Regulator of G protein signaling (RGS) domain found in the Sorting Nexin14 (SNX14) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX14 (Sorting Nexin14) 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. SNX14 is believed to regulates membrane trafficking in motor neurons.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 340 IREQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDEMLSLHEELQKIYKTYCLDESIDKIRFDPFIVEEI 419
Cdd:cd08722     1 ILDDQRLLFPFMQFLKEEGAVHLLQFCLTVEDFNRRILNPDLTDEEKQSLHKEAQEIYKTYFLPEAPDRIHFPPDIVEEI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1654950348 420 QRIAEGPYIDVVKLQTMRCLFEAYEHVLSLLENVFTPMFCHSDEYFR 466
Cdd:cd08722    81 KQILEGGPEKIVKLRTSRPLFEAYEHVYSLLESVFCPLFCHSDEYFI 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 130 SSKVDASLSEVLELVLENFVYPWYRDVTDDESFVDELRITLRFFASVLVRRIHKVDIPSIITKKLLKAAMKHIEVIVKAR 209
Cdd:pfam02194   1 SPEVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDLASLLLSRLLPLLTSHLEDYRKAE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 210 QKVKN---TEYLQQAALEEYGPELHVALR--------SRRDELQYLRKLTELLFPYILPPKATDCRSLTLLIREILSGSV 278
Cdd:pfam02194  81 EAVRGkklNELDLALASKYLALKPHPALSpvllsssqSREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170       180
                  ....*....|....*....|.
gi 1654950348 279 LLPSLDFLADPDTVNHLLIIF 299
Cdd:pfam02194 161 LLPVINKLSDPDFINELIVKL 181

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin14 (SNX14) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX14 (Sorting Nexin14) 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. SNX14 is believed to regulates membrane trafficking in motor neurons.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 340 IREQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDEMLSLHEELQKIYKTYCLDESIDKIRFDPFIVEEI 419
Cdd:cd08722     1 ILDDQRLLFPFMQFLKEEGAVHLLQFCLTVEDFNRRILNPDLTDEEKQSLHKEAQEIYKTYFLPEAPDRIHFPPDIVEEI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1654950348 420 QRIAEGPYIDVVKLQTMRCLFEAYEHVLSLLENVFTPMFCHSDEYFR 466
Cdd:cd08722    81 KQILEGGPEKIVKLRTSRPLFEAYEHVYSLLESVFCPLFCHSDEYFI 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 130 SSKVDASLSEVLELVLENFVYPWYRDVTDDESFVDELRITLRFFASVLVRRIHKVDIPSIITKKLLKAAMKHIEVIVKAR 209
Cdd:pfam02194   1 SPEVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDLASLLLSRLLPLLTSHLEDYRKAE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 210 QKVKN---TEYLQQAALEEYGPELHVALR--------SRRDELQYLRKLTELLFPYILPPKATDCRSLTLLIREILSGSV 278
Cdd:pfam02194  81 EAVRGkklNELDLALASKYLALKPHPALSpvllsssqSREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170       180
                  ....*....|....*....|.
gi 1654950348 279 LLPSLDFLADPDTVNHLLIIF 299
Cdd:pfam02194 161 LLPVINKLSDPDFINELIVKL 181

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 807 WLHH-LLMGTRILFKNTLEMYTDYYLQCKLEQLFQEHRLVSLITLLRDAIFC-----ENTEPRSLQDKQKGAKQTFEEMM 880
Cdd:pfam08628   1 WLRRrALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPggllaEPPPERTEEEKLRTRKEARKLLL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1654950348 881 NYIPDLIVKCIGEETKYESIRLLFDGLQQPV 911
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQNPR 111

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 1654950348  604 VGHEPEHWSVYRRYLEFYVLESKLTEFHGTFPDAQLPSKRIIGPKNY---EFLKSKREEFQEYLQKLVQHPELSN-SQLL 679
Cdd:smart00312  21 TKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNfseEFIEKRRRGLEKYLQSLLNHPELINhSEVV 100

                   ....*
gi 1654950348  680 ADFLS 684
Cdd:smart00312 101 LEFLE 105

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 1654950348 346 LLFRfmNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDemlslheeLQKIYKTYCLDESIDKIRFDPFIVEEIQriaeg 425
Cdd:pfam00615  13 RLFR--QFLESEFSEENLEFWLACEEFKKADPDEERLKK--------AKEIYNEFLAPGSPKEINLDSDLREEIR----- 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1654950348 426 pyiDVVKLQTMRCLFEAY-EHVLSLLENVFTPMFCHSDeYFRQL 468
Cdd:pfam00615  78 ---ENLEKEPTRDLFDEAqAEVYELMEKDSYPRFLKSP-LYLRL 117

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin14 (SNX14) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX14 (Sorting Nexin14) 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. SNX14 is believed to regulates membrane trafficking in motor neurons.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 340 IREQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDEMLSLHEELQKIYKTYCLDESIDKIRFDPFIVEEI 419
Cdd:cd08722     1 ILDDQRLLFPFMQFLKEEGAVHLLQFCLTVEDFNRRILNPDLTDEEKQSLHKEAQEIYKTYFLPEAPDRIHFPPDIVEEI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1654950348 420 QRIAEGPYIDVVKLQTMRCLFEAYEHVLSLLENVFTPMFCHSDEYFR 466
Cdd:cd08722    81 KQILEGGPEKIVKLRTSRPLFEAYEHVYSLLESVFCPLFCHSDEYFI 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 130 SSKVDASLSEVLELVLENFVYPWYRDVTDDESFVDELRITLRFFASVLVRRIHKVDIPSIITKKLLKAAMKHIEVIVKAR 209
Cdd:pfam02194   1 SPEVDAALDELIDLIIRDFVQSWYSKISSDPEFPNEVRQTLRHALRELSQRLRKVDLASLLLSRLLPLLTSHLEDYRKAE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 210 QKVKN---TEYLQQAALEEYGPELHVALR--------SRRDELQYLRKLTELLFPYILPPKATDCRSLTLLIREILSGSV 278
Cdd:pfam02194  81 EAVRGkklNELDLALASKYLALKPHPALSpvllsssqSREAEQKYLRLLVDGLLPLLLPPEDLESRPVRVLVREILACLV 160

                         170       180
                  ....*....|....*....|.
gi 1654950348 279 LLPSLDFLADPDTVNHLLIIF 299
Cdd:pfam02194 161 LLPVINKLSDPDFINELIVKL 181

Sorting nexin C terminal; This region is found a the C terminal of proteins belonging to the sorting nexin family. It is found on proteins which also contain pfam00787.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 807 WLHH-LLMGTRILFKNTLEMYTDYYLQCKLEQLFQEHRLVSLITLLRDAIFC-----ENTEPRSLQDKQKGAKQTFEEMM 880
Cdd:pfam08628   1 WLRRrALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPggllaEPPPERTEEEKLRTRKEARKLLL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1654950348 881 NYIPDLIVKCIGEETKYESIRLLFDGLQQPV 911
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQNPR 111

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 1654950348 342 EQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDrilrpelSNDEMLSLHEELQKIYKTYCLDESIDKIRFDPFIVEEIQR 421
Cdd:cd07440     2 RDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKK-------TTSSDEELKSKAKEIYDKYISKDAPKEINIPESIREEIEE 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1654950348 422 IAEGPYIDvvklqtMRCLFEAYEHVLSLLENVFTPMFCHSDEYFR 466
Cdd:cd07440    75 NLEEPYPD------PDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

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 1654950348 566 KISIpyVDFFEDPSSERKEkkerIPVFCIDVER--NDRRAVGhepehWSVYRRYLEFYVLESKLTEFHGTFPDAQLPSKR 643
Cdd:cd06876    21 RVSI--QSYISDVEEEGKE----FVVYLIEVQRlnNDDQSSG-----WVVARRYSEFLELHKYLKKRYPGVLKLDFPQKR 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1654950348 644 IIGPKNYE--FLKSKREEFQEYLQKLVQHPELSNSQLLADFLS 684
Cdd:cd06876    90 KISLKYSKtlLVEERRKALEKYLQELLKIPEVCEDEEFRKFLS 132

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; 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. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 581 ERKEKKERIPVFCIDVERNdrravghEPEHWSVYRRYLEFYVLESKLTEFHGTFPDAqLPSKRIIGPK-NYEFLKSKREE 659
Cdd:cd07276    12 EVMEERARFTVYKIRVENK-------VGDSWFVFRRYTDFVRLNDKLKQMFPGFRLS-LPPKRWFKDNfDPDFLEERQLG 83

                          90       100
                  ....*....|....*....|....
gi 1654950348 660 FQEYLQKLVQHPELSNSQLLADFL 683
Cdd:cd07276    84 LQAFVNNIMAHKDIAKCKLVREFF 107

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 1654950348 608 PEHWSVYRRYLEFYVLESKLTEFHGTFPDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLVQHpelsNSQLLADFLSPNG 687
Cdd:cd07277    29 DDEWNVYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVEERRKRLQVYLRRVVNT----LIQTSPELTACPS 104

                          90
                  ....*....|.
gi 1654950348 688 GETqfLDKILP 698
Cdd:cd07277   105 KET--LIKLLP 113

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 1654950348 592 FCIDVERndrravGHEPEH-WSVYRRYLEFYVLESKLtEFHGTfpDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLVQH 670
Cdd:cd06871    24 YIIRVQR------GPSPENsWQVIRRYNDFDLLNASL-QISGI--SLPLPPKKLIGNMDREFIAERQQGLQNYLNVILMN 94

                          90       100
                  ....*....|....*....|....
gi 1654950348 671 PELSNSQLLADFLSPNGGETQFLD 694
Cdd:cd06871    95 PILASCLPVKKFLDPNNYSANFTE 118

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 1654950348 583 KEKKERIPVFCIDVERNDRRAvghEPEHWSVYRRYLEFYVLESKLTEFHGTFPDAQLPSKRIIGPKNYEFLKSKREEFQE 662
Cdd:cd06873    16 KEHGKTYAVYAISVTRIYPNG---QEESWHVYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKTFNNLDRAFLEKRRKMLNQ 92

                          90       100
                  ....*....|....*....|....*..
gi 1654950348 663 YLQKLVQHPELSNS----QLLADFLSP 685
Cdd:cd06873    93 YLQSLLNPEVLDANpglqEIVLDFLEP 119

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 1654950348 612 SVYRRYLEFYVLESKLTEFHGTFPDAQLPSKRIIgpKNY--EFLKSKREE---------FQEYLQKLVQHPELSNSQLLA 680
Cdd:cd06867    29 EVKRRYSEFESLRKNLTRLYPTLIIPPIPEKHSL--KDYakKPSKAKNDAkiierrkrmLQRFLNRCLQHPILRNDIVFQ 106

                  ....*.
gi 1654950348 681 DFLSPN 686
Cdd:cd06867   107 KFLDPN 112

The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; 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 fungal proteins similar to Saccharomyces cerevisiae Vam7p. They contain an N-terminal PX domain and a C-terminal SNARE domain. The SNARE (Soluble NSF attachment protein receptor) family of proteins are integral membrane proteins that serve as key factors for vesicular trafficking. Vam7p is anchored at the vacuolar membrane through the specific interaction of its PX domain with phosphatidylinositol-3-phosphate (PI3P) present in bilayers. It plays an essential role in vacuole fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1654950348 611 WSVYRRYLEFYVLESKLT-EFHGTFPdAQLPSKRII--GPKNYEFLKSKREEFQEYLQKLVQHPE--LSNSQLLADFLS 684
Cdd:cd06897    29 YTVSRRYSEFVALHKQLEsEVGIEPP-YPLPPKSWFlsTSSNPKLVEERRVGLEAFLRALLNDEDsrWRNSPAVKEFLN 106

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; 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. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. 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. 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 1654950348 584 EKKERIPVFCIDVERNDRRavghepehWSVYRRYLEFYVLESKLTEFHGTFPDAqLPSKRIIGPKNYEFLKSKREEFQEY 663
Cdd:cd06875    12 ETVEGYTVYIIEVKVGSVE--------WTVKHRYSDFAELHDKLVAEHKVDKDL-LPPKKLIGNKSPSFVEKRRKELEIY 82

                          90       100       110
                  ....*....|....*....|....*....|
gi 1654950348 664 LQKLVQHPELSNSQLLADFLSPNGGETQFL 693
Cdd:cd06875    83 LQTLLSFFQKTMPRELAHFLDFHKYEIIGL 112

The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; 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. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. Through its SH3 domain, SNX9 binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1654950348 612 SVYRRYLEF-YVLESKLTEFHGTFPDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLVQHPELSNSQLLADFLS 684
Cdd:cd07285    33 SVNHRYKHFdWLYERLLVKFGLAIPIPSLPDKQVTGRFEEEFIKMRMERLQAWMTRMCRHPVISESEVFQQFLN 106

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 591 VFCIDVERNDRRAVghepehwsVYRRYLEFYVLESKLTEFHGTfPDaqLPSKRIIGpKNYEFLKSKREEFQEYLQKLVQH 670
Cdd:cd06880    21 VFTIEVLVNGRRHT--------VEKRYSEFHALHKKLKKSIKT-PD--FPPKRVRN-WNPKVLEQRRQGLEAYLQGLLKI 88

                          90
                  ....*....|...
gi 1654950348 671 PELsnSQLLADFL 683
Cdd:cd06880    89 NEL--PKQLLDFL 99

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 346 LLFRfmNFLKQEGAVHVLQFCLTVEEFNDRILRPELSNDemlslheeLQKIYKTYCLDESIDKIRFDPFIVEEIQriaeg 425
Cdd:pfam00615  13 RLFR--QFLESEFSEENLEFWLACEEFKKADPDEERLKK--------AKEIYNEFLAPGSPKEINLDSDLREEIR----- 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1654950348 426 pyiDVVKLQTMRCLFEAY-EHVLSLLENVFTPMFCHSDeYFRQL 468
Cdd:pfam00615  78 ---ENLEKEPTRDLFDEAqAEVYELMEKDSYPRFLKSP-LYLRL 117

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 607 EPEHWSVYRRYLEFYVLESKLTEFH-GTF--PdaqLPSKRIIG-PK-NYEFLKSKREEFQEYLQKLVQHPELSNSQLLAD 681
Cdd:cd06859    33 KKSEFSVLRRYSDFLWLYERLVEKYpGRIvpP---PPEKQAVGrFKvKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRL 109

                  ..
gi 1654950348 682 FL 683
Cdd:cd06859   110 FL 111

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; 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. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1654950348 607 EPEHWSVYRRYLEFYVLESKLTEFHGTFPDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLVQHPELSNSQLLADFLS 684
Cdd:cd06861    33 EVSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNFVEQRRAALEKMLRKIANHPVLQKDPDFRLFLE 110

The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. 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. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1654950348 610 HWSVyrRYLEFYVLESKLTEFHGTFPDAQLPSKRIIgPKNYEFLKSKREEFQEYLQKLVQHPELSNSQLLADFL 683
Cdd:cd06885    30 HCSV--RYSQLHGLNEQLKKEFGNRKLPPFPPKKLL-PLTPAQLEERRLQLEKYLQAVVQDPRIANSDIFNSFL 100

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 609 EHWSVYRRYLEFYVLESKLTEFHGTFPDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLV 668
Cdd:cd06874    30 ETWTVFRRYSRFRELHKTMKLKYPEVAALEFPPKKLFGNKSERVAKERRRQLETYLRNFF 89

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1654950348 594 IDVERNDRRAVGHEP--EHWSVYRRYLEFYVLESKLTEFHG--TFPDAQLPSKRI----IGPKNYEFLKSKREEFQEYLQ 665
Cdd:cd06893    32 LDVQSEQNPNAASEQplATHTVNRRFREFLTLQTRLEENPKfrKIMNVKGPPKRLfdlpFGNMDKDKIEARRGLLETFLR 111

                          90       100
                  ....*....|....*....|.
gi 1654950348 666 KLVQHPELSNSQLLADFLSPN 686
Cdd:cd06893   112 QLCSIPEISNSEEVQEFLAYG 132

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 1654950348 613 VYRRYLEFYVLESKLTEfhgTFPDA------QLPSKRIIGPK----NYEFLKSKREEFQEYLQKLVQHPELSNSQLLADF 682
Cdd:cd07280    41 AYKRYSEFVQLREALLD---EFPRHkrneipQLPPKVPWYDSrvnlNKAWLEKRRRGLQYFLNCVLLNPVFGGSPVVKEF 117

                  ...
gi 1654950348 683 LSP 685
Cdd:cd07280   118 LLP 120