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 13385878 283 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 362
Cdd:cd07664   1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 363 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRETEAKMMVANKPDK 442
Cdd:cd07664  81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13385878 443 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKAVIIKYLESLVQTQQQLIKYWEAFLPEAK 516
Cdd:cd07664 161 LQQAKDEIKEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 234

Sorting nexin, N-terminal domain; These proteins bins to the cytoplasmic domain of plasma membrane receptors. and are involved in endocytic protein trafficking. The N-terminal domain appears to be specific to sorting nexins 1 and 2.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13385878     3 AEREPPPLGDVKPTDFEELE------DGEDLFTSTVSTlessPSSPEPASLPAEDISANSNGSKPVEVVLDDDREDLFA 75
Cdd:pfam03700   1 SEREPPPFPDSEDPEPEDAAgdgdsdEGEDIFTGTVST----LGSSPSSPEPASLPFTNSNGPKTNGVHSDDDQQDLFA 75

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 13385878 283 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 362
Cdd:cd07664   1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 363 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRETEAKMMVANKPDK 442
Cdd:cd07664  81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13385878 443 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKAVIIKYLESLVQTQQQLIKYWEAFLPEAK 516
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 13385878 142 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 221
Cdd:cd07282   1 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 13385878 222 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 265
Cdd:cd07282  81 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 124

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878   170 LSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVgyIVPPAPEKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQRTVKH 249
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSV--IIPPLPPKRWLG----------RYNEEFIEKRRKGLEQYLQRLLQH 68

                          90
                  ....*....|....*.
gi 13385878   250 PTLLQDPDLRQFLESS 265
Cdd:pfam00787  69 PELRNSEVLLEFLESD 84

Sorting nexin, N-terminal domain; These proteins bins to the cytoplasmic domain of plasma membrane receptors. and are involved in endocytic protein trafficking. The N-terminal domain appears to be specific to sorting nexins 1 and 2.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13385878     3 AEREPPPLGDVKPTDFEELE------DGEDLFTSTVSTlessPSSPEPASLPAEDISANSNGSKPVEVVLDDDREDLFA 75
Cdd:pfam03700   1 SEREPPPFPDSEDPEPEDAAgdgdsdEGEDIFTGTVST----LGSSPSSPEPASLPFTNSNGPKTNGVHSDDDQQDLFA 75

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 13385878 283 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 362
Cdd:cd07664   1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 363 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRETEAKMMVANKPDK 442
Cdd:cd07664  81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13385878 443 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKAVIIKYLESLVQTQQQLIKYWEAFLPEAK 516
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 13385878 283 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 362
Cdd:cd07665   1 KMFNKATDAVSKMTIKMNESDVWFEEKLQEVECEEQRLRKLHAVVETLVNHRKELALNTALFAKSLAMLGSSEDNTALSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 363 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRETEAKMMVANKPDK 442
Cdd:cd07665  81 ALSQLAEVEEKIEQLHQEQANNDFFLLAELLADYIRLLSAVRGAFDQRMKTWQRWQDAQAMLQKKREAEARLLWANKPDK 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13385878 443 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKAVIIKYLESLVQTQQQLIKYWEAFLPEAK 516
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 13385878 142 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 221
Cdd:cd07282   1 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 13385878 222 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 265
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 13385878 142 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLhvGYIVPPAPEKSIVGMTKVKV 221
Cdd:cd06859   1 FEISVTDPVKVGDGMSAYVVYRVTTKTNLPDFKKSEFSVLRRYSDFLWLYERLVEKYP--GRIVPPPPEKQAVGRFKVKF 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 13385878 222 gkedssstEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 265
Cdd:cd06859  79 --------EFIEKRRAALERFLRRIAAHPVLRKDPDFRLFLESD 114

The Bin/Amphiphysin/Rvs (BAR) domain of yeast Sorting Nexin Vps5p; 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. Vsp5p is the yeast counterpart of human SNX1 and is part of the retromer complex, which functions in the endosome-to-Golgi retrieval of vacuolar protein sorting receptor Vps10p, the Golgi-resident membrane protein A-ALP, and endopeptidase Kex2. 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 13385878 301 ESDAWFEEKQQQFENLDQQLRKLHASVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSRALSQLAEVEEKIDQLHQE 380
Cdd:cd07627   1 EPDEWFIEKKQYLDSLESQLKQLYKSLELVSSQRKELASATEEFAETLEALSSLELSKSLSDLLAALAEVQKRIKESLER 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 381 QAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRETEAKMMVANK--PDKIQQAKNEIREWEAKVQ 458
Cdd:cd07627  81 QALQDVLTLGVTLDEYIRSIGSVRAAFAQRQKLWQYWQSAESELSKKKAQLEKLKRQGKtqQEKLNSLLSELEEAERRAS 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 13385878 459 QGERDFEQISKTIRKEVGRFEKERVKDFKAVIIKYLESLVQTQQQLIKYWEAFL 512
Cdd:cd07627 161 ELKKEFEEVSELIKSELERFERERVEDFRNSVEIYLESAIESQKELIELWETFY 214

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 13385878 144 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIVgmtkvkVGK 223
Cdd:cd06860   3 ITVDNPEKHVTTLETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEES--HPTHIIPPLPEKHSV------KGL 74

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 13385878 224 EDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 262
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 13385878    146 VSDPEKVGDGMNAYMAYRVTTKTSLSMFSksefsVKRRFSDFLGLHSKLasKYLHVGYIVPPAPEKsivgmtkVKVGKED 225
Cdd:smart00312   1 VVEPEKIGDGKHYYYVIEIETKTGLEEWT-----VSRRYSDFLELHSKL--KKHFPRSILPPLPGK-------KLFGRLN 66

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 13385878    226 SSSTEFVEKRRAALERYLQRTVKHPTLLQ-DPDLRQFLE 263
Cdd:smart00312  67 NFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFLE 105

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 143 EIGVSDPEKVGDGMNAYMAYRVTTKTSlsmfSKSEFSVKRRFSDFLGLHSKLASKYLhvGYIVPPAPEKSIVGMTkvkvg 222
Cdd:cd06093   1 SVSIPDYEKVKDGGKKYVVYIIEVTTQ----GGEEWTVYRRYSDFEELHEKLKKKFP--GVILPPLPPKKLFGNL----- 69

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 13385878 223 kedssSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 264
Cdd:cd06093  70 -----DPEFIEERRKQLEQYLQSLLNHPELRNSEELKEFLEL 106

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 13385878 142 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIVGmtkvkv 221
Cdd:cd07284   1 IFITVDEPESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEA--HPTLIIPPLPEKFVMK------ 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 13385878 222 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 262
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 13385878  51 DISANSNGSKPVEV----VLDDDREDLFAEAteevSLDSPERELILSSEPSPAVTPVTPTTLIAPRieskSISAPVIFDR 126
Cdd:COG5391  31 STVKNNDGSPVNSSikstPLDIQKRYSGFES----SAKLPRISDAPSFVPPPGGHTISYTIAIHDS----KIHSRASEFR 102

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 127 S-RDEIEE----------EANGDIFD--IEIGVSDPEKVGDGM---NAYMAYRVTTKTSLSMFSKSEF---SVKRRFSDF 187
Cdd:COG5391 103 SlRDMLSLllptslqpplSTSHTILDyfISSTVSNPQSLTLLVdsrDKHTSYEIITVTNLPSFQLRESrplVVRRRYSDF 182

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 188 LGLHSKLASKYLhvGYIVPPAPEKSIVGMTkvkvgKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDP----------D 257
Cdd:COG5391 183 ESLHSILIKLLP--LCAIPPLPSKKSNSEY-----YGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNYKnsksweshstL 255

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 258 LRQFLE------SSELPRAVNTQALSGAGILRMVNKAADAVNKMTIKMNEsdawFEEKQQQFENLDQQL-RKLHASVEAL 330
Cdd:COG5391 256 LSSFIEnrksvpTPLSLDLTSTTQELDMERKELNESTSKAIHNILSIFSL----FEKILIQLESEEESLtRLLESLNNLL 331

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 331 VCHRKELSANTAAFAK---SAAMLGNSEDHTALS---RALSQLAEVEEKIDQL-----HQEQAFADFYMFSELLSDYIRL 399
Cdd:COG5391 332 LLVLNFSGVFAKRLEQnqnSILNEGVVQAETLRSslkELLTQLQDEIKSRESLiltdsNLEKLTDQNLEDVEELSRSLRK 411

                       410       420       430       440       450       460       470       480
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 400 IAAVKGVFDHRMKcwqkwedAQITLLKKRETEAKMMVANKPDK-IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRF 478
Cdd:COG5391 412 NSSQRAVVSQQPE-------GLTSFSKLSYKLRDFVQEKSRSKsIESLQQDKEKLEEQLAIAEKDAQEINEELKNELKFF 484

                       490       500       510
                ....*....|....*....|....*....|.
gi 13385878 479 EKERVKDFKAVIIKYLESLVQTQQQLIKYWE 509
Cdd:COG5391 485 FSVRNSDLEKILKSVADSHIEWAEENLEIWK 515

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 13385878 144 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIVGmtkvkvGK 223
Cdd:cd07283   3 VTVDDPKKHVCTMETYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEES--QPTHLIPPLPEKFVVK------GV 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 13385878 224 EDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 264
Cdd:cd07283  75 VDRFSEEFVETRRKALDKFLKRIADHPVLSFNEHFNVFLTA 115

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 13385878 142 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLA--SKylhvgYIVPPAPEKSIVGMTKV 219
Cdd:cd06894   2 LEIDVVNPQTHGVGKKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSELErdSK-----IVVPPLPGKALKRQLPF 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 13385878 220 KvGKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLE 263
Cdd:cd06894  77 R-GDDGIFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQ 119

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 13385878 141 DIEIGVSDPEKVgdgmnaymAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIV-----G 215
Cdd:cd07291   6 DIPDALSERDKV--------KFTVHTKTTLPSFQSPDFSVTRQHEDFIWLHDALIETEDYAGLIIPPAPPKPDFdgpreK 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 13385878 216 MTKVKVGKEDSSSTEFVEKRR--------------AALERYLQRTVKHPTLLQDPDLRQFLE 263
Cdd:cd07291  78 MQKLGEGEGSMTKEEFAKMKQeleaeylavfkktvQVHEVFLQRLSSHPSLSKDRNFHIFLE 139

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 13385878 138 DIFDIEIgvsDPEKvgDGM-NAYMAYRVTTKtslsmfsKSEFSVKRRFSDFLGLHSKLASKYLHvgYIVPPAPEKSIVGm 216
Cdd:cd06866   1 DTVTVEL---VPEK--KGLfLKHVEYEVSSK-------RFKSTVYRRYSDFVWLHEYLLKRYPY--RMVPALPPKRIGG- 65

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 13385878 217 tkvkvgkedSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 265
Cdd:cd06866  66 ---------SADREFLEARRRGLSRFLNLVARHPVLSEDELVRTFLTEP 105

The phosphoinositide binding Phox Homology domain of Sorting Nexins 5 and 6; 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. Members of this subfamily include SNX5, SNX6, and similar proteins. They contain 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. SNX5 and SNX6 may be components 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 141 DIEIGVSDPEKVgdgmnaymAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVGYIVPPAPEKS--IVGMTK 218
Cdd:cd06892   6 DISDALSERDKV--------KFTVHTKTTLPTFQKPEFSVTRQHEEFVWLHDTLVENEDYAGLIIPPAPPKPdfDASREK 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 13385878 219 V-KVGKEDSSST-EFVEKRRAALERY---------------LQRTVKHPTLLQDPDLRQFLE 263
Cdd:cd06892  78 LqKLGEGEGSMTkEEFEKMKQELEAEylaifkktvamhevfLRRLASHPVLRNDANFRVFLE 139

The phosphoinositide binding Phox Homology domain of fungal Grd19; 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. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. 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 13385878 142 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVgyIVPPAPEKSIVgmtkvkv 221
Cdd:cd07295   2 LEIEVRNPKTHGIGRGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERESPRV--MIPPLPGKIFT------- 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 13385878 222 gkeDSSSTEFVEKRRAALERYLQRTVKHPtLLQDPD--LRQFLESSE 266
Cdd:cd07295  73 ---NRFSDEVIEERRQGLETFLQSVAGHP-LLQTGSkvLAAFLQDPK 115

The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX41 and SNX42 (also called Atg20p) form dimers with SNX4, and are required in protein recycling from the sorting endosome (post-Golgi endosome) back to the late Golgi in yeast.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13385878 143 EIGVSDPEKVGDGMN-AYMAYRVTTKTSlsmfsksefSVKRRFSDFLGLHSKLASkyLHVGYIVPPAPEK-SIVG-MTKV 219
Cdd:cd06867   1 PIQIVDAGKSSEGGSgSYIVYVIRLGGS---------EVKRRYSEFESLRKNLTR--LYPTLIIPPIPEKhSLKDyAKKP 69

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 13385878 220 KVGKEDSsstEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLE 263
Cdd:cd06867  70 SKAKNDA---KIIERRKRMLQRFLNRCLQHPILRNDIVFQKFLD 110

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 13385878 146 VSDPEKVGDGmnaYMAYRVTTKtslsMFSK------SEFSVKRRFSDFLGLHSKLASKY--LHVGYIVPPAPEKSIVGmt 217
Cdd:cd06881   7 VTDTRRHKKG---YTEYKITSK----VFSRsvpedvSEVVVWKRYSDFKKLHRELSRLHkqLYLSGSFPPFPKGKYFG-- 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 13385878 218 kvkvgkedSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLE 263
Cdd:cd06881  78 --------RFDAAVIEERRQAILELLDFVGNHPALYQSSAFQQFFE 115