The phosphoinositide binding Phox Homology domain of Sorting Nexin 30; 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. SNX30 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX30 has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  82 LFVTVDDPKKHVSTMETYITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEDSQPTHLIPPLPEKFVMKGVVDRFSE 161
Cdd:cd07283   1 LFVTVDDPKKHVCTMETYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRFSE 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 62955569 162 EFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSAK 197
Cdd:cd07283  81 EFVETRRKALDKFLKRIADHPVLSFNEHFNVFLTAK 116

The phosphoinositide binding Phox Homology domain of Sorting Nexin 30; 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. SNX30 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX30 has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  82 LFVTVDDPKKHVSTMETYITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEDSQPTHLIPPLPEKFVMKGVVDRFSE 161
Cdd:cd07283   1 LFVTVDDPKKHVCTMETYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRFSE 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 62955569 162 EFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSAK 197
Cdd:cd07283  81 EFVETRRKALDKFLKRIADHPVLSFNEHFNVFLTAK 116

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  79 TRDLFVTVDDPKKHVSTME---TYITYRVCTKTTRTEFDL---PEYSVRRRYQDFDWLRIKLEDSQPTHLIPPLPEK-FV 151
Cdd:COG5391 128 DYFISSTVSNPQSLTLLVDsrdKHTSYEIITVTNLPSFQLresRPLVVRRRYSDFESLHSILIKLLPLCAIPPLPSKkSN 207

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 152 MKGVVDRFSEEFVETRRKALDKFLKRVADHPVLS-------FNEHFNAFLSAKDLNKRQGLALLTKMGESVkyvtggykl 224
Cdd:COG5391 208 SEYYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSnyknsksWESHSTLLSSFIENRKSVPTPLSLDLTSTT--------- 278

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 225 RGRPVEFAAMGEYLDMFTQKLGTIDRIAQRIIKEQTEFLMELREYGPVYSSWSSFEEDLHEPL---------EGVSGCVS 295
Cdd:COG5391 279 QELDMERKELNESTSKAIHNILSIFSLFEKILIQLESEEESLTRLLESLNNLLLLVLNFSGVFakrleqnqnSILNEGVV 358

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 296 NCSSALEELTEDMSEdFLPVLREYVLYIESMKNVLKKRDQVQAEYETKLEAVVF--RED-------------KKTPM--- 357
Cdd:COG5391 359 QAETLRSSLKELLTQ-LQDEIKSRESLILTDSNLEKLTDQNLEDVEELSRSLRKnsSQRavvsqqpegltsfSKLSYklr 437

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 358 PTDVEKCQDR----------------------VECFNADLKADWDRWQNNKRQDFRQLLTGMADKNIQYYEKCLAAWESL 415
Cdd:COG5391 438 DFVQEKSRSKsieslqqdkekleeqlaiaekdAQEINEELKNELKFFFSVRNSDLEKILKSVADSHIEWAEENLEIWKSV 517

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins 7 and 30; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. This subfamily consists of SNX7, SNX30, and similar proteins. The specific functions of SNX7 and SNX30 have not been elucidated. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 218 VTGGYKLRGRPVEFAAMGEYLDMFTQKLGTIDRIAQRIIKEQTEFLMELREYGPVYSSWSSFEEDLHEPLEGVSGCVSNC 297
Cdd:cd07624   3 TSTMYLLKNRSPEFDKMNEYLTLFGEKLGTIERISQRIHKERIEYFDELKEYSPIFQLWSASETELAPLLEGVSSAVERC 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 298 SSALEELTEDMSEDFLPVLREYVLYIESMKNVLKKRDQVQAEYETKLEAVvfrEDKKTPMPTDVEKCQDRVECFNADLKA 377
Cdd:cd07624  83 TAALEVLLSDHEFVFLPPLREYLLYSDAVKDVLKRRDQFQIEYELSVEEL---NKKRLELLKEVEKLQDKLECANADLKA 159

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 62955569 378 DWDRWQNNKRQDFRQLLTGMADKNIQYYEKCLAAWESLIPL 418
Cdd:cd07624 160 DLERWKQNKRQDLKKILLDMAEKQIQYYEQCLAAWEEVLPA 200

The phosphoinositide binding Phox Homology domain of Sorting Nexin 30; 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. SNX30 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX30 has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  82 LFVTVDDPKKHVSTMETYITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEDSQPTHLIPPLPEKFVMKGVVDRFSE 161
Cdd:cd07283   1 LFVTVDDPKKHVCTMETYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRFSE 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 62955569 162 EFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSAK 197
Cdd:cd07283  81 EFVETRRKALDKFLKRIADHPVLSFNEHFNVFLTAK 116

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  82 LFVTVDDPKKHVSTMETYITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEDSQPTHLIPPLPEKFVMKGVVDRFSE 161
Cdd:cd07284   1 IFITVDEPESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFVMKGMVERFNE 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 62955569 162 EFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSAK 197
Cdd:cd07284  81 DFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 116

The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX domain. 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 62955569  82 LFVTVDDPKKHV-STMETYITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEDSQPTHLIPPLPEKFVMKGVV-DRF 159
Cdd:cd06863   1 LECLVSDPQKELdGSSDTYISYLITTKTNLPSFSRKEFKVRRRYSDFVFLHECLSNDFPACVVPPLPDKHRLEYITgDRF 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 62955569 160 SEEFVETRRKALDKFLKRVADHPVLSFNEHFNAFLS 195
Cdd:cd06863  81 SPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFLE 116

The phosphoinositide binding Phox Homology domain of Sorting Nexins 9 and 18; 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 SNX9, SNX18, and similar proteins. They contain an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  84 VTVDDPKKH--VSTMETYITYRVCTKTTRTefdlpeySVRRRYQDFDWLRIKLEDSQPTHLIPPLPEKfvmkGVVDRFSE 161
Cdd:cd06862   3 CTVTNPKKEskFKGLKSFIAYQITPTHTNV-------TVSRRYKHFDWLYERLVEKYSCIAIPPLPEK----QVTGRFEE 71

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 62955569 162 EFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSAKD 198
Cdd:cd06862  72 DFIEKRRERLELWMNRLARHPVLSQSEVFRHFLTCTD 108

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  84 VTVDDPKKHVST-----METYITYRVCTKTTRT--EFDLPE--YSVRRRYQDFDWLRIKLEDSQPTHLIPPLPEKFVM-- 152
Cdd:cd06864   3 ITVTEAEKRTGGsamnlKETYTVYLIETKIVEHesEEGLSKklSSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAMfm 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 62955569 153 --KGVVDRFSEEFVETRRKALDKFLKRVADHPVLSFNEHFNAFL 194
Cdd:cd06864  83 wqKLSSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFL 126

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 62955569  84 VTVDDPKKHVSTME------TYITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEDSQPTHLIPPLPEKFVMKGVVd 157
Cdd:cd06865   2 ITVSDPKKEQEPSRvplggpPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQV- 80

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 62955569 158 RFSEEFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSA 196
Cdd:cd06865  81 MQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLTL 119

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  84 VTVDDPKKHVSTMETYITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEdSQPTH---LIPPLPEKFVMK------G 154
Cdd:cd07282   3 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLA-SKYLHvgyIVPPAPEKSIVGmtkvkvG 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 62955569 155 VVDRFSEEFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSA 196
Cdd:cd07282  82 KEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 123

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 62955569  82 LFVTVDDPKKHVSTMETYITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLED--SQPTHLIPPLPEKFVMK------ 153
Cdd:cd07281   1 LKVSITDPEKIGDGMNAYVVYKVTTQTSLLMFRSKHFTVKRRFSDFLGLYEKLSEkhSQNGFIVPPPPEKSLIGmtkvkv 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 62955569 154 GVVDRFSEEFVETRRKALDKFLKRVADHPVLSFNEHFNAFL 194
Cdd:cd07281  81 GKEDSSSAEFLERRRAALERYLQRIVSHPSLLQDPDVREFL 121

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3 and related 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. This subfamily is composed of SNX3, SNX12, and fungal Grd19. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. SNX3/Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  82 LFVTVDDPKKHVSTMETYITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEdSQPTHLIPPLPEK-----FVMKGVV 156
Cdd:cd06894   2 LEIDVVNPQTHGVGKKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSELE-RDSKIVVPPLPGKalkrqLPFRGDD 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 62955569 157 DRFSEEFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSAKDL 199
Cdd:cd06894  81 GIFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQEETI 123

The Bin/Amphiphysin/Rvs (BAR) domain of yeast Sorting Nexin Atg24p; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. Atg24p is involved in membrane fusion events at the vacuolar surface during pexophagy. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 230 EFAAMGEYLDMFTQKLGTIDRIAQRIIKEQTEFLMELREYGPVYSSWSSFE-EDLHEPLEGVSGCVSNCSSALEELTEDM 308
Cdd:cd07628   5 EFLEIREKSDKLDENLTKIDKIFAKVVKRQSDLSVDYADLATQFQKLGSLEsGEITEPFKIFSESLSQFSTSLRVLNKYT 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 309 SEDFLPVLREYVLYIESMKNVLKKRDQVQAEYETKLEAVVFREdkktpmptdVEKCQDRVECFNADLKADWDRWQNNKRQ 388
Cdd:cd07628  85 DENYLTSLKDLLHYILSLKNLIKLRDQKQLDYEELSDYLLTDE---------VENAKETSDAFNKEVLKEYPNFERIKKQ 155

                       170       180
                ....*....|....*....|....*....
gi 62955569 389 DFRQLLTGMADKNIQYYEKCLAAWESLIP 417
Cdd:cd07628 156 EIKDSLGALADGHIDFYQGLVEDWEKVEP 184

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3; 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. SNX3 associates with early endosomes through a PX domain-mediated interaction with phosphatidylinositol-3-phosphate (PI3P). It associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer. SNX3 is required for the formation of multivesicular bodies, which function as transport intermediates to late endosomes. It also promotes cell surface expression of the amiloride-sensitive epithelial Na+ channel (ENaC), which is critical in sodium homeostasis and maintenance of extracellular fluid volume.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  99 YITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEDSQPThLIPPLPEKFVMKGVVDR-----FSEEFVETRRKALDK 173
Cdd:cd07293  19 FTTYEIRLKTNLPIFKLKESTVRRRYSDFEWLRSELERESKV-VVPPLPGKALFRQLPFRgddgiFDDSFIEERKQGLEQ 97

                        90       100
                ....*....|....*....|.
gi 62955569 174 FLKRVADHPVLSFNEHFNAFL 194
Cdd:cd07293  98 FLNKVAGHPLAQNERCLHMFL 118

The phosphoinositide binding Phox Homology domain of Sorting Nexin 12; 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. The specific function of SNX12 has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  82 LFVTVDDPKKHVSTMETYITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEDSQPThLIPPLPEKFVMKGVVDR--- 158
Cdd:cd07294   4 LEIDIFNPQTVGVGRNRFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSKI-VVPPLPGKALKRQLPFRgde 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 62955569 159 --FSEEFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSAKDLNK 201
Cdd:cd07294  83 giFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQDETIDR 127

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 62955569 119 SVRRRYQDFDWLRIKLEDSQPTHLIPPLPEKFVMKGVvdrfSEEFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSA 196
Cdd:cd06866  31 TVYRRYSDFVWLHEYLLKRYPYRMVPALPPKRIGGSA----DREFLEARRRGLSRFLNLVARHPVLSEDELVRTFLTE 104

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 4; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It is also implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and leptin. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 231 FAAMGEYLDMFTQKLGTIDRIAQRIIKEQTEFLMELREYGPVYSSWSSFEEDLHEPLEGVSGCVSNCSSALEELTEDmSE 310
Cdd:cd07622  16 FEDLKNYSDELQTNLNNLLKVRARLAERLYGVYKIHANYGRVFSEWSAIEKEMGDGLQKAGHYMDSYAASIDNGLED-EE 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 311 DFLPVLREYVLYIESMKNVLKKRDQVQAEYETKLEAVVfreDKKTPMPTDVEKCQDRVECFNADLKADWDRWQNNKRQDF 390
Cdd:cd07622  95 LIADQLKEYLFFADSLRAVCKKHELLQYDLEKAEDALA---NKKQQGEEAVKEAKDELNEFVKKALEDVERFKKQKVRDL 171

                       170       180
                ....*....|....*....|..
gi 62955569 391 RQLLTGMADKNIQYYEKCLAAW 412
Cdd:cd07622 172 KEILISYAKLQIKLAKKGLQTW 193

The phosphoinositide binding Phox Homology domain of Sorting Nexin 5; 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. SNX5, abundantly expressed in macrophages, regulates macropinocytosis, a process that enables cells to internalize large amounts of external solutes. It may also be a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, acting as a mammalian equivalent of yeast Vsp17p. It also binds the Fanconi anaemia complementation group A protein (FANCA). SNX5 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to other sorting nexins including SNX1-2. The PX-BAR structural unit helps determine the specific membrane-targeting of some SNXs. The PX domain of SNX5 binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,4)P2. SNX5 is localized to a subdomain of early endosome and is recruited to the plasma membrane following EGF stimulation and elevation of PI(3,4)P2 levels.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 100 ITYRVCTKTTRTEFDLPEYSVRRRYQDFDWLRIKLEDSQPTH--LIPPLPEKFVMKGVVDRF-----------SEEFVET 166
Cdd:cd07291  17 VKFTVHTKTTLPSFQSPDFSVTRQHEDFIWLHDALIETEDYAglIIPPAPPKPDFDGPREKMqklgegegsmtKEEFAKM 96

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 62955569 167 RRK------ALDK--------FLKRVADHPVLSFNEHFNAFL 194
Cdd:cd07291  97 KQEleaeylAVFKktvqvhevFLQRLSSHPSLSKDRNFHIFL 138

The Bin/Amphiphysin/Rvs (BAR) domain of yeast Sorting Nexin Atg20p; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. The function of Atg20p is unknown but it has been shown to interact with Atg11p, which plays a role in linking cargo molecules with vesicle-forming components. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 246 GTIDRIAQRIIKEQTEFLMELREYGPVYSSWSSFE--EDLHEPLEGVSGCVSNCSSALEELTEDMSEDFLPVLREYVLYI 323
Cdd:cd07629  22 GGMEKVNRRITKRLGDLAEDMADLGGRFNAFSLEEqkSELAEALEKVGQAVDSTYLATEALVGSLYYNINEPLSESAQFA 101

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 324 ESMKNVLKKRDQVQAEYETKleavvfredKKTPMPTDVEKCQDRVECFNADLKADWDRWQNNKRQDFRQLLTGMADKNIQ 403
Cdd:cd07629 102 GVVRELLKYRKLKHVQYEMT---------KDSLLESALVAASDDLVISSTIKQKDLPRFQREREADLREILKNYSKYHKD 172

                       170
                ....*....|..
gi 62955569 404 YYEKCLAAWESL 415
Cdd:cd07629 173 WAKQNLEAWKEA 184

The phosphoinositide binding Phox Homology domain of Sorting Nexin 19; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX19 contains an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. These domains are also found in SNX13 and SNX14, which also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNX19 interacts with IA-2, a major autoantigen found in type-1 diabetes. It inhibits the conversion of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to PI(3,4,5)P3, which leads in the decrease of protein phosphorylation in the Akt signaling pathway, resulting in apoptosis. SNX19 may also be implicated in coronary heart disease and thyroid oncocytic tumors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569 112 EFDLPEYSVRRRYQDFDWLRIKLEDSQ----------PTHLIPPLPekfvmkgvVDRFSEEFVETRRKALDKFLKRVADH 181
Cdd:cd06893  45 EQPLATHTVNRRFREFLTLQTRLEENPkfrkimnvkgPPKRLFDLP--------FGNMDKDKIEARRGLLETFLRQLCSI 116

                        90
                ....*....|....
gi 62955569 182 PVLSFNEHFNAFLS 195
Cdd:cd06893 117 PEISNSEEVQEFLA 130

The phosphoinositide binding Phox Homology domain of RPK118-like proteins; 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 human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase domain. 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. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  83 FVTVDDPKKHVSTMETY-ITYRVCTKttRTEFDLPEYSVRRRYQDF-----DWLRIKLEDSQPTHLIPPlpekFVMKGVV 156
Cdd:cd07287   4 FYTVTDPRRHPKGYTVYkVTARIVSR--KNPEDVQEIVVWKRYSDFkklhkDLWQIHKNLCRQSELFPP----FAKAKVF 77

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 62955569 157 DRFSEEFVETRRKALDKFLKRVADHPVLSFNEHFNAFL 194
Cdd:cd07287  78 GRFDESVIEERRQCAEDLLQFSANIPALYNSSQLEDFF 115

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62955569 118 YSVRRRYQDFDWLRIKLEDSQPTHLIPPLPEKFVMKGVvdrfSEEFVETRRKALDKFLKRVADHPVLSFNEHFNAFLSA 196
Cdd:cd06877  44 WSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRRIFGPK----SYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSP 118

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; 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 SNX20, SNX21, and similar proteins. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62955569  85 TVDDPKKHvstmetYITYRVCTKTTrTEFDLPEYSVRRRYQDFDWLRIKLEDSQPtHLIPPLpeKFVMKGVVDRFSEEFV 164
Cdd:cd07279  10 TVKEGEKK------YVVYQLAVVQT-GDPDTQPAFIERRYSDFLKLYKALRKQHP-QLMAKV--SFPRKVLMGNFSSELI 79