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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1616025245   91 FELLRVLGKGGYGKVFQVRKVtgaNTGKIFAMKVLKKamiVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 170
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDK---KTGKLVAIKVIKK---KKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYL 74

                           90       100
                   ....*....|....*....|....*....
gi 1616025245  171 ILEYLSGGELFMQLEREGIFMEDTAWPFL 199
Cdd:smart00220  75 VMEYCEGGDLFDLLKKRGRLSEDEARFYL 103

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1616025245  91 FELLRVLGKGGYGKVfqvRKVTGANTGKIFAMKVLKKAMIVRnAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 170
Cdd:PTZ00263   20 FEMGETLGTGSFGRV---RIAKHKGTGEYYAIKCLKKREILK-MKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVYF 95

                          90       100
                  ....*....|....*....|....*
gi 1616025245 171 ILEYLSGGELFMQLEREGIFMEDTA 195
Cdd:PTZ00263   96 LLEFVVGGELFTHLRKAGRFPNDVA 120

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 1616025245  97 LGKGGYGKVFQVRKVtgaNTGKIFAMKVLKKAMIVRNaKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYLS 176
Cdd:cd05123     1 LGKGSFGKVLLVRKK---DTGKLYAMKVLRKKEIIKR-KEVEHTLNERNILERVNHPFIVKLHYAFQTEEKLYLVLDYVP 76

                          90
                  ....*....|....*....
gi 1616025245 177 GGELFMQLEREGIFMEDTA 195
Cdd:cd05123    77 GGELFSHLSKEGRFPEERA 95

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 1616025245  91 FELLRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKH-PFIVDLIYAFQTGGKLY 169
Cdd:cd05614     2 FELLKVLGTGAYGKVFLVRKVSGHDANKLYAMKVLRKAALVQKAKTVEHTRTERNVLEHVRQsPFLVTLHYAFQTDAKLH 81

                          90       100
                  ....*....|....*....|....
gi 1616025245 170 LILEYLSGGELFMQLEREGIFMED 193
Cdd:cd05614    82 LILDYVSGGELFTHLYQRDHFSED 105

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. 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, 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 MSK1 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 1616025245  91 FELLRVLGKGGYGKVFQVRKVTGANTGKIFAMKVLKKAMIVRNAKDTAHTKAERNILEEVKH-PFIVDLIYAFQTGGKLY 169
Cdd:cd05613     2 FELLKVLGTGAYGKVFLVRKVSGHDAGKLYAMKVLKKATIVQKAKTAEHTRTERQVLEHIRQsPFLVTLHYAFQTDTKLH 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1616025245 170 LILEYLSGGELFMQLEREGIFMEDTAWPFLTKKL----HLRALGM 210
Cdd:cd05613    82 LILDYINGGELFTHLSQRERFTENEVQIYIGEIVlaleHLHKLGI 126

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 1616025245  95 RVLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMIVRNaKDTAHTKAERNIL-EEVKHPFIVDLIYAFQTGGKLYLILE 173
Cdd:cd05575     1 KVIGKGSFGKVLLARH---KAEGKLYAVKVLQKKAILKR-NEVKHIMAERNVLlKNVKHPFLVGLHYSFQTKDKLYFVLD 76

                          90       100
                  ....*....|....*....|..
gi 1616025245 174 YLSGGELFMQLEREGIFMEDTA 195
Cdd:cd05575    77 YVNGGELFFHLQRERHFPEPRA 98

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. 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 NDR 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 1616025245  91 FELLRVLGKGGYGKVFQVRKVTganTGKIFAMKVLKKA-MIVRNakDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLY 169
Cdd:cd05599     3 FEPLKVIGRGAFGEVRLVRKKD---TGHVYAMKKLRKSeMLEKE--QVAHVRAERDILAEADNPWVVKLYYSFQDEENLY 77

                          90       100
                  ....*....|....*....|....*.
gi 1616025245 170 LILEYLSGGELFMQLEREGIFMEDTA 195
Cdd:cd05599    78 LIMEFLPGGDMMTLLMKKDTLTEEET 103

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 1616025245  95 RVLGKGGYGKVFQVRKVTganTGKIFAMKVLKKAMIVrnAKD-TAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILE 173
Cdd:cd05571     1 KVLGKGTFGKVILCREKA---TGELYAIKILKKEVII--AKDeVAHTLTENRVLQNTRHPFLTSLKYSFQTNDRLCFVME 75

                          90       100
                  ....*....|....*....|..
gi 1616025245 174 YLSGGELFMQLEREGIFMEDTA 195
Cdd:cd05571    76 YVNGGELFFHLSRERVFSEDRT 97

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 1616025245  97 LGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMIVRNaKDTAHTKAERNILEEV---KHPFIVDLIYAFQTGGKLYLILE 173
Cdd:cd05586     1 IGKGTFGQVYQVRK---KDTRRIYAMKVLSKKVIVAK-KEVAHTIGERNILVRTaldESPFIVGLKFSFQTPTDLYLVTD 76

                          90       100
                  ....*....|....*....|..
gi 1616025245 174 YLSGGELFMQLEREGIFMEDTA 195
Cdd:cd05586    77 YMSGGELFWHLQKEGRFSEDRA 98

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 1616025245  96 VLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMIVRNAKDTaHTKAERNILEEVKHPFIVDLIYAFQTGGKLYLILEYL 175
Cdd:cd05585     1 VIGKGSFGKVMQVRK---KDTSRIYALKTIRKAHIVSRSEVT-HTLAERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFI 76

                          90
                  ....*....|....*
gi 1616025245 176 SGGELFMQLEREGIF 190
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 1616025245  94 LRVLGKGGYGKVFQVRkvtGANTGKIFAMKVLKKAMIVrNAKDTAHTKAERNIL-EEVKHPFIVDLIYAFQTGGKLYLIL 172
Cdd:cd05604     1 LKVIGKGSFGKVLLAK---RKRDGKYYAVKVLQKKVIL-NRKEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTDKLYFVL 76

                          90       100
                  ....*....|....*....|...
gi 1616025245 173 EYLSGGELFMQLEREGIFMEDTA 195
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 1616025245  87 RPECFELLRVLGKGGYGKVFQVRKVTGAntgKIFAMKVLKKAMIVRNaKDTAHTKAERNIL-EEVKHPFIVDLIYAFQTG 165
Cdd:cd05602     5 KPSDFHFLKVIGKGSFGKVLLARHKSDE---KFYAVKVLQKKAILKK-KEEKHIMSERNVLlKNVKHPFLVGLHFSFQTT 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1616025245 166 GKLYLILEYLSGGELFMQLEREGIFMEDTA 195
Cdd:cd05602    81 DKLYFVLDYINGGELFYHLQRERCFLEPRA 110

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 1616025245  91 FELLRVLGKGGYGKVFQVRKVTganTGKIFAMKVLKKAMIVRNaKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 170
Cdd:cd05598     3 FEKIKTIGVGAFGEVSLVRKKD---TNALYAMKTLRKKDVLKR-NQVAHVKAERDILAEADNEWVVKLYYSFQDKENLYF 78

                          90       100
                  ....*....|....*....|....*
gi 1616025245 171 ILEYLSGGELFMQLEREGIFMEDTA 195
Cdd:cd05598    79 VMDYIPGGDLMSLLIKKGIFEEDLA 103

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 1616025245  76 ETSVNRGPEKIRPECFELLRVLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKAMIVrnAKD-TAHTKAERNILEEVKHPF 154
Cdd:cd05594    12 EVSLTKPKHKVTMNDFEYLKLLGKGTFGKVILVKE---KATGRYYAMKILKKEVIV--AKDeVAHTLTENRVLQNSRHPF 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1616025245 155 IVDLIYAFQTGGKLYLILEYLSGGELFMQLEREGIFMEDTA 195
Cdd:cd05594    87 LTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRA 127

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 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 1616025245  91 FELLRVLGKGGYGKVFQVRKVTganTGKIFAMKVLKKAMIVRNAKdTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 170
Cdd:cd05581     3 FKFGKPLGEGSYSTVVLAKEKE---TGKEYAIKVLDKRHIIKEKK-VKYVTIEKEVLSRLAHPGIVKLYYTFQDESKLYF 78

                          90       100
                  ....*....|....*....|....*
gi 1616025245 171 ILEYLSGGELFMQLEREGIFMEDTA 195
Cdd:cd05581    79 VLEYAPNGDLLEYIRKYGSLDEKCT 103

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 1616025245  91 FELLRVLGKGGYGKVFQVR-KvtgaNTGKIFAMKVLKKAMIVRNakdtahtKAERNILEEVK------HPFIVDLIYAFQ 163
Cdd:cd14007     2 FEIGKPLGKGKFGNVYLAReK----KSGFIVALKVISKSQLQKS-------GLEHQLRREIEiqshlrHPNILRLYGYFE 70

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1616025245 164 TGGKLYLILEYLSGGELFMQLEREGIFMEDTA 195
Cdd:cd14007    71 DKKRIYLILEYAPNGELYKELKKQKRFDEKEA 102

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 1616025245  89 ECFELLRVLGKGGYGKVFQVRKVtgaNTGKIFAMKVLKKAMIVRnaKDT-AHTKAERNILEEVKHPFIVDLIYAFQTGGK 167
Cdd:cd05629     1 EDFHTVKVIGKGAFGEVRLVQKK---DTGKIYAMKTLLKSEMFK--KDQlAHVKAERDVLAESDSPWVVSLYYSFQDAQY 75

                          90       100
                  ....*....|....*....|....*.
gi 1616025245 168 LYLILEYLSGGELFMQLEREGIFMED 193
Cdd:cd05629    76 LYLIMEFLPGGDLMTMLIKYDTFSED 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 1616025245  91 FELLRVLGKGGYGKVfqvRKVTGANTGKIFAMKVLKKAMIVrnAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 170
Cdd:cd14003     2 YELGKTLGEGSFGKV---KLARHKLTGEKVAIKIIDKSKLK--EEIEEKIKREIEIMKLLNHPNIIKLYEVIETENKIYL 76

                          90       100
                  ....*....|....*....|....*
gi 1616025245 171 ILEYLSGGELFMQLEREGIFMEDTA 195
Cdd:cd14003    77 VMEYASGGELFDYIVNNGRLSEDEA 101

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1616025245  89 ECFELLRVLGKGGYGKVFQVRKvtgANTGKIFAMKVLKKA-MIVRNAkdTAHTKAERNILEEVKHPFIVDLIYAFQTGGK 167
Cdd:cd05610     4 EEFVIVKPISRGAFGKVYLGRK---KNNSKLYAVKVVKKAdMINKNM--VHQVQAERDALALSKSPFIVHLYYSLQSANN 78

                          90       100
                  ....*....|....*....|....*...
gi 1616025245 168 LYLILEYLSGGELFMQLEREGIFMEDTA 195
Cdd:cd05610    79 VYLVMEYLIGGDVKSLLHIYGYFDEEMA 106

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to 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 1616025245  91 FELLRVLGKGGYGKVFQVRKVTganTGKIFAMKVLKKAMIVRNAKDTaHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 170
Cdd:cd14663     2 YELGRTLGEGTFAKVKFARNTK---TGESVAIKIIDKEQVAREGMVE-QIKREIAIMKLLRHPNIVELHEVMATKTKIFF 77

                          90       100
                  ....*....|....*....|....*
gi 1616025245 171 ILEYLSGGELFMQLEREGIFMEDTA 195
Cdd:cd14663    78 VMELVTGGELFSKIAKNGRLKEDKA 102

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 1616025245  91 FELLRVLGKGGYGKVfQVrkVTGANTGKIFAMKVLKKAMIVrnAKD-TAHTKAERNILEEVKHPFIVDLIYAFQTGGKLY 169
Cdd:cd05601     3 FEVKNVIGRGHFGEV-QV--VKEKATGDIYAMKVLKKSETL--AQEeVSFFEEERDIMAKANSPWITKLQYAFQDSENLY 77

                          90       100
                  ....*....|....*....|....*..
gi 1616025245 170 LILEYLSGGELFMQLER-EGIFMEDTA 195
Cdd:cd05601    78 LVMEYHPGGDLLSLLSRyDDIFEESMA 104

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 1616025245  91 FELLRVLGKGGYGkvfQVRKVTGANTGKIFAMKVLKKAMIVRNaKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLYL 170
Cdd:cd05627     4 FESLKVIGRGAFG---EVRLVQKKDTGHIYAMKILRKADMLEK-EQVAHIRAERDILVEADGAWVVKMFYSFQDKRNLYL 79

                          90       100
                  ....*....|....*....|...
gi 1616025245 171 ILEYLSGGELFMQLEREGIFMED 193
Cdd:cd05627    80 IMEFLPGGDMMTLLMKKDTLSEE 102

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1616025245  90 CFELLRVLGKGGYGKVFQVRKVtgaNTGKIFAMKVLKkamiVRNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLY 169
Cdd:cd05122     1 LFEILEKIGKGGFGVVYKARHK---KTGQIVAIKKIN----LESKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELW 73

                          90
                  ....*....|.
gi 1616025245 170 LILEYLSGGEL 180
Cdd:cd05122    74 IVMEFCSGGSL 84

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek 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 1616025245  91 FELLRVLGKGGYGKVFQVRKVtgaNTGKIFAMKVLK-KAMivrNAKDTAHTKAERNILEEVKHPFIVDLIYAFQTGGKLY 169
Cdd:cd08215     2 YEKIRVIGKGSFGSAYLVRRK---SDGKLYVLKEIDlSNM---SEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLC 75

                          90
                  ....*....|....*..
gi 1616025245 170 LILEYLSGGELFMQLER 186
Cdd:cd08215    76 IVMEYADGGDLAQKIKK 92

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 1616025245  95 RVLGKGGYGKVF--QVRKvtganTGKIFAMKVLKKAMIVRNaKDTAHTKAERNILE-EVKHPFIVDLIYAFQTGGKLYLI 171
Cdd:cd05592     1 KVLGKGSFGKVMlaELKG-----TNQYFAIKALKKDVVLED-DDVECTMIERRVLAlASQHPFLTHLFCTFQTESHLFFV 74

                          90       100
                  ....*....|....*....|....
gi 1616025245 172 LEYLSGGELFMQLEREGIFMEDTA 195
Cdd:cd05592    75 MEYLNGGDLMFHIQQSGRFDEDRA 98