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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710198     1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPIP---DSLSPDITDFLRLCFKKDSRQR 77
Cdd:smart00220  163 MAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKPKPPFPppeWDISPEAKDLIRKLLVKDPEKR 242

                            90
                    ....*....|..
gi 1063710198    78 PDAKTLLSHPWI 89
Cdd:smart00220  243 LTAEEALQHPFF 254

Serine/threonine protein kinase [Signal transduction mechanisms];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPIPD---SLSPDITDFLRLCFKKDSRQR 77
Cdd:COG0515    175 MAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPPPSElrpDLPPALDAIVLRALAKDPEER 254

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1063710198   78 P-DAKTLLshpwirnsrRALRSSLRHSGTIR 107
Cdd:COG0515    255 YqSAAELA---------AALRAVLRSLAAAA 276

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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDL-QPMPALYRIVQ-DDTPPIPDSLSPDITDFLRLCFKKDSRQRP 78
Cdd:cd06606    168 MAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPWSELgNPVAALFKIGSsGEPPPIPEHLSEEAKDFLRKCLQRDPKKRP 247

                           90
                   ....*....|.
gi 1063710198   79 DAKTLLSHPWI 89
Cdd:cd06606    248 TADELLQHPFL 258

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 1063710198    1 MAPEVI--ELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQD-DTPPIPDSLSPDITDFLRLCFKKDSRQR 77
Cdd:cd06632    168 MAPEVImqKNSGYGLAVDIWSLGCTVLEMATGKPPWSQYEGVAAIFKIGNSgELPPIPDHLSPDAKDFIRLCLQRDPEDR 247

                           90
                   ....*....|..
gi 1063710198   78 PDAKTLLSHPWI 89
Cdd:cd06632    248 PTASQLLEHPFV 259

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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPIPDS--LSPDITDFLRLCFKKDSRQRP 78
Cdd:cd05122    164 MAPEVIQGKPYGFKADIWSLGITAIEMAEGKPPYSELPPMKALFLIATNGPPGLRNPkkWSKEFKDFLKKCLQKDPEKRP 243

                           90
                   ....*....|.
gi 1063710198   79 DAKTLLSHPWI 89
Cdd:cd05122    244 TAEQLLKHPFI 254

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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDD--TPPIPDSLSPDITDFLRLCFKKDSRQRP 78
Cdd:cd06631    176 MAPEVINETGHGRKSDIWSIGCTVFEMATGKPPWADMNPMAAIFAIGSGRkpVPRLPDKFSPEARDFVHACLTRDQDERP 255

                           90
                   ....*....|.
gi 1063710198   79 DAKTLLSHPWI 89
Cdd:cd06631    256 SAEQLLKHPFI 266

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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIvQDDTPP---IPDSLSPDITDFLRLCFKKDSRQR 77
Cdd:cd06612    166 MAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFMI-PNKPPPtlsDPEKWSPEFNDFVKKCLVKDPEER 244

                           90
                   ....*....|..
gi 1063710198   78 PDAKTLLSHPWI 89
Cdd:cd06612    245 PSAIQLLQHPFI 256

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 1063710198    1 MAPEVIEL---SGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPiP-----DSLSPDITDFLRLCFKK 72
Cdd:cd06613    164 MAPEVAAVerkGGYDGKCDIWALGITAIELAELQPPMFDLHPMRALFLIPKSNFDP-PklkdkEKWSPDFHDFIKKCLTK 242

                           90
                   ....*....|....*..
gi 1063710198   73 DSRQRPDAKTLLSHPWI 89
Cdd:cd06613    243 NPKKRPTATKLLQHPFV 259

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK 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 1063710198    1 MAPEVIE--LSGVCAASDIWSVGCTIIELLTCVPPYYDLQ-PMPALYRI-VQDDTPPIPDSLSPDITDFLRLCFKKDSRQ 76
Cdd:cd06624    176 MAPEVIDkgQRGYGPPADIWSLGCTIIEMATGKPPFIELGePQAAMFKVgMFKIHPEIPESLSEEAKSFILRCFEPDPDK 255

                           90
                   ....*....|...
gi 1063710198   77 RPDAKTLLSHPWI 89
Cdd:cd06624    256 RATASDLLQDPFL 268

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 1063710198    1 MAPEVIELS--GVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDT-PPIPDS--LSPDITDFLRLCFKKDSR 75
Cdd:cd06629    177 MAPEVIHSQgqGYSAKVDIWSLGCVVLEMLAGRRPWSDDEAIAAMFKLGNKRSaPPVPEDvnLSPEALDFLNACFAIDPR 256

                           90
                   ....*....|....
gi 1063710198   76 QRPDAKTLLSHPWI 89
Cdd:cd06629    257 DRPTAAELLSHPFL 270

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-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 1063710198    1 MAPEVIelsgVC---------AASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPI--PDSLSPDITDFLRLC 69
Cdd:cd06608    180 MAPEVI----ACdqqpdasydARCDVWSLGITAIELADGKPPLCDMHPMRALFKIPRNPPPTLksPEKWSKEFNDFISEC 255

                           90       100
                   ....*....|....*....|
gi 1063710198   70 FKKDSRQRPDAKTLLSHPWI 89
Cdd:cd06608    256 LIKNYEQRPFTEELLEHPFI 275

Catalytic domain of the Protein Serine/Threonine Kinase, 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. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The 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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPY--YDLQPMPAL-YRIV-QDDTPPIPDSLSPDITDFLRLCFKKDSRQ 76
Cdd:cd06630    175 MAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWnaEKISNHLALiFKIAsATTPPPIPEHLSPGLRDVTLRCLELQPED 254

                           90
                   ....*....|.
gi 1063710198   77 RPDAKTLLSHP 87
Cdd:cd06630    255 RPPARELLKHP 265

Catalytic domain of an Uncharacterized subfamily 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 uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPP-IPDSLSPDITDFLRLCFKKDSRqRPD 79
Cdd:cd06653    176 MSPEVISGEGYGRKADVWSVACTVVEMLTEKPPWAEYEAMAAIFKIATQPTKPqLPDGVSDACRDFLRQIFVEEKR-RPT 254

                           90
                   ....*....|
gi 1063710198   80 AKTLLSHPWI 89
Cdd:cd06653    255 AEFLLRHPFV 264

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and 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. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRI-VQDDTPPIPDSLSPDITDFLRlCFKKDSRQRPD 79
Cdd:cd06651    181 MSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKIaTQPTNPQLPSHISEHARDFLG-CIFVEARHRPS 259

                   ....*....
gi 1063710198   80 AKTLLSHPW 88
Cdd:cd06651    260 AEELLRHPF 268

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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDtPPIPDSLSPDITDFLRLCFKKDSRQRPDA 80
Cdd:cd14007    165 LPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVD-IKFPSSVSPEAKDLISKLLQKDPSKRLSL 243

                           90
                   ....*....|
gi 1063710198   81 KTLLSHPWIR 90
Cdd:cd14007    244 EQVLNHPWIK 253

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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIvQDDTPPI---PDSLSPDITDFLRLCFKKDSRQR 77
Cdd:cd06648    170 MAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRI-RDNEPPKlknLHKVSPRLRSFLDRMLVRDPAQR 248

                           90
                   ....*....|...
gi 1063710198   78 PDAKTLLSHPWIR 90
Cdd:cd06648    249 ATAAELLNHPFLA 261

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRI-VQDDTPPIPDSLSPDITDFLRLCFkKDSRQRPD 79
Cdd:cd06652    176 MSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPWAEFEAMAAIFKIaTQPTNPQLPAHVSDHCRDFLKRIF-VEAKLRPS 254

                           90
                   ....*....|
gi 1063710198   80 AKTLLSHPWI 89
Cdd:cd06652    255 ADELLRHTFV 264

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. 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). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, 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. 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. 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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPI--PDSLSPDITDFLRLCFKKDSRQRP 78
Cdd:cd06647    170 MAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELqnPEKLSAIFRDFLNRCLEMDVEKRG 249

                           90
                   ....*....|..
gi 1063710198   79 DAKTLLSHPWIR 90
Cdd:cd06647    250 SAKELLQHPFLK 261

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 1063710198    1 MAPEVIelsgVCAAS---------DIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPI--PDSLSPDITDFLRLC 69
Cdd:cd06643    170 MAPEVV----MCETSkdrpydykaDVWSLGVTLIEMAQIEPPHHELNPMRVLLKIAKSEPPTLaqPSRWSPEFKDFLRKC 245

                           90       100       110
                   ....*....|....*....|....*....|
gi 1063710198   70 FKKDSRQRPDAKTLLSHPWI--RNSRRALR 97
Cdd:cd06643    246 LEKNVDARWTTSQLLQHPFVsvLVSNKPLR 275

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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPIPDSLSPDITDFLRLCFKKDSRQRPDA 80
Cdd:cd06641    168 MAPEVIKQSAYDSKADIWSLGITAIELARGEPPHSELHPMKVLFLIPKNNPPTLEGNYSKPLKEFVEACLNKEPSFRPTA 247

                           90
                   ....*....|....
gi 1063710198   81 KTLLSHPWIRNSRR 94
Cdd:cd06641    248 KELLKHKFILRNAK 261

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 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 1063710198    1 MAPEVI----ELSGVCAASDIWSVGCTIIELLTCVPPYYDLQ-PMPALYRIVQDDTPPIP-DSLSPDITDFLRLCFKKDS 74
Cdd:cd06617    170 MAPERInpelNQKGYDVKSDVWSLGITMIELATGRFPYDSWKtPFQQLKQVVEEPSPQLPaEKFSPEFQDFVNKCLKKNY 249

                           90
                   ....*....|....*
gi 1063710198   75 RQRPDAKTLLSHPWI 89
Cdd:cd06617    250 KERPNYPELLQHPFF 264

Catalytic domain of Fungal Nak1-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 Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), 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. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 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 1063710198    1 MAPEVIeLSGVC--AASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPIPD-SLSPDITDFLRLCFKKDSRQR 77
Cdd:cd06917    168 MAPEVI-TEGKYydTKADIWSLGITTYEMATGNPPYSDVDALRAVMLIPKSKPPRLEGnGYSPLLKEFVAACLDEEPKDR 246

                           90       100
                   ....*....|....*....|....
gi 1063710198   78 PDAKTLLSHPWIRNSRRALRSSLR 101
Cdd:cd06917    247 LSADELLKSKWIKQHSKTPTSVLK 270

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK 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. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. 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). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPI--PDSLSPDITDFLRLCFKKDSRQRP 78
Cdd:cd06656    182 MAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELqnPERLSAVFRDFLNRCLEMDVDRRG 261

                           90
                   ....*....|..
gi 1063710198   79 DAKTLLSHPWIR 90
Cdd:cd06656    262 SAKELLQHPFLK 273

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 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 1063710198    1 MAPEVIELSGVCA---ASDIWSVGCTIIELLTCVPPYYDLQ-PMPALYRIVQDDTPPIP--DSLSPDITDFLRLCFKKDS 74
Cdd:cd06618    181 MAPERIDPPDNPKydiRADVWSLGISLVELATGQFPYRNCKtEFEVLTKILNEEPPSLPpnEGFSPDFCSFVDLCLTKDH 260

                           90
                   ....*....|....*.
gi 1063710198   75 RQRPDAKTLLSHPWIR 90
Cdd:cd06618    261 RYRPKYRELLQHPFIR 276

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which 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). 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 protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPI--PDSLSPDITDFLRLCFKKDSRQRP 78
Cdd:cd06654    183 MAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLIATNGTPELqnPEKLSAIFRDFLNRCLEMDVEKRG 262

                           90
                   ....*....|....*
gi 1063710198   79 DAKTLLSHPWIRNSR 93
Cdd:cd06654    263 SAKELLQHQFLKIAK 277

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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIvQDDTPPI---PDSLSPDITDFLRLCFKKDSRQR 77
Cdd:cd06659    184 MAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKRL-RDSPPPKlknSHKASPVLRDFLERMLVRDPQER 262

                           90
                   ....*....|..
gi 1063710198   78 PDAKTLLSHPWI 89
Cdd:cd06659    263 ATAQELLDHPFL 274

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 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 1063710198    1 MAPEVI---ELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPI-PDSLSPDITDFLRLCFKKDSRQ 76
Cdd:cd06633    184 MAPEVIlamDEGQYDGKVDIWSLGITCIELAERKPPLFNMNAMSALYHIAQNDSPTLqSNEWTDSFRGFVDYCLQKIPQE 263

                           90
                   ....*....|....*..
gi 1063710198   77 RPDAKTLLSHPWIRNSR 93
Cdd:cd06633    264 RPSSAELLRHDFVRRER 280

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. 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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRIVQDDTPPIPDSLSPDITDFLRLCFKKDSRQRPDA 80
Cdd:cd08222    172 MSPEVLKHEGYNSKSDIWSLGCILYEMCCLKHAFDGQNLLSVMYKIVEGETPSLPDKYSKELNAIYSRMLNKDPALRPSA 251

                   ....*....
gi 1063710198   81 KTLLSHPWI 89
Cdd:cd08222    252 AEILKIPFI 260

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which 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. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK 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 1063710198    1 MAPEVIELSGVCAASDIWSVGCTIIELLTCVPPYYDLQPMPALYRI-VQDDTPPIPDSLSPDITDFLRLCFKKDSRQRPD 79
Cdd:cd14061    168 MAPEVIKSSTFSKASDVWSYGVLLWELLTGEVPYKGIDGLAVAYGVaVNKLTLPIPSTCPEPFAQLMKDCWQPDPHDRPS 247

                   ....*
gi 1063710198   80 AKTLL 84
Cdd:cd14061    248 FADIL 252