamily. CDC2L6 is an associated protein of Mediator, a multiprotein complex that provides a platform to connect transcriptional and chromatin regulators and cofactors, in order to activate and mediate RNA polymerase II transcription. CDC2L6 is localized mainly in the nucleus amd exerts an opposing effect to CDK8 in VP16-dependent transcriptional activation by being a negative regulator. 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 CDC2L6 subfamily is part of 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 2217360504   9 KPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07867   136 KPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 215

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLLL 168
Cdd:cd07867   216 IFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLLL 295

                         170       180
                  ....*....|....*....|...
gi 2217360504 169 QKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07867   296 QKLLTMDPTKRITSEQALQDPYF 318

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504    9 KPANILVMgegpERGRVKIADMGFARLFNSPLKpladLDPVVVTFWYRAPELLLGaRHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:smart00220 124 KPENILLD----EDGHVKLADFGLARQLDPGEK----LTTFVGTPEYMAPEVLLG-KGYGKAVDIWSLGVILYELLTGKP 194

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504   89 IFHcrqediktsnpfHHDQLDRIFSVMGFPadkdweDIRKMPEYPTLQKDFRRttyansslikymekhkvkpdskvflLL 168
Cdd:smart00220 195 PFP------------GDDQLLELFKKIGKP------KPPFPPPEWDISPEAKD-------------------------LI 231

                          170       180
                   ....*....|....*....|...
gi 2217360504  169 QKLLTMDPTKRITSEQALQDPYF 191
Cdd:smart00220 232 RKLLVKDPEKRLTAEEALQHPFF 254

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504   9 KPANILVMgegpERGRVKIADMGFARLFNSPlkPLADLDPVVVTFWYRAPELLLGARhYTKAIDIWAIGCIFAELLTSEP 88
Cdd:COG0515   134 KPANILLT----PDGRVKLIDFGIARALGGA--TLTQTGTVVGTPGYMAPEQARGEP-VDPRSDVYSLGVTLYELLTGRP 206

                  ...
gi 2217360504  89 IFH 91
Cdd:COG0515   207 PFD 209

Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L6 is also called CDK8-like and was previously referred to as CDK11. However, this is a confusing nomenclature as CDC2L6 is distinct from CDC2L1, which is represented by the two protein products from its gene, called CDK11(p110) and CDK11(p58), as well as the caspase-processed CDK11(p46). CDK11(p110), CDK11(p58), and CDK11(p46)do not belong to this subfamily. CDC2L6 is an associated protein of Mediator, a multiprotein complex that provides a platform to connect transcriptional and chromatin regulators and cofactors, in order to activate and mediate RNA polymerase II transcription. CDC2L6 is localized mainly in the nucleus amd exerts an opposing effect to CDK8 in VP16-dependent transcriptional activation by being a negative regulator. 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 CDC2L6 subfamily is part of 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 2217360504   9 KPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07867   136 KPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 215

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLLL 168
Cdd:cd07867   216 IFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLLL 295

                         170       180
                  ....*....|....*....|...
gi 2217360504 169 QKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07867   296 QKLLTMDPTKRITSEQALQDPYF 318

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK8 can act 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 (RNAP II)-dependent transcription. CDK8 phosphorylates cyclin H, a subunit of the general transcription factor TFIIH, which results in the inhibition of TFIIH-dependent phosphorylation of the C-terminal domain of RNAP II, facilitating the inhibition of transcription. It has also been shown to promote transcription by a mechanism that is likely to involve RNAP II phosphorylation. CDK8 also functions as a stimulus-specific positive coregulator of p53 transcriptional responses. 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 subfamily is part of 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 2217360504   9 KPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07868   151 KPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 230

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLLL 168
Cdd:cd07868   231 IFHCRQEDIKTSNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLL 310

                         170       180
                  ....*....|....*....|...
gi 2217360504 169 QKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07868   311 QKLLTMDPIKRITSEQAMQDPYF 333

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 2217360504   5 REIaKPANILVMGegpeRGRVKIADMGFARLFNSPLKPlaDLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELL 84
Cdd:cd07840   128 RDI-KGSNILINN----DGVLKLADFGLARPYTKENNA--DYTNRVITLWYRPPELLLGATRYGPEVDMWSVGCILAELF 200

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  85 TSEPIFHCRQEdiktsnpfhHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKdfrRTTYANSSLIKYmekhKVKPDSKV 164
Cdd:cd07840   201 TGKPIFQGKTE---------LEQLEKIFELCGSPTEENWPGVSDLPWFENLKP---KKPYKRRLREVF----KNVIDPSA 264

                         170       180
                  ....*....|....*....|....*..
gi 2217360504 165 FLLLQKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07840   265 LDLLDKLLTLDPKKRISADQALQHEYF 291

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504   9 KPANILVmgegPERGRVKIADMGFARLFNSPLKPLAdldPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07841   129 KPNNLLI----ASDGVLKLADFGLARSFGSPNRKMT---HQVVTRWYRAPELLFGARHYGVGVDMWSVGCIFAELLLRVP 201

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFHcRQEDIktsnpfhhDQLDRIFSVMGFPADKDWEDIRKMPEY----PTLQKDFRRT-TYANSSLIKymekhkvkpdsk 163
Cdd:cd07841   202 FLP-GDSDI--------DQLGKIFEALGTPTEENWPGVTSLPDYvefkPFPPTPLKQIfPAASDDALD------------ 260

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 2217360504 164 vflLLQKLLTMDPTKRITSEQALQDPYFQEDPLPT 198
Cdd:cd07841   261 ---LLQRLLTLNPNKRITARQALEHPYFSNDPAPT 292

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504   9 KPANILVmgegPERGRVKIADMGFARLFNSPLKPLaDLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07834   130 KPSNILV----NSNCDLKICDFGLARGVDPDEDKG-FLTEYVVTRWYRAPELLLSSKKYTKAIDIWSVGCIFAELLTRKP 204

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFhcrqediKTSNPFHhdQLDRIFSVMGFPadkDWEDIRKMPeyptlqkdfrrttyaNSSLIKYME---KHKVKPDSKVF 165
Cdd:cd07834   205 LF-------PGRDYID--QLNLIVEVLGTP---SEEDLKFIS---------------SEKARNYLKslpKKPKKPLSEVF 257

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2217360504 166 L--------LLQKLLTMDPTKRITSEQALQDPYFQE--DPLPTldvfAGCQIPYPKREFLNEDDPEE 222
Cdd:cd07834   258 PgaspeaidLLEKMLVFNPKKRITADEALAHPYLAQlhDPEDE----PVAKPPFDFPFFDDEELTIE 320

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 2217360504   9 KPANILVmgegPERGRVKIADMGFARL--FNSPLkpladlDPVVVTFWYRAPELLLGArHYTKAIDIWAIGCIFAELLTS 86
Cdd:cd07838   134 KPQNILV----TSDGQVKLADFGLARIysFEMAL------TSVVVTLWYRAPEVLLQS-SYATPVDMWSVGCIFAELFNR 202

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  87 EPIFhCRQEDIktsnpfhhDQLDRIFSVMGFPADKDWedirkmPEYPTLQKD-FRRTTYAN-SSLIKYMEKHKVKpdskv 164
Cdd:cd07838   203 RPLF-RGSSEA--------DQLGKIFDVIGLPSEEEW------PRNSALPRSsFPSYTPRPfKSFVPEIDEEGLD----- 262

                         170       180
                  ....*....|....*....|....*..
gi 2217360504 165 flLLQKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07838   263 --LLKKMLTFNPHKRISAFEALQHPYF 287

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504   9 KPANILVMGEGpergRVKIADMGFARLFNSplKPLADLDPV----VVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELL 84
Cdd:cd07852   134 KPSNILLNSDC----RVKLADFGLARSLSQ--LEEDDENPVltdyVATRWYRAPEILLGSTRYTKGVDMWSVGCILGEML 207

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  85 TSEPIFHcrqediKTSNpfhHDQLDRIFSVMGFPADKDWEDIrkmpeyptlqkdfrRTTYAnSSLIKYMEKHKVKPDSKV 164
Cdd:cd07852   208 LGKPLFP------GTST---LNQLEKIIEVIGRPSAEDIESI--------------QSPFA-ATMLESLPPSRPKSLDEL 263

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 2217360504 165 FL--------LLQKLLTMDPTKRITSEQALQDPYFQE----DPLPTLD 200
Cdd:cd07852   264 FPkaspdaldLLKKLLVFNPNKRLTAEEALRHPYVAQfhnpADEPSLP 311

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504   5 REIaKPANILVmgegPERGRVKIADMGFARLFNSPLKPLadLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELL 84
Cdd:cd07832   124 RDL-KPANLLI----SSTGVLKIADFGLARLFSEEDPRL--YSHQVATRWYRAPELLYGSRKYDEGVDLWAVGCIFAELL 196

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  85 TSEPIFHCRqEDIktsnpfhhDQLDRIFSVMGFPADKDWEDIRKMPEYPTLqkdfrrtTYANSSLIKyMEKHKVKPDSKV 164
Cdd:cd07832   197 NGSPLFPGE-NDI--------EQLAIVLRTLGTPNEKTWPELTSLPDYNKI-------TFPESKGIR-LEEIFPDCSPEA 259

                         170       180
                  ....*....|....*....|....*..
gi 2217360504 165 FLLLQKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07832   260 IDLLKGLLVYNPKKRLSAEEALRHPYF 286

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504   5 REIaKPANILVmgegPERGRVKIADMGFARLFNSPlkPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELL 84
Cdd:cd07833   124 RDI-KPENILV----SESGVLKLCDFGFARALTAR--PASPLTDYVATRWYRAPELLVGDTNYGKPVDVWAIGCIMAELL 196

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  85 TSEPIFHCRQEdiktsnpfhHDQLDRIFSVMGFPADKDWEDIRKMPEyptlqkdFRRTTYANSSLIKYME-KHKVKPDSK 163
Cdd:cd07833   197 DGEPLFPGDSD---------IDQLYLIQKCLGPLPPSHQELFSSNPR-------FAGVAFPEPSQPESLErRYPGKVSSP 260

                         170       180
                  ....*....|....*....|....*...
gi 2217360504 164 VFLLLQKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07833   261 ALDFLKACLRMDPKERLTCDELLQHPYF 288

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 2217360504   5 REIaKPANILVmgeGPERGRVKIADMGFARLfnspLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELL 84
Cdd:cd14137   130 RDI-KPQNLLV---DPETGVLKLCDFGSAKR----LVPGEPNVSYICSRYYRAPELIFGATDYTTAIDIWSAGCVLAELL 201

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  85 TSEPIFHCRqedikTSNpfhhDQLDRIFSVMGFPADkdwEDIRKM-PEYPtlqkDFRRTTYANSSLIKYMEKHkvkPDSK 163
Cdd:cd14137   202 LGQPLFPGE-----SSV----DQLVEIIKVLGTPTR---EQIKAMnPNYT----EFKFPQIKPHPWEKVFPKR---TPPD 262

                         170       180       190
                  ....*....|....*....|....*....|
gi 2217360504 164 VFLLLQKLLTMDPTKRITSEQALQDPYFQE 193
Cdd:cd14137   263 AIDLLSKILVYNPSKRLTALEALAHPFFDE 292

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 2217360504   9 KPANILVmgegPERGRVKIADMGFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07861   128 KPQNLLI----DNKGVIKLADFGLARAFGIPVRVYTH---EVVTLWYRAPEVLLGSPRYSTPVDIWSIGTIFAEMATKKP 200

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFHCRQEDiktsnpfhhDQLDRIFSVMGFPADKDWEDIRKMPEY----PTLQKDFRRTTYANSslikymekhkvkpDSKV 164
Cdd:cd07861   201 LFHGDSEI---------DQLFRIFRILGTPTEDIWPGVTSLPDYkntfPKWKKGSLRTAVKNL-------------DEDG 258

                         170       180
                  ....*....|....*....|....*..
gi 2217360504 165 FLLLQKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07861   259 LDLLEKMLIYDPAKRISAKKALVHPYF 285

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 2217360504   9 KPANILVmgegPERGRVKIADMGFARLFNSplkplaDLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07851   145 KPSNLAV----NEDCELKILDFGLARHTDD------EMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGKT 214

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFhcRQEDiktsnpfHHDQLDRIFSVMGFPADK-----DWED----IRKMPEYPtlQKDFRRT-TYANSSLIKymekhkv 158
Cdd:cd07851   215 LF--PGSD-------HIDQLKRIMNLVGTPDEEllkkiSSESarnyIQSLPQMP--KKDFKEVfSGANPLAID------- 276

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 2217360504 159 kpdskvflLLQKLLTMDPTKRITSEQALQDPYFQE--DP 195
Cdd:cd07851   277 --------LLEKMLVLDPDKRITAAEALAHPYLAEyhDP 307

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 2217360504   9 KPANILVMGEgpeRGRVKIADMGFARLFNSPLkpladLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd05118   128 KPENILINLE---LGQLKLADFGLARSFTSPP-----YTPYVATRWYRAPEVLLGAKPYGSSIDIWSLGCILAELLTGRP 199

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFhcrqediktSNPFHHDQLDRIFSVMGFPADKDwedirkmpeyptlqkdfrrttyansslikymekhkvkpdskvflLL 168
Cdd:cd05118   200 LF---------PGDSEVDQLAKIVRLLGTPEALD--------------------------------------------LL 226

                         170       180
                  ....*....|....*....|...
gi 2217360504 169 QKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd05118   227 SKMLKYDPAKRITASQALAHPYF 249

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504   9 KPANILVMgegpERGRVKIADMGFARLFNSPLKpladLDPVVVTFWYRAPELLLGARhYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07863   135 KPENILVT----SGGQVKLADFGLARIYSCQMA----LTPVVVTLWYRAPEVLLQST-YATPVDMWSVGCIFAEMFRRKP 205

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFHCRQEdiktsnpfhHDQLDRIFSVMGFPADKDWedirkmPEYPTLQK-DFR-RTTYANSSLIKYMEKHKVKpdskvfl 166
Cdd:cd07863   206 LFCGNSE---------ADQLGKIFDLIGLPPEDDW------PRDVTLPRgAFSpRGPRPVQSVVPEIEESGAQ------- 263

                         170       180
                  ....*....|....*....|....*
gi 2217360504 167 LLQKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07863   264 LLLEMLTFNPHKRISAFRALQHPFF 288

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 2217360504   9 KPANILVmgeGPERGRVKIADMGFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07837   136 KPQNLLV---DKQKGLLKIADLGLGRAFTIPIKSYTH---EIVTLWYRAPEVLLGSTHYSTPVDMWSVGCIFAEMSRKQP 209

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFHCRQEdiktsnpfhHDQLDRIFSVMGFPADKDWEDIRKMP---EYPTLQ-KDFrrttyanSSLIKYMEKHKVKpdskv 164
Cdd:cd07837   210 LFPGDSE---------LQQLLHIFRLLGTPNEEVWPGVSKLRdwhEYPQWKpQDL-------SRAVPDLEPEGVD----- 268

                         170       180
                  ....*....|....*....|....*..
gi 2217360504 165 flLLQKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07837   269 --LLTKMLAYDPAKRISAKAALQHPYF 293

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 2217360504   9 KPANILVmgegPERGRVKIADMGFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEP 88
Cdd:cd07844   125 KPQNLLI----SERGELKLADFGLARAKSVPSKTYSN---EVVTLWYRPPDVLLGSTEYSTSLDMWGVGCIFYEMATGRP 197

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2217360504  89 IFhcrqEDIKTSNpfhhDQLDRIFSVMGFPADKDWEDIRKMPEYptlqKDFRRTTYANSSLIKYMEKHKVKPDSkvFLLL 168
Cdd:cd07844   198 LF----PGSTDVE----DQLHKIFRVLGTPTEETWPGVSSNPEF----KPYSFPFYPPRPLINHAPRLDRIPHG--EELA 263

                         170       180
                  ....*....|....*....|...
gi 2217360504 169 QKLLTMDPTKRITSEQALQDPYF 191
Cdd:cd07844   264 LKFLQYEPKKRISAAEAMKHPYF 286