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 1958750993 209 HPTLTFNEDFKVFLTAEAWELSSYKKQGPGLLSRMGQTVRAVASSMRGVKNRPDEFTEMNNFIETFSQKINLIDKISQRI 288
Cdd:cd07666     1 HPTLTFNEDFKIFLTAQAWELSSHKKQGPGLLSRMGQTVKAVASSVRGVKNRPEEFTEMNEYVEAFSQKINVLDKISQRI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 289 YKEERDYFDEMKEYGPIHTLWSTSEEDLVDTLKGIASCIDQCCKATEKRMSGLSEALLPVVHEYVLYSEMLVGVMKRRDQ 368
Cdd:cd07666    81 YKEQREYFEELKEYGPIYTLWSASEEELADSLKGMASCIDRCCKATDKRMKGLSEQLLPVIHEYVLYSETLMGVIKRRDQ 160

                         170       180
                  ....*....|....*....|.
gi 1958750993 369 IQAELDSKVEALTYKKADADL 389
Cdd:cd07666   161 IQAELDSKVEALANKKADRDL 181

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 7; 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. The specific function of SNX7 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 1958750993 209 HPTLTFNEDFKVFLTAEAWELSSYKKQGPGLLSRMGQTVRAVASSMRGVKNRPDEFTEMNNFIETFSQKINLIDKISQRI 288
Cdd:cd07666     1 HPTLTFNEDFKIFLTAQAWELSSHKKQGPGLLSRMGQTVKAVASSVRGVKNRPEEFTEMNEYVEAFSQKINVLDKISQRI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 289 YKEERDYFDEMKEYGPIHTLWSTSEEDLVDTLKGIASCIDQCCKATEKRMSGLSEALLPVVHEYVLYSEMLVGVMKRRDQ 368
Cdd:cd07666    81 YKEQREYFEELKEYGPIYTLWSASEEELADSLKGMASCIDRCCKATDKRMKGLSEQLLPVIHEYVLYSETLMGVIKRRDQ 160

                         170       180
                  ....*....|....*....|.
gi 1958750993 369 IQAELDSKVEALTYKKADADL 389
Cdd:cd07666   161 IQAELDSKVEALANKKADRDL 181

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 141 FDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKgmveRFNDDFIETRRKALHKFLNRIADHPTLTFNEDFKV 220
Cdd:pfam00787   4 FSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLG----RYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLE 79

                  ....*
gi 1958750993 221 FLTAE 225
Cdd:pfam00787  80 FLESD 84

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993  72 FSKDASLMDMNsFSPMMPTSPLSMINQIKFedgpdlKDLFITVDAPESH---VTTIETFITYRIVTKTSRGEFDSSEFE- 147
Cdd:COG5391   100 EFRSLRDMLSL-LLPTSLQPPLSTSHTILD------YFISSTVSNPQSLtllVDSRDKHTSYEIITVTNLPSFQLRESRp 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 148 --VRRRYQDFLWLKGKLEEAHPTLIIPPLPEK-FIVKGMVERFNDDFIETRRKALHKFLNRIADHPTLT---FNEDFKVF 221
Cdd:COG5391   173 lvVRRRYSDFESLHSILIKLLPLCAIPPLPSKkSNSEYYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSnykNSKSWESH 252

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 222 LTaeawELSSYKKQgpgllsRMGQTVRAVASSMRGVKNRPDEFTEMNNFIETFSQKINLIDKISQRIYKEERDYFDEMKE 301
Cdd:COG5391   253 ST----LLSSFIEN------RKSVPTPLSLDLTSTTQELDMERKELNESTSKAIHNILSIFSLFEKILIQLESEEESLTR 322

                  ....
gi 1958750993 302 YGPI 305
Cdd:COG5391   323 LLES 326

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 7; 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. The specific function of SNX7 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 1958750993 209 HPTLTFNEDFKVFLTAEAWELSSYKKQGPGLLSRMGQTVRAVASSMRGVKNRPDEFTEMNNFIETFSQKINLIDKISQRI 288
Cdd:cd07666     1 HPTLTFNEDFKIFLTAQAWELSSHKKQGPGLLSRMGQTVKAVASSVRGVKNRPEEFTEMNEYVEAFSQKINVLDKISQRI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 289 YKEERDYFDEMKEYGPIHTLWSTSEEDLVDTLKGIASCIDQCCKATEKRMSGLSEALLPVVHEYVLYSEMLVGVMKRRDQ 368
Cdd:cd07666    81 YKEQREYFEELKEYGPIYTLWSASEEELADSLKGMASCIDRCCKATDKRMKGLSEQLLPVIHEYVLYSETLMGVIKRRDQ 160

                         170       180
                  ....*....|....*....|.
gi 1958750993 369 IQAELDSKVEALTYKKADADL 389
Cdd:cd07666   161 IQAELDSKVEALANKKADRDL 181

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 1958750993 110 LFITVDAPESHVTTIETFITYRIVTKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKGMVERFND 189
Cdd:cd06860     1 LFITVDNPEKHVTTLETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVKGLLDRFSP 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1958750993 190 DFIETRRKALHKFLNRIADHPTLTFNEDFKVFLTA 224
Cdd:cd06860    81 EFVATRMRALHKFLNRIVEHPVLSFNEHLKVFLTA 115

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 30; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Sorting nexins (SNXs) are Phox homology (PX) domain containing proteins that are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in their lipid-binding specificity, subcellular localization and specific function in the endocytic pathway. A subset of SNXs also contain BAR domains. The PX-BAR structural unit determines the specific membrane targeting of SNXs. The specific function of SNX30 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 1958750993 209 HPTLTFNEDFKVFLTAEawELSSYKKQGPGLLSRMGQTVRAVASSMRgVKNRPDEFTEMNNFIETFSQKINLIDKISQRI 288
Cdd:cd07667     1 HPVLSFNEHFNVFLTAK--DLNAYKKQGIALLSKMGESVKYVTGGYK-LRSRPLEFAAIGDYLDTFALKLGTIDRIAQRI 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 289 YKEERDYFDEMKEYGPIHTLWSTSEEDLVDTLKGIASCIDQCCKATEKRMSGLSEALLPVVHEYVLYSEMLVGVMKRRDQ 368
Cdd:cd07667    78 IKEEIEYLVELREYGPVYSTWSGLEGELAEPLEGVSACIGNCSTALEELTEDMTEDFLPVLREYILYSESMKNVLKKRDQ 157

                         170
                  ....*....|....*...
gi 1958750993 369 IQAELDSKVEALTYKKAD 386
Cdd:cd07667   158 VQAEYEAKLEAVALRKEE 175

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 1958750993 110 LFITVDAPESHVTTIETFITYRIVTKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVkGMVeRFND 189
Cdd:cd06859     1 FEISVTDPVKVGDGMSAYVVYRVTTKTNLPDFKKSEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAV-GRF-KVKF 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958750993 190 DFIETRRKALHKFLNRIADHPTLTFNEDFKVFLTAE 225
Cdd:cd06859    79 EFIEKRRAALERFLRRIAAHPVLRKDPDFRLFLESD 114

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 141 FDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKgmveRFNDDFIETRRKALHKFLNRIADHPTLTFNEDFKV 220
Cdd:pfam00787   4 FSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLG----RYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLE 79

                  ....*
gi 1958750993 221 FLTAE 225
Cdd:pfam00787  80 FLESD 84

The phosphoinositide binding Phox Homology domain of SNX-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 112 ITVDAPESHVTTIE------TFITYRIVTKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKGMVe 185
Cdd:cd06865     2 ITVSDPKKEQEPSRvplggpPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQV- 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1958750993 186 RFNDDFIETRRKALHKFLNRIADHPTLTFNEDFKVFLTAE 225
Cdd:cd06865    81 MQSAEFIEQRRVALEKYLNRLAAHPVIGLSDELRVFLTLQ 120

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 1958750993 112 ITVDAPESHVTTIETFITYRIVTKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEA--HPTLIIPPLPEKFIVkGMV----- 184
Cdd:cd07282     3 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIV-GMTkvkvg 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1958750993 185 --ERFNDDFIETRRKALHKFLNRIADHPTLTFNEDFKVFL 222
Cdd:cd07282    82 keDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFL 121

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 1958750993 112 ITVDAP--ESHVTTIETFITYRIV-TKTSRgefdssefEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKgmveRFN 188
Cdd:cd06862     3 CTVTNPkkESKFKGLKSFIAYQITpTHTNV--------TVSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTG----RFE 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958750993 189 DDFIETRRKALHKFLNRIADHPTLTFNEDFKVFLTAE---AWElsSYKKQ 235
Cdd:cd06862    71 EDFIEKRRERLELWMNRLARHPVLSQSEVFRHFLTCTdekDWK--SGKRK 118

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 1958750993 259 NRPDEFTEMNNFIETFSQKINLIDKISQRIYKEERDYFDEMKEYGPIHTLWSTSEED----LVDTLKGIASCIDQCCKAT 334
Cdd:cd07596     1 EEDQEFEEAKDYILKLEEQLKKLSKQAQRLVKRRRELGSALGEFGKALIKLAKCEEEvggeLGEALSKLGKAAEELSSLS 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958750993 335 EKRMSGLSEALLPVVHEYVLYSEMLVGVMKRRDQIQAELDSKVEALTYKKADAD 388
Cdd:cd07596    81 EAQANQELVKLLEPLKEYLRYCQAVKETLDDRADALLTLQSLKKDLASKKAQLE 134

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 1958750993 110 LFITVDAPESHVTTIETFITYRIVTKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEaHPTLIIPPLPEKFIVKGMVER--- 186
Cdd:cd06894     2 LEIDVVNPQTHGVGKKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSELER-DSKIVVPPLPGKALKRQLPFRgdd 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958750993 187 --FNDDFIETRRKALHKFLNRIADHPTLTFNEDFKVFLTAEA 226
Cdd:cd06894    81 giFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQEET 122

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 1958750993 114 VDAPESHVTTIETFITYRIVTKTSrgefdssefEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEK-----FIVKGMVERFN 188
Cdd:cd06867     5 VDAGKSSEGGSGSYIVYVIRLGGS---------EVKRRYSEFESLRKNLTRLYPTLIIPPIPEKhslkdYAKKPSKAKND 75

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958750993 189 DDFIETRRKALHKFLNRIADHPTLTFNEDFKVFLTAE 225
Cdd:cd06867    76 AKIIERRKRMLQRFLNRCLQHPILRNDIVFQKFLDPN 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993  72 FSKDASLMDMNsFSPMMPTSPLSMINQIKFedgpdlKDLFITVDAPESH---VTTIETFITYRIVTKTSRGEFDSSEFE- 147
Cdd:COG5391   100 EFRSLRDMLSL-LLPTSLQPPLSTSHTILD------YFISSTVSNPQSLtllVDSRDKHTSYEIITVTNLPSFQLRESRp 172

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 148 --VRRRYQDFLWLKGKLEEAHPTLIIPPLPEK-FIVKGMVERFNDDFIETRRKALHKFLNRIADHPTLT---FNEDFKVF 221
Cdd:COG5391   173 lvVRRRYSDFESLHSILIKLLPLCAIPPLPSKkSNSEYYGDRFSDEFIEERRQSLQNFLRRVSTHPLLSnykNSKSWESH 252

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 222 LTaeawELSSYKKQgpgllsRMGQTVRAVASSMRGVKNRPDEFTEMNNFIETFSQKINLIDKISQRIYKEERDYFDEMKE 301
Cdd:COG5391   253 ST----LLSSFIEN------RKSVPTPLSLDLTSTTQELDMERKELNESTSKAIHNILSIFSLFEKILIQLESEEESLTR 322

                  ....
gi 1958750993 302 YGPI 305
Cdd:COG5391   323 LLES 326

The phosphoinositide binding Phox Homology domain of Sorting Nexin 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. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. 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 1958750993 113 TVDAP--ESHVTTIETFITYRIVTKtsrgefdSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKfivkGMVERFNDD 190
Cdd:cd07286     4 TIDDPtkQTKFKGMKSYISYKLVPS-------HTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEK----QATGRFEED 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1958750993 191 FIETRRKALHKFLNRIADHPTLTFNEDFKVFLTAEAWELSSYKK 234
Cdd:cd07286    73 FISKRRKGLIWWMDHMCSHPVLARCDAFQHFLTCPSTDEKAWKQ 116

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 1958750993 112 ITVDAPESHVTTIET-FITYRIVTKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEkfivKGMVERFND- 189
Cdd:cd06898     2 VEVRDPRTHKEDDWGsYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPP----KNLFGRFNNe 77

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1958750993 190 DFIETRRKALHKFLNRIADHPTLTFNEDFKVFL 222
Cdd:cd06898    78 GFIEERQQGLQDFLEKVLQTPLLLSDSRLHLFL 110

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 1958750993 114 VDAPESHVTTIET----FITYRIVTKTSrgEFDSSEFEVRRRYQDFLWLKGKLEEAHPT---LIIPPLPEKFIVKGMVER 186
Cdd:cd07280     5 VNVGDYTIVGGDTgggaYVVWKITIETK--DLIGSSIVAYKRYSEFVQLREALLDEFPRhkrNEIPQLPPKVPWYDSRVN 82

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958750993 187 FNDDFIETRRKALHKFLNRIADHPTLTFNEDFKVFL 222
Cdd:cd07280    83 LNKAWLEKRRRGLQYFLNCVLLNPVFGGSPVVKEFL 118

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 1958750993 134 TKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEA--HPTLIIPPLP---------EKFIVKG-------------MVERFND 189
Cdd:cd06892    23 TKTTLPTFQKPEFSVTRQHEEFVWLHDTLVENedYAGLIIPPAPpkpdfdasrEKLQKLGegegsmtkeefekMKQELEA 102

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958750993 190 DFIETRRK--ALHK-FLNRIADHPTLTFNEDFKVFL 222
Cdd:cd06892   103 EYLAIFKKtvAMHEvFLRRLASHPVLRNDANFRVFL 138

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 146 FEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKfivKGMVERfNDDFIETRRKALHKFLNRIADHPTLTFNEDFKVFLTAE 225
Cdd:cd06877    44 WSVLRRYNEFYVLESKLTEFHGEFPDAPLPSR---RIFGPK-SYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSPN 119

The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. Through its SH3 domain, SNX9 binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 124 IETFITYRIV-TKTSRgefdssefEVRRRYQDFLWLKGKLEEAHPTLI-IPPLPEKFIVKgmveRFNDDFIETRRKALHK 201
Cdd:cd07285    17 LKSYIEYQLTpTNTNR--------SVNHRYKHFDWLYERLLVKFGLAIpIPSLPDKQVTG----RFEEEFIKMRMERLQA 84

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1958750993 202 FLNRIADHPTLTFNEDFKVFLT---AEAWELSSYKKQ 235
Cdd:cd07285    85 WMTRMCRHPVISESEVFQQFLNfrdEKEWKTGKRKAE 121

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; 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. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 127 FITYRIVTKTSRGEFdsseFEVRRRYQDFLWLKGKLEEAHPTLIIpPLPEKFIVKgmvERFNDDFIETRRKALHKFLNRI 206
Cdd:cd07276    20 FTVYKIRVENKVGDS----WFVFRRYTDFVRLNDKLKQMFPGFRL-SLPPKRWFK---DNFDPDFLEERQLGLQAFVNNI 91

                  ....*.
gi 1958750993 207 ADHPTL 212
Cdd:cd07276    92 MAHKDI 97

The phosphoinositide binding Phox Homology domain of Sorting Nexin 19; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX19 contains an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. These domains are also found in SNX13 and SNX14, which also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNX19 interacts with IA-2, a major autoantigen found in type-1 diabetes. It inhibits the conversion of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to PI(3,4,5)P3, which leads in the decrease of protein phosphorylation in the Akt signaling pathway, resulting in apoptosis. SNX19 may also be implicated in coronary heart disease and thyroid oncocytic tumors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 139 GEFDSSEFEVRRRYQDFLWLKGKLEEaHPTLiipplpEKFI-VKGMVERFND--------DFIETRRKALHKFLNRIADH 209
Cdd:cd06893    44 SEQPLATHTVNRRFREFLTLQTRLEE-NPKF------RKIMnVKGPPKRLFDlpfgnmdkDKIEARRGLLETFLRQLCSI 116

                          90
                  ....*....|...
gi 1958750993 210 PTLTFNEDFKVFL 222
Cdd:cd06893   117 PEISNSEEVQEFL 129

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; 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. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 126 TFITYRI-VTKTSRGEFDSSeFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKGMverfNDDFIETRRKALHKFLN 204
Cdd:cd06873    21 TYAVYAIsVTRIYPNGQEES-WHVYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKTFNNL----DRAFLEKRRKMLNQYLQ 95

                          90
                  ....*....|....*...
gi 1958750993 205 RIADHPTLTFNEDFKVFL 222
Cdd:cd06873    96 SLLNPEVLDANPGLQEIV 113

The phosphoinositide binding Phox Homology domain of RPK118-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 bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 111 FITVDAPESHVTTIETF-ITYRIVTKtsRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTL-----IIPPLPeKFIVKGmv 184
Cdd:cd07287     4 FYTVTDPRRHPKGYTVYkVTARIVSR--KNPEDVQEIVVWKRYSDFKKLHKDLWQIHKNLcrqseLFPPFA-KAKVFG-- 78

                          90       100
                  ....*....|....*....|....*...
gi 1958750993 185 eRFNDDFIETRRKALHKFLNRIADHPTL 212
Cdd:cd07287    79 -RFDESVIEERRQCAEDLLQFSANIPAL 105

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; 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. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958750993 111 FITVDAPESHVTT-IETFITYRIVTKTSRGefDSSEFEVRRRYQDFLWLKGKLEEAHPTLI-----IPPLPEKFIVKgmv 184
Cdd:cd07288     4 FYSVTDPRTHPKGyTEYKVTAQFISKKQPE--DVKEVVVWKRYSDLKKLHGELAYTHRNLFrrqeeFPPFPRAQVFG--- 78

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958750993 185 eRFNDDFIETRRKALHKFLNRIADHPTLTFNEDFKVFL 222
Cdd:cd07288    79 -RFEAAVIEERRNAAEAMLLFTVNIPALYNSPQLKEFF 115