Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1716950952   1 MLISNEGHIKLTDFGLSKVTLNRDINMMDILTTPSMAKPRQDYSRTPGQVLSLISSLGFNTP 62
Cdd:cd05610   135 MLISNEGHIKLTDFGLSKVTLNRELNMMDILTTPSMAKPKNDYSRTPGQVLSLISSLGFNTP 196

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1716950952   1 MLISNEGHIKLTDFGLSKVTLNRDINMMDILTTPSMAKPRQDYSRTPGQVLSLISSLGFNTP 62
Cdd:cd05610   135 MLISNEGHIKLTDFGLSKVTLNRELNMMDILTTPSMAKPKNDYSRTPGQVLSLISSLGFNTP 196

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1716950952  579 GTPDYLAPELLLGRAHGFltsgpAVDWWALGVCLFEFLTGIPPF-NDETPQQVFQNILKRDIPWPEGEEKLSDNAQSAVE 657
Cdd:smart00220 158 GTPEYMAPEVLLGKGYGK-----AVDIWSLGVILYELLTGKPPFpGDDQLLELFKKIGKPKPPFPPPEWDISPEAKDLIR 232

                           90       100
                   ....*....|....*....|..
gi 1716950952  658 ILLTIDDTKRAGMKELKRHPLF 679
Cdd:smart00220 233 KLLVKDPEKRLTAEEALQHPFF 254

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1716950952 575 GRILGTPDYLAPELLLGRAhgfltSGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWP 642
Cdd:COG0515   166 GTVVGTPGYMAPEQARGEP-----VDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPPP 228

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase 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 1716950952 563 KSVRRGVAPVDDGRILGTPDYLAPELLLGRAHGFltsgpAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWP 642
Cdd:cd05579   154 QKKSNGAPEKEDRRIVGTPDYLAPEILLGQGHGK-----TVDWWSLGVILYEFLVGIPPFHAETPEEIFQNILNGKIEWP 228

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1716950952 643 EGEEkLSDNAQSAVEILLTIDDTKRAGMK---ELKRHPLFSDVDW 684
Cdd:cd05579   229 EDPE-VSDEAKDLISKLLTPDPEKRLGAKgieEIKNHPFFKGIDW 272

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-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 1716950952 547 QQTPNQIKSGTPYRTPKSVRRgvapVDDGRILGTPDYLAPELLLGRAHGfltsgPAVDWWALGVCLFEFLTGIPPFNDET 626
Cdd:cd05573   164 SVNTLFQDNVLARRRPHKQRR----VRAYSAVGTPDYIAPEVLRGTGYG-----PECDWWSLGVILYEMLYGFPPFYSDS 234

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1716950952 627 PQQVFQNIL--KRDIPWPEgEEKLSDNAQSAVEILLTiDDTKRAGM-KELKRHPLFSDVDWENLQHQTMPFIPQPDDETD 703
Cdd:cd05573   235 LVETYSKIMnwKESLVFPD-DPDVSPEAIDLIRRLLC-DPEDRLGSaEEIKAHPFFKGIDWENLRESPPPFVPELSSPTD 312

                  ....*
gi 1716950952 704 TSYFE 708
Cdd:cd05573   313 TSNFD 317

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1716950952   1 MLISNEGHIKLTDFGLSKVTLNRDINMMDILTTPSMAKPRQDYSRTPGQVLSLISSLGFNTP 62
Cdd:cd05610   135 MLISNEGHIKLTDFGLSKVTLNRELNMMDILTTPSMAKPKNDYSRTPGQVLSLISSLGFNTP 196

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-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 1716950952 529 SYPMAITPTQKRRSCMPHQQTPNQIKSGTPYRTPKSVRRGVAPVddgrilGTPDYLAPELLLGRAHGFltsgpAVDWWAL 608
Cdd:cd05574   150 SKQSSVTPPPVRKSLRKGSRRSSVKSIEKETFVAEPSARSNSFV------GTEEYIAPEVIKGDGHGS-----AVDWWTL 218

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1716950952 609 GVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEgEEKLSDNAQSAVEILLTIDDTKRAGMK----ELKRHPLFSDVDW 684
Cdd:cd05574   219 GILLYEMLYGTTPFKGSNRDETFSNILKKELTFPE-SPPVSSEAKDLIRKLLVKDPSKRLGSKrgasEIKRHPFFRGVNW 297

                         170
                  ....*....|....*.
gi 1716950952 685 ENLQHQTMPFIPQPDD 700
Cdd:cd05574   298 ALIRNMTPPIIPRPDD 313

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK 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 1716950952 579 GTPDYLAPELLLGRAHGFL-TSGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNIL--KRDIPWPEgEEKLSDNAQSA 655
Cdd:cd05601   165 GTPDYIAPEVLTSMNGGSKgTYGVECDWWSLGIVAYEMLYGKTPFTEDTVIKTYSNIMnfKKFLKFPE-DPKVSESAVDL 243

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1716950952 656 VEILLTiDDTKRAGMKELKRHPLFSDVDWENLQHQTMPFIPQPDDETDTSYFE-------ARNTAQHLTVSGFS 722
Cdd:cd05601   244 IKGLLT-DAKERLGYEGLCCHPFFSGIDWNNLRQTVPPFVPTLTSDDDTSNFDefepkktRPSYENFNKSKGFS 316

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB 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 PI3K.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1716950952 579 GTPDYLAPELLLGRAHGfltsgPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAVEI 658
Cdd:cd05571   157 GTPEYLAPEVLEDNDYG-----RAVDWWGLGVVMYEMMCGRLPFYNRDHEVLFELILMEEVRFP---STLSPEAKSLLAG 228

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1716950952 659 LLTIDDTKRAG-----MKELKRHPLFSDVDWENLQHQTM--PFIPQPDDETDTSYFEARNTAQ 714
Cdd:cd05571   229 LLKKDPKKRLGggprdAKEIMEHPFFASINWDDLYQKKIppPFKPQVTSETDTRYFDEEFTAE 291

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1716950952 579 GTPDYLAPELLLGRAHGFltsgpAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGeekLSDNAQSAVEI 658
Cdd:cd05123   155 GTPEYLAPEVLLGKGYGK-----AVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKILKSPLKFPEY---VSPEAKSLISG 226

                          90       100
                  ....*....|....*....|....
gi 1716950952 659 LLTIDDTKRAG---MKELKRHPLF 679
Cdd:cd05123   227 LLQKDPTKRLGsggAEEIKAHPFF 250

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-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 1716950952 573 DDGRI-----LGTPDYLAPELLLGRAHGFLTSGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNIL--KRDIPWPEGE 645
Cdd:cd05597   154 EDGTVqssvaVGTPDYISPEILQAMEDGKGRYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMnhKEHFSFPDDE 233

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1716950952 646 EKLSDNAQSAVEILLTIDDTK--RAGMKELKRHPLFSDVDWENLQHQTMPFIPQPDDETDTSYFE 708
Cdd:cd05597   234 DDVSEEAKDLIRRLICSRERRlgQNGIDDFKKHPFFEGIDWDNIRDSTPPYIPEVTSPTDTSNFD 298

Catalytic domain of Yeast Protein Kinase 1-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 fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-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 1716950952 579 GTPDYLAPELLLGraHGFLTsgpAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGEEKlsdNAQSAVEI 658
Cdd:cd05585   156 GTPEYLAPELLLG--HGYTK---AVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKILQEPLRFPDGFDR---DAKDLLIG 227

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1716950952 659 LLTIDDTKR---AGMKELKRHPLFSDVDWENLQHQTM--PFIPQPDDETDTSYFEARNTAQ 714
Cdd:cd05585   228 LLNRDPTKRlgyNGAQEIKNHPFFDQIDWKRLLMKKIqpPFKPAVENAIDTSNFDEEFTRE 288

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma 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 1716950952 579 GTPDYLAPELLLGRAHGfltsgPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAVEI 658
Cdd:cd05593   177 GTPEYLAPEVLEDNDYG-----RAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEDIKFP---RTLSADAKSLLSG 248

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1716950952 659 LLTIDDTKRAG-----MKELKRHPLFSDVDWENLQHQTM--PFIPQPDDETDTSYFEARNTAQHLTVS 719
Cdd:cd05593   249 LLIKDPNKRLGggpddAKEIMRHSFFTGVNWQDVYDKKLvpPFKPQVTSETDTRYFDEEFTAQTITIT 316

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS 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 1716950952 579 GTPDYLAPELLLGRAHGFLtsgpaVDWWALGVCLFEFLTGIPPFNDETPQQVFQNIlkrdIPWPE-----GEEKLSDNAQ 653
Cdd:cd05598   167 GTPNYIAPEVLLRTGYTQL-----CDWWSVGVILYEMLVGQPPFLAQTPAETQLKV----INWRTtlkipHEANLSPEAK 237

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1716950952 654 SAVEILLTiDDTKRAGMK---ELKRHPLFSDVDWENLQHQTMPFIPQPDDETDTSYFE 708
Cdd:cd05598   238 DLILRLCC-DAEDRLGRNgadEIKAHPFFAGIDWEKLRKQKAPYIPTIRHPTDTSNFD 294

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta 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 1716950952 579 GTPDYLAPELLLGRAHGfltsgPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAVEI 658
Cdd:cd05595   157 GTPEYLAPEVLEDNDYG-----RAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEIRFP---RTLSPEAKSLLAG 228

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1716950952 659 LLTIDDTKRAG-----MKELKRHPLFSDVDWENLQHQTM--PFIPQPDDETDTSYFEARNTAQHLTVS 719
Cdd:cd05595   229 LLKKDPKQRLGggpsdAKEVMEHRFFLSINWQDVVQKKLlpPFKPQVTSEVDTRYFDDEFTAQSITIT 296

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC 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 1716950952 579 GTPDYLAPELLLGRAHGfltsgPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGeekLSDNAQSAVEI 658
Cdd:cd05587   159 GTPDYIAPEIIAYQPYG-----KSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKS---LSKEAVSICKG 230

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1716950952 659 LLTIDDTKR-----AGMKELKRHPLFSDVDWENLQHQTM--PFIPQPDDETDTSYFEARNTAQHLTVS 719
Cdd:cd05587   231 LLTKHPAKRlgcgpTGERDIKEHPFFRRIDWEKLERREIqpPFKPKIKSPRDAENFDKEFTKEPPVLT 298

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA 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 1716950952 579 GTPDYLAPELLLGRAHGfltsgPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGeekLSDNAQSAVEI 658
Cdd:cd14209   160 GTPEYLAPEIILSKGYN-----KAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSH---FSSDLKDLLRN 231

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1716950952 659 LLTIDDTKR-----AGMKELKRHPLFSDVDWENLQHQTM--PFIPQPDDETDTSYFE 708
Cdd:cd14209   232 LLQVDLTKRfgnlkNGVNDIKNHKWFATTDWIAIYQRKVeaPFIPKLKGPGDTSNFD 288

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha 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 1716950952 579 GTPDYLAPELLLGRAHGfltsgPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAVEI 658
Cdd:cd05594   188 GTPEYLAPEVLEDNDYG-----RAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFP---RTLSPEAKSLLSG 259

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1716950952 659 LLTIDDTKRAG-----MKELKRHPLFSDVDWENLQHQTM--PFIPQPDDETDTSYFEARNTAQHLTVS 719
Cdd:cd05594   260 LLKKDPKQRLGggpddAKEIMQHKFFAGIVWQDVYEKKLvpPFKPQVTSETDTRYFDEEFTAQMITIT 327

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-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 1716950952 579 GTPDYLAPELLLGRAHGFltsgpAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILkRDIPW-PegeEKLSDNAQSAVE 657
Cdd:cd05592   158 GTPDYIAPEILKGQKYNQ-----SVDWWSFGVLLYEMLIGQSPFHGEDEDELFWSIC-NDTPHyP---RWLTKEAASCLS 228

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1716950952 658 ILLTIDDTKRAGMKE-----LKRHPLFSDVDWENLQHQTM--PFIPQPDDETDTSYFE 708
Cdd:cd05592   229 LLLERNPEKRLGVPEcpagdIRDHPFFKTIDWDKLERREIdpPFKPKVKSANDVSNFD 286

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K 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 1716950952 579 GTPDYLAPELLLGRAHGfltsgPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAVEI 658
Cdd:cd05584   162 GTIEYMAPEILTRSGHG-----KAVDWWSLGALMYDMLTGAPPFTAENRKKTIDKILKGKLNLP---PYLTNEARDLLKK 233

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1716950952 659 LLTIDDTKRAG-----MKELKRHPLFSDVDWENL--QHQTMPFIPQPDDETDTSYFEARNTAQ 714
Cdd:cd05584   234 LLKRNVSSRLGsgpgdAEEIKAHPFFRHINWDDLlaKKVEPPFKPLLQSEEDVSQFDSKFTKQ 296

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN 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 1716950952 579 GTPDYLAPELLLGRAHgflTSgpAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAVEI 658
Cdd:cd05589   163 GTPEFLAPEVLTDTSY---TR--AVDWWGLGVLIYEMLVGESPFPGDDEEEVFDSIVNDEVRYP---RFLSTEAISIMRR 234

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1716950952 659 LLTIDDTKRAG-----MKELKRHPLFSDVDWENLQHQTM--PFIPQPDDETDTSYFEARNTAQ 714
Cdd:cd05589   235 LLRKNPERRLGaserdAEDVKKQPFFRNIDWEALLARKIkpPFVPTIKSPEDVSNFDEEFTSE 297

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 1716950952 579 GTPDYLAPELLLGRAHGFltsgpAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAVEI 658
Cdd:cd14007   160 GTLDYLPPEMVEGKEYDY-----KVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIKFP---SSVSPEAKDLISK 231

                          90
                  ....*....|....*....
gi 1716950952 659 LLTIDDTKRAGMKELKRHP 677
Cdd:cd14007   232 LLQKDPSKRLSLEQVLNHP 250

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-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 1716950952 579 GTPDYLAPELLLGRAhGFltsGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGeeKLSDNAQSAVEI 658
Cdd:cd05586   158 GTTEYLAPEVLLDEK-GY---TKMVDFWSLGVLVFEMCCGWSPFYAEDTQQMYRNIAFGKVRFPKD--VLSDEGRSFVKG 231

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1716950952 659 LLTIDDTKRAGM----KELKRHPLFSDVDWENLQHQ--TMPFIPQPDDETDTSYFEARNT 712
Cdd:cd05586   232 LLNRNPKHRLGAhddaVELKEHPFFADIDWDLLSKKkiTPPFKPIVDSDTDVSNFDPEFT 291