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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      280 EFADKKISQEFMKMWKKEFAEQWNQAASCIDTSMELWYRITLLLERHEKRIMQMVHERNFFETLVDNFSEVTPKLYPV-Q 358
Cdd:cd07597   2 EFTDKKLSEAAKVLLPPDFQEQWANSRERIRRLLESWTKLRVLAERYEKRSQQQAADRAEFARLLNSLGELTARLYPWaG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      359 QNDTILDINNNLSIIKKHLETTSSICKQETEEISGTLSPKFKIFTDILLSLRSLFERYKIMAANNVVELQRHVELNKEKL 438
Cdd:cd07597  82 DSDTWGDINEGLSSLSKHFQLLSDLSEDEARAEEDGVLEKLKLQLDLLVSLRDLFERHEKLSLNNIQRLLKRIELNKKKL 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      439 ESMKGKPDVSGAEYDRIKKIIQKDRRSIIEQSNRAWLIRQCILEEFTIFQETQFLITRAFQDWAKLNSNHAGLKLNEWEK 518
Cdd:cd07597 162 ESLRAKPDVKGAEVDKLEASIIKDKESIANQLNRSWFIRECILEETQLFQETQFLLTSILQEFVKDEIQYHSELANVWER 241

                ....*
6Q0X_A      519 LVTSI 523
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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A         182 SPSEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRI--GSQNADQLFLKKRRIGLSRFINLVMKHPKLSN-DDLVLT 258
Cdd:smart00312  23 TGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLfgRLNNFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLE 102

                   ...
6Q0X_A         259 FLT 261
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      280 EFADKKISQEFMKMWKKEFAEQWNQAASCIDTSMELWYRITLLLERHEKRIMQMVHERNFFETLVDNFSEVTPKLYPV-Q 358
Cdd:cd07597   2 EFTDKKLSEAAKVLLPPDFQEQWANSRERIRRLLESWTKLRVLAERYEKRSQQQAADRAEFARLLNSLGELTARLYPWaG 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      359 QNDTILDINNNLSIIKKHLETTSSICKQETEEISGTLSPKFKIFTDILLSLRSLFERYKIMAANNVVELQRHVELNKEKL 438
Cdd:cd07597  82 DSDTWGDINEGLSSLSKHFQLLSDLSEDEARAEEDGVLEKLKLQLDLLVSLRDLFERHEKLSLNNIQRLLKRIELNKKKL 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      439 ESMKGKPDVSGAEYDRIKKIIQKDRRSIIEQSNRAWLIRQCILEEFTIFQETQFLITRAFQDWAKLNSNHAGLKLNEWEK 518
Cdd:cd07597 162 ESLRAKPDVKGAEVDKLEASIIKDKESIANQLNRSWFIRECILEETQLFQETQFLLTSILQEFVKDEIQYHSELANVWER 241

                ....*
6Q0X_A      519 LVTSI 523
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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A        280 EFADKKISQEFMKMWKKEFAEQWNQAASCIDTSMELWYRITLLLERHEKRIMQMVHERNFFETLVDNFSEVTPKLYPVQQ 359
Cdd:pfam19566   7 EFTGRSLPPGLEDSLPPTLEELFETVRSGVRRSAELYINLCNLMERLVKRNEGLAADHGRFSLSLNSLTDASADTYAIDT 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A        360 NDTILdINNNLSIIKKHLETTSSICKQET---EEisGTLSpKFKIFTDILLSLRSLFERYKIMAANNVVELQRHVELNKE 436
Cdd:pfam19566  87 NDVPL-LNDGLSATAKHLSTAQSLLEDEArawDE--GVLE-DLKRQRDALVSMRDMFDRRDRLDKDNIPQLERRIQANEA 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A        437 KLESMKGKPD--VSGAEYDRIKKIIQKDRRSIIEQSNRAWLIRQCILEEFTIFQETQFLITRAFQDWAKLNSNHAGLKLN 514
Cdd:pfam19566 163 KLANLRAKPEgmVKPGEIEKVEEAIIKDKESIVQQHARGVFIKECLRDELVYFQQSQYHVSRLHQDWAQERVKYAELQAD 242

                         250
                  ....*....|...
6Q0X_A        515 EWEKLVTSIMDMP 527
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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A         182 SPSEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRI--GSQNADQLFLKKRRIGLSRFINLVMKHPKLSN-DDLVLT 258
Cdd:smart00312  23 TGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLfgRLNNFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLE 102

                   ...
6Q0X_A         259 FLT 261
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
6Q0X_A      184 SEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNaDQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFLT 261
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      188 TVVRRYSDFLWLREILLKRYPFRMIPELPPKR-------IGSQNADQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFL 260
Cdd:cd06864  47 SLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRamfmwqkLSSDTFDPDFVERRRAGLENFLLRVAGHPELCQDKIFLEFL 126

                .
6Q0X_A      261 T 261
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      167 HANYLVKHLIALPSTSPSEErTVVRRYSDFLWLREILLKRYPFRMIPELPPKR-IGSQNADqlFLKKRRIGLSRFINLVM 245
Cdd:cd06861  18 HTVYTVRTRTTSPNFEVSSF-SVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQsVGRFDDN--FVEQRRAALEKMLRKIA 94

                        90
                ....*....|....*.
6Q0X_A      246 KHPKLSNDDLVLTFLT 261
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      187 RTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQlFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFLTVrTDL 266
Cdd:cd06862  32 VTVSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRFEED-FIEKRRERLELWMNRLARHPVLSQSEVFRHFLTC-TDE 109

                ....
6Q0X_A      267 TSWR 270
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      181 TSPSEERTVVRRYSDFLWLREILLKRYPfRMIPELPPKRIGSQNADQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFL 260
Cdd:cd06870  28 SVGRSSWFVFRRYAEFDKLYESLKKQFP-ASNLKIPGKRLFGNNFDPDFIKQRRAGLDEFIQRLVSDPKLLNHPDVRAFL 106

                ..
6Q0X_A      261 TV 262
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      184 SEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQL---FLKKRRIGLSRFINLVMKHPKLSNDDLVLTFL 260
Cdd:cd07284  34 SSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFVMKGMVERFnedFIETRRKALHKFLNRIADHPTLTFNEDFKIFL 113

                .
6Q0X_A      261 T 261
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      186 ERTVVRRYSDFLWLREiLLKRYPFRMIPELPPKRIGSQNA--------DQLFLKKRRIGLSRFINLVMKHPKLSNDDLVL 257
Cdd:cd06894  37 ESSVRRRYSDFEWLRS-ELERDSKIVVPPLPGKALKRQLPfrgddgifEEEFIEERRKGLETFINKVAGHPLAQNEKCLH 115

                ...
6Q0X_A      258 TFL 260
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
6Q0X_A      188 TVVRRYSDFLWLREILLKRY-PFRMIPeLPPKRIgSQNADQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFLTV 262
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      188 TVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQLfLKKRRIGLSRFINLVMKHPKLSNDDLVL 257
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      167 HANYLVKHLIALPSTSPSEErTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQL--FLKKRRIGLSRFINLV 244
Cdd:cd06865  23 YISYKVTTRTNIPSYTHGEF-TVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVESQVMQSaeFIEQRRVALEKYLNRL 101

                        90
                ....*....|....*...
6Q0X_A      245 MKHPKLSNDDLVLTFLTV 262
Cdd:cd06865 102 AAHPVIGLSDELRVFLTL 119

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
6Q0X_A      188 TVVRRYSDFLWLREILLKRYPfrmIPELPPKRIgsQNADQLFLKKRRIGLSRFINLVMKHPKLSNddLVLTFLTVRT 264
Cdd:cd06880  34 TVEKRYSEFHALHKKLKKSIK---TPDFPPKRV--RNWNPKVLEQRRQGLEAYLQGLLKINELPK--QLLDFLGVRH 103

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      182 SPSEERTVVRRYSDFLWLREILlkRYPFRMIPeLPPKR-IGsqNADQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFL 260
Cdd:cd06871  33 SPENSWQVIRRYNDFDLLNASL--QISGISLP-LPPKKlIG--NMDREFIAERQQGLQNYLNVILMNPILASCLPVKKFL 107

                .
6Q0X_A      261 T 261
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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6Q0X_A      184 SEERTVVRRYSDFLWLREILLKRYPFR--MIPELPPK--------RIGSQNADQL-FLKKRRIGLSRFINLVMKHPKLSN 252
Cdd:cd07281  34 SKHFTVKRRFSDFLGLYEKLSEKHSQNgfIVPPPPEKsligmtkvKVGKEDSSSAeFLERRRAALERYLQRIVSHPSLLQ 113

                ....*...
6Q0X_A      253 DDLVLTFL 260
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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6Q0X_A      192 RYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQlfLKKRRIGLSRFINLVMKHPKLSNDDLVLTFL 260
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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6Q0X_A      188 TVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSQ-NADQLFLKKRRIGLSRFINLVMKHP--KLSNDDLVLTFL 260
Cdd:cd06897  30 TVSRRYSEFVALHKQLESEVGIEPPYPLPPKSWFLStSSNPKLVEERRVGLEAFLRALLNDEdsRWRNSPAVKEFL 105

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.

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6Q0X_A      188 TVVRRYSDFLWLREILLKRYPFRMIPELPPKR-IGSQNADQLFLKKRRIGLSRFINLVMKHPKLSNDDLVLTFLT 261
Cdd:cd06876  58 VVARRYSEFLELHKYLKKRYPGVLKLDFPQKRkISLKYSKTLLVEERRKALEKYLQELLKIPEVCEDEEFRKFLS 132

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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6Q0X_A      189 VVRRYSDFLWLREILLKRYPFRMIPELPP-KRIGSQNADQLFLkKRRIGLSRFINLVMK-HPKLSNDDLVLTF 259
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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6Q0X_A      166 KHANYLVKHLIALPSTSPSEERTVV-RRYSDFLWLREILLKRYPFRMIPELPPKRIGSQNADQLFLKKRRIGLSRFINLV 244
Cdd:cd07279  14 GEKKYVVYQLAVVQTGDPDTQPAFIeRRYSDFLKLYKALRKQHPQLMAKVSFPRKVLMGNFSSELIAERSRAFEQFLGHI 93

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6Q0X_A      245 MKHPKLSNDDLVLTFLT 261
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.

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6Q0X_A      181 TSPSEERTVVRRYSDFLWLREILLKRYPFRMIPELPPKRIGSqNADQLFLKKRRIGLS----RFINLVMKHPKLSNDDLV 256
Cdd:cd06874  26 TVLDETWTVFRRYSRFRELHKTMKLKYPEVAALEFPPKKLFG-NKSERVAKERRRQLEtylrNFFSVCLKLPACPLYPKV 104

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6Q0X_A      257 LTFLTVRT--DLTSWRKQATYD 276
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.

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6Q0X_A      191 RRYSDFLWLREILLKRYPF--------RMIPELPPKRIGSQNADqlfLKKRRIG-LSRFI-NLVMKHPKLSNDDLVLTFL 260
Cdd:cd06882  39 RRYRQFFALQSKLEERFGPeagssaydCTLPTLPGKIYVGRKAE---IAERRIPlLNRYMkELLSLPVWVLMDEDVRLFF 115