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 1907129997  80 SNIVFMSTKAVLVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAY 159
Cdd:cd13995   125 SNIVFMSTKAVLVDFGLSVQMTEDVYVPKDLRGTEIYMSPEVILCRGHNTKADIYSLGATIIHMQTGSPPWVRRYPRSAY 204

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907129997 160 PSYLYIIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHEAL 211
Cdd:cd13995   205 PSYLYIIHKQAPPLEDIAQDCSPAMRELLEAALERNPNHRSSAAELLKHEAL 256

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 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 1907129997  80 SNIVFMSTKAVLVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAY 159
Cdd:cd13995   125 SNIVFMSTKAVLVDFGLSVQMTEDVYVPKDLRGTEIYMSPEVILCRGHNTKADIYSLGATIIHMQTGSPPWVRRYPRSAY 204

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907129997 160 PSYLYIIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHEAL 211
Cdd:cd13995   205 PSYLYIIHKQAPPLEDIAQDCSPAMRELLEAALERNPNHRSSAAELLKHEAL 256

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907129997  80 SNIVFMST-KAVLVDFGLsVKMTEDVYLPKD--LRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPR 156
Cdd:COG0515   136 ANILLTPDgRVKLIDFGI-ARALGGATLTQTgtVVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPA 214

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907129997 157 SAypsYLYIIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKhEALNPPREDQPRCQSLDSALFERKRLLS 236
Cdd:COG0515   215 EL---LRAHLREPPPPPSELRPDLPPALDAIVLRALAKDPEERYQSAAELA-AALRAVLRSLAAAAAAAAAAAAAAAAAA 290

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1907129997 237 RKELQLPENIADSSCTGSTEESEVLRRQRSLYIDLGALAG 276
Cdd:COG0515   291 AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAPAAAAAAA 330

NIMA-related protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907129997  79 ASNIVFMSTKAV-LVDFGLSVKMTEDVYL--PKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYP 155
Cdd:PTZ00267  197 SANIFLMPTGIIkLGDFGFSKQYSDSVSLdvASSFCGTPYYLAPELWERKRYSKKADMWSLGVILYELLTLHRPFKGPSQ 276

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907129997 156 RSAYPSYLYIIHKQAPplediagdC--SPGMRELIEAALERNPNHRPKAADLLKHEAL 211
Cdd:PTZ00267  277 REIMQQVLYGKYDPFP--------CpvSSGMKALLDPLLSKNPALRPTTQQLLHTEFL 326

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 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 1907129997  80 SNIVFMSTKAVLVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAY 159
Cdd:cd13995   125 SNIVFMSTKAVLVDFGLSVQMTEDVYVPKDLRGTEIYMSPEVILCRGHNTKADIYSLGATIIHMQTGSPPWVRRYPRSAY 204

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907129997 160 PSYLYIIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHEAL 211
Cdd:cd13995   205 PSYLYIIHKQAPPLEDIAQDCSPAMRELLEAALERNPNHRSSAAELLKHEAL 256

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK 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 1907129997  79 ASNI-VFMSTKAVLVDFGLSVKMTEDVYLP--KDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWvKRYp 155
Cdd:cd06606   127 GANIlVDSDGVVKLADFGCAKRLAEIATGEgtKSLRGTPYWMAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPW-SEL- 204

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907129997 156 RSAYPSYLYIIHKQAPPleDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHE 209
Cdd:cd06606   205 GNPVAALFKIGSSGEPP--PIPEHLSEEAKDFLRKCLQRDPKKRPTADELLQHP 256

Catalytic domain of Mammalian Ste20-like protein kinase 3-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 MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-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 1907129997  79 ASNIVFMSTKAV-LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRS 157
Cdd:cd06609   126 AANILLSEEGDVkLADFGVSGQLTSTMSKRNTFVGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLHPMR 205

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907129997 158 AypsyLYIIHKQAPP-LEDiaGDCSPGMRELIEAALERNPNHRPKAADLLKHE 209
Cdd:cd06609   206 V----LFLIPKNNPPsLEG--NKFSKPFKDFVELCLNKDPKERPSAKELLKHK 252

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907129997  80 SNIVFMST-KAVLVDFGLsVKMTEDVYLPKD--LRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPR 156
Cdd:COG0515   136 ANILLTPDgRVKLIDFGI-ARALGGATLTQTgtVVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPA 214

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907129997 157 SAypsYLYIIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKhEALNPPREDQPRCQSLDSALFERKRLLS 236
Cdd:COG0515   215 EL---LRAHLREPPPPPSELRPDLPPALDAIVLRALAKDPEERYQSAAELA-AALRAVLRSLAAAAAAAAAAAAAAAAAA 290

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1907129997 237 RKELQLPENIADSSCTGSTEESEVLRRQRSLYIDLGALAG 276
Cdd:COG0515   291 AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAPAAAAAAA 330

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 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 1907129997  68 HEDKEKNGVQTASNIVFMSTKAV-LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTG 146
Cdd:cd06641   118 HSEKKIHRDIKAANVLLSEHGEVkLADFGVAGQLTDTQIKRN*FVGTPFWMAPEVIKQSAYDSKADIWSLGITAIELARG 197

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907129997 147 TPPWVKRYPRSAypsyLYIIHKQAPPLedIAGDCSPGMRELIEAALERNPNHRPKAADLLKHE 209
Cdd:cd06641   198 EPPHSELHPMKV----LFLIPKNNPPT--LEGNYSKPLKEFVEACLNKEPSFRPTAKELLKHK 254

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 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 1907129997  81 NIVFMSTKAV-LVDFGLSvKMTEDVYLPKDLRGTEIYMSPEVILCR--GHSTKADIYSLGATLIHMQTGTPPWvkryprS 157
Cdd:cd06632   132 NILVDTNGVVkLADFGMA-KHVEAFSFAKSFKGSPYWMAPEVIMQKnsGYGLAVDIWSLGCTVLEMATGKPPW------S 204

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907129997 158 AYPSYLYII----HKQAPPLEDiagDCSPGMRELIEAALERNPNHRPKAADLLKH 208
Cdd:cd06632   205 QYEGVAAIFkignSGELPPIPD---HLSPDAKDFIRLCLQRDPEDRPTASQLLEH 256

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 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 1907129997  79 ASNIVFMSTKAV-LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRS 157
Cdd:cd06612   127 AGNILLNEEGQAkLADFGVSGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMR 206

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907129997 158 AypsyLYIIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKH 208
Cdd:cd06612   207 A----IFMIPNKPPPTLSDPEKWSPEFNDFVKKCLVKDPEERPSAIQLLQH 253

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-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 1907129997  91 LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCR---GHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAypsyLYIIH 167
Cdd:cd06613   138 LADFGVSAQLTATIAKRKSFIGTPYWMAPEVAAVErkgGYDGKCDIWALGITAIELAELQPPMFDLHPMRA----LFLIP 213

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1907129997 168 K---QAPPLEDiAGDCSPGMRELIEAALERNPNHRPKAADLLKHE 209
Cdd:cd06613   214 KsnfDPPKLKD-KEKWSPDFHDFIKKCLTKNPKKRPTATKLLQHP 257

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 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 1907129997  91 LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRG-----HSTKADIYSLGATLIHMQTGTPPWVKRYPRSAypsyLYI 165
Cdd:cd06644   151 LADFGVSAKNVKTLQRRDSFIGTPYWMAPEVVMCETmkdtpYDYKADIWSLGITLIEMAQIEPPHHELNPMRV----LLK 226

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1907129997 166 IHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKH 208
Cdd:cd06644   227 IAKSEPPTLSQPSKWSMEFRDFLKTALDKHPETRPSAAQLLEH 269

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK 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 1907129997  91 LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAYPSylyiIHKQA 170
Cdd:cd06659   158 LSDFGFCAQISKDVPKRKSLVGTPYWMAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKR----LRDSP 233

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907129997 171 PPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHEALnpPREDQPRC 221
Cdd:cd06659   234 PPKLKNSHKASPVLRDFLERMLVRDPQERATAQELLDHPFL--LQTGLPEC 282

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907129997 107 PKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWvkryPRSAYPSYLYIIHKQAPPLEDIAGDCSPGMRE 186
Cdd:pfam00069 117 LTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPF----PGINGNEIYELIIDQPYAFPELPSNLSEEAKD 192

                          90       100
                  ....*....|....*....|..
gi 1907129997 187 LIEAALERNPNHRPKAADLLKH 208
Cdd:pfam00069 193 LLKKLLKKDPSKRLTATQALQH 214

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK 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 1907129997  80 SNIVFMSTKAV-LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPwvkrYPRSA 158
Cdd:cd06623   129 SNLLINSKGEVkIADFGISKVLENTLDQCNTFVGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFP----FLPPG 204

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907129997 159 YPSY---LYIIHKQAPPLEDiAGDCSPGMRELIEAALERNPNHRPKAADLLKHEALN 212
Cdd:cd06623   205 QPSFfelMQAICDGPPPSLP-AEEFSPEFRDFISACLQKDPKKRPSAAELLQHPFIK 260

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK 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 1907129997  91 LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAypsyLYIIHKQA 170
Cdd:cd06648   144 LSDFGFCAQVSKEVPRRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQA----MKRIRDNE 219

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1907129997 171 PPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHEAL 211
Cdd:cd06648   220 PPKLKNLHKVSPRLRSFLDRMLVRDPAQRATAAELLNHPFL 260

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK 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 1907129997  68 HED-KEKNGVQTASNIVFMStkavlvDFGLSVKMTEDVYLPKDLRGTEIYMSPEviLCRGHST-----KADIYSLGATLI 141
Cdd:cd14008   131 HRDiKPENLLLTADGTVKIS------DFGVSEMFEDGNDTLQKTAGTPAFLAPE--LCDGDSKtysgkAADIWALGVTLY 202

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907129997 142 HMQTGTPPWVKrypRSAYPSYLYIIHKQAPPleDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHE 209
Cdd:cd14008   203 CLVFGRLPFNG---DNILELYEAIQNQNDEF--PIPPELSPELKDLLRRMLEKDPEKRITLKEIKEHP 265

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK 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 1907129997  80 SNIVFMSTKAV-LVDFGLSVKMTEDVylPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGT---PPWVKRYP 155
Cdd:cd06605   129 SNILVNSRGQVkLCDFGVSGQLVDSL--AKTFVGTRSYMAPERISGGKYTVKSDIWSLGLSLVELATGRfpyPPPNAKPS 206

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907129997 156 RSAYPSYLYIIHKQAPPLEdiAGDCSPGMRELIEAALERNPNHRPKAADLLKH 208
Cdd:cd06605   207 MMIFELLSYIVDEPPPLLP--SGKFSPDFQDFVSQCLQKDPTERPSYKELMEH 257

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 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 1907129997  93 DFGLSvKMTEDVY---LPKDLRGTEIYMSPEVI--LCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAYpsYLYIIH 167
Cdd:cd06629   151 DFGIS-KKSDDIYgnnGATSMQGSVFWMAPEVIhsQGQGYSAKVDIWSLGCVVLEMLAGRRPWSDDEAIAAM--FKLGNK 227

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1907129997 168 KQAPPL-EDIagDCSPGMRELIEAALERNPNHRPKAADLLKHE 209
Cdd:cd06629   228 RSAPPVpEDV--NLSPEALDFLNACFAIDPRDRPTAAELLSHP 268

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC 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 1907129997  89 AVLVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWvkrypRSAYPSYLY--II 166
Cdd:cd05123   132 IKLTDFGLAKELSSDGDRTYTFCGTPEYLAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPF-----YAENRKEIYekIL 206

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1907129997 167 HKQ--APPlediagDCSPGMRELIEAALERNPNHR 199
Cdd:cd05123   207 KSPlkFPE------YVSPEAKSLISGLLQKDPTKR 235

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek 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 1907129997  83 VFMSTK--AVLVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRyprsayp 160
Cdd:cd08217   141 IFLDSDnnVKLGDFGLARVLSHDSSFAKTYVGTPYYMSPELLNEQSYDEKSDIWSLGCLIYELCALHPPFQAA------- 213

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1907129997 161 SYLYIIHK-QAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKH 208
Cdd:cd08217   214 NQLELAKKiKEGKFPRIPSRYSSELNEVIKSMLNVDPDKRPSVEELLQL 262

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 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 1907129997  93 DFGLSVKMTEDVYLPKD------LRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWvkryPRSAYPSYLYII 166
Cdd:cd06628   149 DFGISKKLEANSLSTKNngarpsLQGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLTGTHPF----PDCTQMQAIFKI 224

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1907129997 167 HKQAPPleDIAGDCSPGMRELIEAALERNPNHRPKAADLLKH 208
Cdd:cd06628   225 GENASP--TIPSNISSEARDFLEKTFEIDHNKRPTADELLKH 264

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK 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 1907129997  64 LSPRHEDKEKNGVQTASNIVFMSTKAV-LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILC-----RGHSTKADIYSLG 137
Cdd:cd06637   124 LSHLHQHKVIHRDIKGQNVLLTENAEVkLVDFGVSAQLDRTVGRRNTFIGTPYWMAPEVIACdenpdATYDFKSDLWSLG 203

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907129997 138 ATLIHMQTGTPPWVKRYPRSAypsyLYIIHKQ-APPLEdiAGDCSPGMRELIEAALERNPNHRPKAADLLKHEAL-NPPR 215
Cdd:cd06637   204 ITAIEMAEGAPPLCDMHPMRA----LFLIPRNpAPRLK--SKKWSKKFQSFIESCLVKNHSQRPSTEQLMKHPFIrDQPN 277

                         170
                  ....*....|
gi 1907129997 216 EDQPRCQSLD 225
Cdd:cd06637   278 ERQVRIQLKD 287

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek 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 1907129997  79 ASNIvFMSTKAV--LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEviLCRGH--STKADIYSLGATLIHMQTGTPPWvkry 154
Cdd:cd08215   131 TQNI-FLTKDGVvkLGDFGISKVLESTTDLAKTVVGTPYYLSPE--LCENKpyNYKSDIWALGCVLYELCTLKHPF---- 203

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907129997 155 prSAY--PSYLY-IIHKQAPPLEDIAgdcSPGMRELIEAALERNPNHRPKAADLLKHEAL 211
Cdd:cd08215   204 --EANnlPALVYkIVKGQYPPIPSQY---SSELRDLVNSMLQKDPEKRPSANEILSSPFI 258