MIT: domain contained within Microtubule Interacting and Trafficking molecules. This MIT domain sub-family is found in sorting nexin 15 and related proteins. The molecular function of the MIT domain is unclear.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462541747  48 DYLVDAATQIRLALERDVSEDYEAAFNHYQNGVDVLLRGIHVDPNKERREAVKLKITKYLRRAEEIFNCHLQRLL 122
Cdd:cd02677     1 DYLEQAAELIRLALEKEEEGDYEAAFEFYRAGVDLLLKGVQGDSSPERREAVKRKIAEYLKRAEEILRLHLSRSL 75

MIT: domain contained within Microtubule Interacting and Trafficking molecules. This MIT domain sub-family is found in sorting nexin 15 and related proteins. The molecular function of the MIT domain is unclear.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462541747  48 DYLVDAATQIRLALERDVSEDYEAAFNHYQNGVDVLLRGIHVDPNKERREAVKLKITKYLRRAEEIFNCHLQRLL 122
Cdd:cd02677     1 DYLEQAAELIRLALEKEEEGDYEAAFEFYRAGVDLLLKGVQGDSSPERREAVKRKIAEYLKRAEEILRLHLSRSL 75

MIT (microtubule interacting and transport) domain; The MIT domain forms an asymmetric three-helix bundle and binds ESCRT-III (endosomal sorting complexes required for transport) substrates.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462541747  50 LVDAATQIRLALERDVSEDYEAAFNHYQNGVDVLLRGIHVDPNKERREAVKLKITKYLRRAEEIFN 115
Cdd:pfam04212   1 LSKALELVKKAVEEDNAGNYEEALELYKEALDYLLLALKETKNEERRELLRAKIAEYLERAEELKE 66

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462541747 117 HLQRLLSSGASpSAVQLVQDPATGGTFVVKSLPRCHMVSRERLTIIP---------HgvPYMTKLLRYFVSEDSIFLHLE 187
Cdd:pfam00069   2 EVLRKLGSGSF-GTVYKAKHRDTGKIVAIKKIKKEKIKKKKDKNILReikilkklnH--PNIVRLYDAFEDKDNLYLVLE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462541747 188 ---------HVQEVGGISE---------------------------------------LTEACDWWSFGSLLYELLTG-M 218
Cdd:pfam00069  79 yveggslfdLLSEKGAFSEreakfimkqileglesgsslttfvgtpwymapevlggnpYGPKVDVWSLGCILYELLTGkP 158

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462541747 219 ALSQSHPSGIQAHTQLQ------LPEWLSRPAASLLTELLQFEPTRRLGMGEggvskLKSHPFF 276
Cdd:pfam00069 159 PFPGINGNEIYELIIDQpyafpeLPSNLSEEAKDLLKKLLKKDPSKRLTATQ-----ALQHPWF 217

MIT: domain contained within Microtubule Interacting and Trafficking molecules. This MIT domain sub-family is found in sorting nexin 15 and related proteins. The molecular function of the MIT domain is unclear.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462541747  48 DYLVDAATQIRLALERDVSEDYEAAFNHYQNGVDVLLRGIHVDPNKERREAVKLKITKYLRRAEEIFNCHLQRLL 122
Cdd:cd02677     1 DYLEQAAELIRLALEKEEEGDYEAAFEFYRAGVDLLLKGVQGDSSPERREAVKRKIAEYLKRAEEILRLHLSRSL 75

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 2462541747 199 TEACDWWSFGSLLYELLTGmalsQSHPSGIQA--------HTQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKL 270
Cdd:cd05592   174 NQSVDWWSFGVLLYEMLIG----QSPFHGEDEdelfwsicNDTPHYPRWLTKEAASCLSLLLERNPEKRLGVPECPAGDI 249

                          90
                  ....*....|....
gi 2462541747 271 KSHPFFSTIQWSKL 284
Cdd:cd05592   250 RDHPFFKTIDWDKL 263

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 2462541747 199 TEACDWWSFGSLLYELLTGMALSQSHpSGIQAHTQ-----LQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLKSH 273
Cdd:cd05582   175 TQSADWWSFGVLMFEMLTGSLPFQGK-DRKETMTMilkakLGMPQFLSPEAQSLLRALFKRNPANRLGAGPDGVEEIKRH 253

                          90
                  ....*....|.
gi 2462541747 274 PFFSTIQWSKL 284
Cdd:cd05582   254 PFFATIDWNKL 264

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 2462541747 201 ACDWWSFGSLLYELLTG---------MALSQSHPSGIqahtqLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLK 271
Cdd:cd05580   178 AVDWWALGILIYEMLAGyppffdenpMKIYEKILEGK-----IRFPSFFDPDAKDLIKRLLVVDLTKRLGNLKNGVEDIK 252

                          90
                  ....*....|...
gi 2462541747 272 SHPFFSTIQWSKL 284
Cdd:cd05580   253 NHPWFAGIDWDAL 265

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 2462541747 200 EACDWWSFGSLLYELLTGMA--------LSQSHPSGIQAHTQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLK 271
Cdd:cd05583   181 KAVDWWSLGVLTYELLTGASpftvdgerNSQSEISKRILKSHPPIPKTFSAEAKDFILKLLEKDPKKRLGAGPRGAHEIK 260

                  ....*...
gi 2462541747 272 SHPFFSTI 279
Cdd:cd05583   261 EHPFFKGL 268

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 2462541747 203 DWWSFGSLLYELLTGMA--LSQSHP---SGIqAHTQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGvSKLKSHPFFS 277
Cdd:cd05575   178 DWWCLGAVLYEMLYGLPpfYSRDTAemyDNI-LHKPLRLRTNVSPSARDLLEGLLQKDRTKRLGSGNDF-LEIKNHSFFR 255

                  ....*...
gi 2462541747 278 TIQWSKLV 285
Cdd:cd05575   256 PINWDDLE 263

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 2462541747 201 ACDWWSFGSLLYELLTG----MALSQSHPSGIQAHTQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLKSHPFF 276
Cdd:cd05584   180 AVDWWSLGALMYDMLTGappfTAENRKKTIDKILKGKLNLPPYLTNEARDLLKKLLKRNVSSRLGSGPGDAEEIKAHPFF 259

                  ....*...
gi 2462541747 277 STIQWSKL 284
Cdd:cd05584   260 RHINWDDL 267

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 2462541747 201 ACDWWSFGSLLYELLTGM---ALSQSHPSGI-----QAHTQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLKS 272
Cdd:cd05572   172 SVDYWSLGILLYELLTGRppfGGDDEDPMKIyniilKGIDKIEFPKYIDKNAKNLIKQLLRRNPEERLGYLKGGIRDIKK 251

                          90
                  ....*....|.
gi 2462541747 273 HPFFSTIQWSK 283
Cdd:cd05572   252 HKWFEGFDWEG 262

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 2462541747 193 GGISELTEACDWWSFGSLLYELLTGMAL--------SQSHPSGIQAHTQLQLPEWLSRPAASLLTELLQFEPTRRLGMGE 264
Cdd:cd05613   180 GGDSGHDKAVDWWSLGVLMYELLTGASPftvdgeknSQAEISRRILKSEPPYPQEMSALAKDIIQRLLMKDPKKRLGCGP 259

                          90       100
                  ....*....|....*....|
gi 2462541747 265 GGVSKLKSHPFFSTIQWSKL 284
Cdd:cd05613   260 NGADEIKKHPFFQKINWDDL 279

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 2462541747 199 TEACDWWSFGSLLYELLTGMA--LSQShpsgiQAHTQLQLPEW-----------LSRPAASLLTELLQFEPTRrlgMGEG 265
Cdd:cd05598   183 TQLCDWWSVGVILYEMLVGQPpfLAQT-----PAETQLKVINWrttlkipheanLSPEAKDLILRLCCDAEDR---LGRN 254

                          90       100
                  ....*....|....*....|
gi 2462541747 266 GVSKLKSHPFFSTIQWSKLV 285
Cdd:cd05598   255 GADEIKAHPFFAGIDWEKLR 274

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. 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-delta 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 2462541747 199 TEACDWWSFGSLLYELLTGmalsQSHPSG---------IQAHTQlQLPEWLSRPAASLLTELLQFEPTRRLGMgeggVSK 269
Cdd:cd05620   174 TFSVDWWSFGVLLYEMLIG----QSPFHGddedelfesIRVDTP-HYPRWITKESKDILEKLFERDPTRRLGV----VGN 244

                          90
                  ....*....|....*
gi 2462541747 270 LKSHPFFSTIQWSKL 284
Cdd:cd05620   245 IRGHPFFKTINWTAL 259

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK 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 2462541747 203 DWWSFGSLLYELLTGMALSQSHPSGIQAH--------TQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLKSHP 274
Cdd:cd05577   177 DWFALGCMLYEMIAGRSPFRQRKEKVDKEelkrrtleMAVEYPDSFSPEARSLCEGLLQKDPERRLGCRGGSADEVKEHP 256

                          90
                  ....*....|
gi 2462541747 275 FFSTIQWSKL 284
Cdd:cd05577   257 FFRSLNWQRL 266

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 2462541747 201 ACDWWSFGSLLYELLTGMAlsqshPSGIQAHTQL---------QLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLK 271
Cdd:cd05571   175 AVDWWGLGVVMYEMMCGRL-----PFYNRDHEVLfelilmeevRFPSTLSPEAKSLLAGLLKKDPKKRLGGGPRDAKEIM 249

                          90
                  ....*....|....
gi 2462541747 272 SHPFFSTIQWSKLV 285
Cdd:cd05571   250 EHPFFASINWDDLY 263

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. 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, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta 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 2462541747 200 EACDWWSFGSLLYELLTGMA---------LSQShpsgIQAHtQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKL 270
Cdd:cd05616   180 KSVDWWAFGVLLYEMLAGQApfegededeLFQS----IMEH-NVAYPKSMSKEAVAICKGLMTKHPGKRLGCGPEGERDI 254

                          90
                  ....*....|....
gi 2462541747 271 KSHPFFSTIQWSKL 284
Cdd:cd05616   255 KEHAFFRYIDWEKL 268

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 2462541747 201 ACDWWSFGSLLYELLTGMA--LSQSHPSGIQ--AHTQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLKSHPFF 276
Cdd:cd05595   175 AVDWWGLGVVMYEMMCGRLpfYNQDHERLFEliLMEEIRFPRTLSPEAKSLLAGLLKKDPKQRLGGGPSDAKEVMEHRFF 254

                  ....*....
gi 2462541747 277 STIQWSKLV 285
Cdd:cd05595   255 LSINWQDVV 263

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462541747 117 HLQRLLSSGASpSAVQLVQDPATGGTFVVKSLPRCHMVSRERLTIIP---------HgvPYMTKLLRYFVSEDSIFLHLE 187
Cdd:pfam00069   2 EVLRKLGSGSF-GTVYKAKHRDTGKIVAIKKIKKEKIKKKKDKNILReikilkklnH--PNIVRLYDAFEDKDNLYLVLE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462541747 188 ---------HVQEVGGISE---------------------------------------LTEACDWWSFGSLLYELLTG-M 218
Cdd:pfam00069  79 yveggslfdLLSEKGAFSEreakfimkqileglesgsslttfvgtpwymapevlggnpYGPKVDVWSLGCILYELLTGkP 158

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462541747 219 ALSQSHPSGIQAHTQLQ------LPEWLSRPAASLLTELLQFEPTRRLGMGEggvskLKSHPFF 276
Cdd:pfam00069 159 PFPGINGNEIYELIIDQpyafpeLPSNLSEEAKDLLKKLLKKDPSKRLTATQ-----ALQHPWF 217

Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The beta-ARK 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 2462541747 203 DWWSFGSLLYELLTGMALSQSHPSG----IQAHT---QLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLKSHPF 275
Cdd:cd05606   179 DWFSLGCMLYKLLKGHSPFRQHKTKdkheIDRMTltmNVELPDSFSPELKSLLEGLLQRDVSKRLGCLGRGATEVKEHPF 258

                  ....*....
gi 2462541747 276 FSTIQWSKL 284
Cdd:cd05606   259 FKGVDWQQV 267

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. 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, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha 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 2462541747 200 EACDWWSFGSLLYELLTGMA---------LSQShpsgIQAHtQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKL 270
Cdd:cd05615   190 RSVDWWAYGVLLYEMLAGQPpfdgededeLFQS----IMEH-NVSYPKSLSKEAVSICKGLMTKHPAKRLGCGPEGERDI 264

                          90
                  ....*....|....
gi 2462541747 271 KSHPFFSTIQWSKL 284
Cdd:cd05615   265 REHAFFRRIDWDKL 278

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 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 2462541747 203 DWWSFGSLLYELLTGMALSQSHPSGIQ--------AHTQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLKSHP 274
Cdd:cd05630   183 DWWALGCLLYEMIAGQSPFQQRKKKIKreeverlvKEVPEEYSEKFSPQARSLCSMLLCKDPAERLGCRGGGAREVKEHP 262

                          90
                  ....*....|....*
gi 2462541747 275 FFSTIQWSKLVGALV 289
Cdd:cd05630   263 LFKKLNFKRLGAGML 277

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 2462541747 201 ACDWWSFGSLLYELLTGmalsqSHPSGIQAHTQL---------QLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLK 271
Cdd:cd14209   178 AVDWWALGVLIYEMAAG-----YPPFFADQPIQIyekivsgkvRFPSHFSSDLKDLLRNLLQVDLTKRFGNLKNGVNDIK 252

                          90
                  ....*....|...
gi 2462541747 272 SHPFFSTIQWSKL 284
Cdd:cd14209   253 NHKWFATTDWIAI 265

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS1 functions as a tumor suppressor and is implicated in cell cycle regulation. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. Promoter methylation, loss of heterozygosity, and missense mutations targeting the LATS1 gene have also been found in human sarcomas and ovarian cancers. In addition, decreased expression of LATS1 is associated with an aggressive phenotype and poor prognosis. LATS1 induces G2 arrest and promotes cytokinesis. It may be a component of the mitotic exit network in higher eukaryotes. The LATS1 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 2462541747 199 TEACDWWSFGSLLYELLTGMA--LSQS----HPSGIQAHTQLQLPEW--LSRPAASLLTELLQfEPTRRLgmGEGGVSKL 270
Cdd:cd05625   226 TQLCDWWSVGVILFEMLVGQPpfLAQTpletQMKVINWQTSLHIPPQakLSPEASDLIIKLCR-GPEDRL--GKNGADEI 302

                          90
                  ....*....|..
gi 2462541747 271 KSHPFFSTIQWS 282
Cdd:cd05625   303 KAHPFFKTIDFS 314

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 2462541747 201 ACDWWSFGSLLYELLTGMA--LSQSHPSGIQA--HTQLQLPEWLSRPAASLLTELLQFEPTRRLGMGEGGVSKLKSHPFF 276
Cdd:cd05593   195 AVDWWGLGVVMYEMMCGRLpfYNQDHEKLFELilMEDIKFPRTLSADAKSLLSGLLIKDPNKRLGGGPDDAKEIMRHSFF 274

                  ....*
gi 2462541747 277 STIQW 281
Cdd:cd05593   275 TGVNW 279

MIT: domain contained within Microtubule Interacting and Trafficking molecules. The MIT domain is found in sorting nexins, the nuclear thiol protease PalBH, the AAA protein spastin and archaebacterial proteins with similar domain architecture, vacuolar sorting proteins and others. The molecular function of the MIT domain is unclear.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462541747  50 LVDAATQ-IRLALERDVSEDYEAAFNHYQNGVDVLLRGIHVDPNKERREAVKLKITKYLRRAEEI 113
Cdd:cd02656     2 LLQQAKElIKQAVKEDEDGNYEEALELYKEALDYLLQALKAEKEPKLRKLLRKKVKEYLDRAEFL 66

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462541747 202 CDWWSFGSLLYELLTGM------ALSQSHpSGIQAHTQ-LQLP---EWLSRPAASLLTELLQFEPTRrlgMGEGGVSKLK 271
Cdd:cd05597   189 CDWWSLGVCMYEMLYGEtpfyaeSLVETY-GKIMNHKEhFSFPddeDDVSEEAKDLIRRLICSRERR---LGQNGIDDFK 264

                          90
                  ....*....|...
gi 2462541747 272 SHPFFSTIQWSKL 284
Cdd:cd05597   265 KHPFFEGIDWDNI 277

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 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 2462541747 183 FLHLEHVQEVGGISELTEACDWWSFGSLLYELLTG------MALSQSHPSGIQAHTQLQLPE--WLSRPAASLLTELLQf 254
Cdd:cd05622   239 YISPEVLKSQGGDGYYGRECDWWSVGVFLYEMLVGdtpfyaDSLVGTYSKIMNHKNSLTFPDdnDISKEAKNLICAFLT- 317