PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530379867   25 EVLMNGRKHFVEKRYSEFHALHKKLKKCIKT---PEIPSK-HVRNWVPKVLEQRRQGLETYLQAVILENE-ELPKLFLDF 99
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSviiPPLPPKrWLGRYNEEFIEKRRKGLEQYLQRLLQHPElRNSEVLLEF 80

                  ....
gi 530379867  100 LNVR 103
Cdd:pfam00787  81 LESD 84

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530379867  29 NGRKHFVEKRYSEFHALHKKLKKCIKT---PEIPSKHV------RNWVPKVLEQRRQGLETYLQAVILENeELPKLFL-- 97
Cdd:COG5391  169 ESRPLVVRRRYSDFESLHSILIKLLPLcaiPPLPSKKSnseyygDRFSDEFIEERRQSLQNFLRRVSTHP-LLSNYKNsk 247

                         90       100       110
                 ....*....|....*....|....*....|
gi 530379867  98 DFLNVRHLPSLPKAEScGSFDETESEESSK 127
Cdd:COG5391  248 SWESHSTLLSSFIENR-KSVPTPLSLDLTS 276

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 530379867   2 EVYIPSFRYEEsDLERGYTVFKIEV-LMNGRKHFVEKRYSEFHALHKKLKKCIKT---PEIPSKH-VRNWVPKVLEQRRQ 76
Cdd:cd06093    1 SVSIPDYEKVK-DGGKKYVVYIIEVtTQGGEEWTVYRRYSDFEELHEKLKKKFPGvilPPLPPKKlFGNLDPEFIEERRK 79

                         90       100
                 ....*....|....*....|....*.
gi 530379867  77 GLETYLQAvILENEEL--PKLFLDFL 100
Cdd:cd06093   80 QLEQYLQS-LLNHPELrnSEELKEFL 104

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530379867   25 EVLMNGRKHFVEKRYSEFHALHKKLKKCIKT---PEIPSK-HVRNWVPKVLEQRRQGLETYLQAVILENE-ELPKLFLDF 99
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSviiPPLPPKrWLGRYNEEFIEKRRKGLEQYLQRLLQHPElRNSEVLLEF 80

                  ....
gi 530379867  100 LNVR 103
Cdd:pfam00787  81 LESD 84

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530379867   2 EVYIPSFryeesDLERGYTVFKIEVLMNGRKHFVEKRYSEFHALHKKL---KKCIKTPEIPSKHVRNWVPKVLEQRRQGL 78
Cdd:cd06875    5 KIRIPSA-----ETVEGYTVYIIEVKVGSVEWTVKHRYSDFAELHDKLvaeHKVDKDLLPPKKLIGNKSPSFVEKRRKEL 79

                         90       100
                 ....*....|....*....|...
gi 530379867  79 ETYLQAV-ILENEELPKLFLDFL 100
Cdd:cd06875   80 EIYLQTLlSFFQKTMPRELAHFL 102

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530379867   5 IPSFRYEESDLERGYTVFKIEVlmNGRKHFVeKRYSEFHALHKKLKK---CIKTPEIPSKHVRNWVPKVLEQRRQGLETY 81
Cdd:cd06885    4 IPDTQELSDEGGSTYVAYNIHI--NGVLHCS-VRYSQLHGLNEQLKKefgNRKLPPFPPKKLLPLTPAQLEERRLQLEKY 80

                 ....
gi 530379867  82 LQAV 85
Cdd:cd06885   81 LQAV 84

The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; 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. SNX27 contains an N-terminal PDZ domain followed by a PX domain and a Ras-Associated (RA) domain. It binds G protein-gated potassium (Kir3) channels, which play a role in neuronal excitability control, through its PDZ domain. SNX27 downregulates Kir3 channels by promoting their movement in the endosome, reducing surface expression and increasing degradation. SNX27 also associates with 5-hydroxytryptamine type 4 receptor (5-HT4R), cytohesin associated scaffolding protein (CASP), and diacylglycerol kinase zeta, and may play a role in their intracellular trafficking and endocytic recycling. The SNX27 PX domain preferentially binds to phosphatidylinositol-3-phosphate (PI3P) and is important for targeting to the early endosome.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530379867   1 MEVYIPSFRYEESDLERgYTVFKIEvlMNGRkHFVEKRYSEFHALHKKLKKCIKT---PEIPSKHVRNWVPKVLEQRRQG 77
Cdd:cd06886    4 VPISIPDYKHVEQNGEK-FVVYNIY--MAGR-QLCSRRYREFANLHQNLKKEFPDfqfPKLPGKWPFSLSEQQLDARRRG 79

                 ....*...
gi 530379867  78 LETYLQAV 85
Cdd:cd06886   80 LEQYLEKV 87

The phosphoinositide binding Phox Homology domain of the fungal protein YPT35; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of YPT35 proteins from the fungal subkingdom Dikarya. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of YPT35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to members of the Yip1p protein family, which localize to the ER and Golgi. YPT35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530379867  15 LERGYTVFKIEVLMN---GRKHFVEKRYSEFHALHKKLKKCIKT------PEIPSKHV-----RNWVPKVLEQRRQGLET 80
Cdd:cd07280   18 GGGAYVVWKITIETKdliGSSIVAYKRYSEFVQLREALLDEFPRhkrneiPQLPPKVPwydsrVNLNKAWLEKRRRGLQY 97

                 ....*..
gi 530379867  81 YLQAVIL 87
Cdd:cd07280   98 FLNCVLL 104

The phosphoinositide binding Phox Homology domain of Sorting Nexin 20; 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. 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. The PX domain of SNX20 binds PIs and targets the SNX20/PSGL-1 complex to endosomes. SNX20 may function in the sorting and cycling of PSGL-1 into endosomes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530379867   5 IPSFRYEESDLERgYTVFKIEVLMNG----RKHFVEKRYSEFHALHKKLKKC----IKTPEIPSKHV-RNWVPKVLEQRR 75
Cdd:cd07300    5 IPSARIIEQTISK-HVVYQIIVIQTGsfdcNKVVIERRYSDFLKLHQELLSDfseeLEDVVFPKKKLtGNFSEEIIAERR 83

                         90       100
                 ....*....|....*....|....*.
gi 530379867  76 QGLETYL-QAVILENEELPKLFLDFL 100
Cdd:cd07300   84 VALRDYLtLLYSLRFVRRSQAFQDFL 109

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 530379867  35 VEKRYSEFHALHKKLKKC-IKTPEIPSKHVRNWVPKVLEQRRQGLETYLQAV----ILENEELPKLFLD 98
Cdd:cd06871   40 VIRRYNDFDLLNASLQISgISLPLPPKKLIGNMDREFIAERQQGLQNYLNVIlmnpILASCLPVKKFLD 108

The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; 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. The function of SNX25 is not yet known. It has been found in exosomes from human malignant pleural effusions. SNX25 shows the same domain architecture as SNX13 and SNX14, 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 530379867  35 VEKRYSEFHALHKKLKKC------IKTPEIPSKHVRNWVPKVLEQRRQGLETYLQAvILENEEL 92
Cdd:cd06878   52 VTRKLSEFHDLHRKLKECsswlkkVELPSLSKKWFKSIDKKFLDKSKNQLQKYLQF-ILEDETL 114

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 530379867  11 EESDLERGYTVFKIEV-LMNGRKHFVEKRYSEFHALHKKL------------KKCIkTPEIPSKHVRNWVPKVLEQRRQG 77
Cdd:cd06882   12 EEKRGFTNYYVFVIEVkTKGGSKYLIYRRYRQFFALQSKLeerfgpeagssaYDCT-LPTLPGKIYVGRKAEIAERRIPL 90

                 ....*.
gi 530379867  78 LETYLQ 83
Cdd:cd06882   91 LNRYMK 96

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 530379867  14 DLERGYTVFKIEVLMN----GRKH-FVEKRYSEFHALHKKLKK---CIKTPEIPSKHV--RNWVPKVLEQRRQGLETYLQ 83
Cdd:cd06898   13 DDWGSYTDYEIFLHTNsmcfTLKTsCVRRRYSEFVWLRNRLQKnalLIQLPSLPPKNLfgRFNNEGFIEERQQGLQDFLE 92

                 ...
gi 530379867  84 AVI 86
Cdd:cd06898   93 KVL 95

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530379867  35 VEKRYSEFHALHKKLKKciKTPEIPS------KHVRNWVPKVLEQRRQGLETYLQaVILENEEL---PKLF---LDFL 100
Cdd:cd06873   43 VYRRYSDFHDLHMRLKE--KFPNLSKlsfpgkKTFNNLDRAFLEKRRKMLNQYLQ-SLLNPEVLdanPGLQeivLDFL 117

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 530379867  31 RKHFVEKRYSEFHALHKKLKK---CIKTPEIPSKHVRN-WVPKVLEQRRQGLETYLQAV 85
Cdd:cd07295   36 RVSSVRRRYSDFEYFRDILERespRVMIPPLPGKIFTNrFSDEVIEERRQGLETFLQSV 94

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 530379867  19 YTVFKIEVLMNGRKHFVEKRYSEFHALHKKLKKC---IKTPEIPSKHV-RNWVPKVLEQRRQGLETYLQAVI 86
Cdd:cd06874   18 HFEFEVKITVLDETWTVFRRYSRFRELHKTMKLKypeVAALEFPPKKLfGNKSERVAKERRRQLETYLRNFF 89

The phosphoinositide binding Phox Homology domain of RPK118-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to human RPK118, which contains an N-terminal PX domain, a Microtubule Interacting and Trafficking (MIT) domain, and a kinase domain. RPK118 binds sphingosine kinase, a key enzyme in the synthesis of sphingosine 1-phosphate (SPP), a lipid messenger involved in many cellular events. RPK118 may be involved in transmitting SPP-mediated signaling. It also binds the antioxidant peroxiredoxin-3 (PRDX3) and may be involved in the transport of PRDX3 from the cytoplasm to its site of function in the mitochondria. Members of this subfamily also show similarity to sorting nexin 15 (SNX15), which contains PX and MIT domains but does not contain a kinase domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNX15 plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530379867  16 ERGYTVFKIEVLMNGRKH-------FVEKRYSEFHALHKKLKKCIKT---------PEIPSKHVRNWVPKVLEQRRQGLE 79
Cdd:cd07287   14 PKGYTVYKVTARIVSRKNpedvqeiVVWKRYSDFKKLHKDLWQIHKNlcrqselfpPFAKAKVFGRFDESVIEERRQCAE 93

                 ....
gi 530379867  80 TYLQ 83
Cdd:cd07287   94 DLLQ 97

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 530379867  14 DLERGYTVFKI----EVLMNGRKHF-VEKRYSEF----HALHKKLKKCIkTPEIPSKHV-----RNWVpkvlEQRRQGLE 79
Cdd:cd06861   13 DLTSAHTVYTVrtrtTSPNFEVSSFsVLRRYRDFrwlyRQLQNNHPGVI-VPPPPEKQSvgrfdDNFV----EQRRAALE 87

                         90       100
                 ....*....|....*....|..
gi 530379867  80 TYLQAV----ILENEELPKLFL 97
Cdd:cd06861   88 KMLRKIanhpVLQKDPDFRLFL 109

The phosphoinositide binding Phox Homology domain of Sorting Nexin 8 and yeast Mvp1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX8 and the yeast counterpart Mvp1p are involved in sorting and delivery of late-Golgi proteins, such as carboxypeptidase Y, to vacuoles.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530379867  35 VEKRYSEFHALHKKLKKCI---KTPEIPSKHV-RNWVPKVLEQRRQGLETYLQAV----ILENEELPKLFL 97
Cdd:cd06866   32 VYRRYSDFVWLHEYLLKRYpyrMVPALPPKRIgGSADREFLEARRRGLSRFLNLVarhpVLSEDELVRTFL 102