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 569000819   2 IKICDFGFARILI-PGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLG 80
Cdd:cd07847  139 IKLCDFGFARILTgPGDDYTDYVATRWYRAPELLVGDTQYGPPVDVWAIGCVFAELLTGQPLWPGKSDVDQLYLIRKTLG 218

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569000819  81 KLIPRHQSIFRSNQFFRGISIPEPEDMETLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07847  219 DLIPRHQQIFSTNQFFKGLSIPEPETREPLESKFPNISSPALSFLKGCLQMDPTERLSCEELLEHPYF 286

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. 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 CDKL1/4 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 569000819   2 IKICDFGFARILI-PGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLG 80
Cdd:cd07847  139 IKLCDFGFARILTgPGDDYTDYVATRWYRAPELLVGDTQYGPPVDVWAIGCVFAELLTGQPLWPGKSDVDQLYLIRKTLG 218

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569000819  81 KLIPRHQSIFRSNQFFRGISIPEPEDMETLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07847  219 DLIPRHQQIFSTNQFFKGLSIPEPETREPLESKFPNISSPALSFLKGCLQMDPTERLSCEELLEHPYF 286

cyclin-dependent protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000819   3 KICDFGFARILI---------------PGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKS 67
Cdd:PTZ00024 159 KIADFGLARRYGyppysdtlskdetmqRREEMTSKVVTLWYRAPELLMGAEKYHFAVDMWSVGCIFAELLTGKPLFPGEN 238

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000819  68 DVDQLYLIIRTLGKLIPRHQSIFRSNQFFRGISIPEPEDMETLeekFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAY 147
Cdd:PTZ00024 239 EIDQLGRIFELLGTPNEDNWPQAKKLPLYTEFTPRKPKDLKTI---FPNASDDAIDLLQSLLKLNPLERISAKEALKHEY 315

                 ....
gi 569000819 148 FESF 151
Cdd:PTZ00024 316 FKSD 319

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569000819   2 IKICDFGFARILIPGDAYTDYVA--TRWYRAPELLVGDtKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIR 77
Cdd:COG0515  146 VKLIDFGIARALGGATLTQTGTVvgTPGYMAPEQARGE-PVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLR 222

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. 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 CDKL1/4 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 569000819   2 IKICDFGFARILI-PGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLG 80
Cdd:cd07847  139 IKLCDFGFARILTgPGDDYTDYVATRWYRAPELLVGDTQYGPPVDVWAIGCVFAELLTGQPLWPGKSDVDQLYLIRKTLG 218

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569000819  81 KLIPRHQSIFRSNQFFRGISIPEPEDMETLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07847  219 DLIPRHQQIFSTNQFFKGLSIPEPETREPLESKFPNISSPALSFLKGCLQMDPTERLSCEELLEHPYF 286

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. 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 CDKL2/3 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 569000819   1 MIKICDFGFARILI-PGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTL 79
Cdd:cd07846  138 VVKLCDFGFARTLAaPGEVYTDYVATRWYRAPELLVGDTKYGKAVDVWAVGCLVTEMLTGEPLFPGDSDIDQLYHIIKCL 217

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569000819  80 GKLIPRHQSIFRSNQFFRGISIPEPEDMETLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07846  218 GNLIPRHQELFQKNPLFAGVRLPEVKEVEPLERRYPKLSGVVIDLAKKCLHIDPDKRPSCSELLHHEFF 286

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 569000819   1 MIKICDFGFARILIPGDA--YTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRT 78
Cdd:cd07832  138 VLKIADFGLARLFSEEDPrlYSHQVATRWYRAPELLYGSRKYDEGVDLWAVGCIFAELLNGSPLFPGENDIEQLAIVLRT 217

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569000819  79 LG----KLIPRHQSIFRSNQffrgISIPEpEDMETLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07832  218 LGtpneKTWPELTSLPDYNK----ITFPE-SKGIRLEEIFPDCSPEAIDLLKGLLVYNPKKRLSAEEALRHPYF 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. 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 569000819   1 MIKICDFGFARIL-IPGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTL 79
Cdd:cd07829  136 VLKLADFGLARAFgIPLRTYTHEVVTLWYRAPEILLGSKHYSTAVDIWSVGCIFAELITGKPLFPGDSEIDQLFKIFQIL 215

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569000819  80 G----------KLIPRHQSIFrsnqffrgiSIPEPEDmetLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07829  216 GtpteeswpgvTKLPDYKPTF---------PKWPKND---LEKVLPRLDPEGIDLLSKMLQYNPAKRISAKEALKHPYF 282

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 569000819   2 IKICDFGFARILIPgDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLGK 81
Cdd:cd05118  141 LKLADFGLARSFTS-PPYTPYVATRWYRAPEVLLGAKPYGSSIDIWSLGCILAELLTGRPLFPGDSEVDQLAKIVRLLGT 219

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569000819  82 liprhqsifrsnqffrgisipepedmetleekfsnvqPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd05118  220 -------------------------------------PEALDLLSKMLKYDPAKRITASQALAHPYF 249

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. 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 CDKL5 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 569000819   1 MIKICDFGFARILIPG-DA-YTDYVATRWYRAPELLVGdTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRT 78
Cdd:cd07848  138 VLKLCDFGFARNLSEGsNAnYTEYVATRWYRSPELLLG-APYGKAVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKV 216

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569000819  79 LGKLIPRHQSIFRSNQFFRGISIPEPEDMETLEEKFSNV-QPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07848  217 LGPLPAEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGIlSGVLLDLMKNLLKLNPTDRYLTEQCLNHPAF 287

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 569000819   2 IKICDFGFARILIP--GDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTL 79
Cdd:cd07840  143 LKLADFGLARPYTKenNADYTNRVITLWYRPPELLLGATRYGPEVDMWSVGCILAELFTGKPIFQGKTELEQLEKIFELC 222

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000819  80 GKLIPRHQSIFRSNQFFRGISIPEPEDmETLEEKFSNVQ-PVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07840  223 GSPTEENWPGVSDLPWFENLKPKKPYK-RRLREVFKNVIdPSALDLLDKLLTLDPKKRISADQALQHEYF 291

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000819     1 MIKICDFGFARILIPGDAYTDYVATRWYRAPELLVGdTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRtlg 80
Cdd:smart00220 135 HVKLADFGLARQLDPGEKLTTFVGTPEYMAPEVLLG-KGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIG--- 210

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569000819    81 kliprhqsifrsnqffrgisipepEDMETLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:smart00220 211 ------------------------KPKPPFPPPEWDISPEAKDLIRKLLVKDPEKRLTAEEALQHPFF 254

Catalytic domain of the Serine/Threonine Kinases, Plant TDY 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 TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. 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 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY 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 569000819   2 IKICDFGFARILI---PGDAY-TDYVATRWYRAPELlVGD--TKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLI 75
Cdd:cd07859  142 LKICDFGLARVAFndtPTAIFwTDYVATRWYRAPEL-CGSffSKYTPAIDIWSIGCIFAEVLTGKPLFPGKNVVHQLDLI 220

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569000819  76 IRTLGKLIPRHQSIFRSNQFFRGISIPEPEDMETLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYFES 150
Cdd:cd07859  221 TDLLGTPSPETISRVRNEKARRYLSSMRKKQPVPFSQKFPNADPLALRLLERLLAFDPKDRPTAEEALADPYFKG 295

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 569000819   2 IKICDFGFARIL-IPGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLG 80
Cdd:cd07845  147 LKIADFGLARTYgLPAKPMTPKVVTLWYRAPELLLGCTTYTTAIDMWAVGCILAELLAHKPLLPGKSEIEQLDLIIQLLG 226

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569000819  81 KliPrHQSI---FRSNQFFRGISIPEpEDMETLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07845  227 T--P-NESIwpgFSDLPLVGKFTLPK-QPYNNLKHKFPWLSEAGLRLLNFLLMYDPKKRATAEEALESSYF 293

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 569000819   2 IKICDFGFARIL-IPGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLG 80
Cdd:cd07835  138 LKLADFGLARAFgVPVRTYTHEVVTLWYRAPEILLGSKHYSTPVDIWSVGCIFAEMVTRRPLFPGDSEIDQLFRIFRTLG 217

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000819  81 ----------KLIPRHQSIFrsnqffrgisiP--EPEDMETLeekFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07835  218 tpdedvwpgvTSLPDYKPTF-----------PkwARQDLSKV---VPSLDEDGLDLLSQMLVYDPAKRISAKAALQHPYF 283

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 569000819   2 IKICDFGFARILipGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLGK 81
Cdd:cd07851  157 LKILDFGLARHT--DDEMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGKTLFPGSDHIDQLKRIMNLVGT 234

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569000819  82 ----LIPRHQSIfRSNQFFRGISIPEPEDMETLeekFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYFESF 151
Cdd:cd07851  235 pdeeLLKKISSE-SARNYIQSLPQMPKKDFKEV---FSGANPLAIDLLEKMLVLDPDKRITAAEALAHPYLAEY 304

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases 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 p38alpha 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 569000819   2 IKICDFGFARIliPGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLGK 81
Cdd:cd07877  159 LKILDFGLARH--TDDEMTGYVATRWYRAPEIMLNWMHYNQTVDIWSVGCIMAELLTGRTLFPGTDHIDQLKLILRLVGT 236

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569000819  82 LIPRHQSIFRSNQFFRGI-SIPEPEDMeTLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYFESFQE 153
Cdd:cd07877  237 PGAELLKKISSESARNYIqSLTQMPKM-NFANVFIGANPLAVDLLEKMLVLDSDKRITAAQALAHAYFAQYHD 308

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. 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 Pho85 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 569000819   2 IKICDFGFARIL-IPGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLG 80
Cdd:cd07836  139 LKLADFGLARAFgIPVNTFSNEVVTLWYRAPDVLLGSRTYSTSIDIWSVGCIMAEMITGRPLFPGTNNEDQLLKIFRIMG 218

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569000819  81 ----KLIPRhqsIFRSNQFFRGISIPEPEDMETLeekFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07836  219 tpteSTWPG---ISQLPEYKPTFPRYPPQDLQQL---FPHADPLGIDLLHRLLQLNPELRISAHDALQHPWF 284

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 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 569000819   2 IKICDFGFARILIPgdAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLGK 81
Cdd:cd07856  147 LKICDFGLARIQDP--QMTGYVSTRYYRAPEIMLTWQKYDVEVDIWSAGCIFAEMLEGKPLFPGKDHVNQFSIITELLGT 224

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569000819  82 lIPRH--QSIFRSNQFFRGISIPEPEDMeTLEEKFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYFESFQE 153
Cdd:cd07856  225 -PPDDviNTICSENTLRFVQSLPKRERV-PFSEKFKNADPDAIDLLEKMLVFDPKKRISAAEALAHPYLAPYHD 296

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 569000819   2 IKICDFGFARiliPGDA-YTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLIIRTLG 80
Cdd:cd07880  157 LKILDFGLAR---QTDSeMTGYVVTRWYRAPEVILNWMHYTQTVDIWSVGCIMAEMLTGKPLFKGHDHLDQLMEIMKVTG 233

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569000819  81 ----KLIPRHQSIFRSNqFFRGISIPEPEDMETLeekFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYFESFQE 153
Cdd:cd07880  234 tpskEFVQKLQSEDAKN-YVKKLPRFRKKDFRSL---LPNANPLAVNVLEKMLVLDAESRITAAEALAHPYFEEFHD 306

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 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 569000819   2 IKICDFGFARILI--PGDA---YTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDVDQLYLII 76
Cdd:cd07855  148 LKIGDFGMARGLCtsPEEHkyfMTEYVATRWYRAPELMLSLPEYTQAIDMWSVGCIFAEMLGRRQLFPGKNYVHQLQLIL 227

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000819  77 RTLGKliPRHQSIF-----RSNQFFRGISIPEPEDMETLeekFSNVQPVALSFMKGCLKMNPDERLTCAQLLDSAYFESF 151
Cdd:cd07855  228 TVLGT--PSQAVINaigadRVRRYIQNLPNKQPVPWETL---YPKADQQALDLLSQMLRFDPSERITVAEALQHPFLAKY 302

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 569000819   2 IKICDFGFARIL-IPGDAYTDYVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSDV-DQLYLIIRTL 79
Cdd:cd07844  137 LKLADFGLARAKsVPSKTYSNEVVTLWYRPPDVLLGSTEYSTSLDMWGVGCIFYEMATGRPLFPGSTDVeDQLHKIFRVL 216

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569000819  80 GKLIPRHQSIFRSNQFFRGISIPEPEDmETLEEKFSNVQPV--ALSFMKGCLKMNPDERLTCAQLLDSAYF 148
Cdd:cd07844  217 GTPTEETWPGVSSNPEFKPYSFPFYPP-RPLINHAPRLDRIphGEELALKFLQYEPKKRISAAEAMKHPYF 286

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 569000819   2 IKICDFGFARI-------LIPGDAYtdyVATRWYRAPELLVGDTKYGSSVDVWAVGCVFAELLTGQPLWPGKSD------ 68
Cdd:cd07842  151 VKIGDLGLARLfnaplkpLADLDPV---VVTIWYRAPELLLGARHYTKAIDIWAIGCIFAELLTLEPIFKGREAkikksn 227

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569000819  69 ---VDQLYLIIRTLG----------KLIPRHQsifrsnQFFRGISIPE--PEDMETLEEKFSNVQPVALSFMKGCLKMNP 133
Cdd:cd07842  228 pfqRDQLERIFEVLGtptekdwpdiKKMPEYD------TLKSDTKASTypNSLLAKWMHKHKKPDSQGFDLLRKLLEYDP 301

                        170
                 ....*....|....*
gi 569000819 134 DERLTCAQLLDSAYF 148
Cdd:cd07842  302 TKRITAEEALEHPYF 316