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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8568081   34 DQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVM 113
Cdd:cd14209   1 DDFDRIKTLGTGSFGRVMLVRHKETGNYYAMKILDKQKVVKLKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVM 80

                        90       100       110
                ....*....|....*....|....*....|.
gi 8568081  114 EYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd14209  81 EYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 111

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 8568081   34 DQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVM 113
Cdd:cd14209   1 DDFDRIKTLGTGSFGRVMLVRHKETGNYYAMKILDKQKVVKLKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVM 80

                        90       100       110
                ....*....|....*....|....*....|.
gi 8568081  114 EYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd14209  81 EYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 111

protein kinase A catalytic subunit; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8568081    33 LDQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMV 112
Cdd:PTZ00263  17 LSDFEMGETLGTGSFGRVRIAKHKGTGEYYAIKCLKKREILKMKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVYFL 96

                         90       100       110
                 ....*....|....*....|....*....|..
gi 8568081   113 MEYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:PTZ00263  97 LEFVVGGELFTHLRKAGRFPNDVAKFYHAELV 128

Serine/threonine protein kinase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8568081   29 NTAHLDQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSN 108
Cdd:COG0515   2 SALLLGRYRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAADPEARERFRREARALARLNHPNIVRVYDVGEEDGR 81

                        90       100       110
                ....*....|....*....|....*....|....*
gi 8568081  109 LYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQI 143
Cdd:COG0515  82 PYLVMEYVEGESLADLLRRRGPLPPAEALRILAQL 116

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 8568081   34 DQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVM 113
Cdd:cd14209   1 DDFDRIKTLGTGSFGRVMLVRHKETGNYYAMKILDKQKVVKLKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVM 80

                        90       100       110
                ....*....|....*....|....*....|.
gi 8568081  114 EYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd14209  81 EYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 111

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 8568081   42 LGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPGGEM 121
Cdd:cd05123   1 LGKGSFGKVLLVRKKDTGKLYAMKVLRKKEIIKRKEVEHTLNERNILERVNHPFIVKLHYAFQTEEKLYLVLDYVPGGEL 80

                        90       100
                ....*....|....*....|...
gi 8568081  122 FSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05123  81 FSHLSKEGRFPEERARFYAAEIV 103

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 8568081   34 DQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVM 113
Cdd:cd05573   1 DDFEVIKVIGRGAFGEVWLVRDKDTGQVYAMKILRKSDMLKREQIAHVRAERDILADADSPWIVRLHYAFQDEDHLYLVM 80

                        90       100       110
                ....*....|....*....|....*....|.
gi 8568081  114 EYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05573  81 EYMPGGDLMNLLIKYDVFPEETARFYIAELV 111

protein kinase A catalytic subunit; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8568081    33 LDQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMV 112
Cdd:PTZ00263  17 LSDFEMGETLGTGSFGRVRIAKHKGTGEYYAIKCLKKREILKMKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVYFL 96

                         90       100       110
                 ....*....|....*....|....*....|..
gi 8568081   113 MEYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:PTZ00263  97 LEFVVGGELFTHLRKAGRFPNDVAKFYHAELV 128

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 8568081   40 KTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPGG 119
Cdd:cd05571   1 KVLGKGTFGKVILCREKATGELYAIKILKKEVIIAKDEVAHTLTENRVLQNTRHPFLTSLKYSFQTNDRLCFVMEYVNGG 80

                        90       100
                ....*....|....*....|....*
gi 8568081  120 EMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05571  81 ELFFHLSRERVFSEDRTRFYGAEIV 105

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK 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 8568081   42 LGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPGGEM 121
Cdd:cd05572   1 LGVGGFGRVELVQLKSKGRTFALKCVKKRHIVQTRQQEHIFSEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLGGEL 80

                        90       100
                ....*....|....*....|...
gi 8568081  122 FSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05572  81 WTILRDRGLFDEYTARFYTACVV 103

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 8568081   34 DQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVM 113
Cdd:cd05598   1 SMFEKIKTIGVGAFGEVSLVRKKDTNALYAMKTLRKKDVLKRNQVAHVKAERDILAEADNEWVVKLYYSFQDKENLYFVM 80

                        90       100       110
                ....*....|....*....|....*....|.
gi 8568081  114 EYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05598  81 DYIPGGDLMSLLIKKGIFEEDLARFYIAELV 111

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC 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 8568081   40 KTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRIL-QAVNFPFLVKLEFSFKDNSNLYMVMEYVPG 118
Cdd:cd05570   1 KVLGKGSFGKVMLAERKKTDELYAIKVLKKEVIIEDDDVECTMTEKRVLaLANRHPFLTGLHACFQTEDRLYFVMEYVNG 80

                        90       100
                ....*....|....*....|....*.
gi 8568081  119 GEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05570  81 GDLMFHIQRARRFTEERARFYAAEIC 106

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 8568081   45 GSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPGGEMFSH 124
Cdd:cd05579   4 GAYGRVYLAKKKSTGDLYAIKVIKKRDMIRKNQVDSVLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDLYSL 83

                        90       100
                ....*....|....*....|
gi 8568081  125 LRRIGRFSEPHARFYAAQIV 144
Cdd:cd05579  84 LENVGALDEDVARIYIAEIV 103

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 8568081   40 KTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPGG 119
Cdd:cd05595   1 KLLGKGTFGKVILVREKATGRYYAMKILRKEVIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGG 80

                        90       100
                ....*....|....*....|....*
gi 8568081  120 EMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05595  81 ELFFHLSRERVFTEDRARFYGAEIV 105

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 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 8568081   35 QFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVME 114
Cdd:cd05578   1 HFQILRVIGKGSFGKVCIVQKKDTKKMFAMKYMNKQKCIEKDSVRNVLNELEILQELEHPFLVNLWYSFQDEEDMYMVVD 80

                        90       100       110
                ....*....|....*....|....*....|
gi 8568081  115 YVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05578  81 LLLGGDLRYHLQQKVKFSEETVKFYICEIV 110

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 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 8568081   40 KTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRIL-QAVNFPFLVKLEFSFKDNSNLYMVMEYVPG 118
Cdd:cd05603   1 KVIGKGSFGKVLLAKRKCDGKFYAVKVLQKKTILKKKEQNHIMAERNVLlKNLKHPFLVGLHYSFQTSEKLYFVLDYVNG 80

                        90       100
                ....*....|....*....|....*
gi 8568081  119 GEMFSHLRRIGRFSEPHARFYAAQI 143
Cdd:cd05603  81 GELFFHLQRERCFLEPRARFYAAEV 105

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 8568081   24 ESPAQNTAH----LDQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKL 99
Cdd:cd05593   1 EMDASTTHHkrktMNDFDYLKLLGKGTFGKVILVREKASGKYYAMKILKKEVIIAKDEVAHTLTESRVLKNTRHPFLTSL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 8568081  100 EFSFKDNSNLYMVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05593  81 KYSFQTKDRLCFVMEYVNGGELFFHLSRERVFSEDRTRFYGAEIV 125

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 8568081   39 IKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKlKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEYVPG 118
Cdd:cd14003   5 GKTLGEGSFGKVKLARHKLTGEKVAIKIIDKSKLKE-EIEEKIKREIEIMKLLNHPNIIKLYEVIETENKIYLVMEYASG 83

                        90       100
                ....*....|....*....|....*.
gi 8568081  119 GEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd14003  84 GELFDYIVNNGRLSEDEARRFFQQLI 109

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 8568081   40 KTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQ-AVNFPFLVKLEFSFKDNSNLYMVMEYVPG 118
Cdd:cd05592   1 KVLGKGSFGKVMLAELKGTNQYFAIKALKKDVVLEDDDVECTMIERRVLAlASQHPFLTHLFCTFQTESHLFFVMEYLNG 80

                        90       100
                ....*....|....*....|....*.
gi 8568081  119 GEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05592  81 GDLMFHIQQSGRFDEDRARFYGAEII 106

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. 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. The nPKC-eta 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 8568081   40 KTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQ-AVNFPFLVKLEFSFKDNSNLYMVMEYVPG 118
Cdd:cd05590   1 RVLGKGSFGKVMLARLKESGRLYAVKVLKKDVILQDDDVECTMTEKRILSlARNHPFLTQLYCCFQTPDRLFFVMEFVNG 80

                        90       100
                ....*....|....*....|....*.
gi 8568081  119 GEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05590  81 GDLMFHIQKSRRFDEARARFYAAEIT 106

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 8568081   39 IKTLGTGSFGRVMLVKhKETGNH----YAMKILDKQKVVK-LKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVM 113
Cdd:cd05584   1 LKVLGKGGYGKVFQVR-KTTGSDkgkiFAMKVLKKASIVRnQKDTAHTKAERNILEAVKHPFIVDLHYAFQTGGKLYLIL 79

                        90       100       110
                ....*....|....*....|....*....|.
gi 8568081  114 EYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05584  80 EYLSGGELFMHLEREGIFMEDTACFYLAEIT 110

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 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 8568081   39 IKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRIL-QAVNFPFLVKLEFSFKDNSNLYMVMEYVP 117
Cdd:cd05604   1 LKVIGKGSFGKVLLAKRKRDGKYYAVKVLQKKVILNRKEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTDKLYFVLDFVN 80

                        90       100
                ....*....|....*....|....*.
gi 8568081  118 GGEMFSHLRRIGRFSEPHARFYAAQI 143
Cdd:cd05604  81 GGELFFHLQRERSFPEPRARFYAAEI 106

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 8568081   36 FERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVMEY 115
Cdd:cd05601   3 FEVKNVIGRGHFGEVQVVKEKATGDIYAMKVLKKSETLAQEEVSFFEEERDIMAKANSPWITKLQYAFQDSENLYLVMEY 82

                        90       100       110
                ....*....|....*....|....*....|
gi 8568081  116 VPGGEMFSHL-RRIGRFSEPHARFYAAQIV 144
Cdd:cd05601  83 HPGGDLLSLLsRYDDIFEESMARFYLAELV 112

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 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 8568081   36 FERIKTLGTGSFGRVMLVKH---KETGNHYAMKILDKQKVV-KLKQIEHTLNEKRILQAV-NFPFLVKLEFSFKDNSNLY 110
Cdd:cd05614   2 FELLKVLGTGAYGKVFLVRKvsgHDANKLYAMKVLRKAALVqKAKTVEHTRTERNVLEHVrQSPFLVTLHYAFQTDAKLH 81

                        90       100       110
                ....*....|....*....|....*....|....
gi 8568081  111 MVMEYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05614  82 LILDYVSGGELFTHLYQRDHFSEDEVRFYSGEII 115

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 8568081   36 FERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVN---FPFLVKLEFSFKDNSNLYMV 112
Cdd:cd05589   1 FRCIAVLGRGHFGKVLLAEYKPTGELFAIKALKKGDIIARDEVESLMCEKRIFETVNsarHPFLVNLFACFQTPEHVCFV 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 8568081  113 MEYVPGGEMFSHLRRiGRFSEPHARFYAAQIV 144
Cdd:cd05589  81 MEYAAGGDLMMHIHE-DVFSEPRAVFYAACVV 111

Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group is composed of fungal NDR-like proteins including Saccharomyces cerevisiae CBK1 (or CBK1p), Schizosaccharomyces pombe Orb6 (or Orb6p), Ustilago maydis Ukc1 (or Ukc1p), and Neurospora crassa Cot1. Like NDR kinase, group members contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. CBK1 is an essential component in the RAM (regulation of Ace2p activity and cellular morphogenesis) network. CBK1 and Orb6 play similar roles in coordinating cell morphology with cell cycle progression. Ukc1 is involved in morphogenesis, pathogenicity, and pigment formation. Cot1 plays a role in polar tip extension.The fungal NDR 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 8568081   34 DQFERIKTLGTGSFGRVMLVKHKETGNHYAMKILDKQKVVKLKQIEHTLNEKRILQAVNFPFLVKLEFSFKDNSNLYMVM 113
Cdd:cd05629   1 EDFHTVKVIGKGAFGEVRLVQKKDTGKIYAMKTLLKSEMFKKDQLAHVKAERDVLAESDSPWVVSLYYSFQDAQYLYLIM 80

                        90       100       110
                ....*....|....*....|....*....|.
gi 8568081  114 EYVPGGEMFSHLRRIGRFSEPHARFYAAQIV 144
Cdd:cd05629  81 EFLPGGDLMTMLIKYDTFSEDVTRFYMAECV 111