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 1800417255  488 ILANTFYREHFGMYMERMDKRALISFWESVEHLKNANKNEIPQLVGEIYQNFFVESK-EISVEKSLYKEIQQCLVGNKGI 566
Cdd:cd08720      1 ILANVFGRKYLSQFLERMDSQALIGFWEAVEELRSANKSEWHQLGAEIFYTFIVEPTaEIKVDKSLRKRIEQFLLGDKGP 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1800417255  567 EVFYKIQEDVYETLKDRYYPSFIVSDLYEK 596
Cdd:cd08720     81 EVFYEVQENVVETLEEKYYPSFVVSDQYKQ 110

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  166 DKALKEVFDYSYRDYILSWYGNLSRDEG---QLYHLLLEdfweIARQLHHRLSHVDVVKVVCNDVVRTLLTHF------- 235
Cdd:pfam02194    5 DAALDELIDLIIRDFVQSWYSKISSDPEfpnEVRQTLRH----ALRELSQRLRKVDLASLLLSRLLPLLTSHLedyrkae 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  236 ----------CDLKAANARHEEQPRPFVLHACLRNSDD---EVRFLQTCSRVLVFCLLPSKDVQSLSLRIMLAEILTTKV 302
Cdd:pfam02194   81 eavrgkklneLDLALASKYLALKPHPALSPVLLSSSQSreaEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                          170
                   ....*....|....*....
gi 1800417255  303 LKPVVELLSNPDYINQMLL 321
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 1800417255  488 ILANTFYREHFGMYMERMDKRALISFWESVEHLKNANKNEIPQLVGEIYQNFFVESK-EISVEKSLYKEIQQCLVGNKGI 566
Cdd:cd08720      1 ILANVFGRKYLSQFLERMDSQALIGFWEAVEELRSANKSEWHQLGAEIFYTFIVEPTaEIKVDKSLRKRIEQFLLGDKGP 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1800417255  567 EVFYKIQEDVYETLKDRYYPSFIVSDLYEK 596
Cdd:cd08720     81 EVFYEVQENVVETLEEKYYPSFVVSDQYKQ 110

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  485 FEDILANTFYREHFGMYMERMDKRALISFWESVEHLKNA-NKNEIPQLVGEIYQNFFVES--KEISVEKSLYKEIQQCLV 561
Cdd:pfam00615    2 FDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKAdPDEERLKKAKEIYNEFLAPGspKEINLDSDLREEIRENLE 81

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1800417255  562 GNKGIEVFYKIQEDVYETLKDRYYPSFIVSDLYEKL 597
Cdd:pfam00615   82 KEPTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

PX domain; PX domains bind to phosphoinositides.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  742 KNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPSlsKLPFKSIDQKFMEKSKNQLNKFLQNLLSDERLCQSEALYAFLSPS 821
Cdd:pfam00787    7 EEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPP--KRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLESD 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 1800417255   485 FEDILANTFYREHFGMYMERMDKRALISFWESVE-HLKNANKNEIPQLVGEIYQNFFVE--SKEISVEKSLYKEIQQCLV 561
Cdd:smart00315    2 LESLLSDPIGRLLFREFLESEFSEENLEFWLAVEeFKKAEDDEERIAKAREIYDKFLSPnaPKEVNLDSDLREKIEENLE 81

                            90       100       110
                    ....*....|....*....|....*....|....*..
gi 1800417255   562 GNK-GIEVFYKIQEDVYETLKDRYYPSFIVSDLYEKL 597
Cdd:smart00315   82 SEEpPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

reticulocyte binding/rhoptry protein; This model represents a group of paralogous families in plasmodium species alternately annotated as reticulocyte binding protein, 235-kDa family protein and rhoptry protein. Rhoptry protein is localized on the cell surface and is extremely large (although apparently lacking in repeat structure) and is important for the process of invasion of the RBCs by the parasite. These proteins are found in P. falciparum, P. vivax and P. yoelii.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  331 NEHHKRAYTYAPSYEDFIKLINSNSDVEFLKQLRESVQTSALLILEPNSALAKSYPPLEKENRVSAryqiVVEIIQATT- 409
Cdd:TIGR01612  856 NNCKEKIDSEHEQFAELTNKIKAEISDDKLNDYEKKFNDSKSLINEINKSIEEEYQNINTLKKVDE----YIKICENTKe 931

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  410 -ISSFPQlKRHKGKETAAMKADLLRARNM--KRYINQ----LTVAKKQCEKRIRilggpaydqqeDGALDEGEGPQSQKI 482
Cdd:TIGR01612  932 sIEKFHN-KQNILKEILNKNIDTIKESNLieKSYKDKfdntLIDKINELDKAFK-----------DASLNDYEAKNNELI 999

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  483 LQFEDILANTFYREHFGMYMERMDKRALISfwESVEHLKNANKNeIPQLVGEIYQNFFVESKEISVE-----KSLYKEIQ 557
Cdd:TIGR01612 1000 KYFNDLKANLGKNKENMLYHQFDEKEKATN--DIEQKIEDANKN-IPNIEIAIHTSIYNIIDEIEKEigkniELLNKEIL 1076

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  558 QclVGNKGIEVFYKIQEdvyeTLKDRYYPSFIvsdlyeklliKEEE-KHASQMISNKDEMGPRDE-------AGEEAVDD 629
Cdd:TIGR01612 1077 E--EAEINITNFNEIKE----KLKHYNFDDFG----------KEENiKYADEINKIKDDIKNLDQkidhhikALEEIKKK 1140

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1800417255  630 GTNQINEQASfAVNKLRELNEKLEYK---RQALNSIQN-APKPDKKI-----VSKLKDEIILIEKERTDLQ 691
Cdd:TIGR01612 1141 SENYIDEIKA-QINDLEDVADKAISNddpEEIEKKIENiVTKIDKKKniydeIKKLLNEIAEIEKDKTSLE 1210

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 1800417255  488 ILANTFYREHFGMYMERMDKRALISFWESVEHLKNANKNEIPQLVGEIYQNFFVESK-EISVEKSLYKEIQQCLVGNKGI 566
Cdd:cd08720      1 ILANVFGRKYLSQFLERMDSQALIGFWEAVEELRSANKSEWHQLGAEIFYTFIVEPTaEIKVDKSLRKRIEQFLLGDKGP 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1800417255  567 EVFYKIQEDVYETLKDRYYPSFIVSDLYEK 596
Cdd:cd08720     81 EVFYEVQENVVETLEEKYYPSFVVSDQYKQ 110

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  485 FEDILANTFYREHFGMYMERMDKRALISFWESVEHLKNA-NKNEIPQLVGEIYQNFFVES--KEISVEKSLYKEIQQCLV 561
Cdd:pfam00615    2 FDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKAdPDEERLKKAKEIYNEFLAPGspKEINLDSDLREEIRENLE 81

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1800417255  562 GNKGIEVFYKIQEDVYETLKDRYYPSFIVSDLYEKL 597
Cdd:pfam00615   82 KEPTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  166 DKALKEVFDYSYRDYILSWYGNLSRDEG---QLYHLLLEdfweIARQLHHRLSHVDVVKVVCNDVVRTLLTHF------- 235
Cdd:pfam02194    5 DAALDELIDLIIRDFVQSWYSKISSDPEfpnEVRQTLRH----ALRELSQRLRKVDLASLLLSRLLPLLTSHLedyrkae 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  236 ----------CDLKAANARHEEQPRPFVLHACLRNSDD---EVRFLQTCSRVLVFCLLPSKDVQSLSLRIMLAEILTTKV 302
Cdd:pfam02194   81 eavrgkklneLDLALASKYLALKPHPALSPVLLSSSQSreaEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                          170
                   ....*....|....*....
gi 1800417255  303 LKPVVELLSNPDYINQMLL 321
Cdd:pfam02194  161 LLPVINKLSDPDFINELIV 179

PX domain; PX domains bind to phosphoinositides.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  742 KNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPSlsKLPFKSIDQKFMEKSKNQLNKFLQNLLSDERLCQSEALYAFLSPS 821
Cdd:pfam00787    7 EEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPP--KRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLESD 84

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  718 EENGEQLPCYFVMVSLQEVGGVETkNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPSLSKLPFKSIDQKFMEKSKNQLNK 797
Cdd:cd06876     32 EEEGKEFVVYLIEVQRLNNDDQSS-GWVVARRYSEFLELHKYLKKRYPGVLKLDFPQKRKISLKYSKTLLVEERRKALEK 110

                           90       100
                   ....*....|....*....|..
gi 1800417255  798 FLQNLLSDERLCQSEALYAFLS 819
Cdd:cd06876    111 YLQELLKIPEVCEDEEFRKFLS 132

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 1800417255  709 ASITSGEVTEENGEQLPCYFVMVSLQEVGGVEtKNWTVPRRLSEFQNLHRKLSECVPSLKKVQLPslSKLPFKSIDQKFM 788
Cdd:cd06873      7 AVIINTGIVKEHGKTYAVYAISVTRIYPNGQE-ESWHVYRRYSDFHDLHMRLKEKFPNLSKLSFP--GKKTFNNLDRAFL 83

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1800417255  789 EKSKNQLNKFLQNLLSDERLCQS----EALYAFLSP 820
Cdd:cd06873     84 EKRRKMLNQYLQSLLNPEVLDANpglqEIVLDFLEP 119

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 1800417255  489 LANTFYREHFGMYMERMDKRALISFWESVEHLKNAN--KNEIPQLVGEIYQNFFVE--SKEISVEKSLYKEIQQCLVG-N 563
Cdd:cd07440      1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTssDEELKSKAKEIYDKYISKdaPKEINIPESIREEIEENLEEpY 80

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1800417255  564 KGIEVFYKIQEDVYETLKDRYYPSFIVSDLYEK 596
Cdd:cd07440     81 PDPDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

Regulator of G protein signaling (RGS) domain found in the RGS6 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS6 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). Other members of the R7 subfamily (Neuronal RGS) include: RGS7, 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. RGS6 exists in multiple splice isoforms with identical RGS domains, but possess complete or incomplete GGL domains and distinct N- and C-terminal domains. RGS6 interacts with SCG10, a neuronal growth-associated protein and therefore regulates neuronal differentiation. Another RGS6-binding protein is DMAP1, a component of the Dnmt1 complex involved in repression of newly replicated genes. Mutations of a critical residue required for interaction of RGS6 protein with G proteins did not affect the ability of RGS6 to interact with both SCG10 and DMAP1. 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  485 FEDILANTFYREHFGMYMERMDKRALISFWESVEHLKNANKNEIPQLVGEIYQNFFVESKE--ISVEKSLYKEIQQClVG 562
Cdd:cd08737     10 LDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPsaINLDSHSYEKTSQN-VK 88

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1800417255  563 NKGIEVFYKIQEDVYETLKDRYYPSFIVSDLYEKLLI 599
Cdd:cd08737     89 DPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 125

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  483 LQFEDILANTFYREHFGMYMERMDKRALISFWESVEHLKNANKNEIPQLVGEIYQNFFVES--KEISVEKSLYKEIQQCL 560
Cdd:cd08705      7 FSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYGPQSQVPEKVQEIYQEFLAPGapSWINIDSKTMEITLKNL 86

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1800417255  561 vGNKGIEVFYKIQEDVYETLKDRYYPSFIVSDLY 594
Cdd:cd08705     87 -KDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIY 119

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  731 VSLQEVGGVETKNWTVPRRLSEFQNLHRKLSEcVPSLkKVQLPSLSKLPfKSIDQKFMEKSKNQLNKFLQNLLSDERLCQ 810
Cdd:cd06872     20 VYSVAVTDNENETWVVKRRFRNFETLHRRLKE-VPKY-NLELPPKRFLS-SSLDGAFIEERCKLLDKYLKDLLVIEKVAE 96

                   ....*....
gi 1800417255  811 SEALYAFLS 819
Cdd:cd06872     97 SHEVWSFLS 105

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 1800417255  709 ASITSGEVTEENgEQLPCYFVMVSlqevggVETKNWTVPRRLSEFqnlhRKLSEcvpSLKKvQLPSLS-KLPFKSI---- 783
Cdd:cd06870      6 SIPSSDEDREKK-KRFTVYKVVVS------VGRSSWFVFRRYAEF----DKLYE---SLKK-QFPASNlKIPGKRLfgnn 70

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1800417255  784 -DQKFMEKSKNQLNKFLQNLLSDERLCQSEALYAFL 818
Cdd:cd06870     71 fDPDFIKQRRAGLDEFIQRLVSDPKLLNHPDVRAFL 106

reticulocyte binding/rhoptry protein; This model represents a group of paralogous families in plasmodium species alternately annotated as reticulocyte binding protein, 235-kDa family protein and rhoptry protein. Rhoptry protein is localized on the cell surface and is extremely large (although apparently lacking in repeat structure) and is important for the process of invasion of the RBCs by the parasite. These proteins are found in P. falciparum, P. vivax and P. yoelii.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  331 NEHHKRAYTYAPSYEDFIKLINSNSDVEFLKQLRESVQTSALLILEPNSALAKSYPPLEKENRVSAryqiVVEIIQATT- 409
Cdd:TIGR01612  856 NNCKEKIDSEHEQFAELTNKIKAEISDDKLNDYEKKFNDSKSLINEINKSIEEEYQNINTLKKVDE----YIKICENTKe 931

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  410 -ISSFPQlKRHKGKETAAMKADLLRARNM--KRYINQ----LTVAKKQCEKRIRilggpaydqqeDGALDEGEGPQSQKI 482
Cdd:TIGR01612  932 sIEKFHN-KQNILKEILNKNIDTIKESNLieKSYKDKfdntLIDKINELDKAFK-----------DASLNDYEAKNNELI 999

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  483 LQFEDILANTFYREHFGMYMERMDKRALISfwESVEHLKNANKNeIPQLVGEIYQNFFVESKEISVE-----KSLYKEIQ 557
Cdd:TIGR01612 1000 KYFNDLKANLGKNKENMLYHQFDEKEKATN--DIEQKIEDANKN-IPNIEIAIHTSIYNIIDEIEKEigkniELLNKEIL 1076

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  558 QclVGNKGIEVFYKIQEdvyeTLKDRYYPSFIvsdlyeklliKEEE-KHASQMISNKDEMGPRDE-------AGEEAVDD 629
Cdd:TIGR01612 1077 E--EAEINITNFNEIKE----KLKHYNFDDFG----------KEENiKYADEINKIKDDIKNLDQkidhhikALEEIKKK 1140

                          330       340       350       360       370       380       390
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1800417255  630 GTNQINEQASfAVNKLRELNEKLEYK---RQALNSIQN-APKPDKKI-----VSKLKDEIILIEKERTDLQ 691
Cdd:TIGR01612 1141 SENYIDEIKA-QINDLEDVADKAISNddpEEIEKKIENiVTKIDKKKniydeIKKLLNEIAEIEKDKTSLE 1210

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; 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. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  744 WTVPRRLSEFQNLHRKLSECVPSLKKVQLPslSKLPFKSIDQKFMEKSKNQLNKFLQNLLSderLCQSealyafLSPSPD 823
Cdd:cd06874     32 WTVFRRYSRFRELHKTMKLKYPEVAALEFP--PKKLFGNKSERVAKERRRQLETYLRNFFS---VCLK------LPACPL 100

                           90
                   ....*....|....*....
gi 1800417255  824 YLKVIDVQGKKNSFSLSSF 842
Cdd:cd06874    101 YPKVGRTLSKATLCDFSPF 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  738 GVETKN-WTVPRRLSEFQNLHRKLSECVPSLkkvQLPslSKLPFKSIDQKFMEKSKNQLNKFLQNLLSDERLCQSEALYA 816
Cdd:cd06871     31 GPSPENsWQVIRRYNDFDLLNASLQISGISL---PLP--PKKLIGNMDREFIAERQQGLQNYLNVILMNPILASCLPVKK 105

                   ....
gi 1800417255  817 FLSP 820
Cdd:cd06871    106 FLDP 109

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  708 KASITSgevTEENGEQLPCYFVM-VSLQ-EVGGVETKNWTVPRRLSEFQNLHRKLSE-------CVPSLKKVQLPSLSKL 778
Cdd:cd07281      2 KVSITD---PEKIGDGMNAYVVYkVTTQtSLLMFRSKHFTVKRRFSDFLGLYEKLSEkhsqngfIVPPPPEKSLIGMTKV 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1800417255  779 PFKSIDQ---KFMEKSKNQLNKFLQNLLSDERLCQSEALYAFL 818
Cdd:cd07281     79 KVGKEDSssaEFLERRRAALERYLQRIVSHPSLLQDPDVREFL 121

Regulator of G protein signaling (RGS) domain found in the RGS2 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS2 protein. RGS2 is a member of R4/RGS subfamily of RGS 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. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G- alpha subunit which leads to G protein deactivation and promotes desensitization. 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. RGS2 plays important roles in the regulation of blood pressure and the pathogenesis of human hypertension, as well as in bone formation in osteoblasts. Outside of the GPCR pathway RGS2 interacts with calmodulin, beta- COP, tubulin, PKG1-alpha, and TRPV6.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1800417255  485 FEDILANTFYREHFGMYMERMDKRALISFWESVEHLKnanKNEIPQLVG----EIYQNFFVES--KEISVEKSLYKEIQQ 558
Cdd:cd08709      1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFK---KTKSPQKLTskakKIYTDFIEKEapKEINIDFQTKTLIAQ 77

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1800417255  559 CLvGNKGIEVFYKIQEDVYETLKDRYYPSFIVSDLYEK 596
Cdd:cd08709     78 NI-QEATSGCFTAAQKRVYSLMENNSYPRFLESEFYQE 114