The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 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. This subfamily consists of SNX7, SNX30, and similar proteins. They harbor 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, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789  91 LFVTVDDPKKHVCTMETYITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRFSE 170
Cdd:cd06860   1 LFITVDNPEKHVTTLETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVKGLLDRFSP 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 33859789 171 EFVETRRKALDKFLKRITDHPVLSFNEHFNVFLTAK 206
Cdd:cd06860  81 EFVATRMRALHKFLNRIVEHPVLSFNEHLKVFLTAK 116

The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 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. This subfamily consists of SNX7, SNX30, and similar proteins. They harbor 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, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789  91 LFVTVDDPKKHVCTMETYITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRFSE 170
Cdd:cd06860   1 LFITVDNPEKHVTTLETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVKGLLDRFSP 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 33859789 171 EFVETRRKALDKFLKRITDHPVLSFNEHFNVFLTAK 206
Cdd:cd06860  81 EFVATRMRALHKFLNRIVEHPVLSFNEHLKVFLTAK 116

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789  93 VTVDDPKKHVCTME---TYITYRITTKSTRVEFDL---PEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEK-FVVKGVV 165
Cdd:COG5391 133 STVSNPQSLTLLVDsrdKHTSYEIITVTNLPSFQLresRPLVVRRRYSDFESLHSILIKLLPLCAIPPLPSKkSNSEYYG 212

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789 166 DRFSEEFVETRRKALDKFLKRITDHPVLS-------FNEHFNVFLTAKDLNAYKKQGIAL-LSRVGESVKHvtGGYKLRS 237
Cdd:COG5391 213 DRFSDEFIEERRQSLQNFLRRVSTHPLLSnyknsksWESHSTLLSSFIENRKSVPTPLSLdLTSTTQELDM--ERKELNE 290

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789 238 RplefaaisdyLDTFALKLGTIDRIAQRIIKE------------EIEYLVELREygpvystwSALEGELAEPLE-----G 300
Cdd:COG5391 291 S----------TSKAIHNILSIFSLFEKILIQleseeesltrllESLNNLLLLV--------LNFSGVFAKRLEqnqnsI 352

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789 301 VSACIGNCSTALEELTDDITeEFLPVLREYVLYSDSMKGVLKKRDQVQAEYEAKLEAVALRKEERPKV------------ 368
Cdd:COG5391 353 LNEGVVQAETLRSSLKELLT-QLQDEIKSRESLILTDSNLEKLTDQNLEDVEELSRSLRKNSSQRAVVsqqpegltsfsk 431

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789 369 ------PADVEKCQDR----------------------MECFNADLKADMERWQSNKRHDFRQLLVGLADKNIQYYEKCL 420
Cdd:COG5391 432 lsyklrDFVQEKSRSKsieslqqdkekleeqlaiaekdAQEINEELKNELKFFFSVRNSDLEKILKSVADSHIEWAEENL 511

                ....*
gi 33859789 421 MAWES 425
Cdd:COG5391 512 EIWKS 516

BAR domain; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different protein families. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysin, endophilin, BRAP and Nadrin. BAR domains are also frequently found alongside domains that determine lipid specificity, like pfam00169 and pfam00787 domains in beta centaurins and sorting nexins respectively.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789   265 RIIKEEIEYLVELREYGPVYSTWSALEGELAEPLEGVSACIG-----------------NCSTALEELTDDITEEFLPVL 327
Cdd:pfam03114  44 KLQKDTKGYLQPNPGARAKQTVLEQPEELLAESMIEAGKDLGedssfgkaledygealkRLAQLLEQLDDRVETNFLDPL 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789   328 REYVLYSDSMKGVLKKRDQVQAEYEAKLEAV-ALRKEERPKVPA------DVEKCQDRMECFNADLKADMERWQSNKRHD 400
Cdd:pfam03114 124 RNLLKEFKEIQKHRKKLERKRLDYDAAKTRVkKAKKKKSSKAKDesqaeeELRKAQAKFEESNEQLKALLPNLLSLEVEF 203

                         170       180
                  ....*....|....*....|
gi 33859789   401 FRQLLVGLADKNIQYYEKCL 420
Cdd:pfam03114 204 VVNQLVAFVEAQLDFHRQCY 223

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 33859789 227 KHVTGGYKLRSRPLEFAAISDYLDTFALKLGTIDRIAQRIIKEEIEYLVELREYGPVYSTWSALEGELAEPLEGVSACIG 306
Cdd:cd07624   1 RNTSTMYLLKNRSPEFDKMNEYLTLFGEKLGTIERISQRIHKERIEYFDELKEYSPIFQLWSASETELAPLLEGVSSAVE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789 307 NCSTALEELTDDITEEFLPVLREYVLYSDSMKGVLKKRDQVQAEYEAKLEAVALRKEErpkVPADVEKCQDRMECFNADL 386
Cdd:cd07624  81 RCTAALEVLLSDHEFVFLPPLREYLLYSDAVKDVLKRRDQFQIEYELSVEELNKKRLE---LLKEVEKLQDKLECANADL 157

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 33859789 387 KADMERWQSNKRHDFRQLLVGLADKNIQYYEKCLMAWESIIPL 429
Cdd:cd07624 158 KADLERWKQNKRQDLKKILLDMAEKQIQYYEQCLAAWEEVLPA 200

The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 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. This subfamily consists of SNX7, SNX30, and similar proteins. They harbor 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, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789  91 LFVTVDDPKKHVCTMETYITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRFSE 170
Cdd:cd06860   1 LFITVDNPEKHVTTLETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVKGLLDRFSP 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 33859789 171 EFVETRRKALDKFLKRITDHPVLSFNEHFNVFLTAK 206
Cdd:cd06860  81 EFVATRMRALHKFLNRIVEHPVLSFNEHLKVFLTAK 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 33859789  91 LFVTVDDPKKHVCTMETYITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRFSE 170
Cdd:cd07284   1 IFITVDEPESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFVMKGMVERFNE 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 33859789 171 EFVETRRKALDKFLKRITDHPVLSFNEHFNVFLTAK 206
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 33859789  91 LFVTVDDPKKHVC-TMETYITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVV-DRF 168
Cdd:cd06863   1 LECLVSDPQKELDgSSDTYISYLITTKTNLPSFSRKEFKVRRRYSDFVFLHECLSNDFPACVVPPLPDKHRLEYITgDRF 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 33859789 169 SEEFVETRRKALDKFLKRITDHPVLSFNEHFNVFLT 204
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 33859789  93 VTVDDPKKH--VCTMETYITYRITTKSTRVefdlpeySVRRRYQDFDWLRNKLEESQPTHLIPPLPEKfvvkGVVDRFSE 170
Cdd:cd06862   3 CTVTNPKKEskFKGLKSFIAYQITPTHTNV-------TVSRRYKHFDWLYERLVEKYSCIAIPPLPEK----QVTGRFEE 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 33859789 171 EFVETRRKALDKFLKRITDHPVLSFNEHFNVFLTAKDLNAYK 212
Cdd:cd06862  72 DFIEKRRERLELWMNRLARHPVLSQSEVFRHFLTCTDEKDWK 113

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 33859789  93 VTVDDPKKHVCTME------TYITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVd 166
Cdd:cd06865   2 ITVSDPKKEQEPSRvplggpPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQV- 80

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 33859789 167 RFSEEFVETRRKALDKFLKRITDHPVLSFNEHFNVFLTA 205
Cdd:cd06865  81 MQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLTL 119

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 33859789  93 VTVDDPKKH-----VCTMETYITYRITTKSTR--VEFDLPE--YSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVV-- 161
Cdd:cd06864   3 ITVTEAEKRtggsaMNLKETYTVYLIETKIVEheSEEGLSKklSSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAMfm 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 33859789 162 --KGVVDRFSEEFVETRRKALDKFLKRITDHPVLSFNEHFNVFLT 204
Cdd:cd06864  83 wqKLSSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFLT 127

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 33859789  93 VTVDDPKKHVCTMETYITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLeESQPTH---LIPPLPEKFVVK------G 163
Cdd:cd07282   3 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKL-ASKYLHvgyIVPPAPEKSIVGmtkvkvG 81

                        90       100       110
                ....*....|....*....|....*....|
gi 33859789 164 VVDRFSEEFVETRRKALDKFLKRITDHPVL 193
Cdd:cd07282  82 KEDSSSTEFVEKRRAALERYLQRTVKHPTL 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 33859789     97 DPKKHVCTMETYITYRITTKStrvefDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKfVVKGVVDRFSEEFVETR 176
Cdd:smart00312   3 EPEKIGDGKHYYYVIEIETKT-----GLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGK-KLFGRLNNFSEEFIEKR 76

                           90       100
                   ....*....|....*....|....*....
gi 33859789    177 RKALDKFLKRITDHPVLS-FNEHFNVFLT 204
Cdd:smart00312  77 RRGLEKYLQSLLNHPELInHSEVVLEFLE 105

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 33859789 241 EFAAISDYLDTFALKLGTIDRIAQRIIKEEIEYLVELREYGPVYSTWSALE-GELAEPLEGVSACIGNCSTALEELTDDI 319
Cdd:cd07628   5 EFLEIREKSDKLDENLTKIDKIFAKVVKRQSDLSVDYADLATQFQKLGSLEsGEITEPFKIFSESLSQFSTSLRVLNKYT 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789 320 TEEFLPVLREYVLYSDSMKGVLKKRDQVQAEYEAkLEAVALRKEerpkvpadVEKCQDRMECFNADLKADMERWQSNKRH 399
Cdd:cd07628  85 DENYLTSLKDLLHYILSLKNLIKLRDQKQLDYEE-LSDYLLTDE--------VENAKETSDAFNKEVLKEYPNFERIKKQ 155

                       170       180
                ....*....|....*....|....*....
gi 33859789 400 DFRQLLVGLADKNIQYYEKCLMAWESIIP 428
Cdd:cd07628 156 EIKDSLGALADGHIDFYQGLVEDWEKVEP 184

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 33859789  91 LFVTVDDPKKHVCTMETYITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLEEsQPTHLIPPLPEK-----FVVKGVV 165
Cdd:cd06894   2 LEIDVVNPQTHGVGKKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSELER-DSKIVVPPLPGKalkrqLPFRGDD 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 33859789 166 DRFSEEFVETRRKALDKFLKRITDHPVLSFNEHFNVFLTAKDL 208
Cdd:cd06894  81 GIFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQEETI 123

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789  93 VTVDDPKKHVCTMET-YITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEkfvvKGVVDRF-SE 170
Cdd:cd06898   2 VEVRDPRTHKEDDWGsYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPP----KNLFGRFnNE 77

                        90       100       110
                ....*....|....*....|....*....|...
gi 33859789 171 EFVETRRKALDKFLKRITDHPVLSFNEHFNVFL 203
Cdd:cd06898  78 GFIEERQQGLQDFLEKVLQTPLLLSDSRLHLFL 110

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 33859789  91 LFVTVDDPKKHVCTMETYITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLEESQPThLIPPLPEKFVVKGVVDR--- 167
Cdd:cd07293   2 LEIDVTNPQTVGVGRGRFTTYEIRLKTNLPIFKLKESTVRRRYSDFEWLRSELERESKV-VVPPLPGKALFRQLPFRgdd 80

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 33859789 168 --FSEEFVETRRKALDKFLKRITDHPVLSFNEHFNVFL 203
Cdd:cd07293  81 giFDDSFIEERKQGLEQFLNKVAGHPLAQNERCLHMFL 118

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789  95 VDDPKK--HVCTMETYITYRITTKSTrvefdlpEYSVRRRYQDFDWLRNKLEESQPTHL-IPPLPEKfvvkGVVDRFSEE 171
Cdd:cd07285   5 VADPRKgsKMYGLKSYIEYQLTPTNT-------NRSVNHRYKHFDWLYERLLVKFGLAIpIPSLPDK----QVTGRFEEE 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 33859789 172 FVETRRKALDKFLKRITDHPVLSFNEHFNVFLTAKDLNAYK 212
Cdd:cd07285  74 FIKMRMERLQAWMTRMCRHPVISESEVFQQFLNFRDEKEWK 114

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 33859789 227 KHVTGGYKLRSRPLEFAAISDYLDTFALKLGTIDRIAQRIIKEEIEYLVELREYGPVYSTWSALEGELAEPLEGvsacIG 306
Cdd:cd07622   1 KALNASFRLRNPDKRFEDLKNYSDELQTNLNNLLKVRARLAERLYGVYKIHANYGRVFSEWSAIEKEMGDGLQK----AG 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789 307 NCSTALEELTDDITEE---FLPVLREYVLYSDSMKGVLKKRDQVQAEYEAKLEAVALRKEErpkVPADVEKCQDRMECFN 383
Cdd:cd07622  77 HYMDSYAASIDNGLEDeelIADQLKEYLFFADSLRAVCKKHELLQYDLEKAEDALANKKQQ---GEEAVKEAKDELNEFV 153

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*...
gi 33859789 384 ADLKADMERWQSNKRHDFRQLLVGLADKNIQYYEKCLMAWESIIPLLQ 431
Cdd:cd07622 154 KKALEDVERFKKQKVRDLKEILISYAKLQIKLAKKGLQTWTNIKECLQ 201

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 33859789 109 ITYRITTKSTRVEFDLPEYSVRRRYQDFDWLRNKLEESQPTH--LIPPLPEKFVVKGVVDRF-----------SEEFVET 175
Cdd:cd07291  17 VKFTVHTKTTLPSFQSPDFSVTRQHEDFIWLHDALIETEDYAglIIPPAPPKPDFDGPREKMqklgegegsmtKEEFAKM 96

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 33859789 176 RRK------ALDK--------FLKRITDHPVLSFNEHFNVFL 203
Cdd:cd07291  97 KQEleaeylAVFKktvqvhevFLQRLSSHPSLSKDRNFHIFL 138

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 33859789 120 VEFDLPEYSVRRRYQDFDWLRNKLEESQ----------PTHLIPPLPekfvvKGVVDRfseEFVETRRKALDKFLKRITD 189
Cdd:cd06893  44 SEQPLATHTVNRRFREFLTLQTRLEENPkfrkimnvkgPPKRLFDLP-----FGNMDK---DKIEARRGLLETFLRQLCS 115

                        90
                ....*....|....
gi 33859789 190 HPVLSFNEHFNVFL 203
Cdd:cd06893 116 IPEISNSEEVQEFL 129

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 33859789 119 RVEFDLPE-YSVRRRYQDFDWLRNKLEESQPTHLIPPLPEK--FVVKgvvdrfSEEFVETRRKALDKFLKRITDHPVLSF 195
Cdd:cd06877  35 RAKGHEPQhWSVLRRYNEFYVLESKLTEFHGEFPDAPLPSRriFGPK------SYEFLESKREIFEEFLQKLLQKPELRG 108

                        90
                ....*....|
gi 33859789 196 NEHFNVFLTA 205
Cdd:cd06877 109 SELLYDFLSP 118

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-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 have similarity to sorting nexin 15 (SNX15), which contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) 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. Other members of this subfamily contain an additional C-terminal kinase domain, similar to human RPK118, which binds sphingosine kinase and the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of proteins such as PRDX3 from the cytoplasm to its site of function in the mitochondria.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33859789  94 TVDDPKKHvctMETYITYRITTK--STRVEFDLPEYSVRRRYQDFdwlrNKL-EESQPTH-------LIPPLPEKFVVKg 163
Cdd:cd06881   6 TVTDTRRH---KKGYTEYKITSKvfSRSVPEDVSEVVVWKRYSDF----KKLhRELSRLHkqlylsgSFPPFPKGKYFG- 77

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 33859789 164 vvdRFSEEFVETRRKALDKFLKRITDHPVLSFNEHFNVF 202
Cdd:cd06881  78 ---RFDAAVIEERRQAILELLDFVGNHPALYQSSAFQQF 113