The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159 166 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHVSVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 245
Cdd:cd07664    1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159 246 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKREAEAKMMVANKPDK 325
Cdd:cd07664   81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 503774159 326 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 399
Cdd:cd07664  161 LQQAKDEIKEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 234

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 2; 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. 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 effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. 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 503774159 166 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHVSVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 245
Cdd:cd07664    1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159 246 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKREAEAKMMVANKPDK 325
Cdd:cd07664   81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 503774159 326 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 399
Cdd:cd07664  161 LQQAKDEIKEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 234

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 503774159  25 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 104
Cdd:cd07282    1 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 503774159 105 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 148
Cdd:cd07282   81 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 124

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159   53 LSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVgyIVPPAPEKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQRTVKH 132
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSV--IIPPLPPKRWLG----------RYNEEFIEKRRKGLEQYLQRLLQH 68

                          90
                  ....*....|....*.
gi 503774159  133 PTLLQDPDLRQFLESS 148
Cdd:pfam00787  69 PELRNSEVLLEFLESD 84

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 2; 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. 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 effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. 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 503774159 166 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHVSVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 245
Cdd:cd07664    1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159 246 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKREAEAKMMVANKPDK 325
Cdd:cd07664   81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 503774159 326 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 399
Cdd:cd07664  161 LQQAKDEIKEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 234

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 1; 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. 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 effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. SNX1 is localized to a microdomain in early endosomes where it regulates cation-independent mannose-6-phosphate receptor retrieval to the trans Golgi network. 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 503774159 166 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHVSVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 245
Cdd:cd07665    1 KMFNKATDAVSKMTIKMNESDVWFEEKLQEVECEEQRLRKLHAVVETLVNHRKELALNTALFAKSLAMLGSSEDNTALSR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159 246 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKREAEAKMMVANKPDK 325
Cdd:cd07665   81 ALSQLAEVEEKIEQLHQEQANNDFFLLAELLADYIRLLSAVRGAFDQRMKTWQRWQDAQAMLQKKREAEARLLWANKPDK 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 503774159 326 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 399
Cdd:cd07665  161 LQQAKDEIAEWESRVTQYERDFERISATVRKEVIRFEKEKSKDFKNHIIKYLETLLHSQQQLVKYWEAFLPEAK 234

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 503774159  25 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 104
Cdd:cd07282    1 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 503774159 105 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 148
Cdd:cd07282   81 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 124

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159  25 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLhvGYIVPPAPEKSIVGMTKVKV 104
Cdd:cd06859    1 FEISVTDPVKVGDGMSAYVVYRVTTKTNLPDFKKSEFSVLRRYSDFLWLYERLVEKYP--GRIVPPPPEKQAVGRFKVKF 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 503774159 105 gkedssstEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 148
Cdd:cd06859   79 --------EFIEKRRAALERFLRRIAAHPVLRKDPDFRLFLESD 114

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins; 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. 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 503774159 184 ESDAWFEEKQQQFENLDQQLRKLHVSVEALVCHRKELSANTAAFAKSAAMLGNSEDH--TALSRALSQLAEVEEKIDQLH 261
Cdd:cd07596    1 EEDQEFEEAKDYILKLEEQLKKLSKQAQRLVKRRRELGSALGEFGKALIKLAKCEEEvgGELGEALSKLGKAAEELSSLS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159 262 QEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKREAEAKMMVAN--KPDKIQQAKNEIREWEAK 339
Cdd:cd07596   81 EAQANQELVKLLEPLKEYLRYCQAVKETLDDRADALLTLQSLKKDLASKKAQLEKLKAAPgiKPAKVEELEEELEEAESA 160

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 503774159 340 VQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPE 397
Cdd:cd07596  161 LEEARKRYEEISERLKEELKRFHEERARDLKAALKEFARLQVQYAEKIAEAWESLLPE 218

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 503774159  27 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIVgmtkvkVGK 106
Cdd:cd06860    3 ITVDNPEKHVTTLETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEES--HPTHIIPPLPEKHSV------KGL 74

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 503774159 107 EDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 145
Cdd:cd06860   75 LDRFSPEFVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

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 503774159    29 VSDPEKVGDGMNAYMAYRVTTKTSLSMFSksefsVKRRFSDFLGLHSKLasKYLHVGYIVPPAPEKsivgmtkVKVGKED 108
Cdd:smart00312   1 VVEPEKIGDGKHYYYVIEIETKTGLEEWT-----VSRRYSDFLELHSKL--KKHFPRSILPPLPGK-------KLFGRLN 66

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 503774159   109 SSSTEFVEKRRAALERYLQRTVKHPTLLQ-DPDLRQFLE 146
Cdd:smart00312  67 NFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFLE 105

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159   53 LSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVgyIVPPAPEKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQRTVKH 132
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSV--IIPPLPPKRWLG----------RYNEEFIEKRRKGLEQYLQRLLQH 68

                          90
                  ....*....|....*.
gi 503774159  133 PTLLQDPDLRQFLESS 148
Cdd:pfam00787  69 PELRNSEVLLEFLESD 84

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 503774159  25 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIVGmtkvkv 104
Cdd:cd07284    1 IFITVDEPESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEA--HPTLIIPPLPEKFVMK------ 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 503774159 105 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 145
Cdd:cd07284   73 GMVERFNEDFIETRRKALHKFLNRIADHPTLTFNEDFKIFL 113

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159  24 DIEIGVSDPEKVGDGM---NAYMAYRVTTKTSLSMFSKSEF---SVKRRFSDFLGLHSKLASKYLhvGYIVPPAPEKSIV 97
Cdd:COG5391  130 FISSTVSNPQSLTLLVdsrDKHTSYEIITVTNLPSFQLRESrplVVRRRYSDFESLHSILIKLLP--LCAIPPLPSKKSN 207

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159  98 GMTkvkvgKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDP----------DLRQFLE------SSELPRAVNTQALSG 161
Cdd:COG5391  208 SEY-----YGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNYKnsksweshstLLSSFIEnrksvpTPLSLDLTSTTQELD 282

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159 162 AGILRMVNKAADAVNKMTIKMNEsdawFEEKQQQFENLDQQL-RKLHVSVEALVCHRKELSANTAAFAK---SAAMLGNS 237
Cdd:COG5391  283 MERKELNESTSKAIHNILSIFSL----FEKILIQLESEEESLtRLLESLNNLLLLVLNFSGVFAKRLEQnqnSILNEGVV 358

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159 238 EDHTALSRA-------LSQLAEVEEKIDQLHQ-EQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITL-L 308
Cdd:COG5391  359 QAETLRSSLkelltqlQDEIKSRESLILTDSNlEKLTDQNLEDVEELSRSLRKNSSQRAVVSQQPEGLTSFSKLSYKLrD 438

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159 309 KKREAEAKmmvaNKPDKIQQAKNEIREweaKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLI 388
Cdd:COG5391  439 FVQEKSRS----KSIESLQQDKEKLEE---QLAIAEKDAQEINEELKNELKFFFSVRNSDLEKILKSVADSHIEWAEENL 511

                 ....
gi 503774159 389 KYWE 392
Cdd:COG5391  512 EIWK 515

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 503774159  25 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylhVGYIVPPAPEKSIVGMTKVKv 104
Cdd:cd07293    2 LEIDVTNPQTVGVGRGRFTTYEIRLKTNLPIFKLKESTVRRRYSDFEWLRSELERE---SKVVVPPLPGKALFRQLPFR- 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 503774159 105 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLE 146
Cdd:cd07293   78 GDDGIFDDSFIEERKQGLEQFLNKVAGHPLAQNERCLHMFLQ 119

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 503774159  25 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylhVGYIVPPAPEKSIVGMTKVKv 104
Cdd:cd07294    4 LEIDIFNPQTVGVGRNRFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERD---SKIVVPPLPGKALKRQLPFR- 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 503774159 105 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESSELPR 152
Cdd:cd07294   80 GDEGIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQDETIDR 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159  21 DIFDIEIgvsDPEKvgDGM-NAYMAYRVTTKtslsmfsKSEFSVKRRFSDFLGLHSKLASKYLHvgYIVPPAPEKSIVGm 99
Cdd:cd06866    1 DTVTVEL---VPEK--KGLfLKHVEYEVSSK-------RFKSTVYRRYSDFVWLHEYLLKRYPY--RMVPALPPKRIGG- 65

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 503774159 100 tkvkvgkedSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 148
Cdd:cd06866   66 ---------SADREFLEARRRGLSRFLNLVARHPVLSEDELVRTFLTEP 105

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 503774159  29 VSDPE-KVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIVGMTKVKvgke 107
Cdd:cd06898    4 VRDPRtHKEDDWGSYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKN--ALLIQLPSLPPKNLFGRFNNE---- 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 503774159 108 dssstEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 147
Cdd:cd06898   78 -----GFIEERQQGLQDFLEKVLQTPLLLSDSRLHLFLQT 112

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 503774159  38 GMNAYMAYRVTTktslsmfSKSEFSVKRRFSDFLGLHSKLASKYLHVgyIVPPAPEKSIVGmtkvkvgkedSSSTEFVEK 117
Cdd:cd06862   16 GLKSFIAYQITP-------THTNVTVSRRYKHFDWLYERLVEKYSCI--AIPPLPEKQVTG----------RFEEDFIEK 76

                         90       100       110
                 ....*....|....*....|....*....|..
gi 503774159 118 RRAALERYLQRTVKHPTLLQDPDLRQFLESSE 149
Cdd:cd06862   77 RRERLELWMNRLARHPVLSQSEVFRHFLTCTD 108

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159  40 NAYMAYRVTTKTSLSmfsksEFSVKRRFSDFLGLHSKLASkylHVGYIVP-PAPEKSIVgmtkvkvgKEDSSSTEFVEKR 118
Cdd:cd06897   13 KPYTVYNIQVRLPLR-----SYTVSRRYSEFVALHKQLES---EVGIEPPyPLPPKSWF--------LSTSSNPKLVEER 76

                         90       100       110
                 ....*....|....*....|....*....|
gi 503774159 119 RAALERYLQRTVKHP-TLLQD-PDLRQFLE 146
Cdd:cd06897   77 RVGLEAFLRALLNDEdSRWRNsPAVKEFLN 106

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 503774159  41 AYMAYRVTTKTSLSmfSKSEFSVKRRFSDFLGLHSKLASKY-LHVGYIVPPAPEKSIVGMTKVKVGKEdsssteFVEKRR 119
Cdd:cd07280   21 AYVVWKITIETKDL--IGSSIVAYKRYSEFVQLREALLDEFpRHKRNEIPQLPPKVPWYDSRVNLNKA------WLEKRR 92

                         90       100
                 ....*....|....*....|....*...
gi 503774159 120 AALERYLQRTVKHPTLLQDPDLRQFLES 147
Cdd:cd07280   93 RGLQYFLNCVLLNPVFGGSPVVKEFLLP 120

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 503774159  29 VSDPEKVGDGmnaYMAYRVTTKtslsMFSK------SEFSVKRRFSDFLGLHSKLASKY--LHVGYIVPPAPEKSIVGmt 100
Cdd:cd06881    7 VTDTRRHKKG---YTEYKITSK----VFSRsvpedvSEVVVWKRYSDFKKLHRELSRLHkqLYLSGSFPPFPKGKYFG-- 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 503774159 101 kvkvgkedSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLE 146
Cdd:cd06881   78 --------RFDAAVIEERRQAILELLDFVGNHPALYQSSAFQQFFE 115

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 503774159  60 EFSVKRRFSDFLGLHSKLASKYLHVGYIVPPapeKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQRTV-KHPTLLQD 138
Cdd:cd06875   30 EWTVKHRYSDFAELHDKLVAEHKVDKDLLPP---KKLIG----------NKSPSFVEKRRKELEIYLQTLLsFFQKTMPR 96

                 ....*...
gi 503774159 139 PdLRQFLE 146
Cdd:cd06875   97 E-LAHFLD 103