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 688617890  69 LLFDIPSARIISQTISKHVVYQVVVIRSGSYDCERVAIERRYSDFLHLHQELLSDFSEELEDVVFPKKKMTRNFSEEIIA 148
Cdd:cd07300    1 LLFEIPSARIIEQTISKHVVYQIIVIQTGSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNFSEEIIA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 688617890 149 ERRVALRDYLTQLYSLRFVRKSQAFQSFFTHQEL 182
Cdd:cd07300   81 ERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

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 688617890  69 LLFDIPSARIISQTISKHVVYQVVVIRSGSYDCERVAIERRYSDFLHLHQELLSDFSEELEDVVFPKKKMTRNFSEEIIA 148
Cdd:cd07300    1 LLFEIPSARIIEQTISKHVVYQIIVIQTGSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNFSEEIIA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 688617890 149 ERRVALRDYLTQLYSLRFVRKSQAFQSFFTHQEL 182
Cdd:cd07300   81 ERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

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 688617890    84 SKHVVYQVVVIRSGSYdcERVAIERRYSDFLHLHQELLSDFSeeleDVVFPK---KK---MTRNFSEEIIAERRVALRDY 157
Cdd:smart00312  10 GKHYYYVIEIETKTGL--EEWTVSRRYSDFLELHSKLKKHFP----RSILPPlpgKKlfgRLNNFSEEFIEKRRRGLEKY 83

                           90       100
                   ....*....|....*....|..
gi 688617890   158 LTQLYSLR-FVRKSQAFQSFFT 178
Cdd:smart00312  84 LQSLLNHPeLINHSEVVLEFLE 105

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 688617890  69 LLFDIPSARIISQTISKHVVYQVVVIRSGSYDCERVAIERRYSDFLHLHQELLSDFSEELEDVVFPKKKMTRNFSEEIIA 148
Cdd:cd07300    1 LLFEIPSARIIEQTISKHVVYQIIVIQTGSFDCNKVVIERRYSDFLKLHQELLSDFSEELEDVVFPKKKLTGNFSEEIIA 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 688617890 149 ERRVALRDYLTQLYSLRFVRKSQAFQSFFTHQEL 182
Cdd:cd07300   81 ERRVALRDYLTLLYSLRFVRRSQAFQDFLTHPEL 114

The phosphoinositide binding Phox Homology domain of Sorting Nexin 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. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688617890  69 LLFDIPSARIISQTISKHVVYQVVVIRSGSYDCERVAIERRYSDFLHLHQELLSDFSEELEDVVFPKKKMTRNFSEEIIA 148
Cdd:cd07301    1 LLFEVTDANVVQDAHSKYVLYTIYVIQTGQYDPSPAYISRRYSDFERLHRRLRRLFGGEMAGVSFPRKRLRKNFTAETIA 80

                         90       100
                 ....*....|....*....|....*....
gi 688617890 149 ERRVALRDYLTQLYSLRFVRKSQAFQSFF 177
Cdd:cd07301   81 KRSRAFEQFLCHLHSLPELRASPAFLEFF 109

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 688617890  106 IERRYSDFLHLHQELLSDFSEELeDVVFPKKKMTRNFSEEIIAERRVALRDYLTQLYSLRFVRKSQAFQSFFTHQ 180
Cdd:pfam00787  11 VRRRYSDFVELHKKLLRKFPSVI-IPPLPPKRWLGRYNEEFIEKRRKGLEQYLQRLLQHPELRNSEVLLEFLESD 84

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 688617890    84 SKHVVYQVVVIRSGSYdcERVAIERRYSDFLHLHQELLSDFSeeleDVVFPK---KK---MTRNFSEEIIAERRVALRDY 157
Cdd:smart00312  10 GKHYYYVIEIETKTGL--EEWTVSRRYSDFLELHSKLKKHFP----RSILPPlpgKKlfgRLNNFSEEFIEKRRRGLEKY 83

                           90       100
                   ....*....|....*....|..
gi 688617890   158 LTQLYSLR-FVRKSQAFQSFFT 178
Cdd:smart00312  84 LQSLLNHPeLINHSEVVLEFLE 105

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688617890  85 KHVVYQVVVIRSGSydcervAIERRYSDFLHLHQELLSDFSEELEDVVfPKKKMTRNFSEEIIAERRVALRDYLTQLYSL 164
Cdd:cd06866   17 KHVEYEVSSKRFKS------TVYRRYSDFVWLHEYLLKRYPYRMVPAL-PPKRIGGSADREFLEARRRGLSRFLNLVARH 89

                         90
                 ....*....|....
gi 688617890 165 RFVRKSQAFQSFFT 178
Cdd:cd06866   90 PVLSEDELVRTFLT 103

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688617890  65 RSVKLLFDIPSARIISQTISKHVVYQVVVIRSGSYDCERVAIERRYSDFLHLHQELLSDF-SEELEDVVfPKKKMTRnfs 143
Cdd:cd06869   11 RVTETAGRLSSKKAYFVNRSKHHYEFIIRVRREGEEYRTIYVARRYSDFKKLHHDLKKEFpGKKLPKLP-HKDKLPR--- 86

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 688617890 144 eeiiaER-RVALRDYLTQLYSLRFVRKSQAFQSFFTH 179
Cdd:cd06869   87 -----EKlRLSLRQYLRSLLKDPEVAHSSILQEFLTS 118

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 688617890  72 DIPSARIISQTISKHVVYQVvvirsgsYDCERVAIERRYSDFLHLHQELLSDFSeeleDVVFPK--KKMTRNFSEEIIAE 149
Cdd:cd06886    7 SIPDYKHVEQNGEKFVVYNI-------YMAGRQLCSRRYREFANLHQNLKKEFP----DFQFPKlpGKWPFSLSEQQLDA 75

                         90       100
                 ....*....|....*....|....*....
gi 688617890 150 RRVALRDYLTQLYSLRFVRKSQAFQSFFT 178
Cdd:cd06886   76 RRRGLEQYLEKVCSIRVIGESDIMQDFLS 104

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688617890  73 IPSARIISQTISKHVVYQVVV-IRSGSYDcervaIERRYSDFLHLHQELLSDFSEeLEDVVFPKKKMTRNFSEEIIAERR 151
Cdd:cd07277    5 IPSVFLRGKGSDAHHVYQVYIrIRDDEWN-----VYRRYSEFYELHKKLKKKFPV-VRSFDFPPKKAIGNKDAKFVEERR 78

                 ....*..
gi 688617890 152 VALRDYL 158
Cdd:cd07277   79 KRLQVYL 85

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688617890  73 IPSARIISQTISK-HVVYQVVVIRSGSydceRVAIERRYSDFLHLHQELlsdfSEELEDVVFPKKKMtRNFSEEIIAERR 151
Cdd:cd06880    5 IPSYRLEVDESEKpYTVFTIEVLVNGR----RHTVEKRYSEFHALHKKL----KKSIKTPDFPPKRV-RNWNPKVLEQRR 75

                 ....*..
gi 688617890 152 VALRDYL 158
Cdd:cd06880   76 QGLEAYL 82

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 688617890  83 ISKHVVYQV-VVIRSGSYDCERVAIERRYSDFLHLHQELLSDFSeeleDVVF---PKKKMTRNFSEEIIAERRVALRDYL 158
Cdd:cd06861   15 TSAHTVYTVrTRTTSPNFEVSSFSVLRRYRDFRWLYRQLQNNHP----GVIVpppPEKQSVGRFDDNFVEQRRAALEKML 90

                         90       100
                 ....*....|....*....|
gi 688617890 159 TQLYSLRFVRKSQAFQSFFT 178
Cdd:cd06861   91 RKIANHPVLQKDPDFRLFLE 110

The phosphoinositide binding Phox Homology domain of Sorting Nexins 1 and 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX1, SNX2, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. Both domains have been shown to determine the specific membrane-targeting of SNX1. SNX1 and SNX2 are components of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures effcient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688617890  83 ISKHVVYQVVVIRSGS-YDCERVAIERRYSDFLHLHQELLSDFseeLEDVVF--PKKKMTRNFSEEI--IAERRVALRDY 157
Cdd:cd06859   15 MSAYVVYRVTTKTNLPdFKKSEFSVLRRYSDFLWLYERLVEKY---PGRIVPppPEKQAVGRFKVKFefIEKRRAALERF 91

                         90       100
                 ....*....|....*....|...
gi 688617890 158 LTQLYSLRFVRKSQAFQSFFTHQ 180
Cdd:cd06859   92 LRRIAAHPVLRKDPDFRLFLESD 114

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 688617890  71 FDIP-SARIISQTISKHVVYQVVVirSGSYDCeRVaierRYSDFLHLHQELLSDFSEE-LEDvvFPKKKMtRNFSEEIIA 148
Cdd:cd06885    2 FSIPdTQELSDEGGSTYVAYNIHI--NGVLHC-SV----RYSQLHGLNEQLKKEFGNRkLPP--FPPKKL-LPLTPAQLE 71

                         90       100
                 ....*....|....*....|....*....
gi 688617890 149 ERRVALRDYLTQLYSLRFVRKSQAFQSFF 177
Cdd:cd06885   72 ERRLQLEKYLQAVVQDPRIANSDIFNSFL 100

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 688617890  72 DIPSARIisQTISKHVVYQVVVIRS-GSYDCERVAIERRYSDFLHLHQELlsdfsEELEDVV--------FPKKKMTRNF 142
Cdd:cd07284    6 DEPESHV--TAIETFITYRVMTKTSrSEFDSSEFEVRRRYQDFLWLKGRL-----EEAHPTLiipplpekFVMKGMVERF 78

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 688617890 143 SEEIIAERRVALRDYLTQLYSLRFVRKSQAFQSFFTHQ 180
Cdd:cd07284   79 NEDFIETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 116

The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX 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. 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 688617890  86 HVVYQV-VVIRSGSYDCERVAIERRYSDFLHLHQELLSDFseelEDVVFP----KKKMTR----NFSEEIIAERRVALRD 156
Cdd:cd06863   19 YISYLItTKTNLPSFSRKEFKVRRRYSDFVFLHECLSNDF----PACVVPplpdKHRLEYitgdRFSPEFITRRAQSLQR 94

                         90       100
                 ....*....|....*....|..
gi 688617890 157 YLTQLYSLRFVRKSQAFQSFFT 178
Cdd:cd06863   95 FLRRISLHPVLSQSKILHQFLE 116

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 688617890  86 HVVYQVVVIRSG-SYDCERVAIERRYSDFLHLHQELlsdfSEELEDVVFPKK------KMTRNFSEEIIAERRVALRDYL 158
Cdd:cd06865   23 YISYKVTTRTNIpSYTHGEFTVRRRFRDVVALADRL----AEAYRGAFVPPRpdksvvESQVMQSAEFIEQRRVALEKYL 98

                         90       100
                 ....*....|....*....|..
gi 688617890 159 TQLYSLRFVRKSQAFQSFFTHQ 180
Cdd:cd06865   99 NRLAAHPVIGLSDELRVFLTLQ 120

The phosphoinositide binding Phox Homology domain of Sorting Nexins 7 and 30; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily consists of SNX7, SNX30, and similar proteins. They harbor a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-6, SNX8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of the sorting nexins in this subfamily has yet to be elucidated.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688617890  82 TISKHVVYQVVVIRS-GSYDCERVAIERRYSDFLHLHQELlsdfSEELEDVVFP-------KKKMTRNFSEEIIAERRVA 153
Cdd:cd06860   14 TLETYITYRVTTKTTrSEFDSSEYSVRRRYQDFLWLRQKL----EESHPTHIIPplpekhsVKGLLDRFSPEFVATRMRA 89

                 ....*...
gi 688617890 154 LRDYLTQL 161
Cdd:cd06860   90 LHKFLNRI 97

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 688617890  84 SKHVVYQVVVirsgSYDCERVAIERRYSDFLHLHQELLSDFSEEleDVVFPKKKM-TRNFSEEIIAERRVALRDYLTQLY 162
Cdd:cd06870   18 KRFTVYKVVV----SVGRSSWFVFRRYAEFDKLYESLKKQFPAS--NLKIPGKRLfGNNFDPDFIKQRRAGLDEFIQRLV 91

                 .
gi 688617890 163 S 163
Cdd:cd06870   92 S 92

The phosphoinositide binding Phox Homology domain of Sorting Nexin 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688617890  72 DIPSARIISQTISKHVVYQVVVIRSGsydcerVAIERRYSDFLHLHQELLSDFSeeledVV----FPKKKMTRNFSEEII 147
Cdd:cd07286    6 DDPTKQTKFKGMKSYISYKLVPSHTG------LQVHRRYKHFDWLYARLAEKFP-----VIsvphIPEKQATGRFEEDFI 74

                         90       100       110
                 ....*....|....*....|....*....|.
gi 688617890 148 AERRVALRDYLTQLYSLRFVRKSQAFQSFFT 178
Cdd:cd07286   75 SKRRKGLIWWMDHMCSHPVLARCDAFQHFLT 105

The phosphoinositide binding Phox Homology domain of uncharacterized plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 688617890 106 IERRYSDFLHLHQELLSDFSEELEDVVfPKKKMTRNFSEEIIAERRVALRDYLTQLYSLRFVRKSQAFQSFF 177
Cdd:cd06879   65 VLRRFNDFLKLHTDLKKLFPKKKLPAA-PPKGLLRMKNRALLEERRHSLEEWMGKLLSDIDLSRSVPVASFL 135

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 688617890 106 IERRYSDFLHLHQEL--LSDFsEELEDVVFPKKKM----TRNFSEEIIAERRVALRDYLTQLYSLRFVRKSQAFQSF 176
Cdd:cd06893   53 VNRRFREFLTLQTRLeeNPKF-RKIMNVKGPPKRLfdlpFGNMDKDKIEARRGLLETFLRQLCSIPEISNSEEVQEF 128