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 161075907  32 FEVGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISPFEHQTYCQRTLREITILTRFKHENIIDIRDILRVDSIDQM 111
Cdd:cd07849    1 FDVGPRYQNLSYIGEGAYGMVCSAVHKPTGQKVAIKKISPFEHQTYCLRTLREIKILLRFKHENIIGILDIQRPPTFESF 80

                         90       100
                 ....*....|....*....|...
gi 161075907 112 RDVYIVQCLMETDLYKLLKTQVM 134
Cdd:cd07849   81 KDVYIVQELMETDLYKLIKTQHL 103

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161075907  32 FEVGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISPFEHQTYCQRTLREITILTRFKHENIIDIRDILRVDSIDQM 111
Cdd:cd07849    1 FDVGPRYQNLSYIGEGAYGMVCSAVHKPTGQKVAIKKISPFEHQTYCLRTLREIKILLRFKHENIIGILDIQRPPTFESF 80

                         90       100
                 ....*....|....*....|...
gi 161075907 112 RDVYIVQCLMETDLYKLLKTQVM 134
Cdd:cd07849   81 KDVYIVQELMETDLYKLIKTQHL 103

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161075907   38 YIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISPfEHQT--YCQRTLREITILTRFKHENIIDIRDILRVDSidqmrDVY 115
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKK-EKIKkkKDKNILREIKILKKLNHPNIVRLYDAFEDKD-----NLY 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 161075907  116 IVQCLME-TDLYKLLKTQVmVLPDIWLKFIerittidMWCIILAITPNTKTEYNC 169
Cdd:pfam00069  75 LVLEYVEgGSLFDLLSEKG-AFSEREAKFI-------MKQILEGLESGSSLTTFV 121

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161075907  34 VGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISP--FEHQTYCQRTLREITILTRFKHENIIDIRDILRVDSIdqm 111
Cdd:COG0515    5 LLGRYRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPelAADPEARERFRREARALARLNHPNIVRVYDVGEEDGR--- 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 161075907 112 rdVYIVqclME----TDLYKLLKTQVMVLPDIWLKFIERI 147
Cdd:COG0515   82 --PYLV---MEyvegESLADLLRRRGPLPPAEALRILAQL 116

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161075907  32 FEVGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISPFEHQTYCQRTLREITILTRFKHENIIDIRDILRVDSIDQM 111
Cdd:cd07849    1 FDVGPRYQNLSYIGEGAYGMVCSAVHKPTGQKVAIKKISPFEHQTYCLRTLREIKILLRFKHENIIGILDIQRPPTFESF 80

                         90       100
                 ....*....|....*....|...
gi 161075907 112 RDVYIVQCLMETDLYKLLKTQVM 134
Cdd:cd07849   81 KDVYIVQELMETDLYKLIKTQHL 103

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 161075907  32 FEVGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKIS-PFEHQTYCQRTLREITILTRFKHENIIDIRDILRVDSIDQ 110
Cdd:cd07858    1 FEVDTKYVPIKPIGRGAYGIVCSAKNSETNEKVAIKKIAnAFDNRIDAKRTLREIKLLRHLDHENVIAIKDIMPPPHREA 80

                         90       100
                 ....*....|....*....|.
gi 161075907 111 MRDVYIVQCLMETDLYKLLKT 131
Cdd:cd07858   81 FNDVYIVYELMDTDLHQIIRS 101

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 161075907  33 EVGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKIS-PFEHQTYCQRTLREITILTRFKHENIIDIRDILRVD-SIDQ 110
Cdd:cd07851   12 EVPDRYQNLSPVGSGAYGQVCSAFDTKTGRKVAIKKLSrPFQSAIHAKRTYRELRLLKHMKHENVIGLLDVFTPAsSLED 91

                         90       100
                 ....*....|....*....|....
gi 161075907 111 MRDVYIVQCLMETDLYKLLKTQVM 134
Cdd:cd07851   92 FQDVYLVTHLMGADLNNIVKCQKL 115

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK 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 161075907  37 RYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKIS-PFEHQTYCQRTLREITILTRFKHENIIDIRDILRVD-SIDQMRDV 114
Cdd:cd07850    1 RYQNLKPIGSGAQGIVCAAYDTVTGQNVAIKKLSrPFQNVTHAKRAYRELVLMKLVNHKNIIGLLNVFTPQkSLEEFQDV 80

                         90
                 ....*....|.
gi 161075907 115 YIVQCLMETDL 125
Cdd:cd07850   81 YLVMELMDANL 91

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein 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 p38beta 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 161075907  31 IFEVGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKIS-PFEHQTYCQRTLREITILTRFKHENIIDIRDILR-VDSI 108
Cdd:cd07878   10 VWEVPERYQNLTPVGSGAYGSVCSAYDTRLRQKVAVKKLSrPFQSLIHARRTYRELRLLKHMKHENVIGLLDVFTpATSI 89

                         90       100
                 ....*....|....*....|....
gi 161075907 109 DQMRDVYIVQCLMETDLYKLLKTQ 132
Cdd:cd07878   90 ENFNEVYLVTNLMGADLNNIVKCQ 113

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 161075907  31 IFEVGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKI-SPFEHQTYCQRTLREITILTRFKHENIIDIRDILRVD-SI 108
Cdd:cd07880   10 IWEVPDRYRDLKQVGSGAYGTVCSALDRRTGAKVAIKKLyRPFQSELFAKRAYRELRLLKHMKHENVIGLLDVFTPDlSL 89

                         90       100
                 ....*....|....*....|....
gi 161075907 109 DQMRDVYIVQCLMETDLYKLLKTQ 132
Cdd:cd07880   90 DRFHDFYLVMPFMGTDLGKLMKHE 113

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 161075907  37 RYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKI-SPFEHQTYCQRTLREITILTRFK-HENIIDIRDILRVDSidqMRDV 114
Cdd:cd07852    8 RYEILKKLGKGAYGIVWKAIDKKTGEVVALKKIfDAFRNATDAQRTFREIMFLQELNdHPNIIKLLNVIRAEN---DKDI 84

                         90       100       110
                 ....*....|....*....|....*....|
gi 161075907 115 YIVQCLMETDLYKLLKTQvmVLPDIWLKFI 144
Cdd:cd07852   85 YLVFEYMETDLHAVIRAN--ILEDIHKQYI 112

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 161075907  37 RYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISPFE--------HQTycqrTLREITILTRFKHENIIDIRDILRVDSi 108
Cdd:cd07841    1 RYEKGKKLGEGTYAVVYKARDKETGRIVAIKKIKLGErkeakdgiNFT----ALREIKLLQELKHPNIIGLLDVFGHKS- 75

                         90       100
                 ....*....|....*....|....*...
gi 161075907 109 dqmrDVYIVQCLMETDLYKLLKTQVMVL 136
Cdd:cd07841   76 ----NINLVFEFMETDLEKVIKDKSIVL 99

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 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 161075907  32 FEVGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISPFEHQTyCQRTLREITILTRFKHENIIDIRDIL-------- 103
Cdd:cd07854    1 FDLGSRYMDLRPLGCGSNGLVFSAVDSDCDKRVAVKKIVLTDPQS-VKHALREIKIIRRLDHDNIVKVYEVLgpsgsdlt 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 161075907 104 -RVDSIDQMRDVYIVQCLMETDLYKLLKTQ 132
Cdd:cd07854   80 eDVGSLTELNSVYIVQEYMETDLANVLEQG 109

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK 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 161075907  44 IGEGAYGMVVSADDTLTNQRVAIKKI-SPFEHQTYCQRTLREITILTRFKHENIIDIRDILRVDSIDQMRDVYIVQCLME 122
Cdd:cd07853    8 IGYGAFGVVWSVTDPRDGKRVALKKMpNVFQNLVSCKRVFRELKMLCFFKHDNVLSALDILQPPHIDPFEEIYVVTELMQ 87

                 ....*..
gi 161075907 123 TDLYKLL 129
Cdd:cd07853   88 SDLHKII 94

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 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 161075907  32 FEVGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKIS-PFEHQTYCQRTLREITILTRFKHENIIDIRDILRVD-SID 109
Cdd:cd07874   13 FTVLKRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLSrPFQNQTHAKRAYRELVLMKCVNHKNIISLLNVFTPQkSLE 92

                         90       100
                 ....*....|....*....|....
gi 161075907 110 QMRDVYIVQCLMETDLYKLLKTQV 133
Cdd:cd07874   93 EFQDVYLVMELMDANLCQVIQMEL 116

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 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 161075907  32 FEVGPRYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKIS-PFEHQTYCQRTLREITILTRFKHENIIDIRDILRVD-SID 109
Cdd:cd07876   17 FTVLKRYQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLSrPFQNQTHAKRAYRELVLLKCVNHKNIISLLNVFTPQkSLE 96

                         90       100
                 ....*....|....*....|
gi 161075907 110 QMRDVYIVQCLMETDLYKLL 129
Cdd:cd07876   97 EFQDVYLVMELMDANLCQVI 116

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161075907  44 IGEGAYGMVVSADDTLTNQRVAIKKISPFEHQTYCQRTLREITILTRFKHENIIDIrdilrVDSIDQMRDVYIVqclME- 122
Cdd:cd00180    1 LGKGSFGKVYKARDKETGKKVAVKVIPKEKLKKLLEELLREIEILKKLNHPNIVKL-----YDVFETENFLYLV---MEy 72

                         90       100
                 ....*....|....*....|....*
gi 161075907 123 ---TDLYKLLKTQVMVLPDIWLKFI 144
Cdd:cd00180   73 cegGSLKDLLKENKGPLSEEEALSI 97

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161075907   38 YIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISPfEHQT--YCQRTLREITILTRFKHENIIDIRDILRVDSidqmrDVY 115
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKK-EKIKkkKDKNILREIKILKKLNHPNIVRLYDAFEDKD-----NLY 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 161075907  116 IVQCLME-TDLYKLLKTQVmVLPDIWLKFIerittidMWCIILAITPNTKTEYNC 169
Cdd:pfam00069  75 LVLEYVEgGSLFDLLSEKG-AFSEREAKFI-------MKQILEGLESGSSLTTFV 121

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 161075907  37 RYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISPFEHQTYCQRT-LREITILTRFKHENIIDIRDILRVDsidqmRDVY 115
Cdd:cd07833    2 KYEVLGVVGEGAYGVVLKCRNKATGEIVAIKKFKESEDDEDVKKTaLREVKVLRQLRHENIVNLKEAFRRK-----GRLY 76

                         90
                 ....*....|....*
gi 161075907 116 IVQCLMETDLYKLLK 130
Cdd:cd07833   77 LVFEYVERTLLELLE 91

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 161075907  44 IGEGAYGMVVSADDTLTNQRVAIKK-ISPFEHQTYCQRtLREITILTRFK-HENIIDIRDILRVDsidqmRDVYIVQCLM 121
Cdd:cd07830    7 LGDGTFGSVYLARNKETGELVAIKKmKKKFYSWEECMN-LREVKSLRKLNeHPNIVKLKEVFREN-----DELYFVFEYM 80

                         90
                 ....*....|.
gi 161075907 122 ETDLYKLLKTQ 132
Cdd:cd07830   81 EGNLYQLMKDR 91

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 161075907  38 YIKLAYIGEGAYGMVVSADDTLTNQRVAIKKIS-PFEHQTYCQRTLREITIL---TRFKHENIIDIRDILRVDSIDQMRD 113
Cdd:cd07838    1 YEEVAEIGEGAYGTVYKARDLQDGRFVALKKVRvPLSEEGIPLSTIREIALLkqlESFEHPNVVRLLDVCHGPRTDRELK 80

                         90
                 ....*....|....*..
gi 161075907 114 VYIVQCLMETDLYKLLK 130
Cdd:cd07838   81 LTLVFEHVDQDLATYLD 97

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161075907  37 RYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKI-SPFEHQTYCQRTLREITILTRFKHENIIDIRDILRVDSIDQMR--- 112
Cdd:cd07865   13 KYEKLAKIGQGTFGEVFKARHRKTGQIVALKKVlMENEKEGFPITALREIKILQLLKHENVVNLIEICRTKATPYNRykg 92

                         90
                 ....*....|....*..
gi 161075907 113 DVYIVQCLMETDLYKLL 129
Cdd:cd07865   93 SIYLVFEFCEHDLAGLL 109

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 161075907  38 YIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISpFEHQT--YCQRTLREITILTRFKHENIIDIRDILRVDSidqmrDVY 115
Cdd:cd07835    1 YQKLEKIGEGTYGVVYKARDKLTGEIVALKKIR-LETEDegVPSTAIREISLLKELNHPNIVRLLDVVHSEN-----KLY 74

                         90
                 ....*....|....*.
gi 161075907 116 IVQCLMETDLYKLLKT 131
Cdd:cd07835   75 LVFEFLDLDLKKYMDS 90

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE 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 161075907  44 IGEGAYGMVVSADDTLTNQRVAIKKIsPFEHQTYCQRTLREITILTRFKHENIIDIRdilrvDSIDQMRDVYIVqclME- 122
Cdd:cd05122    8 IGKGGFGVVYKARHKKTGQIVAIKKI-NLESKEKKESILNEIAILKKCKHPNIVKYY-----GSYLKKDELWIV---MEf 78

                         90       100
                 ....*....|....*....|....*
gi 161075907 123 ---TDLYKLLKTQVMVLPDIWLKFI 144
Cdd:cd05122   79 csgGSLKDLLKNTNKTLTEQQIAYV 103

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 161075907  38 YIKLAYIGEGAYGMVVSADDTLTNQRVAIKKIS-PFEHQTYCQRTLREITILTRFKHENIIDIRDILRVDSidqmrDVYI 116
Cdd:cd07861    2 YTKIEKIGEGTYGVVYKGRNKKTGQIVAMKKIRlESEEEGVPSTAIREISLLKELQHPNIVCLEDVLMQEN-----RLYL 76

                         90
                 ....*....|....*
gi 161075907 117 VQCLMETDLYKLLKT 131
Cdd:cd07861   77 VFEFLSMDLKKYLDS 91

cyclin-dependent kinase A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161075907  37 RYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKIS-PFEHQTYCQRTLREITILTRFKHENIIDIRDILRVDsidqmRDVY 115
Cdd:PLN00009   3 QYEKVEKIGEGTYGVVYKARDRVTNETIALKKIRlEQEDEGVPSTAIREISLLKEMQHGNIVRLQDVVHSE-----KRLY 77

                         90
                 ....*....|..
gi 161075907 116 IVQCLMETDLYK 127
Cdd:PLN00009  78 LVFEYLDLDLKK 89

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 161075907  41 LAYIGEGAYGMVVSADDTLTNQRVAIKKISPF-EHQTYCQRTLREITILTRFKHENIIDIRDILRvdsidQMRDVYIVQC 119
Cdd:cd07848    6 LGVVGEGAYGVVLKCRHKETKEIVAIKKFKDSeENEEVKETTLRELKMLRTLKQENIVELKEAFR-----RRGKLYLVFE 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 161075907 120 LMETDLYKLLKTQVM-VLPDIWLKFIERITTIDMWC 154
Cdd:cd07848   81 YVEKNMLELLEEMPNgVPPEKVRSYIYQLIKAIHWC 116

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 161075907  37 RYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISPFEHQTYCQR-TLREITILTRFKHENIIDIRDILR 104
Cdd:cd07847    2 KYEKLSKIGEGSYGVVFKCRNRETGQIVAIKKFVESEDDPVIKKiALREIRMLKQLKHPNLVNLIEVFR 70

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 161075907  44 IGEGAYGMVVSADDTLTNQRVAIKKISPF-EHQTYCQRTLREITILTRFKHENIIDIRDILRV---DSIDQMRDVYIVQC 119
Cdd:cd07866   16 LGEGTFGEVYKARQIKTGRVVALKKILMHnEKDGFPITALREIKILKKLKHPNVVPLIDMAVErpdKSKRKRGSVYMVTP 95

                         90
                 ....*....|
gi 161075907 120 LMETDLYKLL 129
Cdd:cd07866   96 YMDHDLSGLL 105

Catalytic domain of Fungal Pat1-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 Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like 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 161075907  37 RYIKLAYIGEGAYGMVVSADDTLTNQRVAIKKISPFEHQT------YCQRTLREITILTRF-KHENIIDIrdilrVDSID 109
Cdd:cd13993    1 RYQLISPIGEGAYGVVYLAVDLRTGRKYAIKCLYKSGPNSkdgndfQKLPQLREIDLHRRVsRHPNIITL-----HDVFE 75