C-terminal SARAH domain of mammalian STE20-like protein kinase 1 (MST1); MST1, also called serine/threonine-protein kinase 4, MST-1, STE20-like kinase MST1, or serine/threonine-protein kinase (STK) Krs-2, is a STE20 family stress-activated, pro-apoptotic STK which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. It is a key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. This model corresponds to the C-terminal SARAH (Salvador-RassF-Hippo) domain, which mediates homodimerization of MST1. The MST1 SARAH domain also interacts with Rassf1 and Rassf5 by forming a heterodimer which mediates the apoptosis process.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1958762211 356 DYEFLKSWTVEDLQKRLSALDPMMEQEMEEIRQKYRSKRQPILDAIEAK 404
Cdd:cd21887     1 DYEFLKSWSVEELQRRLASLDPMMEQEIEEIRQKYQSKRQPILDAIEAK 49

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211    1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRlRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:smart00220  51 LKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLLK-KRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENIL 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211   81 LNTEGHAKLADFGVAGQLTDTMaKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMI 160
Cdd:smart00220 130 LDEDGHVKLADFGLARQLDPGE-KLTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKK 208

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1958762211  161 PTNPPPTFRKPE-VWSDNFMDFVKQCLVKSPEQRATATQLLQHPFV 205
Cdd:smart00220 209 IGKPKPPFPPPEwDISPEAKDLIRKLLVKDPEKRLTAEEALQHPFF 254

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRlRNKTLTEDEIATILQSTLKGLEYLHFMrkihrdikagnil 80
Cdd:pfam00069  52 LKKLNHPNIVRLYDAFEDKDNLYLVLEYVEGGSLFDLLS-EKGAFSEREAKFIMKQILEGLESGSSL------------- 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 lnteghakladfgvagqltdtmakrNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMI 160
Cdd:pfam00069 118 -------------------------TTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELI 172

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1958762211 161 PTNPPPTFRKPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPFV 205
Cdd:pfam00069 173 IDQPYAFPELPSNLSEEAKDLLKKLLKKDPSKRLTATQALQHPWF 217

C-terminal SARAH domain of mammalian STE20-like protein kinase 1 (MST1); MST1, also called serine/threonine-protein kinase 4, MST-1, STE20-like kinase MST1, or serine/threonine-protein kinase (STK) Krs-2, is a STE20 family stress-activated, pro-apoptotic STK which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. It is a key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. This model corresponds to the C-terminal SARAH (Salvador-RassF-Hippo) domain, which mediates homodimerization of MST1. The MST1 SARAH domain also interacts with Rassf1 and Rassf5 by forming a heterodimer which mediates the apoptosis process.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1958762211 356 DYEFLKSWTVEDLQKRLSALDPMMEQEMEEIRQKYRSKRQPILDAIEAK 404
Cdd:cd21887     1 DYEFLKSWSVEELQRRLASLDPMMEQEIEEIRQKYQSKRQPILDAIEAK 49

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  24 IVMEYCgAGS-VSDIIRLRNKtLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTD-T 101
Cdd:NF033483   84 IVMEYV-DGRtLKDYIREHGP-LSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSStT 161

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1958762211 102 MAKRNTVIGTPFWMAPEviQEIGYNCVA--DIWSLGITAIEMAEGKPPY 148
Cdd:NF033483  162 MTQTNSVLGTVHYLSPE--QARGGTVDArsDIYSLGIVLYEMLTGRPPF 208

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 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:cd05122    51 LKKCKHPNIVKYYGSYLKKDELWIVMEFCSGGSLKDLLKNTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANIL 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 LNTEGHAKLADFGVAGQLTDTMAkRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMI 160
Cdd:cd05122   131 LTSDGEVKLIDFGLSAQLSDGKT-RNTFVGTPYWMAPEVIQGKPYGFKADIWSLGITAIEMAEGKPPYSELPPMKALFLI 209

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1958762211 161 PTNPPPTFRKPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPFV 205
Cdd:cd05122   210 ATNGPPGLRNPKKWSKEFKDFLKKCLQKDPEKRPTAEQLLKHPFI 254

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 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIrLRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:cd06613    51 LKECRHPNIVAYFGSYLRRDKLWIVMEYCGGGSLQDIY-QVTGPLSELQIAYVCRETLKGLAYLHSTGKIHRDIKGANIL 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 LNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQE---IGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAI 157
Cdd:cd06613   130 LTEDGDVKLADFGVSAQLTATIAKRKSFIGTPYWMAPEVAAVerkGGYDGKCDIWALGITAIELAELQPPMFDLHPMRAL 209

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958762211 158 FMIP--TNPPPTFRKPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPFV 205
Cdd:cd06613   210 FLIPksNFDPPKLKDKEKWSPDFHDFIKKCLTKNPKKRPTATKLLQHPFV 259

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 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:cd06614    50 MKECKHPNIVDYYDSYLVGDELWVVMEYMDGGSLTDIITQNPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNIL 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 LNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMI 160
Cdd:cd06614   130 LSKDGSVKLADFGFAAQLTKEKSKRNSVVGTPYWMAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPPYLEEPPLRALFLI 209

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1958762211 161 PTNPPPTFRKPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPFVK 206
Cdd:cd06614   210 TTKGIPPLKNPEKWSPEFKDFLNKCLVKDPEKRPSAEELLQHPFLK 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 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKT--LTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGN 78
Cdd:cd06610    53 MSQCNHPNVVSYYTSFVVGDELWLVMPLLSGGSLLDIMKSSYPRggLDEAIIATVLKEVLKGLEYLHSNGQIHRDVKAGN 132

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  79 ILLNTEGHAKLADFGVAGQLTDTM----AKRNTVIGTPFWMAPEVIQEI-GYNCVADIWSLGITAIEMAEGKPPYADIHP 153
Cdd:cd06610   133 ILLGEDGSVKIADFGVSASLATGGdrtrKVRKTFVGTPCWMAPEVMEQVrGYDFKADIWSFGITAIELATGAAPYSKYPP 212

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958762211 154 MRAIFMIPTNPPPTF---RKPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPF 204
Cdd:cd06610   213 MKVLMLTLQNDPPSLetgADYKKYSKSFRKMISLCLQKDPSKRPTAEELLKHKF 266

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 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 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIirLRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:cd06642    56 LSQCDSPYITRYYGSYLKGTKLWIIMEYLGGGSALDL--LKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVL 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 LNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMI 160
Cdd:cd06642   134 LSEQGDVKLADFGVAGQLTDTQIKRNTFVGTPFWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLI 213

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211 161 PTNPPPTFRKPevWSDNFMDFVKQCLVKSPEQRATATQLLQHPFV-KSAKGAAILRDLIN 219
Cdd:cd06642   214 PKNSPPTLEGQ--HSKPFKEFVEACLNKDPRFRPTAKELLKHKFItRYTKKTSFLTELID 271

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin 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 1958762211   5 DSPHVVKYYGSYFK----NTD-LWIVMEYCGAGSVSDIIR---LRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKA 76
Cdd:cd06638    73 DHPNVVKFYGMYYKkdvkNGDqLWLVLELCNGGSVTDLVKgflKRGERMEEPIIAYILHEALMGLQHLHVNKTIHRDVKG 152

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  77 GNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVI---QEI--GYNCVADIWSLGITAIEMAEGKPPYADI 151
Cdd:cd06638   153 NNILLTTEGGVKLVDFGVSAQLTSTRLRRNTSVGTPFWMAPEVIaceQQLdsTYDARCDVWSLGITAIELGDGDPPLADL 232

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958762211 152 HPMRAIFMIPTNPPPTFRKPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPFV 205
Cdd:cd06638   233 HPMRALFKIPRNPPPTLHQPELWSNEFNDFIRKCLTKDYEKRPTVSDLLQHVFI 286

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin 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 1958762211   5 DSPHVVKYYGSYFKNT-----DLWIVMEYCGAGSVSDIIR---LRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKA 76
Cdd:cd06639    77 NHPNVVKFYGMFYKADqyvggQLWLVLELCNGGSVTELVKgllKCGQRLDEAMISYILYGALLGLQHLHNNRIIHRDVKG 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  77 GNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQ-----EIGYNCVADIWSLGITAIEMAEGKPPYADI 151
Cdd:cd06639   157 NNILLTTEGGVKLVDFGVSAQLTSARLRRNTSVGTPFWMAPEVIAceqqyDYSYDARCDVWSLGITAIELADGDPPLFDM 236

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958762211 152 HPMRAIFMIPTNPPPTFRKPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPFVK 206
Cdd:cd06639   237 HPVKALFKIPRNPPPTLLNPEKWCRGFSHFISQCLIKDFEKRPSVTHLLEHPFIK 291

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO 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 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCgAGSVSDIIRLRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:cd06607    55 LRQLRHPNTIEYKGCYLREHTAWLVMEYC-LGSASDIVEVHKKPLQEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNIL 133

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 LNTEGHAKLADFGVAGqltdTMAKRNTVIGTPFWMAPEVI---QEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAI 157
Cdd:cd06607   134 LTEPGTVKLADFGSAS----LVCPANSFVGTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSAL 209

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 1958762211 158 FMIPTNPPPTFRKPEvWSDNFMDFVKQCLVKSPEQRATATQLLQHPFV 205
Cdd:cd06607   210 YHIAQNDSPTLSSGE-WSDDFRNFVDSCLQKIPQDRPSAEDLLKHPFV 256

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 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 1958762211   8 HVVKYYGSYFKNT------DLWIVMEYCGAGSVSDIIR-LRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:cd06636    74 NIATYYGAFIKKSppghddQLWLVMEFCGAGSVTDLVKnTKGNALKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVL 153

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 LNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQ-----EIGYNCVADIWSLGITAIEMAEGKPPYADIHPMR 155
Cdd:cd06636   154 LTENAEVKLVDFGVSAQLDRTVGRRNTFIGTPYWMAPEVIAcdenpDATYDYRSDIWSLGITAIEMAEGAPPLCDMHPMR 233

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958762211 156 AIFMIPTNPPPTFrKPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPFV 205
Cdd:cd06636   234 ALFLIPRNPPPKL-KSKKWSKKFIDFIEGCLVKNYLSRPSTEQLLKHPFI 282

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 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRlRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:cd06606    53 LSSLKHPNIVRYLGTERTENTLNIFLEYVPGGSLASLLK-KFGKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANIL 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 LNTEGHAKLADFGVAGQL--TDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIH-PMRAI 157
Cdd:cd06606   132 VDSDGVVKLADFGCAKRLaeIATGEGTKSLRGTPYWMAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPWSELGnPVAAL 211

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958762211 158 FMI--PTNPPPTfrkPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPFV 205
Cdd:cd06606   212 FKIgsSGEPPPI---PEHLSEEAKDFLRKCLQRDPKKRPTADELLQHPFL 258

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 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNktLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:cd06648    58 MRDYQHPNIVEMYSSYLVGDELWVVMEFLEGGALTDIVTHTR--MNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSIL 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 LNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMI 160
Cdd:cd06648   136 LTSDGRVKLSDFGFCAQVSKEVPRRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRI 215

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1958762211 161 PTNPPPTFRKPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPFVK 206
Cdd:cd06648   216 RDNEPPKLKNLHKVSPRLRSFLDRMLVRDPAQRATAAELLNHPFLA 261

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. 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 MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 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 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKtLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:cd06646    60 VKECKHCNIVAYFGSYLSREKLWICMEYCGGGSLQDIYHVTGP-LSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANIL 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 LNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVI---QEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAI 157
Cdd:cd06646   139 LTDNGDVKLADFGVAAKITATIAKRKSFIGTPYWMAPEVAaveKNGGYNQLCDIWAVGITAIELAELQPPMFDLHPMRAL 218

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958762211 158 FMIPTN--PPPTFRKPEVWSDNFMDFVKQCLVKSPEQRATATQLLQHPFV 205
Cdd:cd06646   219 FLMSKSnfQPPKLKDKTKWSSTFHNFVKISLTKNPKKRPTAERLLTHLFV 268

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 1958762211   1 MQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRlrNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNIL 80
Cdd:cd06647    58 MRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVT--ETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNIL 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762211  81 LNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMI 160
Cdd:cd06647   136 LGMDGSVKLTDFGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLI 215