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 2827434  283 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHVSVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 362
Cdd:cd07664   1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  363 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKREAEAKMMVANKPDK 442
Cdd:cd07664  81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2827434  443 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434      4 AERELLLWGDGKPTDFEDLE------DGEDLFTSyclhpRVKTHHLQNQPSLPAEDISANSNGPKPTEVVLDDDREDLFA 77
Cdd:pfam03700   1 SEREPPPFPDSEDPEPEDAAgdgdsdEGEDIFTG-----TVSTLGSSPSSPEPASLPFTNSNGPKTNGVHSDDDQQDLFA 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 2827434  283 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHVSVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 362
Cdd:cd07664   1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  363 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKREAEAKMMVANKPDK 442
Cdd:cd07664  81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2827434  443 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 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 2827434  143 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKR-FTDFLGLHTTLPTTYLHVVIFVATSSRKSIVGMTKVKV 221
Cdd:cd07282   1 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRrFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 2827434  222 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 265
Cdd:cd07282  81 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 124

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434      4 AERELLLWGDGKPTDFEDLE------DGEDLFTSyclhpRVKTHHLQNQPSLPAEDISANSNGPKPTEVVLDDDREDLFA 77
Cdd:pfam03700   1 SEREPPPFPDSEDPEPEDAAgdgdsdEGEDIFTG-----TVSTLGSSPSSPEPASLPFTNSNGPKTNGVHSDDDQQDLFA 75

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  142 DIEIGVSDPEKVGDGM---NAYMAYRVTTKTSLSMFSKSEFSVK----RFTDFLGLHTTLPTTYLHVVIFVATSSRKsiv 214
Cdd:COG5391 130 FISSTVSNPQSLTLLVdsrDKHTSYEIITVTNLPSFQLRESRPLvvrrRYSDFESLHSILIKLLPLCAIPPLPSKKS--- 206

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  215 gmtkVKVGKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDP----------DLRQFLE------SSELPRAVNTQALSG 278
Cdd:COG5391 207 ----NSEYYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSNYKnsksweshstLLSSFIEnrksvpTPLSLDLTSTTQELD 282

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  279 AGILRMVNKAADAVNKMTIKMNEsdawFEEKQQQFENLDQQL-RKLHVSVEALVCHRKELSANTAAFAK---SAAMLGNS 354
Cdd:COG5391 283 MERKELNESTSKAIHNILSIFSL----FEKILIQLESEEESLtRLLESLNNLLLLVLNFSGVFAKRLEQnqnSILNEGVV 358

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  355 EDHTALS---RALSQLAEVEEKIDQL-----HQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITL-L 425
Cdd:COG5391 359 QAETLRSslkELLTQLQDEIKSRESLiltdsNLEKLTDQNLEDVEELSRSLRKNSSQRAVVSQQPEGLTSFSKLSYKLrD 438

                       330       340       350       360       370       380       390       400
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  426 KKREAEAKmmvaNKPDKIQQAKNEIREweaKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLI 505
Cdd:COG5391 439 FVQEKSRS----KSIESLQQDKEKLEE---QLAIAEKDAQEINEELKNELKFFFSVRNSDLEKILKSVADSHIEWAEENL 511

                ....
gi 2827434  506 KYWE 509
Cdd:COG5391 512 EIWK 515

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 2827434  283 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHVSVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 362
Cdd:cd07664   1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  363 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKREAEAKMMVANKPDK 442
Cdd:cd07664  81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2827434  443 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 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 2827434  283 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHVSVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 362
Cdd:cd07665   1 KMFNKATDAVSKMTIKMNESDVWFEEKLQEVECEEQRLRKLHAVVETLVNHRKELALNTALFAKSLAMLGSSEDNTALSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  363 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKREAEAKMMVANKPDK 442
Cdd:cd07665  81 ALSQLAEVEEKIEQLHQEQANNDFFLLAELLADYIRLLSAVRGAFDQRMKTWQRWQDAQAMLQKKREAEARLLWANKPDK 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2827434  443 IQQAKNEIREWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 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 2827434  143 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKR-FTDFLGLHTTLPTTYLHVVIFVATSSRKSIVGMTKVKV 221
Cdd:cd07282   1 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRrFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 2827434  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 2827434  143 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVK-RFTDFLGLHTTLPTTYLHVVIFVATSsrKSIVGMTKVKV 221
Cdd:cd06859   1 FEISVTDPVKVGDGMSAYVVYRVTTKTNLPDFKKSEFSVLrRYSDFLWLYERLVEKYPGRIVPPPPE--KQAVGRFKVKF 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 2827434  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 2827434  301 ESDAWFEEKQQQFENLDQQLRKLHVSVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSRALSQLAEVEEKIDQLHQE 380
Cdd:cd07627   1 EPDEWFIEKKQYLDSLESQLKQLYKSLELVSSQRKELASATEEFAETLEALSSLELSKSLSDLLAALAEVQKRIKESLER 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  381 QAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKREAEAKMMVANK--PDKIQQAKNEIREWEAKVQ 458
Cdd:cd07627  81 QALQDVLTLGVTLDEYIRSIGSVRAAFAQRQKLWQYWQSAESELSKKKAQLEKLKRQGKtqQEKLNSLLSELEEAERRAS 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 2827434  459 QGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFL 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 2827434  145 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVK-RFTDFLGLHTTLPTTYLHVVIfVATSSRKSIVGMTkvkvgk 223
Cdd:cd06860   3 ITVDNPEKHVTTLETYITYRVTTKTTRSEFDSSEYSVRrRYQDFLWLRQKLEESHPTHII-PPLPEKHSVKGLL------ 75

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 2827434  224 eDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 262
Cdd:cd06860  76 -DRFSPEFVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 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 2827434     147 VSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSefsvKRFTDFLGLHTTLPTTYLHVVIFVATSsrksivgmtKVKVGKEDS 226
Cdd:smart00312   1 VVEPEKIGDGKHYYYVIEIETKTGLEEWTVS----RRYSDFLELHSKLKKHFPRSILPPLPG---------KKLFGRLNN 67

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2827434     227 SSTEFVEKRRAALERYLQRTVKHPTLLQ-DPDLRQFLE 263
Cdd:smart00312  68 FSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFLE 105

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434      4 AERELLLWGDGKPTDFEDLE------DGEDLFTSyclhpRVKTHHLQNQPSLPAEDISANSNGPKPTEVVLDDDREDLFA 77
Cdd:pfam03700   1 SEREPPPFPDSEDPEPEDAAgdgdsdEGEDIFTG-----TVSTLGSSPSSPEPASLPFTNSNGPKTNGVHSDDDQQDLFA 75

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 2827434  143 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKR-FTDFLGLHTTLPTTylHVVIFVATSSRKSIVGmtkvkv 221
Cdd:cd07284   1 IFITVDEPESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRrYQDFLWLKGRLEEA--HPTLIIPPLPEKFVMK------ 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 2827434  222 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 262
Cdd:cd07284  73 GMVERFNEDFIETRRKALHKFLNRIADHPTLTFNEDFKIFL 113

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434    171 LSMFSKSEFSV-KRFTDFLGLHTTLPTTYLHVVIfvATSSRKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQRTVKH 249
Cdd:pfam00787   1 LPTFSLEEWSVrRRYSDFVELHKKLLRKFPSVII--PPLPPKRWLG----------RYNEEFIEKRRKGLEQYLQRLLQH 68

                          90
                  ....*....|....*.
gi 2827434    250 PTLLQDPDLRQFLESS 265
Cdd:pfam00787  69 PELRNSEVLLEFLESD 84

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 2827434  145 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSV-KRFTDFLGLHTTLPTTylHVVIFVATSSRKSIVGmtkvkvGK 223
Cdd:cd07283   3 VTVDDPKKHVCTMETYITYRVTTKTTRTEFDLPEYSVrRRYQDFDWLRNKLEES--QPTHLIPPLPEKFVVK------GV 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 2827434  224 EDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 264
Cdd:cd07283  75 VDRFSEEFVETRRKALDKFLKRIADHPVLSFNEHFNVFLTA 115

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 2827434  143 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSV-KRFTDFLGLHTTLPTtylHVVIFVATSSRKSIVGMTKVKv 221
Cdd:cd07293   2 LEIDVTNPQTVGVGRGRFTTYEIRLKTNLPIFKLKESTVrRRYSDFEWLRSELER---ESKVVVPPLPGKALFRQLPFR- 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 2827434  222 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLE 263
Cdd:cd07293  78 GDDGIFDDSFIEERKQGLEQFLNKVAGHPLAQNERCLHMFLQ 119

The phosphoinositide binding Phox Homology domain of yeast MDM1p; 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. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434  182 KRFTDFLGLHTTLPTTYlhvvifvatSSRKSIVGMTKVKVGKEdSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQF 261
Cdd:cd06876  61 RRYSEFLELHKYLKKRY---------PGVLKLDFPQKRKISLK-YSKTLLVEERRKALEKYLQELLKIPEVCEDEEFRKF 130

                ...
gi 2827434  262 LES 264
Cdd:cd06876 131 LSQ 133

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 2827434  147 VSDPE-KVGDGMNAYMAYRVTTKT-SLSMFSKSEFSVKRFTDFLGLHTTLPTTylHVVIFVATSSRKSIVGMTKVKvgke 224
Cdd:cd06898   4 VRDPRtHKEDDWGSYTDYEIFLHTnSMCFTLKTSCVRRRYSEFVWLRNRLQKN--ALLIQLPSLPPKNLFGRFNNE---- 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 2827434  225 dssstEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 264
Cdd:cd06898  78 -----GFIEERQQGLQDFLEKVLQTPLLLSDSRLHLFLQT 112

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 2827434  142 DIEIGVSDPEKVgdgmnaymAYRVTTKTSLSMFSKSEFSVKR-FTDFLGLHTTLPTTYLHVVIFVATSSRKSIV-----G 215
Cdd:cd07291   6 DIPDALSERDKV--------KFTVHTKTTLPSFQSPDFSVTRqHEDFIWLHDALIETEDYAGLIIPPAPPKPDFdgpreK 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2827434  216 MTKVKVGKEDSSSTEFVEKRR--------------AALERYLQRTVKHPTLLQDPDLRQFLE 263
Cdd:cd07291  78 MQKLGEGEGSMTKEEFAKMKQeleaeylavfkktvQVHEVFLQRLSSHPSLSKDRNFHIFLE 139

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 2827434  159 AYMAYRVTTKTSLSMFSkSEFSVKRFTDFLGLHTTLPTTY-LHVVIFVATSSRKSIVGMTKVKVGKEdsssteFVEKRRA 237
Cdd:cd07280  21 AYVVWKITIETKDLIGS-SIVAYKRYSEFVQLREALLDEFpRHKRNEIPQLPPKVPWYDSRVNLNKA------WLEKRRR 93

                        90       100
                ....*....|....*....|....*..
gi 2827434  238 ALERYLQRTVKHPTLLQDPDLRQFLES 264
Cdd:cd07280  94 GLQYFLNCVLLNPVFGGSPVVKEFLLP 120

Chromosome condensin MukBEF, ATPase and DNA-binding subunit MukB [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434   225 DSSSTEFVEKRRAALERY--LQRTVKHPTLLQDPDLRQFLESSelpRAVNTQALSGAGILRMVNKAADAVNKMTIKMNES 302
Cdd:COG3096  856 RAQEQQLRQQLDQLKEQLqlLNKLLPQANLLADETLADRLEEL---REELDAAQEAQAFIQQHGKALAQLEPLVAVLQSD 932

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434   303 DAWFEEKQQQFENLDQQLRKLHVSVEALvchrKELSANTAAFA--KSAAMLGNSedhTALSRAL-SQLAEVEEKI----D 375
Cdd:COG3096  933 PEQFEQLQADYLQAKEQQRRLKQQIFAL----SEVVQRRPHFSyeDAVGLLGEN---SDLNEKLrARLEQAEEARrearE 1005

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2827434   376 QLHQEQAfadfymfseLLSDYIRLIAAVKGVFDHRMKCWQKWED--AQITLLKKREAEAKmmVANKPDKIQQA----KNE 449
Cdd:COG3096 1006 QLRQAQA---------QYSQYNQVLASLKSSRDAKQQTLQELEQelEELGVQADAEAEER--ARIRRDELHEElsqnRSR 1074

                        250       260
                 ....*....|....*....|....*
gi 2827434   450 IREWEAKVQQGERDFEQISKTIRKE 474
Cdd:COG3096 1075 RSQLEKQLTRCEAEMDSLQKRLRKA 1099

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins 5 and 6; 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. Members of this subfamily include SNX5, SNX6, the mammalian SNX32, and similar proteins. 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. The function of SNX32 is still unknown. 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 2827434  351 LGNSEdHTALSRALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRea 430
Cdd:cd07621  71 LATSE-PTPLDKFLLKVAETFEKLRKLEGRVASDEDLKLSDTLRYYMRDTQAAKDLLYRRLRCLANYENANKNLEKAR-- 147

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2827434  431 eAKMMVANKPDKIQQAKNEireweakvqqgerDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLV---QTQQQLIK 506
Cdd:cd07621 148 -AKNKDVHAAEAAQQEACE-------------KFESMSESAKQELLDFKTRRVAAFRKNLVELAELEIkhaKAQIQLLK 212