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 1958762213 255 DYEFLKSWTVEDLQKRLSALDPMMEQEMEEIRQKYRSKRQPILDAIEAK 303
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 1958762213    3 KRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPE-VWSDNFMDFV 81
Cdd:smart00220 152 KLTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKPKPPFPPPEwDISPEAKDLI 231

                           90       100
                   ....*....|....*....|...
gi 1958762213   82 KQCLVKSPEQRATATQLLQHPFV 104
Cdd:smart00220 232 RKLLVKDPEKRLTAEEALQHPFF 254

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 1958762213 255 DYEFLKSWTVEDLQKRLSALDPMMEQEMEEIRQKYRSKRQPILDAIEAK 303
Cdd:cd21887     1 DYEFLKSWSVEELQRRLASLDPMMEQEIEEIRQKYQSKRQPILDAIEAK 49

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762213   1 MAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRK--PEVwSDNFM 78
Cdd:COG0515   162 LTQTGTVVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPPPSElrPDL-PPALD 240

                          90       100
                  ....*....|....*....|...
gi 1958762213  79 DFVKQCLVKSPEQR-ATATQLLQ 100
Cdd:COG0515   241 AIVLRALAKDPEERyQSAAELAA 263

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 1958762213   4 RNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVWSDNFMDFVKQ 83
Cdd:cd05122   154 RNTFVGTPYWMAPEVIQGKPYGFKADIWSLGITAIEMAEGKPPYSELPPMKALFLIATNGPPGLRNPKKWSKEFKDFLKK 233

                          90       100
                  ....*....|....*....|.
gi 1958762213  84 CLVKSPEQRATATQLLQHPFV 104
Cdd:cd05122   234 CLQKDPEKRPTAEQLLKHPFI 254

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 1958762213   1 MAKRNTVIGTPFWMAPEVIQ-----EIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVWSD 75
Cdd:cd06608   167 LGRRNTFIGTPYWMAPEVIAcdqqpDASYDARCDVWSLGITAIELADGKPPLCDMHPMRALFKIPRNPPPTLKSPEKWSK 246

                          90       100
                  ....*....|....*....|....*....
gi 1958762213  76 NFMDFVKQCLVKSPEQRATATQLLQHPFV 104
Cdd:cd06608   247 EFNDFISECLIKNYEQRPFTEELLEHPFI 275

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 1958762213   1 MAKRNTVIGTPFWMAPEVI-----QEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVWSD 75
Cdd:cd06611   157 LQKRDTFIGTPYWMAPEVVacetfKDNPYDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKILKSEPPTLDQPSKWSS 236

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1958762213  76 NFMDFVKQCLVKSPEQRATATQLLQHPFVKSAKGAAILRDLINE 119
Cdd:cd06611   237 SFNDFLKSCLVKDPDDRPTAAELLKHPFVSDQSDNKAIKDLLAE 280

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 1958762213   3 KRNTVIGTPFWMAPEVI---QEI--GYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVWSDNF 77
Cdd:cd06638   180 RRNTSVGTPFWMAPEVIaceQQLdsTYDARCDVWSLGITAIELGDGDPPLADLHPMRALFKIPRNPPPTLHQPELWSNEF 259

                          90       100
                  ....*....|....*....|....*..
gi 1958762213  78 MDFVKQCLVKSPEQRATATQLLQHPFV 104
Cdd:cd06638   260 NDFIRKCLTKDYEKRPTVSDLLQHVFI 286

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 1958762213   1 MAKRNTVIGTPFWMAPEVIQ-----EIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFrKPEVWSD 75
Cdd:cd06636   175 VGRRNTFIGTPYWMAPEVIAcdenpDATYDYRSDIWSLGITAIEMAEGAPPLCDMHPMRALFLIPRNPPPKL-KSKKWSK 253

                          90       100
                  ....*....|....*....|....*....
gi 1958762213  76 NFMDFVKQCLVKSPEQRATATQLLQHPFV 104
Cdd:cd06636   254 KFIDFIEGCLVKNYLSRPSTEQLLKHPFI 282

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 1958762213   1 MAKRNTVIGTPFWMAPEVI-----QEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVWSD 75
Cdd:cd06644   164 LQRRDSFIGTPYWMAPEVVmcetmKDTPYDYKADIWSLGITLIEMAQIEPPHHELNPMRVLLKIAKSEPPTLSQPSKWSM 243

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1958762213  76 NFMDFVKQCLVKSPEQRATATQLLQHPFVKSAKGAAILRDLINEA 120
Cdd:cd06644   244 EFRDFLKTALDKHPETRPSAAQLLEHPFVSSVTSNRPLRELVAEA 288

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762213    3 KRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPE-VWSDNFMDFV 81
Cdd:smart00220 152 KLTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKPKPPFPPPEwDISPEAKDLI 231

                           90       100
                   ....*....|....*....|...
gi 1958762213   82 KQCLVKSPEQRATATQLLQHPFV 104
Cdd:smart00220 232 RKLLVKDPEKRLTAEEALQHPFF 254

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 1958762213   3 KRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPevWSDNFMDFVK 82
Cdd:cd06642   157 KRNTFVGTPFWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNSPPTLEGQ--HSKPFKEFVE 234

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958762213  83 QCLVKSPEQRATATQLLQHPFV-KSAKGAAILRDLIN 118
Cdd:cd06642   235 ACLNKDPRFRPTAKELLKHKFItRYTKKTSFLTELID 271

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 1958762213   2 AKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVWSDNFMDFV 81
Cdd:cd06647   158 SKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSAIFRDFL 237

                          90       100
                  ....*....|....*....|....
gi 1958762213  82 KQCLVKSPEQRATATQLLQHPFVK 105
Cdd:cd06647   238 NRCLEMDVEKRGSAKELLQHPFLK 261

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 1958762213   5 NTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIH-PMRAIFMI--PTNPPPTfrkPEVWSDNFMDFV 81
Cdd:cd06606   159 KSLRGTPYWMAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPWSELGnPVAALFKIgsSGEPPPI---PEHLSEEAKDFL 235

                          90       100
                  ....*....|....*....|...
gi 1958762213  82 KQCLVKSPEQRATATQLLQHPFV 104
Cdd:cd06606   236 RKCLQRDPKKRPTADELLQHPFL 258

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 1958762213   5 NTVIGTPFWMAPEVI---QEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEvWSDNFMDFV 81
Cdd:cd06607   155 NSFVGTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNDSPTLSSGE-WSDDFRNFV 233

                          90       100
                  ....*....|....*....|...
gi 1958762213  82 KQCLVKSPEQRATATQLLQHPFV 104
Cdd:cd06607   234 DSCLQKIPQDRPSAEDLLKHPFV 256

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 1958762213   3 KRNTVIGTPFWMAPEVIQE-IGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPtfRKP-EVWSDNFMDF 80
Cdd:cd06917   157 KRSTFVGTPYWMAPEVITEgKYYDTKADIWSLGITTYEMATGNPPYSDVDALRAVMLIPKSKPP--RLEgNGYSPLLKEF 234

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1958762213  81 VKQCLVKSPEQRATATQLLQHPFVK--SAKGAAILRDLIN 118
Cdd:cd06917   235 VAACLDEEPKDRLSADELLKSKWIKqhSKTPTSVLKELIS 274

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It 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 1958762213   2 AKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVWSDNFMDFV 81
Cdd:cd06655   170 SKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSPIFRDFL 249

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1958762213  82 KQCLVKSPEQRATATQLLQHPFVKSAKGAAILRDLI---NEAM 121
Cdd:cd06655   250 NRCLEMDVEKRGSAKELLQHPFLKLAKPLSSLTPLIlaaKEAM 292

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 1958762213   1 MAKRNTVIGTPFWMAPEVI---QEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTN--PPPTFRKPEVWSD 75
Cdd:cd06646   160 IAKRKSFIGTPYWMAPEVAaveKNGGYNQLCDIWAVGITAIELAELQPPMFDLHPMRALFLMSKSnfQPPKLKDKTKWSS 239

                          90       100
                  ....*....|....*....|....*....
gi 1958762213  76 NFMDFVKQCLVKSPEQRATATQLLQHPFV 104
Cdd:cd06646   240 TFHNFVKISLTKNPKKRPTAERLLTHLFV 268

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 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. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in 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 MAP4K3 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 1958762213   1 MAKRNTVIGTPFWMAPEVI---QEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTN--PPPTFRKPEVWSD 75
Cdd:cd06645   162 IAKRKSFIGTPYWMAPEVAaveRKGGYNQLCDIWAVGITAIELAELQPPMFDLHPMRALFLMTKSnfQPPKLKDKMKWSN 241

                          90       100
                  ....*....|....*....|....*....
gi 1958762213  76 NFMDFVKQCLVKSPEQRATATQLLQHPFV 104
Cdd:cd06645   242 SFHHFVKMALTKNPKKRPTAEKLLQHPFV 270

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 1958762213   9 GTPFWMAPEVI--QEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNP--PPTfrkPEVWSDNFMDFVKQC 84
Cdd:cd06632   163 GSPYWMAPEVImqKNSGYGLAVDIWSLGCTVLEMATGKPPWSQYEGVAAIFKIGNSGelPPI---PDHLSPDAKDFIRLC 239

                          90       100
                  ....*....|....*....|
gi 1958762213  85 LVKSPEQRATATQLLQHPFV 104
Cdd:cd06632   240 LQRDPEDRPTASQLLEHPFV 259

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 1958762213   3 KRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVWSDNFMDFVK 82
Cdd:cd06659   173 KRKSLVGTPYWMAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKRLRDSPPPKLKNSHKASPVLRDFLE 252

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958762213  83 QCLVKSPEQRATATQLLQHPFVKSAKGAAILRDLINE 119
Cdd:cd06659   253 RMLVRDPQERATAQELLDHPFLLQTGLPECLVPLIQQ 289

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762213   3 KRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVWSDNFMDFVK 82
Cdd:pfam00069 116 SLTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPELPSNLSEEAKDLLK 195

                          90       100
                  ....*....|....*....|..
gi 1958762213  83 QCLVKSPEQRATATQLLQHPFV 104
Cdd:pfam00069 196 KLLKKDPSKRLTATQALQHPWF 217

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 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 1958762213   1 MAKRNTVIGTPFWMAPEVI---QEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEvWSDNF 77
Cdd:cd06634   165 MAPANSFVGTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNESPALQSGH-WSEYF 243

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958762213  78 MDFVKQCLVKSPEQRATATQLLQHPFVKSAKGAAILRDLINEAMDVKLKRQEAQQR 133
Cdd:cd06634   244 RNFVDSCLQKIPQDRPTSDVLLKHRFLLRERPPTVIMDLIQRTKDAVRELDNLQYR 299

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 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 protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762213   3 KRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVWSDNFMDFVK 82
Cdd:cd06657   172 RRKSLVGTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRDNLPPKLKNLHKVSPSLKGFLD 251

                          90       100
                  ....*....|....*....|....*
gi 1958762213  83 QCLVKSPEQRATATQLLQHPFVKSA 107
Cdd:cd06657   252 RLLVRDPAQRATAAELLKHPFLAKA 276

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762213   5 NTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYA--DIHPMRAIF----MIPTNPPPtfRKP-EVWSDNF 77
Cdd:cd06605   156 KTFVGTRSYMAPERISGGKYTVKSDIWSLGLSLVELATGRFPYPppNAKPSMMIFellsYIVDEPPP--LLPsGKFSPDF 233

                          90       100
                  ....*....|....*....|....*...
gi 1958762213  78 MDFVKQCLVKSPEQRATATQLLQHPFVK 105
Cdd:cd06605   234 QDFVSQCLQKDPTERPSYKELMEHPFIK 261

kinase non-catalytic C-lobe domain; It is an interaction domain identified as being similar to the C-terminal protein kinase catalytic fold (C lobe). Its presence at the N terminus of signalling proteins and the absence of the active-site residues in the catalytic and activation loops suggest that it folds independently and is likely to be non-catalytic. The occurrence of KIND only in metazoa implies that it has evolved from the catalytic protein kinase domain into an interaction domain possibly by keeping the substrate-binding features

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958762213    8 IGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTF-----RKPEVWSD--NFMDF 80
Cdd:smart00750  65 RPDPYFMAPEVIQGQSYTEKADIYSLGITLYEALDYELPYNEERELSAILEILLNGMPADdprdrSNLEGVSAarSFEDF 144

                           90       100
                   ....*....|....*....|....*...
gi 1958762213   81 VKQCLVKSPEQRATATQLLQHPFVKSAK 108
Cdd:smart00750 145 MRLCASRLPQRREAANHYLAHCRALFAE 172

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 1958762213   6 TVIGTPFWMAPEVIQE--IGYNCVADIWSLGITAIEMAEGKPPYADI-HPMRAIF---MIPTNPPptfrKPEVWSDNFMD 79
Cdd:cd06624   168 TFTGTLQYMAPEVIDKgqRGYGPPADIWSLGCTIIEMATGKPPFIELgEPQAAMFkvgMFKIHPE----IPESLSEEAKS 243

                          90       100
                  ....*....|....*....|....*
gi 1958762213  80 FVKQCLVKSPEQRATATQLLQHPFV 104
Cdd:cd06624   244 FILRCFEPDPDKRATASDLLQDPFL 268

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 1958762213   6 TVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPEVwSDNFMDFVKQCL 85
Cdd:cd06652   168 SVTGTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPTNPQLPAHV-SDHCRDFLKRIF 246

                          90
                  ....*....|....*....
gi 1958762213  86 VKSpEQRATATQLLQHPFV 104
Cdd:cd06652   247 VEA-KLRPSADELLRHTFV 264