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 1182918148 467 AWKISIPYVDFFEDPSSERKekkerIPVFCIDVERNDRRAVGHEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKR 546
Cdd:cd06877     2 AWRVSIPYVEMRRDPSNGER-----IYVFCIEVERNDRRAKGHEPQHWSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRR 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1182918148 547 IIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLSPN 589
Cdd:cd06877    77 IFGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSPN 119

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 1182918148 710 WLHH-LLMGTRILFKNTLEMYTDYYLQCKLEQLFQEHRLVSLITLLRDAIFC-----ENTEPRSLQDKQKGAKQTFEEMM 783
Cdd:pfam08628   1 WLRRrALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPggllaEPPPERTEEEKLRTRKEARKLLL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1182918148 784 NYIPDLLVKCIGEETKYESIRLLFDGLQQPV 814
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQNPR 111

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148 467 AWKISIPYVDFFEDPSSERKekkerIPVFCIDVERNDRRAVGHEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKR 546
Cdd:cd06877     2 AWRVSIPYVEMRRDPSNGER-----IYVFCIEVERNDRRAKGHEPQHWSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRR 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1182918148 547 IIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLSPN 589
Cdd:cd06877    77 IFGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSPN 119

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 1182918148 710 WLHH-LLMGTRILFKNTLEMYTDYYLQCKLEQLFQEHRLVSLITLLRDAIFC-----ENTEPRSLQDKQKGAKQTFEEMM 783
Cdd:pfam08628   1 WLRRrALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPggllaEPPPERTEEEKLRTRKEARKLLL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1182918148 784 NYIPDLLVKCIGEETKYESIRLLFDGLQQPV 814
Cdd:pfam08628  81 SLIPDALGSVVGRENAREAARRVFDMLQNPR 111

Domain associated with PX domains; unpubl. observations

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148   76 ISSKVDASLSEVDIPSIITKKLLKAAMKHIEVIVKARQKvKNTEFLQQAALEEYGPE--LHVALRSRRDELHYLRKLTEL 153
Cdd:smart00313  44 ILRQLYRRLSRQDSAHLILYEILKNLISTITNALEAVLR-FASPQIPSTEIDLQYAEtaIHKALSSPSNELTYRRQLVEM 122

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1182918148  154 LFPYILPPKATDCRSLTLLIREILSGSVFLPSLDFLADPDTVNHLLIIFIDDS 206
Cdd:smart00313 123 LLKFLLPEDSLCSRLHRCLLREVLAMQVILPLITHLSDPDTINLCIILLFSSS 175

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 1182918148  240 LKQIREQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDrilrpELSNDEMLSLheeLQKIYKTYCLDESIDKIRFDPFIV 319
Cdd:smart00315   2 LESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKK-----AEDDEERIAK---AREIYDKFLSPNAPKEVNLDSDLR 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1182918148  320 EEIQRIAEGPYIDVvklqtmRCLFEAYEHVLSLLENVFTPMFCHSDEY 367
Cdd:smart00315  74 EKIEENLESEEPPP------DLFDEAQREVYELLEKDSFPRFLESDYY 115

Phox homology (PX) domain protein [Intracellular trafficking and secretion / General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148 456 VSTPNTPRNLAAWKISIpyvdfFEDPSSERKEKKERIPVFCIDVER--NDRRAVGHEPEHWSVYRRYLEFYVLESKLTEF 533
Cdd:COG5391   118 PPLSTSHTILDYFISST-----VSNPQSLTLLVDSRDKHTSYEIITvtNLPSFQLRESRPLVVRRRYSDFESLHSILIKL 192

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148 534 HGAFPDAQLPSKRIIGPKNY-----EFLKSKREEFQEYLQKLLQHPELSNSQ----------LLADFLSPNG--GETQFL 596
Cdd:COG5391   193 LPLCAIPPLPSKKSNSEYYGdrfsdEFIEERRQSLQNFLRRVSTHPLLSNYKnsksweshstLLSSFIENRKsvPTPLSL 272

                  ..
gi 1182918148 597 DK 598
Cdd:COG5391   273 DL 274

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 1182918148 467 AWKISIPYVDFFEDPSSERKekkerIPVFCIDVERNDRRAVGHEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKR 546
Cdd:cd06877     2 AWRVSIPYVEMRRDPSNGER-----IYVFCIEVERNDRRAKGHEPQHWSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRR 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1182918148 547 IIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLSPN 589
Cdd:cd06877    77 IFGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSPN 119

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 1182918148 710 WLHH-LLMGTRILFKNTLEMYTDYYLQCKLEQLFQEHRLVSLITLLRDAIFC-----ENTEPRSLQDKQKGAKQTFEEMM 783
Cdd:pfam08628   1 WLRRrALNALKQVLQQLLGDTIERKLRESVEWLTSEEQVASYIRLLRDALWPggllaEPPPERTEEEKLRTRKEARKLLL 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1182918148 784 NYIPDLLVKCIGEETKYESIRLLFDGLQQPV 814
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 1182918148 245 EQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDrilrpelSNDEMLSLHEELQKIYKTYCLDESIDKIRFDPFIVEEIQR 324
Cdd:cd07440     2 RDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKK-------TTSSDEELKSKAKEIYDKYISKDAPKEINIPESIREEIEE 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1182918148 325 IAEGPYIDvvklqtMRCLFEAYEHVLSLLENVFTPMFCHSDEYFR 369
Cdd:cd07440    75 NLEEPYPD------PDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

Domain associated with PX domains; unpubl. observations

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148   76 ISSKVDASLSEVDIPSIITKKLLKAAMKHIEVIVKARQKvKNTEFLQQAALEEYGPE--LHVALRSRRDELHYLRKLTEL 153
Cdd:smart00313  44 ILRQLYRRLSRQDSAHLILYEILKNLISTITNALEAVLR-FASPQIPSTEIDLQYAEtaIHKALSSPSNELTYRRQLVEM 122

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1182918148  154 LFPYILPPKATDCRSLTLLIREILSGSVFLPSLDFLADPDTVNHLLIIFIDDS 206
Cdd:smart00313 123 LLKFLLPEDSLCSRLHRCLLREVLAMQVILPLITHLSDPDTINLCIILLFSSS 175

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 1182918148  507 VGHEPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNY---EFLKSKREEFQEYLQKLLQHPELSN-SQLL 582
Cdd:smart00312  21 TKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNfseEFIEKRRRGLEKYLQSLLNHPELINhSEVV 100

                   ....*
gi 1182918148  583 ADFLS 587
Cdd:smart00312 101 LEFLE 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148 511 PEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLLQHPelsnSQLLADFLSPNG 590
Cdd:cd07277    29 DDEWNVYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVEERRKRLQVYLRRVVNTL----IQTSPELTACPS 104

                          90
                  ....*....|.
gi 1182918148 591 GETqfLDKILP 601
Cdd:cd07277   105 KET--LIKLLP 113

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 1182918148 480 DPSSERKEKKERIPVFCIDVerndrrAVGHEpeHWSVYRRYLEFYVLESKLTEfhgAFPDAQL--PSKRIIGpKNY--EF 555
Cdd:cd06870     8 PSSDEDREKKKRFTVYKVVV------SVGRS--SWFVFRRYAEFDKLYESLKK---QFPASNLkiPGKRLFG-NNFdpDF 75

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1182918148 556 LKSKREEFQEYLQKLLQHPELSNSQLLADFL 586
Cdd:cd06870    76 IKQRRAGLDEFIQRLVSDPKLLNHPDVRAFL 106

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 1182918148  240 LKQIREQQDLLFRFMNFLKQEGAVHVLQFCLTVEEFNDrilrpELSNDEMLSLheeLQKIYKTYCLDESIDKIRFDPFIV 319
Cdd:smart00315   2 LESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKK-----AEDDEERIAK---AREIYDKFLSPNAPKEVNLDSDLR 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1182918148  320 EEIQRIAEGPYIDVvklqtmRCLFEAYEHVLSLLENVFTPMFCHSDEY 367
Cdd:smart00315  74 EKIEENLESEEPPP------DLFDEAQREVYELLEKDSFPRFLESDYY 115

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1182918148 516 VYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGP-KNYEFLKSKREEFQEYLQKLLQHPE-LSNSQL 581
Cdd:cd06898    39 VRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRfNNEGFIEERQQGLQDFLEKVLQTPLlLSDSRL 106

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 1182918148 515 SVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIgpKNY--EFLKSKREE---------FQEYLQKLLQHPELSNSQLLA 583
Cdd:cd06867    29 EVKRRYSEFESLRKNLTRLYPTLIIPPIPEKHSL--KDYakKPSKAKNDAkiierrkrmLQRFLNRCLQHPILRNDIVFQ 106

                  ....*.
gi 1182918148 584 DFLSPN 589
Cdd:cd06867   107 KFLDPN 112

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 1182918148 487 EKKERIPVFCIDVERNDRRavghepehWSVYRRYLEFYVLESKLTEFHGAFPDAqLPSKRIIGPKNYEFLKSKREEFQEY 566
Cdd:cd06875    12 ETVEGYTVYIIEVKVGSVE--------WTVKHRYSDFAELHDKLVAEHKVDKDL-LPPKKLIGNKSPSFVEKRRKELEIY 82

                          90       100       110
                  ....*....|....*....|....*....|
gi 1182918148 567 LQKLLQHPELSNSQLLADFLSPNGGETQFL 596
Cdd:cd06875    83 LQTLLSFFQKTMPRELAHFLDFHKYEIIGL 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148 512 EHWSVYRRYLEFYVLESKLTEFHG--AFPDAQLPSKRIIG----------PKNYEFLKSKREEFQEYLQKLLQHPELSNS 579
Cdd:cd07281    35 KHFTVKRRFSDFLGLYEKLSEKHSqnGFIVPPPPEKSLIGmtkvkvgkedSSSAEFLERRRAALERYLQRIVSHPSLLQD 114

                  ....*..
gi 1182918148 580 QLLADFL 586
Cdd:cd07281   115 PDVREFL 121

The phosphoinositide binding Phox Homology domain of SNX-like proteins; 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. This subfamily is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148 504 RRAVGHEPEHWSVYRRYLEFYVLESKL-TEFHGAFPDAQlPSKRI---IGPKNYEFLKSKREEFQEYLQKLLQHPELSNS 579
Cdd:cd06865    32 TNIPSYTHGEFTVRRRFRDVVALADRLaEAYRGAFVPPR-PDKSVvesQVMQSAEFIEQRRVALEKYLNRLAAHPVIGLS 110

                  ....*...
gi 1182918148 580 QLLADFLS 587
Cdd:cd06865   111 DELRVFLT 118

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148 494 VFCIDVERNDRRAVghepehwsVYRRYLEFYVLESKLTEFHGAfPDaqLPSKRIIGpKNYEFLKSKREEFQEYLQKLLQH 573
Cdd:cd06880    21 VFTIEVLVNGRRHT--------VEKRYSEFHALHKKLKKSIKT-PD--FPPKRVRN-WNPKVLEQRRQGLEAYLQGLLKI 88

                          90
                  ....*....|...
gi 1182918148 574 PELsnSQLLADFL 586
Cdd:cd06880    89 NEL--PKQLLDFL 99

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 1182918148 510 EPEHWSVYRRYLEFYVLESKLTEFH-GAF--PdaqLPSKRIIG-PK-NYEFLKSKREEFQEYLQKLLQHPELSNSQLLAD 584
Cdd:cd06859    33 KKSEFSVLRRYSDFLWLYERLVEKYpGRIvpP---PPEKQAVGrFKvKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRL 109

                  ..
gi 1182918148 585 FL 586
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 1182918148 510 EPEHWSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLS 587
Cdd:cd06861    33 EVSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNFVEQRRAALEKMLRKIANHPVLQKDPDFRLFLE 110

The phosphoinositide binding Phox Homology domain of Sorting Nexin 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. SNX2 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. Similar to SNX1, SNX2 contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX domain of SNX2 preferentially binds phosphatidylinositol-3-phosphate (PI3P), but not PI(3,4,5)P3. Studies on mice deficient with SNX1 and/or SNX2 suggest that they provide an essential function in embryogenesis and are functionally redundant.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148 514 WSVYRRYLEFYVLESKLTE--FHGAFPDAQLPSKRIIG----------PKNYEFLKSKREEFQEYLQKLLQHPELSNSQL 581
Cdd:cd07282    37 FSVRRRFSDFLGLHSKLASkyLHVGYIVPPAPEKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQRTVKHPTLLQDPD 116

                  ....*
gi 1182918148 582 LADFL 586
Cdd:cd07282   117 LRQFL 121

The phosphoinositide binding Phox Homology domain of Sorting Nexin 7; 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. SNX7 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, SNX30, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX7 has yet to be elucidated.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1182918148 514 WSVYRRYLEFYVLESKLTEFHGAFPDAQLPSKRIIGPK----NYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLS 587
Cdd:cd07284    37 FEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFVMKGMverfNEDFIETRRKALHKFLNRIADHPTLTFNEDFKIFLT 114

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 1182918148 513 HWSVyrRYLEFYVLESKLTEFHGAFPDAQLPSKRIIgPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFL 586
Cdd:cd06885    30 HCSV--RYSQLHGLNEQLKKEFGNRKLPPFPPKKLL-PLTPAQLEERRLQLEKYLQAVVQDPRIANSDIFNSFL 100

The phosphoinositide binding Phox Homology domain of uncharacterized 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 fungal proteins containing a 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1182918148 516 VYRRYLEFYVLeskLTEFHGAFPDAQLPS---KRIIGPKNYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFL 586
Cdd:cd06879    65 VLRRFNDFLKL---HTDLKKLFPKKKLPAappKGLLRMKNRALLEERRHSLEEWMGKLLSDIDLSRSVPVASFL 135

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).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148 512 EHWSVYRRYLEFYVLESKLTEfhgAFPD--AQLPSKRIIGP-------KNYEFLKSKR-EEFQEYLQKLLQHPE-LSNSQ 580
Cdd:cd06890    27 KTRYLCRYYQDFYKLHIALLD---LFPAeaGRNSSKRILPYlpgpvtdVVNDSISLKRlNDLNEYLNELINLPAyIQTSE 103

                  ....*...
gi 1182918148 581 LLADFLSP 588
Cdd:cd06890   104 VVRDFFAN 111

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1182918148 510 EPEHWSVYRRYLEFYVLESKLTEFhgAFPDAQLPSKRIIGPK-NYEFLKSKREEFQEYLQKLLQHPELSNSQLLADFLSP 588
Cdd:cd06872    29 ENETWVVKRRFRNFETLHRRLKEV--PKYNLELPPKRFLSSSlDGAFIEERCKLLDKYLKDLLVIEKVAESHEVWSFLSA 106