Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 202 MKLLPTLSHSNISPVSFATTSESSALIIRVFSEKGTLRDHICKvkpkepflrkycnpkKIQGLELQQIRTFGRQILEALK 281
Cdd:cd00180   42 IEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKE---------------NKGPLSEEEALSILRQLLSALE 106

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 282 FLHDKGFPYGHLHASNVLI-EENTCKLLD-------------VENSLLGLPSYYRPYVTQFRKINTTESiDVYSFGHLLY 347
Cdd:cd00180  107 YLHSNGIIHRDLKPENILLdSDGTVKLADfglakdldsddslLKTTGGTTPPYYAPPELLGGRYYGPKV-DIWSLGVILY 185

                 ..
gi 688608358 348 EM 349
Cdd:cd00180  186 EL 187

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 688608358   49 STDNSWTVIRRYSDFDMLNNSLL--ISGLNLP-LPPKKLLGNMDREFIAERQKGLQAYLNYITQHHILCSCELVKKFL 123
Cdd:pfam00787   4 FSLEEWSVRRRYSDFVELHKKLLrkFPSVIIPpLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFL 81

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 202 MKLLPTLSHSNISPVSFATTSESSALIIRVFSEKGTLRDHICKvkpkepflrkycnpkKIQGLELQQIRTFGRQILEALK 281
Cdd:cd00180   42 IEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKE---------------NKGPLSEEEALSILRQLLSALE 106

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 282 FLHDKGFPYGHLHASNVLI-EENTCKLLD-------------VENSLLGLPSYYRPYVTQFRKINTTESiDVYSFGHLLY 347
Cdd:cd00180  107 YLHSNGIIHRDLKPENILLdSDGTVKLADfglakdldsddslLKTTGGTTPPYYAPPELLGGRYYGPKV-DIWSLGVILY 185

                 ..
gi 688608358 348 EM 349
Cdd:cd00180  186 EL 187

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358   190 DKFLSDKDLQSAM---KLLPTLSHSNIspVSFATTSESSALIIRVFS--EKGTLRDHICKVKPkepflrkycnpkkiqgL 264
Cdd:smart00220  33 KKKKIKKDRERILreiKILKKLKHPNI--VRLYDVFEDEDKLYLVMEycEGGDLFDLLKKRGR----------------L 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358   265 ELQQIRTFGRQILEALKFLHDKGFPYGHLHASNVLI-EENTCKLLD-----------VENSLLGLPSY-------YRPYv 325
Cdd:smart00220  95 SEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLdEDGHVKLADfglarqldpgeKLTTFVGTPEYmapevllGKGY- 173

                          170       180       190
                   ....*....|....*....|....*....|
gi 688608358   326 tqfrkintTESIDVYSFGHLLYEMTYGRPP 355
Cdd:smart00220 174 --------GKAVDIWSLGVILYELLTGKPP 195

glycogen synthase kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 262 QGLELQQIRTFGRQILEALKFLHDKGFPYGHLHASNVLIEENT-----CKLLDVENSLLGLPS-------YYRPYVTQFR 329
Cdd:PTZ00036 165 HALPLFLVKLYSYQLCRALAYIHSKFICHRDLKPQNLLIDPNThtlklCDFGSAKNLLAGQRSvsyicsrFYRAPELMLG 244

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 688608358 330 KINTTESIDVYSFGHLLYEMTYGRP--PDAVPVDQcppapfssIVSVLQSIlsteacktGMPTVSQL-LQTPLFYDV 403
Cdd:PTZ00036 245 ATNYTTHIDLWSLGCIIAEMILGYPifSGQSSVDQ--------LVRIIQVL--------GTPTEDQLkEMNPNYADI 305

Stk1 family PASTA domain-containing Ser/Thr kinase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 272 FGRQILEALKFLHDKGF------PyghlhaSNVLI-EENTCKLLD-------------VENSLLGLPSYYRPyvTQFRKI 331
Cdd:NF033483 112 IMIQILSALEHAHRNGIvhrdikP------QNILItKDGRVKVTDfgiaralssttmtQTNSVLGTVHYLSP--EQARGG 183

                         90       100
                 ....*....|....*....|....
gi 688608358 332 NTTESIDVYSFGHLLYEMTYGRPP 355
Cdd:NF033483 184 TVDARSDIYSLGIVLYEMLTGRPP 207

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358  35 QSHTEYIIRVQrgVSTDNSWTVIRRYSDFDMLNNSLL--ISGLNLP-LPPKKLLGNMDREFIAERQKGLQAYLNYITQHH 111
Cdd:cd06093   15 KKYVVYIIEVT--TQGGEEWTVYRRYSDFEELHEKLKkkFPGVILPpLPPKKLFGNLDPEFIEERRKQLEQYLQSLLNHP 92

                         90
                 ....*....|...
gi 688608358 112 ILCSCELVKKFLD 124
Cdd:cd06093   93 ELRNSEELKEFLE 105

The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (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. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358  20 DTVPLSAVIEASQSLQSHTEYIIRVQRGVSTdnswtVIRRYSDFDMLNNSLL---ISGLNLPLPPKKLLGNMDREFIAER 96
Cdd:cd06866    1 DTVTVELVPEKKGLFLKHVEYEVSSKRFKST-----VYRRYSDFVWLHEYLLkryPYRMVPALPPKRIGGSADREFLEAR 75

                         90       100
                 ....*....|....*....|....*..
gi 688608358  97 QKGLQAYLNYITQHHILCSCELVKKFL 123
Cdd:cd06866   76 RRGLSRFLNLVARHPVLSEDELVRTFL 102

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 688608358    36 SHTEYIIRVQRGVSTDnSWTVIRRYSDFDMLNNSLL--ISGLNLP-LPPKKLLG---NMDREFIAERQKGLQAYLNYITQ 109
Cdd:smart00312  11 KHYYYVIEIETKTGLE-EWTVSRRYSDFLELHSKLKkhFPRSILPpLPGKKLFGrlnNFSEEFIEKRRRGLEKYLQSLLN 89

                           90
                   ....*....|....*.
gi 688608358   110 HHILCS-CELVKKFLD 124
Cdd:smart00312  90 HPELINhSEVVLEFLE 105

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358  51 DNSWTVIRRYSDFDMLNNSLL-----ISGLNLPlpPKKLLGNMDREFIAERQKGLQAYLNYITQHHILCSCELvkkfldt 125
Cdd:cd07277   29 DDEWNVYRRYSEFYELHKKLKkkfpvVRSFDFP--PKKAIGNKDAKFVEERRKRLQVYLRRVVNTLIQTSPEL------- 99

                         90       100
                 ....*....|....*....|.
gi 688608358 126 nnySANYTEIALQQVSMFFRS 146
Cdd:cd07277  100 ---TACPSKETLIKLLPFFGD 117

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 193 LSDKDLQSAMKLlptlSHSNISPV-SFATTSESSALIIRV-----FSEKGTLRDHICKVKPkepflrkycnpkkiqgLEL 266
Cdd:cd14012   44 LLEKELESLKKL----RHPNLVSYlAFSIERRGRSDGWKVyllteYAPGGSLSELLDSVGS----------------VPL 103

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 267 QQIRTFGRQILEALKFLHDKGFPYGHLHASNVLIEEN----TCKLLD------------VENSLLGLPSYYR-PYVTQFR 329
Cdd:cd14012  104 DTARRWTLQLLEALEYLHRNGVVHKSLHAGNVLLDRDagtgIVKLTDyslgktlldmcsRGSLDEFKQTYWLpPELAQGS 183

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 688608358 330 KINTTESiDVYSFGHLLYEMTYGRP-------PDAVPVDQCPPAPFssiVSVLQSILSTEACKTgmPTVSQLL 395
Cdd:cd14012  184 KSPTRKT-DVWDLGLLFLQMLFGLDvlekytsPNPVLVSLDLSASL---QDFLSKCLSLDPKKR--PTALELL 250

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It 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. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358  48 VSTDNSWTVIRRYSDFDMLNNSL--LISGLNLPLPPKKLLG-NMDREFIAERQKGLQAYLNYITQHHILCSCELVKKFLD 124
Cdd:cd06870   28 SVGRSSWFVFRRYAEFDKLYESLkkQFPASNLKIPGKRLFGnNFDPDFIKQRRAGLDEFIQRLVSDPKLLNHPDVRAFLQ 107

                 ..
gi 688608358 125 TN 126
Cdd:cd06870  108 MD 109

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 688608358 168 FLVKDKDQpKEKQVLSWVDLgpdKFLSDKDLQSAM---KLLPTLSHSNIspV----SFATtsESSALIIRVFSEKGTLRD 240
Cdd:cd08215   17 YLVRRKSD-GKLYVLKEIDL---SNMSEKEREEALnevKLLSKLKHPNI--VkyyeSFEE--NGKLCIVMEYADGGDLAQ 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 241 HICKVKPKEPFLRkycnpkkiqglELQQIRTFgRQILEALKFLHDKGFpyghLH----ASNVLI-EENTCKL-------- 307
Cdd:cd08215   89 KIKKQKKKGQPFP-----------EEQILDWF-VQICLALKYLHSRKI----LHrdlkTQNIFLtKDGVVKLgdfgiskv 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 308 ----LDVENSLLGLPsYY--------RPYvtqfrkintTESIDVYSFGHLLYEMTYGRPP-DA-------VPVDQCPPAP 367
Cdd:cd08215  153 lestTDLAKTVVGTP-YYlspelcenKPY---------NYKSDIWALGCVLYELCTLKHPfEAnnlpalvYKIVKGQYPP 222

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 688608358 368 FSSIVS-----VLQSILSTEACKTgmPTVSQLLQTPLF 400
Cdd:cd08215  223 IPSQYSselrdLVNSMLQKDPEKR--PSANEILSSPFI 258

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (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. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX1, SNX2, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1. SNX1 and SNX2 are components of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358  34 LQSHTEYIIRVQrgvsTD------NSWTVIRRYSDFDMLNNSLliSGLNL-----PLPPKKLLG--NMDREFIAERQKGL 100
Cdd:cd06859   15 MSAYVVYRVTTK----TNlpdfkkSEFSVLRRYSDFLWLYERL--VEKYPgrivpPPPEKQAVGrfKVKFEFIEKRRAAL 88

                         90       100
                 ....*....|....*....|...
gi 688608358 101 QAYLNYITQHHILCSCELVKKFL 123
Cdd:cd06859   89 ERFLRRIAAHPVLRKDPDFRLFL 111

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (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. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358  40 YIIRVQR-----GVSTDNSWTVIRRYSDFDMLNNSLL-ISGLN--LPLPPKKLLGNMDREFIAERQKGLQAYLNYITQHH 111
Cdd:cd06877   25 FCIEVERndrraKGHEPQHWSVLRRYNEFYVLESKLTeFHGEFpdAPLPSRRIFGPKSYEFLESKREIFEEFLQKLLQKP 104

                         90
                 ....*....|....*
gi 688608358 112 ILCSCELVKKFLDTN 126
Cdd:cd06877  105 ELRGSELLYDFLSPN 119

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (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. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358  40 YIIRVQR--GVSTDNSWTVIRRYSDFDMLNNSLLISG---LNLPLPPKKLLGNMDREFIAERQKGLQAYLNYITQHHILC 114
Cdd:cd06873   25 YAISVTRiyPNGQEESWHVYRRYSDFHDLHMRLKEKFpnlSKLSFPGKKTFNNLDRAFLEKRRKMLNQYLQSLLNPEVLD 104

                         90
                 ....*....|....
gi 688608358 115 SC----ELVKKFLD 124
Cdd:cd06873  105 ANpglqEIVLDFLE 118

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 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 688608358 179 KQVlSWVDLGPDKFLSDKDLQSAMKLLPTLSHSNISPVSFATTSESSALIIRVFSEKGTLrdhickvkpkEPFLRKYcnp 258
Cdd:cd06632   31 KEV-SLVDDDKKSRESVKQLEQEIALLSKLRHPNIVQYYGTEREEDNLYIFLEYVPGGSI----------HKLLQRY--- 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 259 kkiQGLELQQIRTFGRQILEALKFLHDKGFPYGHLHASNVLIEEN-TCKLLD------VEN-----SLLGLPSYYRPYVT 326
Cdd:cd06632   97 ---GAFEEPVIRLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNgVVKLADfgmakhVEAfsfakSFKGSPYWMAPEVI 173

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 327 QFRKINTTESIDVYSFGHLLYEMTYGRPpdavPVDQCPPAPF------SSIVSVLQSILSTEA------C----KTGMPT 390
Cdd:cd06632  174 MQKNSGYGLAVDIWSLGCTVLEMATGKP----PWSQYEGVAAifkignSGELPPIPDHLSPDAkdfirlClqrdPEDRPT 249

                 ....*...
gi 688608358 391 VSQLLQTP 398
Cdd:cd06632  250 ASQLLEHP 257

The phosphoinositide binding Phox Homology domain of Sorting Nexin 10; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (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. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX10 may be involved in the regulation of endosome homeostasis. Its expression induces the formation of giant vacuoles in mammalian cells.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 688608358  55 TVIRRYSDFDMLNNSLLISGLNL---PLPPKKLLGNM-DREFIAERQKGLQAYLNYITQHHILCSCELVKKFLDTN 126
Cdd:cd06898   38 CVRRRYSEFVWLRNRLQKNALLIqlpSLPPKNLFGRFnNEGFIEERQQGLQDFLEKVLQTPLLLSDSRLHLFLQTQ 113

The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (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. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX41 and SNX42 (also called Atg20p) form dimers with SNX4, and are required in protein recycling from the sorting endosome (post-Golgi endosome) back to the late Golgi in yeast.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358  27 VIEASQS----LQSHTEYIIRVQRGvstdnswTVIRRYSDFDMLNNSL-------LISglnlPLPPKKLLGNM------- 88
Cdd:cd06867    4 IVDAGKSseggSGSYIVYVIRLGGS-------EVKRRYSEFESLRKNLtrlyptlIIP----PIPEKHSLKDYakkpska 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 688608358  89 --DREFIAERQKGLQAYLNYITQHHILCSCELVKKFLDTN 126
Cdd:cd06867   73 knDAKIIERRKRMLQRFLNRCLQHPILRNDIVFQKFLDPN 112

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 688608358 194 SDKDLQSAMKLLPTLSHSNIspVSF--ATTSESSALIIRVFSEKGTLRDhICKvkpkepflrkycnpKKIQGLELQQIRT 271
Cdd:cd05122   40 KKESILNEIAILKKCKHPNI--VKYygSYLKKDELWIVMEFCSGGSLKD-LLK--------------NTNKTLTEQQIAY 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 272 FGRQILEALKFLHDKGFPYGHLHASNVLIEEN-TCKLLDV-----------ENSLLGLPSYYRPYVTQfrKINTTESIDV 339
Cdd:cd05122  103 VCKEVLKGLEYLHSHGIIHRDIKAANILLTSDgEVKLIDFglsaqlsdgktRNTFVGTPYWMAPEVIQ--GKPYGFKADI 180

                        170
                 ....*....|....*.
gi 688608358 340 YSFGHLLYEMTYGRPP 355
Cdd:cd05122  181 WSLGITAIEMAEGKPP 196

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 147 DPKWEVIEPLKDIGWRLRKRYF--------LVKDKDQPKEKQVLSWVDLGPDKFLSD-KDLQSAMKLLPTL-SHSNISPV 216
Cdd:cd05098    5 DPRWELPRDRLVLGKPLGEGCFgqvvlaeaIGLDKDKPNRVTKVAVKMLKSDATEKDlSDLISEMEMMKMIgKHKNIINL 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 217 SFATTSESSALIIRVFSEKGTLRDHIckvKPKEPFLRKYC-NPKKI--QGLELQQIRTFGRQILEALKFLHDKGFPYGHL 293
Cdd:cd05098   85 LGACTQDGPLYVIVEYASKGNLREYL---QARRPPGMEYCyNPSHNpeEQLSSKDLVSCAYQVARGMEYLASKKCIHRDL 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358 294 HASNVLI-EENTCKLLDV------------ENSLLG-LPSYYRPYVTQFRKINTTESiDVYSFGHLLYEMTY--GRPPDA 357
Cdd:cd05098  162 AARNVLVtEDNVMKIADFglardihhidyyKKTTNGrLPVKWMAPEALFDRIYTHQS-DVWSFGVLLWEIFTlgGSPYPG 240

                 ....*
gi 688608358 358 VPVDQ 362
Cdd:cd05098  241 VPVEE 245

The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (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. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688608358  50 TDNSWtviRRYSDFDMLNNSLLISGLNL---PLPPKKLL--------GNMDREFIAERQKGLQAYLNYITQHHILCSCEL 118
Cdd:cd06864   45 LSSLW---RRYSEFELLRNYLVVTYPYVivpPLPEKRAMfmwqklssDTFDPDFVERRRAGLENFLLRVAGHPELCQDKI 121

                 ....*
gi 688608358 119 VKKFL 123
Cdd:cd06864  122 FLEFL 126