The phosphoinositide binding Phox Homology domain of RPK118-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769   11 LARFYTVTEPRRHPRGHTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRHTELFPPFAKAIVFGRF 90
Cdd:cd07287      1 LARFYTVTDPRRHPKGYTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRQSELFPPFAKAKVFGRF 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2024393769   91 DETVIEERRQCAEDLLQFSANIPALYNSKQLEEFFKGG 128
Cdd:cd07287     81 DESVIEERRQCAEDLLQFSANIPALYNSSQLEDFFKGG 118

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 2024393769  258 DYLEKAGELIKLALKKEEEEDYETAFSFYRKGVDLLLEGVQGESSPTRREAVKRKTAEYLMRAEKISTLYHKSS 331
Cdd:cd02677      1 DYLEQAAELIRLALEKEEEGDYEAAFEFYRAGVDLLLKGVQGDSSPERREAVKRKIAEYLKRAEEILRLHLSRS 74

The phosphoinositide binding Phox Homology domain of RPK118-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769   11 LARFYTVTEPRRHPRGHTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRHTELFPPFAKAIVFGRF 90
Cdd:cd07287      1 LARFYTVTDPRRHPKGYTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRQSELFPPFAKAKVFGRF 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2024393769   91 DETVIEERRQCAEDLLQFSANIPALYNSKQLEEFFKGG 128
Cdd:cd07287     81 DESVIEERRQCAEDLLQFSANIPALYNSSQLEDFFKGG 118

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 2024393769  258 DYLEKAGELIKLALKKEEEEDYETAFSFYRKGVDLLLEGVQGESSPTRREAVKRKTAEYLMRAEKISTLYHKSS 331
Cdd:cd02677      1 DYLEQAAELIRLALEKEEEGDYEAAFEFYRAGVDLLLKGVQGDSSPERREAVKRKIAEYLKRAEEILRLHLSRS 74

Microtubule Interacting and Trafficking molecule domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024393769   256 KQDYLEKAGELIKLALKKEEEEDYETAFSFYRKGVDLLLEGVQGESSPTRREAVKRKTAEYLMRAEKISTLY 327
Cdd:smart00745    1 TRDYLSKAKELISKALKADEAGNYEEALELYKKAIEYLLEGIKVESDSKRREALKAKAAEYLDRAEEIKKSL 72

protein kinase A catalytic subunit; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  914 PEDCIQRWAAEMVVALDALHREGIVCRDLNPNNILLN-----------------DR-------------EVGAILEETEA 963
Cdd:PTZ00263   116 PNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDnkghvkvtdfgfakkvpDRtftlcgtpeylapEVIQSKGHGKA 195

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  964 CDWWSLGAILFELLTGktlvecHP-----SGINTHTS-----LSIPDHVSKEARSLIQQLLQFNPAERLGAGVAGVEDIK 1033
Cdd:PTZ00263   196 VDWWTMGVLLYEFIAG------YPpffddTPFRIYEKilagrLKFPNWFDGRARDLVKGLLQTDHTKRLGTLKGGVADVK 269

                          170
                   ....*....|...
gi 2024393769 1034 SHPFFALIEWADL 1046
Cdd:PTZ00263   270 NHPYFHGANWDKL 282

Serine/threonine protein kinase [Signal transduction mechanisms];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  899 QDLDERLAITSRFyiPEDCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDR--------------------EVGAIL 958
Cdd:COG0515     92 ESLADLLRRRGPL--PPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDgrvklidfgiaralggatltQTGTVV 169

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  959 --------------EETEACDWWSLGAILFELLTGK---------TLVECHPSGINTHTSLSIPDhVSKEARSLIQQLLQ 1015
Cdd:COG0515    170 gtpgymapeqargePVDPRSDVYSLGVTLYELLTGRppfdgdspaELLRAHLREPPPPPSELRPD-LPPALDAIVLRALA 248

                   ....*.
gi 2024393769 1016 FNPAER 1021
Cdd:COG0515    249 KDPEER 254

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769    17 VTEPRRHPRGHTVYKVtarIVSRKNPEdvQEIVVWKRYSDFKKLHKDLWQIHKNLcrhteLFPPFAKAIVFGR---FDET 93
Cdd:smart00312    2 VEPEKIGDGKHYYYVI---EIETKTGL--EEWTVSRRYSDFLELHSKLKKHFPRS-----ILPPLPGKKLFGRlnnFSEE 71

                            90       100       110
                    ....*....|....*....|....*....|...
gi 2024393769    94 VIEERRQCAEDLLQFSANIPALYN-SKQLEEFF 125
Cdd:smart00312   72 FIEKRRRGLEKYLQSLLNHPELINhSEVVLEFL 104

The phosphoinositide binding Phox Homology domain of RPK118-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769   11 LARFYTVTEPRRHPRGHTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRHTELFPPFAKAIVFGRF 90
Cdd:cd07287      1 LARFYTVTDPRRHPKGYTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRQSELFPPFAKAKVFGRF 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2024393769   91 DETVIEERRQCAEDLLQFSANIPALYNSKQLEEFFKGG 128
Cdd:cd07287     81 DESVIEERRQCAEDLLQFSANIPALYNSSQLEDFFKGG 118

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily have similarity to sorting nexin 15 (SNX15), which contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein. Other members of this subfamily contain an additional C-terminal kinase domain, similar to human RPK118, which binds sphingosine kinase and the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of proteins such as PRDX3 from the cytoplasm to its site of function in the mitochondria.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769   11 LARFYTVTEPRRHPRGHTVYKVTARIVSRKNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLCRHtELFPPFAKAIVFGRF 90
Cdd:cd06881      1 WSRSFTVTDTRRHKKGYTEYKITSKVFSRSVPEDVSEVVVWKRYSDFKKLHRELSRLHKQLYLS-GSFPPFPKGKYFGRF 79

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2024393769   91 DETVIEERRQCAEDLLQFSANIPALYNSKQLEEFFKGG 128
Cdd:cd06881     80 DAAVIEERRQAILELLDFVGNHPALYQSSAFQQFFEEA 117

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 2024393769  910 RFYIPEDCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDR---------------------------------EVGA 956
Cdd:cd05123     87 EGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDghikltdfglakelssdgdrtytfcgtpeylapEVLL 166

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  957 ILEETEACDWWSLGAILFELLTGKTLVECHPSGINTHT----SLSIPDHVSKEARSLIQQLLQFNPAERLGAGvaGVEDI 1032
Cdd:cd05123    167 GKGYGKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKilksPLKFPEYVSPEAKSLISGLLQKDPTKRLGSG--GAEEI 244

                   ....*.
gi 2024393769 1033 KSHPFF 1038
Cdd:cd05123    245 KAHPFF 250

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 2024393769  901 LDERLAitsRFYIpedciqrwaAEMVVALDALHREGIVCRDLNPNNILLNDR-----------EVGAILEETE------- 962
Cdd:cd05579     90 LDEDVA---RIYI---------AEIVLALEYLHSHGIIHRDLKPDNILIDANghlkltdfglsKVGLVRRQIKlsiqkks 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  963 ------------------------------ACDWWSLGAILFELLTGKT-LVECHPSGINTH-TSLSIP----DHVSKEA 1006
Cdd:cd05579    158 ngapekedrrivgtpdylapeillgqghgkTVDWWSLGVILYEFLVGIPpFHAETPEEIFQNiLNGKIEwpedPEVSDEA 237

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 2024393769 1007 RSLIQQLLQFNPAERLGAGvaGVEDIKSHPFFALIEW 1043
Cdd:cd05579    238 KDLISKLLTPDPEKRLGAK--GIEEIKNHPFFKGIDW 272

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769   900 DLDERlaITSRFYIPEDCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDR--------------------------- 952
Cdd:smart00220   83 DLFDL--LKKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDghvkladfglarqldpgeklttfvgtp 160

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769   953 -----EVgaILEE--TEACDWWSLGAILFELLTGKTLVECHPS--------GINTHTSLSIPDHVSKEARSLIQQLLQFN 1017
Cdd:smart00220  161 eymapEV--LLGKgyGKAVDIWSLGVILYELLTGKPPFPGDDQllelfkkiGKPKPPFPPPEWDISPEAKDLIRKLLVKD 238

                           170       180
                    ....*....|....*....|.
gi 2024393769  1018 PAERLGAgvagvEDIKSHPFF 1038
Cdd:smart00220  239 PEKRLTA-----EEALQHPFF 254

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 2024393769  877 QTAPKREDK-IAVAGEKD----IHQIFQD-------LD-----ERLAITSRF--YIPEDCIQRWAAEMVVALDALHREGI 937
Cdd:cd05597     44 ETACFREERdVLVNGDRRwitkLHYAFQDenylylvMDyycggDLLTLLSKFedRLPEEMARFYLAEMVLAIDSIHQLGY 123

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  938 VCRDLNPNNILL------------------NDREVGA-------------ILEETE--------ACDWWSLGAILFELLT 978
Cdd:cd05597    124 VHRDIKPDNVLLdrnghirladfgsclklrEDGTVQSsvavgtpdyispeILQAMEdgkgrygpECDWWSLGVCMYEMLY 203

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2024393769  979 GKT------LVECHPSGINTHTSLSIPDH---VSKEARSLIQQLLQfNPAERLGAGvaGVEDIKSHPFFALIEW 1043
Cdd:cd05597    204 GETpfyaesLVETYGKIMNHKEHFSFPDDeddVSEEAKDLIRRLIC-SRERRLGQN--GIDDFKKHPFFEGIDW 274

Catalytic domain of fungal Rim15-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 Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-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 2024393769  912 YIPEDCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDR-----------EVGAILEE-------------------- 960
Cdd:cd05611     93 GLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTghlkltdfglsRNGLEKRHnkkfvgtpdylapetilgvg 172

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  961 -TEACDWWSLGAILFELLTGKTlvechPSGINT---------HTSLSIPDHV----SKEARSLIQQLLQFNPAERLGAGv 1026
Cdd:cd05611    173 dDKMSDWWSLGCVIFEFLFGYP-----PFHAETpdavfdnilSRRINWPEEVkefcSPEAVDLINRLLCMDPAKRLGAN- 246

                          170
                   ....*....|....*..
gi 2024393769 1027 aGVEDIKSHPFFALIEW 1043
Cdd:cd05611    247 -GYQEIKSHPFFKSINW 262

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 2024393769  909 SRFYipedciqrwAAEMVVALDALHREGIVCRDLNPNNILLnDRE------------------------VGA-------I 957
Cdd:cd05570     98 ARFY---------AAEICLALQFLHERGIIYRDLKLDNVLL-DAEghikiadfgmckegiwggnttstfCGTpdyiapeI 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  958 LEETE---ACDWWSLGAILFELLTGKT---------LVEChpsgInTHTSLSIPDHVSKEARSLIQQLLQFNPAERLGAG 1025
Cdd:cd05570    168 LREQDygfSVDWWALGVLLYEMLAGQSpfegddedeLFEA----I-LNDEVLYPRWLSREAVSILKGLLTKDPARRLGCG 242

                          170       180
                   ....*....|....*....|.
gi 2024393769 1026 VAGVEDIKSHPFFALIEWADL 1046
Cdd:cd05570    243 PKGEADIKAHPFFRNIDWDKL 263

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 2024393769  908 TSRFYIpedciqrwaAEMVVALDALHREGIVCRDLNPNNILLNDR--------------------------------EVg 955
Cdd:cd05572     94 TARFYT---------ACVVLAFEYLHSRGIIYRDLKPENLLLDSNgyvklvdfgfakklgsgrktwtfcgtpeyvapEI- 163

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  956 aILEE--TEACDWWSLGAILFELLTGK---TLVECHP--------SGINTHTSlsiPDHVSKEARSLIQQLLQFNPAERL 1022
Cdd:cd05572    164 -ILNKgyDFSVDYWSLGILLYELLTGRppfGGDDEDPmkiyniilKGIDKIEF---PKYIDKNAKNLIKQLLRRNPEERL 239

                          170       180
                   ....*....|....*....|.
gi 2024393769 1023 GAGVAGVEDIKSHPFFALIEW 1043
Cdd:cd05572    240 GYLKGGIRDIKKHKWFEGFDW 260

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 2024393769  910 RFyiPEDCIQRWAAEMVVALDALHREGIVCRDLNPNNILLnDREvGAI----------LEE------------------- 960
Cdd:cd05580     97 RF--PNDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLL-DSD-GHIkitdfgfakrVKDrtytlcgtpeylapeiils 172

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  961 ---TEACDWWSLGAILFELLTGktlvecHP-----SGINTHTS-----LSIPDHVSKEARSLIQQLLQFNPAERLGAGVA 1027
Cdd:cd05580    173 kghGKAVDWWALGILIYEMLAG------YPpffdeNPMKIYEKilegkIRFPSFFDPDAKDLIKRLLVVDLTKRLGNLKN 246

                          170
                   ....*....|....*....
gi 2024393769 1028 GVEDIKSHPFFALIEWADL 1046
Cdd:cd05580    247 GVEDIKNHPWFAGIDWDAL 265

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. 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 GRK4-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 2024393769  913 IPEDCIQRWAAEMVVALDALHREGIVCRDLNPNNILLNDR-------------------------EVGAILEE------- 960
Cdd:cd05605     99 FEEERAVFYAAEITCGLEHLHSERIVYRDLKPENILLDDHghvrisdlglaveipegetirgrvgTVGYMAPEvvknery 178

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  961 TEACDWWSLGAILFELLTGKTLVECHPSGINTH--------TSLSIPDHVSKEARSLIQQLLQFNPAERLGAGVAGVEDI 1032
Cdd:cd05605    179 TFSPDWWGLGCLIYEMIEGQAPFRARKEKVKREevdrrvkeDQEEYSEKFSEEAKSICSQLLQKDPKTRLGCRGEGAEDV 258

                          170
                   ....*....|....
gi 2024393769 1033 KSHPFFALIEWADL 1046
Cdd:cd05605    259 KSHPFFKSINFKRL 272

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 2024393769  910 RFYIPEDCIQRWAAEMVVALDALHREGIVCRDLNPNNILLnDREVGAIL-----------EETE---------------- 962
Cdd:cd05614     99 RDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILL-DSEGHVVLtdfglskefltEEKErtysfcgtieymapei 177

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  963 ---------ACDWWSLGAILFELLTG-----------------KTLVECHPSginthtslsIPDHVSKEARSLIQQLLQF 1016
Cdd:cd05614    178 irgksghgkAVDWWSLGILMFELLTGaspftlegekntqsevsRRILKCDPP---------FPSFIGPVARDLLQKLLCK 248

                          170       180       190
                   ....*....|....*....|....*....|
gi 2024393769 1017 NPAERLGAGVAGVEDIKSHPFFALIEWADL 1046
Cdd:cd05614    249 DPKKRLGAGPQGAQEIKEHPFFKGLDWEAL 278

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long 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. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK 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 2024393769  894 IHQIFQDlDERL-------------AITSRFYIPEDCIQRWAAEMVVALDALHREGIVCRDLNPNNILLN---------- 950
Cdd:cd05596     91 LHYAFQD-DKYLymvmdympggdlvNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFVHRDVKPDNMLLDasghlkladf 169

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  951 --------------DREVGA-------ILEETEA-------CDWWSLGAILFELLTGKT------LVECHPSGINTHTSL 996
Cdd:cd05596    170 gtcmkmdkdglvrsDTAVGTpdyispeVLKSQGGdgvygreCDWWSVGVFLYEMLVGDTpfyadsLVGTYGKIMNHKNSL 249

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 2024393769  997 SIPD--HVSKEARSLIQQLLQfNPAERLGAGvaGVEDIKSHPFFALIEW 1043
Cdd:cd05596    250 QFPDdvEISKDAKSLICAFLT-DREVRLGRN--GIEEIKAHPFFKNDQW 295

Microtubule Interacting and Trafficking molecule domain;

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2024393769   256 KQDYLEKAGELIKLALKKEEEEDYETAFSFYRKGVDLLLEGVQGESSPTRREAVKRKTAEYLMRAEKISTLY 327
Cdd:smart00745    1 TRDYLSKAKELISKALKADEAGNYEEALELYKKAIEYLLEGIKVESDSKRREALKAKAAEYLDRAEEIKKSL 72

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-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. This alignment model includes the dimerization domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  877 QTAPKREDK-IAVAGE----KDIHQIFQD-------LD-----ERLAITSRF--YIPEDCIQRWAAEMVVALDALHREGI 937
Cdd:cd05624    115 ETACFREERnVLVNGDcqwiTTLHYAFQDenylylvMDyyvggDLLTLLSKFedKLPEDMARFYIGEMVLAIHSIHQLHY 194

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024393769  938 VCRDLNPNNILLN------------------DREVGA-------------ILEETE--------ACDWWSLGAILFELLT 978
Cdd:cd05624    195 VHRDIKPDNVLLDmnghirladfgsclkmndDGTVQSsvavgtpdyispeILQAMEdgmgkygpECDWWSLGVCMYEMLY 274

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2024393769  979 GKT------LVECHPSGINTHTSLSIPDH---VSKEARSLIQQLLqFNPAERLGAGvaGVEDIKSHPFFALIEWADL 1046
Cdd:cd05624    275 GETpfyaesLVETYGKIMNHEERFQFPSHvtdVSEEAKDLIQRLI-CSRERRLGQN--GIEDFKKHAFFEGLNWENI 348

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 2024393769  914 PEDCIQRWAAEMVVALDALHREGIVCRDLNPNNILLnDR-----------------------------------EVGAIL 958
Cdd:cd05601    100 EESMARFYLAELVLAIHSLHSMGYVHRDIKPENILI-DRtghikladfgsaaklssdktvtskmpvgtpdyiapEVLTSM 178