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 1907130647 161 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 240
Cdd:cd07664     1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130647 241 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRETEAKMMVANKPDK 320
Cdd:cd07664    81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907130647 321 IQQAKNeireEIEEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKAVIIKYLESLVQTQQQLIKYWEAFLPEAK 398
Cdd:cd07664   161 LQQAKD----EIKEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 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 1907130647 161 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 240
Cdd:cd07664     1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130647 241 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRETEAKMMVANKPDK 320
Cdd:cd07664    81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907130647 321 IQQAKNeireEIEEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKAVIIKYLESLVQTQQQLIKYWEAFLPEAK 398
Cdd:cd07664   161 LQQAKD----EIKEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 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 1907130647  20 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 99
Cdd:cd07282     1 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1907130647 100 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 143
Cdd:cd07282    81 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 124

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130647  48 LSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVgyIVPPAPEKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQRTVKH 127
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSV--IIPPLPPKRWLG----------RYNEEFIEKRRKGLEQYLQRLLQH 68

                          90
                  ....*....|....*.
gi 1907130647 128 PTLLQDPDLRQFLESS 143
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 1907130647 161 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 240
Cdd:cd07664     1 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVESLVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130647 241 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRETEAKMMVANKPDK 320
Cdd:cd07664    81 ALSQLAEVEEKIDQLHQDQAFADFYLFSELLGDYIRLIAAVKGVFDQRMKCWQKWQDAQVTLQKKREAEAKLQYANKPDK 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907130647 321 IQQAKNeireEIEEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKAVIIKYLESLVQTQQQLIKYWEAFLPEAK 398
Cdd:cd07664   161 LQQAKD----EIKEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKTVIIKYLESLVQTQQQLIKYWEAFLPEAK 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 1907130647 161 RMVNKAADAVNKMTIKMNESDAWFEEKQQQFENLDQQLRKLHASVEALVCHRKELSANTAAFAKSAAMLGNSEDHTALSR 240
Cdd:cd07665     1 KMFNKATDAVSKMTIKMNESDVWFEEKLQEVECEEQRLRKLHAVVETLVNHRKELALNTALFAKSLAMLGSSEDNTALSR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130647 241 ALSQLAEVEEKIDQLHQEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRETEAKMMVANKPDK 320
Cdd:cd07665    81 ALSQLAEVEEKIEQLHQEQANNDFFLLAELLADYIRLLSAVRGAFDQRMKTWQRWQDAQAMLQKKREAEARLLWANKPDK 160

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907130647 321 IQQAKNeireEIEEWEAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKAVIIKYLESLVQTQQQLIKYWEAFLPEAK 398
Cdd:cd07665   161 LQQAKD----EIAEWESRVTQYERDFERISATVRKEVIRFEKEKSKDFKNHIIKYLETLLHSQQQLVKYWEAFLPEAK 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 1907130647  20 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 99
Cdd:cd07282     1 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLHVGYIVPPAPEKSIVGMTKVKV 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1907130647 100 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 143
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 1907130647  20 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKYLhvGYIVPPAPEKSIVGMTKVKV 99
Cdd:cd06859     1 FEISVTDPVKVGDGMSAYVVYRVTTKTNLPDFKKSEFSVLRRYSDFLWLYERLVEKYP--GRIVPPPPEKQAVGRFKVKF 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1907130647 100 gkedssstEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 143
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 1907130647 179 ESDAWFEEKQQQFENLDQQLRKLHASVEALVCHRKELSANTAAFAKSAAMLGNSEDH--TALSRALSQLAEVEEKIDQLH 256
Cdd:cd07596     1 EEDQEFEEAKDYILKLEEQLKKLSKQAQRLVKRRRELGSALGEFGKALIKLAKCEEEvgGELGEALSKLGKAAEELSSLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130647 257 QEQAFADFYMFSELLSDYIRLIAAVKGVFDHRMKCWQKWEDAQITLLKKRETEAKMMVAN--KPDKIQQAKNEIREEIee 334
Cdd:cd07596    81 EAQANQELVKLLEPLKEYLRYCQAVKETLDDRADALLTLQSLKKDLASKKAQLEKLKAAPgiKPAKVEELEEELEEAE-- 158

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907130647 335 weAKVQQGERDFEQISKTIRKEVGRFEKERVKDFKAVIIKYLESLVQTQQQLIKYWEAFLPE 396
Cdd:cd07596   159 --SALEEARKRYEEISERLKEELKRFHEERARDLKAALKEFARLQVQYAEKIAEAWESLLPE 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 1907130647  22 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIVgmtkvkVGK 101
Cdd:cd06860     3 ITVDNPEKHVTTLETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEES--HPTHIIPPLPEKHSV------KGL 74

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907130647 102 EDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 140
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 1907130647   24 VSDPEKVGDGMNAYMAYRVTTKTSLSMFSksefsVKRRFSDFLGLHSKLasKYLHVGYIVPPAPEKsivgmtkVKVGKED 103
Cdd:smart00312   1 VVEPEKIGDGKHYYYVIEIETKTGLEEWT-----VSRRYSDFLELHSKL--KKHFPRSILPPLPGK-------KLFGRLN 66

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1907130647  104 SSSTEFVEKRRAALERYLQRTVKHPTLLQ-DPDLRQFLE 141
Cdd:smart00312  67 NFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFLE 105

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907130647  48 LSMFSKSEFSVKRRFSDFLGLHSKLASKYLHVgyIVPPAPEKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQRTVKH 127
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSV--IIPPLPPKRWLG----------RYNEEFIEKRRKGLEQYLQRLLQH 68

                          90
                  ....*....|....*.
gi 1907130647 128 PTLLQDPDLRQFLESS 143
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 1907130647  20 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIVGmtkvkv 99
Cdd:cd07284     1 IFITVDEPESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEA--HPTLIIPPLPEKFVMK------ 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1907130647 100 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 140
Cdd:cd07284    73 GMVERFNEDFIETRRKALHKFLNRIADHPTLTFNEDFKIFL 113

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 1907130647  22 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIVGmtkvkvGK 101
Cdd:cd07283     3 VTVDDPKKHVCTMETYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEES--QPTHLIPPLPEKFVVK------GV 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1907130647 102 EDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 142
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 1907130647  20 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylhVGYIVPPAPEKSIVGMTKVKv 99
Cdd:cd07293     2 LEIDVTNPQTVGVGRGRFTTYEIRLKTNLPIFKLKESTVRRRYSDFEWLRSELERE---SKVVVPPLPGKALFRQLPFR- 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1907130647 100 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLE 141
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 1907130647  20 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylhVGYIVPPAPEKSIVGMTKVKv 99
Cdd:cd07294     4 LEIDIFNPQTVGVGRNRFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERD---SKIVVPPLPGKALKRQLPFR- 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907130647 100 GKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESSELPR 147
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 1907130647  16 DIFDIEIgvsDPEKvgDGM-NAYMAYRVTTKtslsmfsKSEFSVKRRFSDFLGLHSKLASKYLHvgYIVPPAPEKSIVGm 94
Cdd:cd06866     1 DTVTVEL---VPEK--KGLfLKHVEYEVSSK-------RFKSTVYRRYSDFVWLHEYLLKRYPY--RMVPALPPKRIGG- 65

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1907130647  95 tkvkvgkedSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 143
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 1907130647  24 VSDPE-KVGDGMNAYMAYRVTTKTSLSMFSKSEFSVKRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIVGMTKVKvgke 102
Cdd:cd06898     4 VRDPRtHKEDDWGSYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKN--ALLIQLPSLPPKNLFGRFNNE---- 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907130647 103 dssstEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 142
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 1907130647  33 GMNAYMAYRVTTktslsmfSKSEFSVKRRFSDFLGLHSKLASKYLHVgyIVPPAPEKSIVGmtkvkvgkedSSSTEFVEK 112
Cdd:cd06862    16 GLKSFIAYQITP-------THTNVTVSRRYKHFDWLYERLVEKYSCI--AIPPLPEKQVTG----------RFEEDFIEK 76

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1907130647 113 RRAALERYLQRTVKHPTLLQDPDLRQFLESSE 144
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 1907130647  35 NAYMAYRVTTKTSLSmfsksEFSVKRRFSDFLGLHSKLASkylHVGYIVP-PAPEKSIVgmtkvkvgKEDSSSTEFVEKR 113
Cdd:cd06897    13 KPYTVYNIQVRLPLR-----SYTVSRRYSEFVALHKQLES---EVGIEPPyPLPPKSWF--------LSTSSNPKLVEER 76

                          90       100       110
                  ....*....|....*....|....*....|
gi 1907130647 114 RAALERYLQRTVKHP-TLLQD-PDLRQFLE 141
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 1907130647  36 AYMAYRVTTKTSLSmfSKSEFSVKRRFSDFLGLHSKLASKY-LHVGYIVPPAPEKSIVGMTKVKVGKEdsssteFVEKRR 114
Cdd:cd07280    21 AYVVWKITIETKDL--IGSSIVAYKRYSEFVQLREALLDEFpRHKRNEIPQLPPKVPWYDSRVNLNKA------WLEKRR 92

                          90       100
                  ....*....|....*....|....*...
gi 1907130647 115 AALERYLQRTVKHPTLLQDPDLRQFLES 142
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 1907130647  24 VSDPEKVGDGmnaYMAYRVTTKtslsMFSK------SEFSVKRRFSDFLGLHSKLASKY--LHVGYIVPPAPEKSIVGmt 95
Cdd:cd06881     7 VTDTRRHKKG---YTEYKITSK----VFSRsvpedvSEVVVWKRYSDFKKLHRELSRLHkqLYLSGSFPPFPKGKYFG-- 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1907130647  96 kvkvgkedSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLE 141
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 1907130647  55 EFSVKRRFSDFLGLHSKLASKYLHVGYIVPPapeKSIVGmtkvkvgkedSSSTEFVEKRRAALERYLQRTV-KHPTLLQD 133
Cdd:cd06875    30 EWTVKHRYSDFAELHDKLVAEHKVDKDLLPP---KKLIG----------NKSPSFVEKRRKELEIYLQTLLsFFQKTMPR 96

                  ....*...
gi 1907130647 134 PdLRQFLE 141
Cdd:cd06875    97 E-LAHFLD 103