The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 8; 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. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles. 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 6323646  260 EFADKKISQEFMKMWKKEFAEQWNQAASCIDTSMELWYRITLLLERHEKRIMQMVHERNFFETLVDNFSEVTPKLYPV-Q 338
Cdd:cd07597   2 EFTDKKLSEAAKVLLPPDFQEQWANSRERIRRLLESWTKLRVLAERYEKRSQQQAADRAEFARLLNSLGELTARLYPWaG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  339 QNDTILDINNNLSIIKKHLETTSSICKQETEEISGTLSPKFKIFTDILLSLRSLFERYKIMAANNVVELQRHVELNKEKL 418
Cdd:cd07597  82 DSDTWGDINEGLSSLSKHFQLLSDLSEDEARAEEDGVLEKLKLQLDLLVSLRDLFERHEKLSLNNIQRLLKRIELNKKKL 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  419 ESMKGKPDVSGAEYDRIKKIIQKDRRSIIEQSNRAWLIRQCILEEFTIFQETQFLITRAFQDWAKLNSNHAGLKLNEWEK 498
Cdd:cd07597 162 ESLRAKPDVKGAEVDKLEASIIKDKESIANQLNRSWFIRECILEETQLFQETQFLLTSILQEFVKDEIQYHSELANVWER 241

                ....*
gi 6323646  499 LVTSI 503
Cdd:cd07597 242 LVPKL 246

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 6323646     162 SPSEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRI--GSQNADQLFLKKRRIGLSRFINLVMKHPKLSN-DDLVLT 238
Cdd:smart00312  23 TGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLfgRLNNFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLE 102

                   ...
gi 6323646     239 FLT 241
Cdd:smart00312 103 FLE 105

The Bin/Amphiphysin/Rvs (BAR) domain of Sorting Nexin 8; 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. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles. 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 6323646  260 EFADKKISQEFMKMWKKEFAEQWNQAASCIDTSMELWYRITLLLERHEKRIMQMVHERNFFETLVDNFSEVTPKLYPV-Q 338
Cdd:cd07597   2 EFTDKKLSEAAKVLLPPDFQEQWANSRERIRRLLESWTKLRVLAERYEKRSQQQAADRAEFARLLNSLGELTARLYPWaG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  339 QNDTILDINNNLSIIKKHLETTSSICKQETEEISGTLSPKFKIFTDILLSLRSLFERYKIMAANNVVELQRHVELNKEKL 418
Cdd:cd07597  82 DSDTWGDINEGLSSLSKHFQLLSDLSEDEARAEEDGVLEKLKLQLDLLVSLRDLFERHEKLSLNNIQRLLKRIELNKKKL 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  419 ESMKGKPDVSGAEYDRIKKIIQKDRRSIIEQSNRAWLIRQCILEEFTIFQETQFLITRAFQDWAKLNSNHAGLKLNEWEK 498
Cdd:cd07597 162 ESLRAKPDVKGAEVDKLEASIIKDKESIANQLNRSWFIRECILEETQLFQETQFLLTSILQEFVKDEIQYHSELANVWER 241

                ....*
gi 6323646  499 LVTSI 503
Cdd:cd07597 242 LVPKL 246

Sorting nexin 8/Mvp1 BAR domain; This is the BAR (Bin/amphiphysin/Rvs) domain of Sortin nexin 8 (Snx8), which can sense, stabilize and induce membrane curvature. These proteins are involved in intracellular protein transport from early endosomes to the trans-Golgi network. Its yeast counterpart, Mvp1 is required for sorting proteins to the vacuole.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646    260 EFADKKISQEFMKMWKKEFAEQWNQAASCIDTSMELWYRITLLLERHEKRIMQMVHERNFFETLVDNFSEVTPKLYPVQQ 339
Cdd:pfam19566   7 EFTGRSLPPGLEDSLPPTLEELFETVRSGVRRSAELYINLCNLMERLVKRNEGLAADHGRFSLSLNSLTDASADTYAIDT 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646    340 NDTILdINNNLSIIKKHLETTSSICKQET---EEisGTLSpKFKIFTDILLSLRSLFERYKIMAANNVVELQRHVELNKE 416
Cdd:pfam19566  87 NDVPL-LNDGLSATAKHLSTAQSLLEDEArawDE--GVLE-DLKRQRDALVSMRDMFDRRDRLDKDNIPQLERRIQANEA 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646    417 KLESMKGKPD--VSGAEYDRIKKIIQKDRRSIIEQSNRAWLIRQCILEEFTIFQETQFLITRAFQDWAKLNSNHAGLKLN 494
Cdd:pfam19566 163 KLANLRAKPEgmVKPGEIEKVEEAIIKDKESIVQQHARGVFIKECLRDELVYFQQSQYHVSRLHQDWAQERVKYAELQAD 242

                         250
                  ....*....|...
gi 6323646    495 EWEKLVTSIMDMP 507
Cdd:pfam19566 243 NWRGLSDELEGMP 255

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 6323646     162 SPSEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRI--GSQNADQLFLKKRRIGLSRFINLVMKHPKLSN-DDLVLT 238
Cdd:smart00312  23 TGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLfgRLNNFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLE 102

                   ...
gi 6323646     239 FLT 241
Cdd:smart00312 103 FLE 105

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6323646  164 SEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNaDQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFLT 241
Cdd:cd06093  29 GEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNL-DPEFIEERRKQLEQYLQSLLNHPELRNSEELKEFLE 105

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 6323646  168 TVVRRYSDFLWLREILLKRYPFRMIPELPPKR-------IGSQNADQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFL 240
Cdd:cd06864  47 SLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRamfmwqkLSSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFL 126

                .
gi 6323646  241 T 241
Cdd:cd06864 127 T 127

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 6323646  147 HANYLVKHLIALPSTSPSEErTVVRRYSDFLWLREILLKRYPFRMIPELPPKR-IGSQNADqlFLKKRRIGLSRFINLVM 225
Cdd:cd06861  18 HTVYTVRTRTTSPNFEVSSF-SVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQsVGRFDDN--FVEQRRAALEKMLRKIA 94

                        90
                ....*....|....*.
gi 6323646  226 KHPKLSNDDLVLTFLT 241
Cdd:cd06861  95 NHPVLQKDPDFRLFLE 110

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 6323646  167 RTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQlFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFLTVrTDL 246
Cdd:cd06862  32 VTVSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRFEED-FIEKRRERLELWMNRLARHPVLSQSEVFRHFLTC-TDE 109

                ....
gi 6323646  247 TSWR 250
Cdd:cd06862 110 KDWK 113

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  161 TSPSEERTVVRRYSDFLWLREILLKRYPfRMIPELPPKRIGSQNADQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFL 240
Cdd:cd06870  28 SVGRSSWFVFRRYAEFDKLYESLKKQFP-ASNLKIPGKRLFGNNFDPDFIKQRRAGLDEFIQRLVSDPKLLNHPDVRAFL 106

                ..
gi 6323646  241 TV 242
Cdd:cd06870 107 QM 108

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 6323646  164 SEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQL---FLKKRRIGLSRFINLVMKHPKLSNDDLVLTFL 240
Cdd:cd07284  34 SSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFVMKGMVERFnedFIETRRKALHKFLNRIADHPTLTFNEDFKIFL 113

                .
gi 6323646  241 T 241
Cdd:cd07284 114 T 114

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 6323646  166 ERTVVRRYSDFLWLREiLLKRYPFRMIPELPPKRIGSQNA--------DQLFLKKRRIGLSRFINLVMKHPKLSNDDLVL 237
Cdd:cd06894  37 ESSVRRRYSDFEWLRS-ELERDSKIVVPPLPGKALKRQLPfrgddgifEEEFIEERRKGLETFINKVAGHPLAQNEKCLH 115

                ...
gi 6323646  238 TFL 240
Cdd:cd06894 116 MFL 118

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 6323646  168 TVVRRYSDFLWLREILLKRY-PFRMIPeLPPKRIgSQNADQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFLTV 242
Cdd:cd06877  45 SVLRRYNEFYVLESKLTEFHgEFPDAP-LPSRRI-FGPKSYEFLESKREIFEEFLQKLLQKPELRGSELLYDFLSP 118

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  168 TVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQLfLKKRRIGLSRFINLVMKHPKLSNDDLVL 237
Cdd:cd07295  39 SVRRRYSDFEYFRDILERESPRVMIPPLPGKIFTNRFSDEV-IEERRQGLETFLQSVAGHPLLQTGSKVL 107

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 6323646  147 HANYLVKHLIALPSTSPSEErTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQL--FLKKRRIGLSRFINLV 224
Cdd:cd06865  23 YISYKVTTRTNIPSYTHGEF-TVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQVMQSaeFIEQRRVALEKYLNRL 101

                        90
                ....*....|....*...
gi 6323646  225 MKHPKLSNDDLVLTFLTV 242
Cdd:cd06865 102 AAHPVIGLSDELRVFLTL 119

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 6323646  166 ERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQL---FLKKRRIGLSRFINLVMKHPKLSNDDLVLTFLTV 242
Cdd:cd07283  36 EYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRFseeFVETRRKALDKFLKRIADHPVLSFNEHFNVFLTA 115

                .
gi 6323646  243 R 243
Cdd:cd07283 116 K 116

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; 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. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  162 SPSEERTVVRRYSDFLWLREILlkRYPFRMIPeLPPKR-IGsqNADQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFL 240
Cdd:cd06871  33 SPENSWQVIRRYNDFDLLNASL--QISGISLP-LPPKKlIG--NMDREFIAERQQGLQNYLNVILMNPILASCLPVKKFL 107

                .
gi 6323646  241 T 241
Cdd:cd06871 108 D 108

The phosphoinositide binding Phox Homology domain of Sorting Nexin 1; 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. SNX1 is both membrane associated and a cytosolic protein that exists as a tetramer in protein complexes. It can associate reversibly with membranes of the endosomal compartment, thereby coating these vesicles. 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 efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. SNX1 contains a Bin/Amphiphysin/Rvs (BAR) domain C-terminal to the PX domain. The PX domain of SNX1 specifically binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,5)P2, while the BAR domain detects membrane curvature. Both domains help determine the specific membrane-targeting of SNX1, which is localized to a microdomain in early endosomes where it regulates cation-independent mannose-6-phosphate receptor retrieval to the trans Golgi network.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  164 SEERTVVRRYSDFLWLREILLKRYPFR--MIPELPPK--------RIGSQNADQL-FLKKRRIGLSRFINLVMKHPKLSN 232
Cdd:cd07281  34 SKHFTVKRRFSDFLGLYEKLSEKHSQNgfIVPPPPEKsligmtkvKVGKEDSSSAeFLERRRAALERYLQRIVSHPSLLQ 113

                ....*...
gi 6323646  233 DDLVLTFL 240
Cdd:cd07281 114 DPDVREFL 121

The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. 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. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 6323646  172 RYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQlfLKKRRIGLSRFINLVMKHPKLSNDDLVLTFL 240
Cdd:cd06885  34 RYSQLHGLNEQLKKEFGNRKLPPFPPKKLLPLTPAQ--LEERRLQLEKYLQAVVQDPRIANSDIFNSFL 100

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6323646  168 TVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQ-NADQLFLKKRRIGLSRFIN--LVMKHPKLSNDDLVLTFL 240
Cdd:cd06897  30 TVSRRYSEFVALHKQLESEVGIEPPYPLPPKSWFLStSSNPKLVEERRVGLEAFLRalLNDEDSRWRNSPAVKEFL 105

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  161 TSPSEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIgSQNADQLFLKKRRIGLSRFINLVMK------HPKLSNdd 234
Cdd:cd06873  35 NGQEESWHVYRRYSDFHDLHMRLKEKFPNLSKLSFPGKKT-FNNLDRAFLEKRRKMLNQYLQSLLNpevldaNPGLQE-- 111

                ....*.
gi 6323646  235 LVLTFL 240
Cdd:cd06873 112 IVLDFL 117

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases similar to the Drosophila PI3K_68D protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. PI3K_68D is a novel PI3K which is widely expressed throughout the Drosophila life cycle. In vitro, it has been shown to phosphorylate PI and PI4P. It is involved in signaling pathways that affect pattern formation of Drosophila wings.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 6323646  169 VVRRYSDFLWLREILLKRYPFRMIPELPP-KRIGSQNADQLFLkKRRIGLSRFINLVMK-HPKLSNDDLVLTF 239
Cdd:cd06884  36 VFRTYKEFLELYQKLCRKFPLAKLHPLSTgSHVGRSNIKSVAE-KRKQDIQQFLNSLFKmAEEVSHSDLVYTF 107

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  146 KHANYLVKHLIALPSTSPSEERTVV-RRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQLFLKKRRIGLSRFINLV 224
Cdd:cd07279  14 GEKKYVVYQLAVVQTGDPDTQPAFIeRRYSDFLKLYKALRKQHPQLMAKVSFPRKVLMGNFSSELIAERSRAFEQFLGHI 93

                        90
                ....*....|....*..
gi 6323646  225 MKHPKLSNDDLVLTFLT 241
Cdd:cd07279  94 LSIPNLRDSKAFLDFLQ 110

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; 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. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. 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 6323646  161 TSPSEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSqNADQLFLKKRRIGLS----RFINLVMKHPKLSNDDLV 236
Cdd:cd06874  26 TVLDETWTVFRRYSRFRELHKTMKLKYPEVAALEFPPKKLFG-NKSERVAKERRRQLEtylrNFFSVCLKLPACPLYPKV 104

                        90       100
                ....*....|....*....|..
gi 6323646  237 LTFLTVRT--DLTSWRKQATYD 256
Cdd:cd06874 105 GRTLSKATlcDFSPFFRKGVFE 126

The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox. It is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase. The PX domain of p40phox is also involved in protein-protein interaction.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6323646  171 RRYSDFLWLREILLKRYPF--------RMIPELPPKRIGSQNADqlfLKKRRIG-LSRFI-NLVMKHPKLSNDDLVLTFL 240
Cdd:cd06882  39 RRYRQFFALQSKLEERFGPeagssaydCTLPTLPGKIYVGRKAE---IAERRIPlLNRYMkELLSLPVWVLMDEDVRLFF 115