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 1297697772 118 LFITVDEPESHVTTIETFITYRIITKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKGMVERFND 197
Cdd:cd07284     1 IFITVDEPESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFVMKGMVERFNE 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1297697772 198 DFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 233
Cdd:cd07284    81 DFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 116

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 1297697772 118 LFITVDEPESHVTTIETFITYRIITKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKGMVERFND 197
Cdd:cd07284     1 IFITVDEPESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFVMKGMVERFNE 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1297697772 198 DFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 233
Cdd:cd07284    81 DFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 116

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 1297697772  124 EPESHVTTIETFITYRIITKTSrgefdSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKfIVKGMVERFNDDFIETR 203
Cdd:smart00312   3 EPEKIGDGKHYYYVIEIETKTG-----LEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGK-KLFGRLNNFSEEFIEKR 76

                           90       100
                   ....*....|....*....|....*....
gi 1297697772  204 RKALHKFLNRIADHPTL-TFNEDFKIFLT 231
Cdd:smart00312  77 RRGLEKYLQSLLNHPELiNHSEVVLEFLE 105

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexins 7 and 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. This subfamily consists of SNX7, SNX30, and similar proteins. The specific functions of SNX7 and SNX30 have not been elucidated. 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 1297697772 257 AVASSMRGVKNRPEEFMEMNNFIELFSQKINLIDKISQRIYKEEREYFDEMKEYGPIHILWSASEEDLVDTLKDVASCID 336
Cdd:cd07624     1 RNTSTMYLLKNRSPEFDKMNEYLTLFGEKLGTIERISQRIHKERIEYFDELKEYSPIFQLWSASETELAPLLEGVSSAVE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297697772 337 RCCKATEKRMSGLSEALLPVVHEYVLYSEMLMGVMKRRDQIQAELDSKVEALTYKKIDtdlqdrswlstlsyrirseeei 416
Cdd:cd07624    81 RCTAALEVLLSDHEFVFLPPLREYLLYSDAVKDVLKRRDQFQIEYELSVEELNKKRLE---------------------- 138

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1297697772 417 wrcatlhiykmifkLPEEIGKLEDKVECANNALKADWERWKQNMQNDIKLAFTDMAEENIHYYEQCLATWESFLTS 492
Cdd:cd07624   139 --------------LLKEVEKLQDKLECANADLKADLERWKQNKRQDLKKILLDMAEKQIQYYEQCLAAWEEVLPA 200

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 1297697772 217 HPTLTFNEDFKIFLTAQawELSSHKKQGPGLLSRMGQTVRAVASSMRgVKNRPEEFMEMNNFIELFSQKINLIDKISQRI 296
Cdd:cd07667     1 HPVLSFNEHFNVFLTAK--DLNAYKKQGIALLSKMGESVKYVTGGYK-LRSRPLEFAAIGDYLDTFALKLGTIDRIAQRI 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297697772 297 YKEEREYFDEMKEYGPIHILWSASEEDLVDTLKDVASCIDRCCKATEKRMSGLSEALLPVVHEYVLYSEMLMGVMKRRDQ 376
Cdd:cd07667    78 IKEEIEYLVELREYGPVYSTWSGLEGELAEPLEGVSACIGNCSTALEELTEDMTEDFLPVLREYILYSESMKNVLKKRDQ 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297697772 377 IQAELDSKVEALTYKKidtdlQDRSwlstlsyrirseeeiwrcatlhiykmifKLPEEIGKLEDKVECANNALKADWERW 456
Cdd:cd07667   158 VQAEYEAKLEAVALRK-----EERP----------------------------KVPTDVEKCQDRVECFNADLKADMERW 204

                         250       260       270
                  ....*....|....*....|....*....|....
gi 1297697772 457 KQNMQNDIKLAFTDMAEENIHYYEQCLATWESFL 490
Cdd:cd07667   205 QNNKRQDFRQLLMGMADKNIQYYEKCLTAWESII 238

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 1297697772 118 LFITVDEPESHVTTIETFITYRIITKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKGMVERFND 197
Cdd:cd07283     1 LFVTVDDPKKHVCTMETYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRFSE 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1297697772 198 DFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 233
Cdd:cd07283    81 EFVETRRKALDKFLKRIADHPVLSFNEHFNVFLTAK 116

The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps5p; 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. 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. The PX domain of Vps5p binds phosphatidylinositol-3-phosphate (PI3P). Similar to SNX1, Vps5p contains 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297697772 120 ITVDEPESHVTTIETFITYRIITKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKgmveRFNDDF 199
Cdd:cd06861     3 ITVGDPHKVGDLTSAHTVYTVRTRTTSPNFEVSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVG----RFDDNF 78

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1297697772 200 IETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 233
Cdd:cd06861    79 VEQRRAALEKMLRKIANHPVLQKDPDFRLFLESE 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297697772 120 ITVDEPESHVTTIETFITYRIITKTSrgefDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKgmveRFNDDF 199
Cdd:cd06093     2 VSIPDYEKVKDGGKKYVVYIIEVTTQ----GGEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFG----NLDPEF 73

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1297697772 200 IETRRKALHKFLNRIADHPTLTFNEDFKIFLT 231
Cdd:cd06093    74 IEERRKQLEQYLQSLLNHPELRNSEELKEFLE 105

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297697772 149 FDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKgmveRFNDDFIETRRKALHKFLNRIADHPTLTFNEDFKI 228
Cdd:pfam00787   4 FSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLG----RYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLE 79

                  ...
gi 1297697772 229 FLT 231
Cdd:pfam00787  80 FLE 82

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 1297697772 120 ITVDEPESHVTTIETFITYRIITKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEA--HPTLIIPPLPEKFIVkGMV----- 192
Cdd:cd07282     3 IGVSDPEKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKylHVGYIVPPAPEKSIV-GMTkvkvg 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1297697772 193 --ERFNDDFIETRRKALHKFLNRIADHPTLTFNEDFKIFL 230
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 1297697772 120 ITVDEP--ESHVTTIETFITYRII-TKTSRgefdssefEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKgmveRFN 196
Cdd:cd06862     3 CTVTNPkkESKFKGLKSFIAYQITpTHTNV--------TVSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTG----RFE 70

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1297697772 197 DDFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 233
Cdd:cd06862    71 EDFIEKRRERLELWMNRLARHPVLSQSEVFRHFLTCT 107

The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; 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. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297697772 120 ITVDEPE-----SHVTTIETFITYRIITKTSRGEFDSSEFE----VRRRYQDFLWLKGKLEEAHPTLIIPPLPEK----F 186
Cdd:cd06864     3 ITVTEAEkrtggSAMNLKETYTVYLIETKIVEHESEEGLSKklssLWRRYSEFELLRNYLVVTYPYVIVPPLPEKramfM 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1297697772 187 IVKGMVERFNDDFIETRRKALHKFLNRIADHPTLTFNEDFKIFLT 231
Cdd:cd06864    83 WQKLSSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFLT 127

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 1297697772 118 LFITVDEPESHVTTIETFITYRIITKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEaHPTLIIPPLPEKFIVKGMVER--- 194
Cdd:cd07293     2 LEIDVTNPQTVGVGRGRFTTYEIRLKTNLPIFKLKESTVRRRYSDFEWLRSELER-ESKVVVPPLPGKALFRQLPFRgdd 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1297697772 195 --FNDDFIETRRKALHKFLNRIADHPtLTFNE 224
Cdd:cd07293    81 giFDDSFIEERKQGLEQFLNKVAGHP-LAQNE 111

The phosphoinositide binding Phox Homology domain of fungal Grd19; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297697772 118 LFITVDEPESHVTTIETFITYRIITKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFivkgMVERFND 197
Cdd:cd07295     2 LEIEVRNPKTHGIGRGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERESPRVMIPPLPGKI----FTNRFSD 77

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1297697772 198 DFIETRRKALHKFLNRIADHPTL-TFNEDFKIFLTAQAW 235
Cdd:cd07295    78 EVIEERRQGLETFLQSVAGHPLLqTGSKVLAAFLQDPKF 116

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 1297697772 127 SHVTTIETFITYRIITKTSrgefdssefEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEK-----FIVKGMVERFNDDFIE 201
Cdd:cd06867    10 SSEGGSGSYIVYVIRLGGS---------EVKRRYSEFESLRKNLTRLYPTLIIPPIPEKhslkdYAKKPSKAKNDAKIIE 80

                          90       100
                  ....*....|....*....|....*....
gi 1297697772 202 TRRKALHKFLNRIADHPTLTFNEDFKIFL 230
Cdd:cd06867    81 RRKRMLQRFLNRCLQHPILRNDIVFQKFL 109

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 1297697772 120 ITVDEPESHVTTIET-FITYRIITKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEkfivKGMVERFND- 197
Cdd:cd06898     2 VEVRDPRTHKEDDWGsYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPP----KNLFGRFNNe 77

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1297697772 198 DFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 233
Cdd:cd06898    78 GFIEERQQGLQDFLEKVLQTPLLLSDSRLHLFLQTQ 113

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 1297697772 136 ITYRIITKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEA--HPTLIIPPLPEKFIVKGMVERFN-----------DDFIET 202
Cdd:cd07291    17 VKFTVHTKTTLPSFQSPDFSVTRQHEDFIWLHDALIETedYAGLIIPPAPPKPDFDGPREKMQklgegegsmtkEEFAKM 96

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1297697772 203 RRK-------------ALHK-FLNRIADHPTLTFNEDFKIFL 230
Cdd:cd07291    97 KQEleaeylavfkktvQVHEvFLQRLSSHPSLSKDRNFHIFL 138

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 1297697772 134 TFITYRIITKTSRGEFdssefEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVKGMVErfNDDFIETRRKALHKFLNR 213
Cdd:cd06897    14 PYTVYNIQVRLPLRSY-----TVSRRYSEFVALHKQLESEVGIEPPYPLPPKSWFLSTSS--NPKLVEERRVGLEAFLRA 86

                          90
                  ....*....|....*....
gi 1297697772 214 IADHPTLTFNED--FKIFL 230
Cdd:cd06897    87 LLNDEDSRWRNSpaVKEFL 105

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; 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 SNX20, SNX21, and similar proteins. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297697772 121 TVDEPESHvttietFITYRIITKTSrGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIipplpEK--FIVKGMVERFNDD 198
Cdd:cd07279    10 TVKEGEKK------YVVYQLAVVQT-GDPDTQPAFIERRYSDFLKLYKALRKQHPQLM-----AKvsFPRKVLMGNFSSE 77

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1297697772 199 FIETRRKALHKFLNRIADHPTLTFNEDFKIFLT 231
Cdd:cd07279    78 LIAERSRAFEQFLGHILSIPNLRDSKAFLDFLQ 110

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 1297697772 132 IETFITYRII-TKTSRgefdssefEVRRRYQDFLWLKGKLEEAHPTLI-IPPLPEKFIVKgmveRFNDDFIETRRKALHK 209
Cdd:cd07285    17 LKSYIEYQLTpTNTNR--------SVNHRYKHFDWLYERLLVKFGLAIpIPSLPDKQVTG----RFEEEFIKMRMERLQA 84

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1297697772 210 FLNRIADHPTLTFNEDFKIFLT---AQAWELSSHKKQ 243
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 1297697772 135 FITYRIITKTSRGEFdsseFEVRRRYQDFLWLKGKLEEAHPTLIIpPLPEKFIVKgmvERFNDDFIETRRKALHKFLNRI 214
Cdd:cd07276    20 FTVYKIRVENKVGDS----WFVFRRYTDFVRLNDKLKQMFPGFRL-SLPPKRWFK---DNFDPDFLEERQLGLQAFVNNI 91

                  ....*.
gi 1297697772 215 ADHPTL 220
Cdd:cd07276    92 MAHKDI 97

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1297697772 154 FEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKfivKGMVERfNDDFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTA 232
Cdd:cd06877    44 WSVLRRYNEFYVLESKLTEFHGEFPDAPLPSR---RIFGPK-SYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSP 118

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 1297697772 135 FITYRIITKTSRGEFDSSEFEVRRRYQDFLWLKGKLEEAHPTLIIPPLPEKFIVkgMVERFNDDFIETRRKALHKFLNRI 214
Cdd:cd06876    38 FVVYLIEVQRLNNDDQSSGWVVARRYSEFLELHKYLKKRYPGVLKLDFPQKRKI--SLKYSKTLLVEERRKALEKYLQEL 115

                          90
                  ....*....|....*..
gi 1297697772 215 ADHPTLTFNEDFKIFLT 231
Cdd:cd06876   116 LKIPEVCEDEEFRKFLS 132

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.