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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130000   65 SNIVFMSTKAV-LVDFGLSVKMTEDVYLpKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWvkrYPRSA 143
Cdd:smart00220 126 ENILLDEDGHVkLADFGLARQLDPGEKL-TTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPF---PGDDQ 201

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1907130000  144 YPSYLYIIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHE 194
Cdd:smart00220 202 LLELFKKIGKPKPPFPPPEWDISPEAKDLIRKLLVKDPEKRLTAEEALQHP 252

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130000  92 PKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWvkryPRSAYPSYLYIIHKQAPPLEDIAGDCSPGMRE 171
Cdd:pfam00069 117 LTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPF----PGINGNEIYELIIDQPYAFPELPSNLSEEAKD 192

                          90       100
                  ....*....|....*....|..
gi 1907130000 172 LIEAALERNPNHRPKAADLLKH 193
Cdd:pfam00069 193 LLKKLLKKDPSKRLTATQALQH 214

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130000  66 NIVFMSTKAVLV-DFGL-------SVKMTEDVYlpkdlrGTEIYMSPEVIlcRGHST--KADIYSLGATLIHMQTGTPPW 135
Cdd:NF033483  137 NILITKDGRVKVtDFGIaralsstTMTQTNSVL------GTVHYLSPEQA--RGGTVdaRSDIYSLGIVLYEMLTGRPPF 208

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907130000 136 VKRYPRS-AYPSylyiIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPK-----AADLLKheALNPPREDQPR 205
Cdd:NF033483  209 DGDSPVSvAYKH----VQEDPPPPSELNPGIPQSLDAVVLKATAKDPDDRYQsaaemRADLET--ALSGQRLNAPK 278

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130000   65 SNIVFMSTKAV-LVDFGLSVKMTEDVYLpKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWvkrYPRSA 143
Cdd:smart00220 126 ENILLDEDGHVkLADFGLARQLDPGEKL-TTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPF---PGDDQ 201

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1907130000  144 YPSYLYIIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHE 194
Cdd:smart00220 202 LLELFKKIGKPKPPFPPPEWDISPEAKDLIRKLLVKDPEKRLTAEEALQHP 252

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. 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 Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-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 1907130000  64 ASNIvfMSTKAVLV---DFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYP 140
Cdd:cd06627   127 GANI--LTTKDGLVklaDFGVATKLNEVEKDENSVVGTPYWMAPEVIEMSGVTTASDIWSVGCTVIELLTGNPPYYDLQP 204

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907130000 141 RSAypsyLY-IIHKQAPPLEDiagDCSPGMRELIEAALERNPNHRPKAADLLKHE 194
Cdd:cd06627   205 MAA----LFrIVQDDHPPLPE---NISPELRDFLLQCFQKDPTLRPSAKELLKHP 252

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 1907130000  64 ASNIVfMSTKAV--LVDFGLSVKMTEDVYlPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPwvkrYPR 141
Cdd:cd05122   126 AANIL-LTSDGEvkLIDFGLSAQLSDGKT-RNTFVGTPYWMAPEVIQGKPYGFKADIWSLGITAIEMAEGKPP----YSE 199

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907130000 142 SAYPSYLYII-HKQAPPLEDIAgDCSPGMRELIEAALERNPNHRPKAADLLKHE 194
Cdd:cd05122   200 LPPMKALFLIaTNGPPGLRNPK-KWSKEFKDFLKKCLQKDPEKRPTAEQLLKHP 252

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. 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 YSK4 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 1907130000  66 NIVFMSTKAV-LVDFGLSVKMTEDVY------LPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKR 138
Cdd:cd06631   133 NIMLMPNGVIkLIDFGCAKRLCINLSsgsqsqLLKSMRGTPYWMAPEVINETGHGRKSDIWSIGCTVFEMATGKPPWADM 212

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907130000 139 YPRSAypsyLYII---HKQAPPLEDiagDCSPGMRELIEAALERNPNHRPKAADLLKH 193
Cdd:cd06631   213 NPMAA----IFAIgsgRKPVPRLPD---KFSPEARDFVHACLTRDQDERPSAEQLLKH 263

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 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 MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-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 1907130000  65 SNIVFMSTKAV-LVDFGLSVKMTEDVYLP--KDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPR 141
Cdd:cd06625   131 ANILRDSNGNVkLGDFGASKRLQTICSSTgmKSVTGTPYWMSPEVINGEGYGRKADIWSVGCTVVEMLTTKPPWAEFEPM 210

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907130000 142 SAypsyLYIIHKQaPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKH 193
Cdd:cd06625   211 AA----IFKIATQ-PTNPQLPPHVSEDARDFLSLIFVRNKKQRPSAEELLSH 257

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 1907130000  66 NIVFMSTKAV-LVDFGLSvKMTEDVYLPKDLRGTEIYMSPEVILCR--GHSTKADIYSLGATLIHMQTGTPPWvkryprS 142
Cdd:cd06632   132 NILVDTNGVVkLADFGMA-KHVEAFSFAKSFKGSPYWMAPEVIMQKnsGYGLAVDIWSLGCTVLEMATGKPPW------S 204

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907130000 143 AYPSYLYII----HKQAPPLEDiagDCSPGMRELIEAALERNPNHRPKAADLLKH 193
Cdd:cd06632   205 QYEGVAAIFkignSGELPPIPD---HLSPDAKDFIRLCLQRDPEDRPTASQLLEH 256

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK 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 1907130000  53 HEDKEKNGVQTASNIVFMS--TKAVLVDFGLSVKMTED-----VYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATL 125
Cdd:cd13991   115 HSRKILHGDVKADNVLLSSdgSDAFLCDFGHAECLDPDglgksLFTGDYIPGTETHMAPEVVLGKPCDAKVDVWSSCCMM 194

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907130000 126 IHMQTGTPPWVKRYprsAYPSYLYIIhKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADL 190
Cdd:cd13991   195 LHMLNGCHPWTQYY---SGPLCLKIA-NEPPPLREIPPSCAPLTAQAIQAGLRKEPVHRASAAEL 255

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 1907130000  76 LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRG-----HSTKADIYSLGATLIHMQTGTPPWVKRYPRSAypsyLYI 150
Cdd:cd06644   151 LADFGVSAKNVKTLQRRDSFIGTPYWMAPEVVMCETmkdtpYDYKADIWSLGITLIEMAQIEPPHHELNPMRV----LLK 226

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1907130000 151 IHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKH 193
Cdd:cd06644   227 IAKSEPPTLSQPSKWSMEFRDFLKTALDKHPETRPSAAQLLEH 269

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. 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 1907130000  76 LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAypsyLYII-HKQ 154
Cdd:cd06614   138 LADFGFAAQLTKEKSKRNSVVGTPYWMAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPPYLEEPPLRA----LFLItTKG 213

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1907130000 155 APPLEDIAGdCSPGMRELIEAALERNPNHRPKAADLLKHEALN 197
Cdd:cd06614   214 IPPLKNPEK-WSPEFKDFLNKCLVKDPEKRPSAEELLQHPFLK 255

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK 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 1907130000  64 ASNIVFMSTKAV-LVDFGLSVKMTEDVYLPKDLR----GTEIYMSPEVI-LCRGHSTKADIYSLGATLIHMQTGTPPWVK 137
Cdd:cd06610   130 AGNILLGEDGSVkIADFGVSASLATGGDRTRKVRktfvGTPCWMAPEVMeQVRGYDFKADIWSFGITAIELATGAAPYSK 209

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907130000 138 rYPRSAypSYLYIIHKQAPPLEDIA--GDCSPGMRELIEAALERNPNHRPKAADLLKH 193
Cdd:cd06610   210 -YPPMK--VLMLTLQNDPPSLETGAdyKKYSKSFRKMISLCLQKDPSKRPTAEELLKH 264

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 1907130000  65 SNIVFMSTKAV-LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPwvkrYPRSA 143
Cdd:cd06623   129 SNLLINSKGEVkIADFGISKVLENTLDQCNTFVGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFP----FLPPG 204

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907130000 144 YPSY---LYIIHKQAPPLEDiAGDCSPGMRELIEAALERNPNHRPKAADLLKHEALN 197
Cdd:cd06623   205 QPSFfelMQAICDGPPPSLP-AEEFSPEFRDFISACLQKDPKKRPSAAELLQHPFIK 260

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK 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 1907130000  53 HEDKEKNGVQTASNIVFMSTKAV-LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILC-----RGHSTKADIYSLGATLI 126
Cdd:cd06643   120 HENKIIHRDLKAGNILFTLDGDIkLADFGVSAKNTRTLQRRDSFIGTPYWMAPEVVMCetskdRPYDYKADVWSLGVTLI 199

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907130000 127 HMQTGTPPWVKRYPRSAypsyLYIIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHEALNPPREDQP 204
Cdd:cd06643   200 EMAQIEPPHHELNPMRV----LLKIAKSEPPTLAQPSRWSPEFKDFLRKCLEKNVDARWTTSQLLQHPFVSVLVSNKP 273

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 1907130000  53 HED-KEKNGVQTASNIVFMStkavlvDFGLSVKMTEDVYLPKDLRGTEIYMSPEviLCRGHST-----KADIYSLGATLI 126
Cdd:cd14008   131 HRDiKPENLLLTADGTVKIS------DFGVSEMFEDGNDTLQKTAGTPAFLAPE--LCDGDSKtysgkAADIWALGVTLY 202

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907130000 127 HMQTGTPPWVKrypRSAYPSYLYIIHKQAPPleDIAGDCSPGMRELIEAALERNPNHRPKAADLLKHE 194
Cdd:cd14008   203 CLVFGRLPFNG---DNILELYEAIQNQNDEF--PIPPELSPELKDLLRRMLEKDPEKRITLKEIKEHP 265

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 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 1907130000  76 LVDFGLSVKMTEDVYLP-----KDLRGTEIYMSPEVIL---CRGHSTKADIYSLGATLIHMQTGTPPWvkryprSAYPSY 147
Cdd:cd06626   140 LGDFGSAVKLKNNTTTMapgevNSLVGTPAYMAPEVITgnkGEGHGRAADIWSLGCVVLEMATGKRPW------SELDNE 213

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907130000 148 LYIIHK----QAPPLEDiAGDCSPGMRELIEAALERNPNHRPKAADLLKHE 194
Cdd:cd06626   214 WAIMYHvgmgHKPPIPD-SLQLSPEGKDFLSRCLESDPKKRPTASELLDHP 263

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-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 1907130000  64 ASNIVFMSTKAV-LVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILC-----RGHSTKADIYSLGATLIHMQTGTPPWVK 137
Cdd:cd06611   131 AGNILLTLDGDVkLADFGVSAKNKSTLQKRDTFIGTPYWMAPEVVACetfkdNPYDYKADIWSLGITLIELAQMEPPHHE 210

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907130000 138 RYPRSAypsyLYIIHKQAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKH 193
Cdd:cd06611   211 LNPMRV----LLKILKSEPPTLDQPSKWSSSFNDFLKSCLVKDPDDRPTAAELLKH 262

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family 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 1907130000  66 NIVFMSTKA----VLVDFGLSVKMTEDVYLpKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPR 141
Cdd:cd05117   129 NILLASKDPdspiKIIDFGLAKIFEEGEKL-KTVCGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGETEQ 207

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907130000 142 SaypsylyiIHKQ---------APPLEDIagdcSPGMRELIEAALERNPNHRPKAADLLKHE 194
Cdd:cd05117   208 E--------LFEKilkgkysfdSPEWKNV----SEEAKDLIKRLLVVDPKKRLTAAEALNHP 257

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 1907130000  64 ASNIVFMST-KAVLVDFGLSVKMTEDVYLPKDLRGTEI--YMSPEVILCRGHSTKADIYSLGATLIHMqtgtppwvkryp 140
Cdd:cd00180   120 PENILLDSDgTVKLADFGLAKDLDSDDSLLKTTGGTTPpyYAPPELLGGRYYGPKVDIWSLGVILYEL------------ 187

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907130000 141 rsaypsylyiihkqapplediagdcsPGMRELIEAALERNPNHRPKAADLLKHE 194
Cdd:cd00180   188 --------------------------EELKDLIRRMLQYDPKKRPSAKELLEHL 215

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 1907130000  68 VFMSTK--AVLVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRyprsayp 145
Cdd:cd08217   141 IFLDSDnnVKLGDFGLARVLSHDSSFAKTYVGTPYYMSPELLNEQSYDEKSDIWSLGCLIYELCALHPPFQAA------- 213

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1907130000 146 SYLYIIHK-QAPPLEDIAGDCSPGMRELIEAALERNPNHRPKAADLLKH 193
Cdd:cd08217   214 NQLELAKKiKEGKFPRIPSRYSSELNEVIKSMLNVDPDKRPSVEELLQL 262

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora 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 1907130000  76 LVDFGLSVKMTEDVylPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSAY----------P 145
Cdd:cd14007   141 LADFGWSVHAPSNR--RKTFCGTLDYLPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKSHQETYkriqnvdikfP 218

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907130000 146 SYLyiihkqapplediagdcSPGMRELIEAALERNPNHRPKAADLLKH 193
Cdd:cd14007   219 SSV-----------------SPEAKDLISKLLQKDPSKRLSLEQVLNH 249

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-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 1907130000  76 LVDFGLSVKMTEDVYLpKDLRGTEIYMSPEVILCRG-HSTKADIYSLGATLIHMQTGTPPW------------VKRYPRs 142
Cdd:cd14003   140 IIDFGLSNEFRGGSLL-KTFCGTPAYAAPEVLLGRKyDGPKADVWSLGVILYAMLTGYLPFdddndsklfrkiLKGKYP- 217

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1907130000 143 aYPSYLyiihkqapplediagdcSPGMRELIEAALERNPNHRPKAADLLKHE 194
Cdd:cd14003   218 -IPSHL-----------------SPDARDLIRRMLVVDPSKRITIEEILNHP 251

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase 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 mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. 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. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130000  64 ASNI-VFMSTKAVLVDFGLSVKMTEDVYLPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWvKRYPRS 142
Cdd:cd13999   119 SLNIlLDENFTVKIADFGLSRIKNSTTEKMTGVVGTPRWMAPEVLRGEPYTEKADVYSFGIVLWELLTGEVPF-KELSPI 197

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1907130000 143 AyPSYLYIIHKQAPPLEDiagDCSPGMRELIEAALERNPNHRPK 186
Cdd:cd13999   198 Q-IAAAVVQKGLRPPIPP---DCPPELSKLIKRCWNEDPEKRPS 237