Regulator of G protein signaling (RGS) domain superfamily; The RGS domain is an essential part of the Regulator of G-protein Signaling (RGS) protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. While inactive, G-alpha-subunits bind GDP, which is released and replaced by GTP upon agonist activation. GTP binding leads to dissociation of the alpha-subunit and the beta-gamma-dimer, allowing them to interact with effectors molecules and propagate signaling cascades associated with cellular growth, survival, migration, and invasion. Deactivation of the G-protein signaling controlled by the RGS domain accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in the reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins are also involved in apoptosis and cell proliferation, as well as modulation of cardiac development. Several RGS proteins can fine-tune immune responses, while others play important roles in neuronal signals modulation. Some RGS proteins are principal elements needed for proper vision.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 437 IMTNPFYRERFGTYMERIDKRALVGFWESAEHLKNANKSEIPQLVSEMYQNFFVESK-EISVEKSLYKEIQQCLVGNRGI 515
Cdd:cd08720     1 ILANVFGRKYLSQFLERMDSQALIGFWEAVEELRSANKSEWHQLGAEIFYTFIVEPTaEIKVDKSLRKRIEQFLLGDKGP 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1732428623 516 EVFSKIQADVSEVLRERYYPSFLVSDLYEK 545
Cdd:cd08720    81 EVFYEVQENVVETLEEKYYPSFVVSDQYKQ 110

PXA domain; This domain is associated with PX domains pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 148 DRVLRDVFDYSYRDYILSWYGNLSRDDG---QLYHLLLDdfweIVKQIRQRLSHVDVVKVVCNDIVKALLTHF------- 217
Cdd:pfam02194   5 DAALDELIDLIIRDFVQSWYSKISSDPEfpnEVRQTLRH----ALRELSQRLRKVDLASLLLSRLLPLLTSHLedyrkae 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 218 ----------CDLKAATARHEEQPRPFVLHACLKDSHD---EVRFLQTCSQVLVLCLLPSKDIQSLSLRTMLAEILTTKV 284
Cdd:pfam02194  81 eavrgkklneLDLALASKYLALKPHPALSPVLLSSSQSreaEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170
                  ....*....|....*....
gi 1732428623 285 LKPVVELLSNPDYINQMLL 303
Cdd:pfam02194 161 LLPVINKLSDPDFINELIV 179

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 25 (SNX25) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX25 (Sorting Nexin 25) protein, a member of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development. SNX25 is a member of the Dopamine receptors (DAR) signalplex and regulates the trafficking of D1 and D2 DARs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 437 IMTNPFYRERFGTYMERIDKRALVGFWESAEHLKNANKSEIPQLVSEMYQNFFVESK-EISVEKSLYKEIQQCLVGNRGI 515
Cdd:cd08720     1 ILANVFGRKYLSQFLERMDSQALIGFWEAVEELRSANKSEWHQLGAEIFYTFIVEPTaEIKVDKSLRKRIEQFLLGDKGP 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1732428623 516 EVFSKIQADVSEVLRERYYPSFLVSDLYEK 545
Cdd:cd08720    81 EVFYEVQENVVETLEEKYYPSFVVSDQYKQ 110

PXA domain; This domain is associated with PX domains pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 148 DRVLRDVFDYSYRDYILSWYGNLSRDDG---QLYHLLLDdfweIVKQIRQRLSHVDVVKVVCNDIVKALLTHF------- 217
Cdd:pfam02194   5 DAALDELIDLIIRDFVQSWYSKISSDPEfpnEVRQTLRH----ALRELSQRLRKVDLASLLLSRLLPLLTSHLedyrkae 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 218 ----------CDLKAATARHEEQPRPFVLHACLKDSHD---EVRFLQTCSQVLVLCLLPSKDIQSLSLRTMLAEILTTKV 284
Cdd:pfam02194  81 eavrgkklneLDLALASKYLALKPHPALSPVLLSSSQSreaEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170
                  ....*....|....*....
gi 1732428623 285 LKPVVELLSNPDYINQMLL 303
Cdd:pfam02194 161 LLPVINKLSDPDFINELIV 179

Domain associated with PX domains; unpubl. observations

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623  147 MDRVLRDVFDYSYRDYILSWYGNLSRDDGQL----YHLLlddfwEIVKQIRQRLSHVDVVKVVCNDIVKALLTHFCDLKA 222
Cdd:smart00313   4 LEEPLQLLISKIIRDYVQGWYKGVSEDPSFLreieQTLE-----YILRQLYRRLSRQDSAHLILYEILKNLISTITNALE 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623  223 ATARH----------EEQPRPFVLHACLKDSHDEVRFLQTCSQVLVLCLLPSKDIQSLSLRTMLAEILTTKVLKPVVELL 292
Cdd:smart00313  79 AVLRFaspqipsteiDLQYAETAIHKALSSPSNELTYRRQLVEMLLKFLLPEDSLCSRLHRCLLREVLAMQVILPLITHL 158

                          170
                   ....*....|.
gi 1732428623  293 SNPDYINQMLL 303
Cdd:smart00313 159 SDPDTINLCII 169

Regulator of G protein signalling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623  434 FEDIMTNPFYRERFGTYMERIDKRALVGFWESAE-HLKNANKSEIPQLVSEMYQNFFVE--SKEISVEKSLYKEIQQCLV 510
Cdd:smart00315   2 LESLLSDPIGRLLFREFLESEFSEENLEFWLAVEeFKKAEDDEERIAKAREIYDKFLSPnaPKEVNLDSDLREKIEENLE 81

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1732428623  511 GNR-GIEVFSKIQADVSEVLRERYYPSFLVSDLYEKL 546
Cdd:smart00315  82 SEEpPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

Actin cytoskeleton-regulatory complex protein END3; Endocytosis is accomplished through the sequential recruitment at endocytic sites of proteins that drive cargo sorting, membrane invagination and vesicle release. End3p is part of the coat module protein complex Pan1, along with Pan1p, Sla1p, and Sla2p. The proteins in this complex are regulated by phosphorylation events. End3p also regulates the cortical actin cytoskeleton. The subunits of the Pan1 complex are homologous to mammalian intersectin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 558 QLASEKDELGSGGEAGEEAVEGTSGVSDPAsfAVIKlRELNEKLEYKRQALSSIQNAPKPDKKI-ISKLKDEILLIEKEC 636
Cdd:pfam12761 106 ELAELEEKLEKVEQAASKRRGGNRDESSKP--ALVK-REFEQLLDYKERQLRELEEGSGKSKPInLKSVREDIDTVEEQV 182

                  ....*....
gi 1732428623 637 TALQLHMAR 645
Cdd:pfam12761 183 DGLESHLSS 191

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 25 (SNX25) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX25 (Sorting Nexin 25) protein, a member of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development. SNX25 is a member of the Dopamine receptors (DAR) signalplex and regulates the trafficking of D1 and D2 DARs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 437 IMTNPFYRERFGTYMERIDKRALVGFWESAEHLKNANKSEIPQLVSEMYQNFFVESK-EISVEKSLYKEIQQCLVGNRGI 515
Cdd:cd08720     1 ILANVFGRKYLSQFLERMDSQALIGFWEAVEELRSANKSEWHQLGAEIFYTFIVEPTaEIKVDKSLRKRIEQFLLGDKGP 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1732428623 516 EVFSKIQADVSEVLRERYYPSFLVSDLYEK 545
Cdd:cd08720    81 EVFYEVQENVVETLEEKYYPSFVVSDQYKQ 110

PXA domain; This domain is associated with PX domains pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 148 DRVLRDVFDYSYRDYILSWYGNLSRDDG---QLYHLLLDdfweIVKQIRQRLSHVDVVKVVCNDIVKALLTHF------- 217
Cdd:pfam02194   5 DAALDELIDLIIRDFVQSWYSKISSDPEfpnEVRQTLRH----ALRELSQRLRKVDLASLLLSRLLPLLTSHLedyrkae 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 218 ----------CDLKAATARHEEQPRPFVLHACLKDSHD---EVRFLQTCSQVLVLCLLPSKDIQSLSLRTMLAEILTTKV 284
Cdd:pfam02194  81 eavrgkklneLDLALASKYLALKPHPALSPVLLSSSQSreaEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170
                  ....*....|....*....
gi 1732428623 285 LKPVVELLSNPDYINQMLL 303
Cdd:pfam02194 161 LLPVINKLSDPDFINELIV 179

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 1732428623 656 WRASITSAE--VTEENGEQMPCYFVRV--NLQEVGGVETKNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPSlsKLPFKS 731
Cdd:cd06877     3 WRVSIPYVEmrRDPSNGERIYVFCIEVerNDRRAKGHEPQHWSVLRRYNEFYVLESKLTEFHGEFPDAPLPS--RRIFGP 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1732428623 732 IDHKFLGKSRNQLNAFLQNLLSDERLFQSEALYAFLSP 769
Cdd:cd06877    81 KSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSP 118

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 1732428623 658 ASITSAEVTEENGEQMPCYFVRVNLQEvggveTKNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPslSKLPFKSIDHKFL 737
Cdd:cd06093     2 VSIPDYEKVKDGGKKYVVYIIEVTTQG-----GEEWTVYRRYSDFEELHEKLKKKFPGVILPPLP--PKKLFGNLDPEFI 74

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1732428623 738 GKSRNQLNAFLQNLLSDERLFQSEALYAFLS 768
Cdd:cd06093    75 EERRKQLEQYLQSLLNHPELRNSEELKEFLE 105

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 691 KNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPslSKLPFKSIDHKFLGKSRNQLNAFLQNLLSDERLFQSEALYAFLSPS 770
Cdd:pfam00787   7 EEWSVRRRYSDFVELHKKLLRKFPSVIIPPLP--PKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLESD 84

Regulator of G protein signalling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623  434 FEDIMTNPFYRERFGTYMERIDKRALVGFWESAE-HLKNANKSEIPQLVSEMYQNFFVE--SKEISVEKSLYKEIQQCLV 510
Cdd:smart00315   2 LESLLSDPIGRLLFREFLESEFSEENLEFWLAVEeFKKAEDDEERIAKAREIYDKFLSPnaPKEVNLDSDLREKIEENLE 81

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1732428623  511 GNR-GIEVFSKIQADVSEVLRERYYPSFLVSDLYEKL 546
Cdd:smart00315  82 SEEpPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

Regulator of G protein signaling (RGS) domain superfamily; The RGS domain is an essential part of the Regulator of G-protein Signaling (RGS) protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. While inactive, G-alpha-subunits bind GDP, which is released and replaced by GTP upon agonist activation. GTP binding leads to dissociation of the alpha-subunit and the beta-gamma-dimer, allowing them to interact with effectors molecules and propagate signaling cascades associated with cellular growth, survival, migration, and invasion. Deactivation of the G-protein signaling controlled by the RGS domain accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in the reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins are also involved in apoptosis and cell proliferation, as well as modulation of cardiac development. Several RGS proteins can fine-tune immune responses, while others play important roles in neuronal signals modulation. Some RGS proteins are principal elements needed for proper vision.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 438 MTNPFYRERFGTYMERIDKRALVGFWESAEHLKNAN--KSEIPQLVSEMYQNFFVE--SKEISVEKSLYKEIQQCLVG-N 512
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTssDEELKSKAKEIYDKYISKdaPKEINIPESIREEIEENLEEpY 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1732428623 513 RGIEVFSKIQADVSEVLRERYYPSFLVSDLYEK 545
Cdd:cd07440    81 PDPDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

Regulator of G protein signaling (RGS) domain found in the RGS11 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS11 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS7, and RGS9, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. RGS11 is expressed exclusively in retinal ON-bipolar neurons in which it forms complexes with G-beta-5 and R7AP (RGS7 anchor protein ) and plays crucial roles in processing the light responses of retinal neurons.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 434 FEDIMTNPFYRERFGTYMERIDKRALVGFWESAEHLKNANKSEIPQLVSEMYQNFFV--ESKEISVEKslyKEIQQCLVG 511
Cdd:cd08740    10 FRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRYGEQSKIPELVDSVYQQFLApgATRWVNIDS---KTMERTLEG 86

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1732428623 512 NRGIE--VFSKIQADVSEVLRERYYPSFLVSDLYEKLM 547
Cdd:cd08740    87 LKQPHryVLDDAQMHIYMLMKKDSYPRFLKSDLYKNLL 124

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 695 VPRRLSEFQNLHRKLSECVPSLKKVQLPSLSKLPF---KSIDHkflgKSRNQLNAFLQNLLS-DERLFQSEALYAFLSPS 770
Cdd:cd06883    34 VFRTFEEFQELHNKLSLLFPSLKLPSFPARVVLGRshiKQVAE----RRKIELNSYLKSLFNaSPEVAESDLVYTFFHPL 109

The phosphoinositide binding Phox Homology domain of Sorting Nexin 19; 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. SNX19 contains an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. These domains are also found in SNX13 and SNX14, which also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNX19 interacts with IA-2, a major autoantigen found in type-1 diabetes. It inhibits the conversion of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to PI(3,4,5)P3, which leads in the decrease of protein phosphorylation in the Akt signaling pathway, resulting in apoptosis. SNX19 may also be implicated in coronary heart disease and thyroid oncocytic tumors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 690 TKNWTVPRRLSEFQNLHRKLSEcVPSLKK---VQLPS--LSKLPFKSIDHKFLGKSRNQLNAFLQNLLSDERLFQSEALY 764
Cdd:cd06893    48 LATHTVNRRFREFLTLQTRLEE-NPKFRKimnVKGPPkrLFDLPFGNMDKDKIEARRGLLETFLRQLCSIPEISNSEEVQ 126

                  ....
gi 1732428623 765 AFLS 768
Cdd:cd06893   127 EFLA 130

Regulator of G protein signaling (RGS) domain found in the RGS7 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS7 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. R7 RGS proteins are key modulators of the pharmacological effects of drugs involved in the development of tolerance and addiction. In addition, RGS7 was found to bind a component of the synaptic fusion complex, snapin, and some other proteins outside of G protein signaling pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 435 EDIMTNPFYRERFGTYMERIDKRALVGFWESAEHLKNANKSEIPQLVSEMYQNFFVES--KEISVEKSLYKEIQQClVGN 512
Cdd:cd08738    10 DEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKKRPIREVPSRVQEIWQEFLAPGapSAINLDSKSYDKTTQN-VKD 88

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1732428623 513 RGIEVFSKIQADVSEVLRERYYPSFLVSDLYEK 545
Cdd:cd08738    89 PGRYTFEDAQEHIYKLMKSDSYPRFIRSSAYQE 121

The phosphoinositide binding Phox Homology domain of Bem1p; 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 Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of Bem1p specifically binds phosphatidylinositol-4-phosphate (PI4P).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 691 KNWTVPRRLSEFQNLHRKLSECVPSL-----KKVQLPSLSK-LPFKSIDHKFLgKSRNQLNAFLQNLLSDERLFQ-SEAL 763
Cdd:cd06890    27 KTRYLCRYYQDFYKLHIALLDLFPAEagrnsSKRILPYLPGpVTDVVNDSISL-KRLNDLNEYLNELINLPAYIQtSEVV 105

                  ....*..
gi 1732428623 764 YAFLSPS 770
Cdd:cd06890   106 RDFFANR 112

The phosphoinositide binding Phox Homology domain of Sorting Nexin 1; 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. SNX1 is both membrane associated and a cytosolic protein that exists as a tetramer in protein complexes. It can associate reversibly with membranes of the endosomal compartment, thereby coating these vesicles. SNX1 is a component 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 efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. SNX1 contains a Bin/Amphiphysin/Rvs (BAR) domain C-terminal to the PX domain. The PX domain of SNX1 specifically binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,5)P2, while the BAR domain detects membrane curvature. Both domains help determine the specific membrane-targeting of SNX1, which is localized to a microdomain in early endosomes where it regulates cation-independent mannose-6-phosphate receptor retrieval to the trans Golgi network.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 667 EENGEQMPCYFV-RVNLQ-EVGGVETKNWTVPRRLSEFQNLHRKLSE-------CVPSLKKVQLPSLSKLPFKSIDH--- 734
Cdd:cd07281     9 EKIGDGMNAYVVyKVTTQtSLLMFRSKHFTVKRRFSDFLGLYEKLSEkhsqngfIVPPPPEKSLIGMTKVKVGKEDSssa 88

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1732428623 735 KFLGKSRNQLNAFLQNLLSDERLFQSEALYAFL 767
Cdd:cd07281    89 EFLERRRAALERYLQRIVSHPSLLQDPDVREFL 121

Regulator of G protein signaling (RGS) domain found in the R7 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R7 (Neuronal RGS) protein subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R7 subfamily includes RGS6, RGS7, RGS9, and RGS11, all of which, in humans, are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes. In addition, R7 proteins were found to bind many other proteins outside of the G protein signaling pathways including: m-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, guanylyl cyclase, among others.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 432 LQFEDIMTNPFYRERFGTYMERIDKRALVGFWESAEHLKNANKSEIPQLVSEMYQNFFVES--KEISVEKSLYKEIQQCL 509
Cdd:cd08705     7 FSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYGPQSQVPEKVQEIYQEFLAPGapSWINIDSKTMEITLKNL 86

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1732428623 510 vGNRGIEVFSKIQADVSEVLRERYYPSFLVSDLY 543
Cdd:cd08705    87 -KDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIY 119

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; 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. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 658 ASITSAEVTEENGEqmpcYFVRVNLqevgGVETKN-WTVPRRLSEFQNLHRKLSECVPSLkkvQLPslSKLPFKSIDHKF 736
Cdd:cd06871    10 CVIEASQNIQSHTE----YIIRVQR----GPSPENsWQVIRRYNDFDLLNASLQISGISL---PLP--PKKLIGNMDREF 76

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1732428623 737 LGKSRNQLNAFLQNLLSDERLFQSEALYAFLSP 769
Cdd:cd06871    77 IAERQQGLQNYLNVILMNPILASCLPVKKFLDP 109

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; 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. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1732428623 697 RRLSEFQNLHRKLSECVPSLKKVQLPSL-SKLPF----KSIDHKFLGKSRNQLNAFLQNLLSDERLFQSEALYAFLSP 769
Cdd:cd07280    43 KRYSEFVQLREALLDEFPRHKRNEIPQLpPKVPWydsrVNLNKAWLEKRRRGLQYFLNCVLLNPVFGGSPVVKEFLLP 120

Regulator of G protein signaling (RGS) domain found in the Axin protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the Axin protein. Axin is a member of the RA/RGS subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, and skeletal and muscle development. The RGS domain of Axin is specifically interacts with the heterotrimeric G-alpha12 protein, but not with closely related G-alpha13, and provides a unique tool to regulate G-alpha12-mediated signaling processes. The RGS domain of Axin also interacts with the tumor suppressor protein APC (Adenomatous Polyposis Coli) in order to control the cytoplasmic level of the proto-oncogene, beta-catenin.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 447 FGTYMERIDKRALVGFWESAEHLKNANKSE--IPQLVSEMYQNFFVESKEISVE-KSLYKEIQQCLVGNRGIE--VFSKI 521
Cdd:cd08707    14 FRTYLEQEGCADLLDFWFACNGFRKMSDSEekRSKLAKAIYRRYIKDNGIVSRQlKPATKSFIKECIKKQQLDpaMFDQA 93

                          90       100
                  ....*....|....*....|..
gi 1732428623 522 QADVSEVLRERYYPSFLVSDLY 543
Cdd:cd08707    94 QTEIQTTMEENTYPSFLKSDIY 115

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 13 (SNX13) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX13 (Sorting Nexin 13) protein, a member of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development. The RGS-domain of SNX13 plays a major role through attenuation of Galphas-mediated signaling and regulates endocytic trafficking and degradation of the epidermal growth factor receptor. Snx13-null mice were embryonic lethal around midgestation which supports an essential role for SNX13 in mouse development and regulation of endocytosis dynamics.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1732428623 447 FGTYMERIDKRALVGFW---------------------ESAEHLKNANKSEIPQLVSEMYQNFFVE--SKEISVEKSLYK 503
Cdd:cd08719    11 FIDFMQSVGGQAYLFFWltvegyrvsaeqqlselhlrqRGGEHQRSDVYEMLRAAALNIYDQYLSEkaSPRVPLDDSLVK 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1732428623 504 EIQQCL-VGNRGIEVFSKIQADVSEVLR--ERYYPSFLVSDLYEK 545
Cdd:cd08719    91 KLLNRLrNDTPSDLWFDDIQQKVFDIMQedERFYPAFKKSPAYVK 135