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 1616024943  41 LRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILE 120
Cdd:cd05584     1 LKVLGKGGYGKVFQVRKTTGSDKGKIFAMKVLKKASIVRNQKDTAHTKAERNILEAVKHPFIVDLHYAFQTGGKLYLILE 80

                          90       100
                  ....*....|....*....|..
gi 1616024943 121 YLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05584    81 YLSGGELFMHLEREGIFMEDTA 102

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 1616024943  41 LRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILE 120
Cdd:cd05584     1 LKVLGKGGYGKVFQVRKTTGSDKGKIFAMKVLKKASIVRNQKDTAHTKAERNILEAVKHPFIVDLHYAFQTGGKLYLILE 80

                          90       100
                  ....*....|....*....|..
gi 1616024943 121 YLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05584    81 YLSGGELFMHLEREGIFMEDTA 102

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1616024943  38 FELLRVLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKamivRNAKDTAHTKA--ERNILEEVKHPFIVDLIYAFQTGGKL 115
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKH---RDTGKIVAIKKIKK----EKIKKKKDKNIlrEIKILKKLNHPNIVRLYDAFEDKDNL 73

                          90       100
                  ....*....|....*....|....*..
gi 1616024943 116 YLILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:pfam00069  74 YLVLEYVEGGSLFDLLSEKGAFSEREA 100

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1616024943  38 FELLRVLGKGGYGKVFQVRKVtgaNTGKIFAMKVLKKAMiVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 117
Cdd:COG0515     9 YRILRLLGRGGMGVVYLARDL---RLGRPVALKVLRPEL-AADPEARERFRREARALARLNHPNIVRVYDVGEEDGRPYL 84

                          90       100
                  ....*....|....*....|....*
gi 1616024943 118 ILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:COG0515    85 VMEYVEGESLADLLRRRGPLPPAEA 109

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 1616024943  41 LRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILE 120
Cdd:cd05584     1 LKVLGKGGYGKVFQVRKTTGSDKGKIFAMKVLKKASIVRNQKDTAHTKAERNILEAVKHPFIVDLHYAFQTGGKLYLILE 80

                          90       100
                  ....*....|....*....|..
gi 1616024943 121 YLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05584    81 YLSGGELFMHLEREGIFMEDTA 102

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK 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 1616024943  43 VLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKH-PFIVDLIYAFQTGGKLYLILEY 121
Cdd:cd05583     1 VLGTGAYGKVFLVRKVGGHDAGKLYAMKVLKKATIVQKAKTAEHTMTERQVLEAVRQsPFLVTLHYAFQTDAKLHLILDY 80

                          90
                  ....*....|....*....
gi 1616024943 122 LSGGELFMQLEREGIFMED 140
Cdd:cd05583    81 VNGGELFTHLYQREHFTES 99

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK 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 1616024943  42 RVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIvrNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEY 121
Cdd:cd05582     1 KVLGQGSFGKVFLVRKITGPDAGTLYAMKVLKKATL--KVRDRVRTKMERDILADVNHPFIVKLHYAFQTEGKLYLILDF 78

                          90
                  ....*....|....*....
gi 1616024943 122 LSGGELFMQLEREGIFMED 140
Cdd:cd05582    79 LRGGDLFTRLSKEVMFTEE 97

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK 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 1616024943  42 RVLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMIVRNaKDTAHTKAERNIL-EEVKHPFIVDLIYAFQTGGKLYLILE 120
Cdd:cd05575     1 KVIGKGSFGKVLLARH---KAEGKLYAVKVLQKKAILKR-NEVKHIMAERNVLlKNVKHPFLVGLHYSFQTKDKLYFVLD 76

                          90       100
                  ....*....|....*....|..
gi 1616024943 121 YLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05575    77 YVNGGELFFHLQRERHFPEPRA 98

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. 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. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-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 1616024943  38 FELLRVLGKGGYGKVFQVRKVtgaNTGKIFAMKVLKKAMIVRNaKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 117
Cdd:cd05580     3 FEFLKTLGTGSFGRVRLVKHK---DSGKYYALKILKKAKIIKL-KQVEHVLNEKRILSEVRHPFIVNLLGSFQDDRNLYM 78

                          90       100
                  ....*....|....*....|....*
gi 1616024943 118 ILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05580    79 VMEYVPGGELFSLLRRSGRFPNDVA 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 1616024943  38 FELLRVLGKGGYGKVFQVRKVTganTGKIFAMKVLKKA-MIVRNakDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLY 116
Cdd:cd05573     3 FEVIKVIGRGAFGEVWLVRDKD---TGQVYAMKILRKSdMLKRE--QIAHVRAERDILADADSPWIVRLHYAFQDEDHLY 77

                          90       100
                  ....*....|....*....|....*.
gi 1616024943 117 LILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05573    78 LVMEYMPGGDLMNLLIKYDVFPEETA 103

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 1616024943  46 KGGYGKVFQVRKVTganTGKIFAMKVLKKA-MIVRNAKDTAhtKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLSG 124
Cdd:cd05579     3 RGAYGRVYLAKKKS---TGDLYAIKVIKKRdMIRKNQVDSV--LAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPG 77

                          90
                  ....*....|....*...
gi 1616024943 125 GELFMQLEREGIFMEDTA 142
Cdd:cd05579    78 GDLYSLLENVGALDEDVA 95

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 1616024943  43 VLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMIVRNAKDTaHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYL 122
Cdd:cd05585     1 VIGKGSFGKVMQVRK---KDTSRIYALKTIRKAHIVSRSEVT-HTLAERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFI 76

                          90
                  ....*....|....*
gi 1616024943 123 SGGELFMQLEREGIF 137
Cdd:cd05585    77 NGGELFHHLQREGRF 91

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 1616024943  41 LRVLGKGGYGKVFQVRkvtGANTGKIFAMKVLKKAMIVrNAKDTAHTKAERNIL-EEVKHPFIVDLIYAFQTGGKLYLIL 119
Cdd:cd05604     1 LKVIGKGSFGKVLLAK---RKRDGKYYAVKVLQKKVIL-NRKEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTDKLYFVL 76

                          90       100
                  ....*....|....*....|...
gi 1616024943 120 EYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05604    77 DFVNGGELFFHLQRERSFPEPRA 99

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 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 1616024943  34 RPECFELLRVLGKGGYGKVFQVRKVTGAntgKIFAMKVLKKAMIVRNaKDTAHTKAERNIL-EEVKHPFIVDLIYAFQTG 112
Cdd:cd05602     5 KPSDFHFLKVIGKGSFGKVLLARHKSDE---KFYAVKVLQKKAILKK-KEEKHIMSERNVLlKNVKHPFLVGLHFSFQTT 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1616024943 113 GKLYLILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05602    81 DKLYFVLDYINGGELFYHLQRERCFLEPRA 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 1616024943  42 RVLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMIVRNaKDTAHTKAERNIL-EEVKHPFIVDLIYAFQTGGKLYLILE 120
Cdd:cd05603     1 KVIGKGSFGKVLLAKR---KCDGKFYAVKVLQKKTILKK-KEQNHIMAERNVLlKNLKHPFLVGLHYSFQTSEKLYFVLD 76

                          90       100
                  ....*....|....*....|..
gi 1616024943 121 YLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05603    77 YVNGGELFFHLQRERCFLEPRA 98

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 1616024943  38 FELLRVLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMIVrnAKD-TAHTKAERNILEEVKHPFIVDLIYAFQTGGKLY 116
Cdd:cd05593    17 FDYLKLLGKGTFGKVILVRE---KASGKYYAMKILKKEVII--AKDeVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLC 91

                          90       100
                  ....*....|....*....|....
gi 1616024943 117 LILEYLSGGELFMQLEREGIFMED 140
Cdd:cd05593    92 FVMEYVNGGELFFHLSRERVFSED 115

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 1616024943  38 FELLRVLGKGGYGKVFQVRKVTganTGKIFAMKVLKKAMIVRNaKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 117
Cdd:cd05578     2 FQILRVIGKGSFGKVCIVQKKD---TKKMFAMKYMNKQKCIEK-DSVRNVLNELEILQELEHPFLVNLWYSFQDEEDMYM 77

                          90       100
                  ....*....|....*....|....*
gi 1616024943 118 ILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05578    78 VVDLLLGGDLRYHLQQKVKFSEETV 102

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 1616024943  38 FELLRVLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMIVRnAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 117
Cdd:cd14209     3 FDRIKTLGTGSFGRVMLVRH---KETGNYYAMKILDKQKVVK-LKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYM 78

                          90       100
                  ....*....|....*....|..
gi 1616024943 118 ILEYLSGGELFMQLEREGIFME 139
Cdd:cd14209    79 VMEYVPGGEMFSHLRRIGRFSE 100

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 1616024943  42 RVLGKGGYGKVFQVRkvtGANTGKIFAMKVLKKAMIVRNaKDTAHTKAERNILE-EVKHPFIVDLIYAFQTGGKLYLILE 120
Cdd:cd05570     1 KVLGKGSFGKVMLAE---RKKTDELYAIKVLKKEVIIED-DDVECTMTEKRVLAlANRHPFLTGLHACFQTEDRLYFVME 76

                          90       100
                  ....*....|....*....|..
gi 1616024943 121 YLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05570    77 YVNGGDLMFHIQRARRFTEERA 98

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family 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 1616024943  38 FELLRVLGKGGYGKVfqvRKVTGANTGKIFAMKVLKKAMIVRnaKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 117
Cdd:cd05117     2 YELGKVLGRGSFGVV---RLAVHKKTGEEYAVKIIDKKKLKS--EDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYL 76

                          90       100
                  ....*....|....*....|....*
gi 1616024943 118 ILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05117    77 VMELCTGGELFDRIVKKGSFSEREA 101

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 1616024943  38 FELLRVLGKGGYGKVfqvRKVTGANTGKIFAMKVLKKAMIVrnAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 117
Cdd:cd14003     2 YELGKTLGEGSFGKV---KLARHKLTGEKVAIKIIDKSKLK--EEIEEKIKREIEIMKLLNHPNIIKLYEVIETENKIYL 76

                          90       100
                  ....*....|....*....|....*
gi 1616024943 118 ILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd14003    77 VMEYASGGELFDYIVNNGRLSEDEA 101

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group 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 1616024943  32 KIRPECFELLRVLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMIVRnAKDTAHTKAERNILEEVKHPFIVDLIYAFQT 111
Cdd:cd05600     7 RLKLSDFQILTQVGQGGYGSVFLARK---KDTGEICALKIMKKKVLFK-LNEVNHVLTERDILTTTNSPWLVKLLYAFQD 82

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1616024943 112 GGKLYLILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05600    83 PENVYLAMEYVPGGDFRTLLNNSGILSEEHA 113

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-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 1616024943  38 FELLRVLGKGGYGKVFQVRKVTGantGKIFAMKVLKKAMIVRnAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 117
Cdd:cd05612     3 FERIKTIGTGTFGRVHLVRDRIS---EHYYALKVMAIPEVIR-LKQEQHVHNEKRVLKEVSHPFIIRLFWTEHDQRFLYM 78

                          90       100
                  ....*....|....*....|....*
gi 1616024943 118 ILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05612    79 LMEYVPGGELFSYLRNSGRFSNSTG 103

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR2 (also called STK38-like) plays a role in proper centrosome duplication. In addition, it is involved in regulating neuronal growth and differentiation, as well as in facilitating neurite outgrowth. NDR2 is also implicated in fear conditioning as it contributes to the coupling of neuronal morphological changes with fear-memory consolidation. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR2 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 1616024943  38 FELLRVLGKGGYGkvfQVRKVTGANTGKIFAMKVLKKAMIVRNaKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 117
Cdd:cd05627     4 FESLKVIGRGAFG---EVRLVQKKDTGHIYAMKILRKADMLEK-EQVAHIRAERDILVEADGAWVVKMFYSFQDKRNLYL 79

                          90       100
                  ....*....|....*....|...
gi 1616024943 118 ILEYLSGGELFMQLEREGIFMED 140
Cdd:cd05627    80 IMEFLPGGDMMTLLMKKDTLSEE 102

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC 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 1616024943  17 EKFEISETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMiVRNAKDTAHTKAERNILEE 96
Cdd:cd05618     1 EKEAMNSRESGKASSSLGLQDFDLLRVIGRGSYAKVLLVRL---KKTERIYAMKVVKKEL-VNDDEDIDWVQTEKHVFEQ 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1616024943  97 VK-HPFIVDLIYAFQTGGKLYLILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05618    77 ASnHPFLVGLHSCFQTESRLFFVIEYVNGGDLMFHMQRQRKLPEEHA 123

Catalytic domain of the Protein Serine/Threonine Kinase, Large Tumor Suppressor 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS2 is an essential mitotic regulator responsible for coordinating accurate cytokinesis completion and governing the stabilization of other mitotic regulators. It is also critical in the maintenance of proper chromosome number, genomic stability, mitotic fidelity, and the integrity of centrosome duplication. Downregulation of LATS2 is associated with poor prognosis in acute lymphoblastic leukemia and breast cancer. The LATS2 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 1616024943  38 FELLRVLGKGGYGKVFQVRKVtgaNTGKIFAMKVLKKAMIVrNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 117
Cdd:cd05626     3 FVKIKTLGIGAFGEVCLACKV---DTHALYAMKTLRKKDVL-NRNQVAHVKAERDILAEADNEWVVKLYYSFQDKDNLYF 78

                          90       100
                  ....*....|....*....|....*
gi 1616024943 118 ILEYLSGGELFMQLEREGIFMEDTA 142
Cdd:cd05626    79 VMDYIPGGDMMSLLIRMEVFPEVLA 103

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 1616024943  38 FELLRVLGKGGYGKVF--QVRkvtgaNTGKIFAMKVLKKAMIVrnAKDTAHT-KAERNILE---EVKHPFIVDLIYAFQT 111
Cdd:cd05589     1 FRCIAVLGRGHFGKVLlaEYK-----PTGELFAIKALKKGDII--ARDEVESlMCEKRIFEtvnSARHPFLVNLFACFQT 73

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1616024943 112 GGKLYLILEYLSGGELFMQLEREgIFMEDTA 142
Cdd:cd05589    74 PEHVCFVMEYAAGGDLMMHIHED-VFSEPRA 103

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR1 (also called STK38) plays a role in proper centrosome duplication. It is highly expressed in thymus, muscle, lung and spleen. It is not an essential protein because mice deficient of NDR1 remain viable and fertile. However, these mice develop T-cell lymphomas and appear to be hypersenstive to carcinogenic treatment. NDR1 appears to also act as a tumor suppressor. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR1 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 1616024943  36 ECFELLRVLGKGGYGkvfQVRKVTGANTGKIFAMKVLKKAMIVRNaKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKL 115
Cdd:cd05628     1 EDFESLKVIGRGAFG---EVRLVQKKDTGHVYAMKILRKADMLEK-EQVGHIRAERDILVEADSLWVVKMFYSFQDKLNL 76