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 530383474  28 LKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07867  135 LKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 214

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLL 187
Cdd:cd07867  215 PIFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLL 294

                        170       180
                 ....*....|....*....|....
gi 530383474 188 LQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07867  295 LQKLLTMDPTKRITSEQALQDPYF 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 530383474  28 LKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07867  135 LKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 214

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLL 187
Cdd:cd07867  215 PIFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLL 294

                        170       180
                 ....*....|....*....|....
gi 530383474 188 LQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07867  295 LQKLLTMDPTKRITSEQALQDPYF 318

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474    28 LKPANILVMgegpERGRVKIADMGFARLFNSPLKpladLDPVVVTFWYRAPELLLGaRHYTKAIDIWAIGCIFAELLTSE 107
Cdd:smart00220 123 LKPENILLD----EDGHVKLADFGLARQLDPGEK----LTTFVGTPEYMAPEVLLG-KGYGKAVDIWSLGVILYELLTGK 193

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474   108 PIFHcrqediktsnpfHHDQLDRIFSVMGFPadkdweDIRKMPEYPTLQKDFRRttyansslikymekhkvkpdskvflL 187
Cdd:smart00220 194 PPFP------------GDDQLLELFKKIGKP------KPPFPPPEWDISPEAKD-------------------------L 230

                          170       180
                   ....*....|....*....|....
gi 530383474   188 LQKLLTMDPTKRITSEQALQDPYF 211
Cdd:smart00220 231 IRKLLVKDPEKRLTAEEALQHPFF 254

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474  28 LKPANILVMgegpERGRVKIADMGFARLFNSPlkPLADLDPVVVTFWYRAPELLLGARhYTKAIDIWAIGCIFAELLTSE 107
Cdd:COG0515  133 IKPANILLT----PDGRVKLIDFGIARALGGA--TLTQTGTVVGTPGYMAPEQARGEP-VDPRSDVYSLGVTLYELLTGR 205

                 ....
gi 530383474 108 PIFH 111
Cdd:COG0515  206 PPFD 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 530383474  28 LKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07867  135 LKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 214

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLL 187
Cdd:cd07867  215 PIFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLL 294

                        170       180
                 ....*....|....*....|....
gi 530383474 188 LQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07867  295 LQKLLTMDPTKRITSEQALQDPYF 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 530383474  28 LKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07868  150 LKPANILVMGEGPERGRVKIADMGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 229

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRQEDIKTSNPFHHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLL 187
Cdd:cd07868  230 PIFHCRQEDIKTSNPYHHDQLDRIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHL 309

                        170       180
                 ....*....|....*....|....
gi 530383474 188 LQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07868  310 LQKLLTMDPIKRITSEQAMQDPYF 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 530383474  28 LKPANILVMGegpeRGRVKIADMGFARLFNSPLKPlaDLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07840  130 IKGSNILINN----DGVLKLADFGLARPYTKENNA--DYTNRVITLWYRPPELLLGATRYGPEVDMWSVGCILAELFTGK 203

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRQEdiktsnpfhHDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKdfrRTTYANSSLIKYmekhKVKPDSKVFLL 187
Cdd:cd07840  204 PIFQGKTE---------LEQLEKIFELCGSPTEENWPGVSDLPWFENLKP---KKPYKRRLREVF----KNVIDPSALDL 267

                        170       180
                 ....*....|....*....|....
gi 530383474 188 LQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07840  268 LDKLLTLDPKKRISADQALQHEYF 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 530383474  28 LKPANILVmgegPERGRVKIADMGFARLFNSPLKPLAdldPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07841  128 LKPNNLLI----ASDGVLKLADFGLARSFGSPNRKMT---HQVVTRWYRAPELLFGARHYGVGVDMWSVGCIFAELLLRV 200

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHcRQEDIktsnpfhhDQLDRIFSVMGFPADKDWEDIRKMPEY----PTLQKDFRRT-TYANSSLIKymekhkvkpds 182
Cdd:cd07841  201 PFLP-GDSDI--------DQLGKIFEALGTPTEENWPGVTSLPDYvefkPFPPTPLKQIfPAASDDALD----------- 260

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 530383474 183 kvflLLQKLLTMDPTKRITSEQALQDPYFQEDPLPT 218
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 530383474  28 LKPANILVmgegPERGRVKIADMGFARLFNSPLKPLaDLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07834  129 LKPSNILV----NSNCDLKICDFGLARGVDPDEDKG-FLTEYVVTRWYRAPELLLSSKKYTKAIDIWSVGCIFAELLTRK 203

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFhcrqediKTSNPFHhdQLDRIFSVMGFPADKDWEDIRkmpeyptlqkdfrrttyaNSSLIKYME---KHKVKPDSKV 184
Cdd:cd07834  204 PLF-------PGRDYID--QLNLIVEVLGTPSEEDLKFIS------------------SEKARNYLKslpKKPKKPLSEV 256

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530383474 185 FL--------LLQKLLTMDPTKRITSEQALQDPYFQE--DPLPTldvfAGCQIPYPKREFLNEDDPEE 242
Cdd:cd07834  257 FPgaspeaidLLEKMLVFNPKKRITADEALAHPYLAQlhDPEDE----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 530383474  28 LKPANILVmgegPERGRVKIADMGFARLFNSPLKpladLDPVVVTFWYRAPELLLGArHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07838  133 LKPQNILV----TSDGQVKLADFGLARIYSFEMA----LTSVVVTLWYRAPEVLLQS-SYATPVDMWSVGCIFAELFNRR 203

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFhCRQEDIktsnpfhhDQLDRIFSVMGFPADKDWedirkmPEYPTLQKD-FRRTTYAN-SSLIKYMEKHKVKpdskvf 185
Cdd:cd07838  204 PLF-RGSSEA--------DQLGKIFDVIGLPSEEEW------PRNSALPRSsFPSYTPRPfKSFVPEIDEEGLD------ 262

                        170       180
                 ....*....|....*....|....*.
gi 530383474 186 lLLQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07838  263 -LLKKMLTFNPHKRISAFEALQHPYF 287

cyclin-dependent protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474  28 LKPANILVmgegPERGRVKIADMGFARLFNSPL-----------KPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAI 96
Cdd:PTZ00024 145 LSPANIFI----NSKGICKIADFGLARRYGYPPysdtlskdetmQRREEMTSKVVTLWYRAPELLMGAEKYHFAVDMWSV 220

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474  97 GCIFAELLTSEPIFHCRQEdiktsnpfhHDQLDRIFSVMGFPADKDWEDIRKMPEY----PTLQKDFRRT-TYANSSLIK 171
Cdd:PTZ00024 221 GCIFAELLTGKPLFPGENE---------IDQLGRIFELLGTPNEDNWPQAKKLPLYteftPRKPKDLKTIfPNASDDAID 291

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 530383474 172 ymekhkvkpdskvflLLQKLLTMDPTKRITSEQALQDPYFQEDPLP 217
Cdd:PTZ00024 292 ---------------LLQSLLKLNPLERISAKEALKHEYFKSDPLP 322

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 530383474  28 LKPANILVmgegPERGRVKIADMGFARLFNSPLKPLadLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07832  126 LKPANLLI----SSTGVLKIADFGLARLFSEEDPRL--YSHQVATRWYRAPELLYGSRKYDEGVDLWAVGCIFAELLNGS 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRqEDIktsnpfhhDQLDRIFSVMGFPADKDWEDIRKMPEYPTLqkdfrrtTYANSSLIKyMEKHKVKPDSKVFLL 187
Cdd:cd07832  200 PLFPGE-NDI--------EQLAIVLRTLGTPNEKTWPELTSLPDYNKI-------TFPESKGIR-LEEIFPDCSPEAIDL 262

                        170       180
                 ....*....|....*....|....
gi 530383474 188 LQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07832  263 LKGLLVYNPKKRLSAEEALRHPYF 286

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 530383474  28 LKPANILVMGegpeRGRVKIADMGFAR-LFNSPlkPLADLdpvVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTS 106
Cdd:cd07830  125 LKPENLLVSG----PEVVKIADFGLAReIRSRP--PYTDY---VSTRWYRAPEILLRSTSYSSPVDIWALGCIMAELYTL 195

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 107 EPIFHCRQEdiktsnpfhHDQLDRIFSVMGFPADKDWedirkmPEYPTL--QKDFRRTTYANSSLikymekHKVKPDSKV 184
Cdd:cd07830  196 RPLFPGSSE---------IDQLYKICSVLGTPTKQDW------PEGYKLasKLGFRFPQFAPTSL------HQLIPNASP 254

                        170       180
                 ....*....|....*....|....*....
gi 530383474 185 FL--LLQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07830  255 EAidLIKDMLRWDPKKRPTASQALQHPYF 283

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the 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. 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 CDK2/3 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 530383474  28 LKPANILVmgegPERGRVKIADMGFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07860  126 LKPQNLLI----NTEGAIKLADFGLARAFGVPVRTYTH---EVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMVTRR 198

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRQEDiktsnpfhhDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYAnsslikymekhKVKP--DSKVF 185
Cdd:cd07860  199 ALFPGDSEI---------DQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPKWARQDFS-----------KVVPplDEDGR 258

                        170       180
                 ....*....|....*....|....*.
gi 530383474 186 LLLQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07860  259 DLLSQMLHYDPNKRISAKAALAHPFF 284

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 530383474  28 LKPANILVmgegPERGRVKIADMGFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07861  127 LKPQNLLI----DNKGVIKLADFGLARAFGIPVRVYTH---EVVTLWYRAPEVLLGSPRYSTPVDIWSIGTIFAEMATKK 199

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRQEDiktsnpfhhDQLDRIFSVMGFPADKDWEDIRKMPEY----PTLQKDFRRTTYANSslikymekhkvkpDSK 183
Cdd:cd07861  200 PLFHGDSEI---------DQLFRIFRILGTPTEDIWPGVTSLPDYkntfPKWKKGSLRTAVKNL-------------DED 257

                        170       180
                 ....*....|....*....|....*...
gi 530383474 184 VFLLLQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07861  258 GLDLLEKMLIYDPAKRISAKKALVHPYF 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 530383474  28 LKPANILVmgegPERGRVKIADMGFARLFNSplkplaDLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07851  144 LKPSNLAV----NEDCELKILDFGLARHTDD------EMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGK 213

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFhcRQEDiktsnpfHHDQLDRIFSVMGFPADK-----DWED----IRKMPEYPtlQKDFRRT-TYANSSLIKymekhk 177
Cdd:cd07851  214 TLF--PGSD-------HIDQLKRIMNLVGTPDEEllkkiSSESarnyIQSLPQMP--KKDFKEVfSGANPLAID------ 276

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 530383474 178 vkpdskvflLLQKLLTMDPTKRITSEQALQDPYFQE--DP 215
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 530383474  28 LKPANILVMGEgpeRGRVKIADMGFARLFNSPLkpladLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd05118  127 LKPENILINLE---LGQLKLADFGLARSFTSPP-----YTPYVATRWYRAPEVLLGAKPYGSSIDIWSLGCILAELLTGR 198

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFhcrqediktSNPFHHDQLDRIFSVMGFPADKDwedirkmpeyptlqkdfrrttyansslikymekhkvkpdskvflL 187
Cdd:cd05118  199 PLF---------PGDSEVDQLAKIVRLLGTPEALD--------------------------------------------L 225

                        170       180
                 ....*....|....*....|....
gi 530383474 188 LQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd05118  226 LSKMLKYDPAKRITASQALAHPYF 249

cyclin-dependent kinase A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474  28 LKPANILVmgeGPERGRVKIADMGFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:PLN00009 128 LKPQNLLI---DRRTNALKLADFGLARAFGIPVRTFTH---EVVTLWYRAPEILLGSRHYSTPVDIWSVGCIFAEMVNQK 201

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRQEDiktsnpfhhDQLDRIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYAnsSLIKYMEKHKVKpdskvflL 187
Cdd:PLN00009 202 PLFPGDSEI---------DELFKIFRILGTPNEETWPGVTSLPDYKSAFPKWPPKDLA--TVVPTLEPAGVD-------L 263

                        170       180
                 ....*....|....*....|....*.
gi 530383474 188 LQKLLTMDPTKRITSEQALQDPYFQE 213
Cdd:PLN00009 264 LSKMLRLDPSKRITARAALEHEYFKD 289

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 530383474  28 LKPANILVmgeGPERGRVKIADMGFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07837  135 LKPQNLLV---DKQKGLLKIADLGLGRAFTIPIKSYTH---EIVTLWYRAPEVLLGSTHYSTPVDMWSVGCIFAEMSRKQ 208

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRQEdiktsnpfhHDQLDRIFSVMGFPADKDWEDIRKMP---EYPTLQ-KDFrrttyanSSLIKYMEKHKVKpdsk 183
Cdd:cd07837  209 PLFPGDSE---------LQQLLHIFRLLGTPNEEVWPGVSKLRdwhEYPQWKpQDL-------SRAVPDLEPEGVD---- 268

                        170       180
                 ....*....|....*....|....*...
gi 530383474 184 vflLLQKLLTMDPTKRITSEQALQDPYF 211
Cdd:cd07837  269 ---LLTKMLAYDPAKRISAKAALQHPYF 293

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK 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 530383474  28 LKPANILVmgegPERGRVKIADMGFARLFNSPLKPLADLdpvVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSE 107
Cdd:cd07858  134 LKPSNLLL----NANCDLKICDFGLARTTSEKGDFMTEY---VVTRWYRAPELLLNCSEYTTAIDVWSVGCIFAELLGRK 206

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530383474 108 PIFHCRQediktsnpfHHDQLDRIFSVMGFPADKDWED---------IRKMPEYPtlQKDFRRttyanssliKYMEKHKV 178
Cdd:cd07858  207 PLFPGKD---------YVHQLKLITELLGSPSEEDLGFirnekarryIRSLPYTP--RQSFAR---------LFPHANPL 266

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530383474 179 KPDskvflLLQKLLTMDPTKRITSEQALQDPYFQedPLPTLDVFAGCQIPYP---KREFLNEDDPEE 242
Cdd:cd07858  267 AID-----LLEKMLVFDPSKRITVEEALAHPYLA--SLHDPSDEPVCQTPFSfdfEEDALTEEDIKE 326