PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413    63 SMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhITQRMQGLQQFLEAVLQTPLLLSDSRLHL 142
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYNEEF-IEKRRKGLEQYLQRLLQHPELRNSEVLLE 79

                  ....*
gi 33416413   143 FLQSQ 147
Cdd:pfam00787  80 FLESD 84

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413   1 TISLPLLITSARGAPGSWcgiqHHAIKQDRKEFISVWVRDpqvhkedfwhTYISYEICLHTNSMCFRKKTSC---VRRRY 77
Cdd:COG5391 114 TSLQPPLSTSHTILDYFI----SSTVSNPQSLTLLVDSRD----------KHTSYEIITVTNLPSFQLRESRplvVRRRY 179

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413  78 SEFVWLRHKLQDNALLIELPKLP--PWNPFFNLNNeFH---ITQRMQGLQQFLEAVLQTPLL-----LSDSRLHLFLQSQ 147
Cdd:COG5391 180 SDFESLHSILIKLLPLCAIPPLPskKSNSEYYGDR-FSdefIEERRQSLQNFLRRVSTHPLLsnyknSKSWESHSTLLSS 258

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 33416413  35 SVWVRDPQVHKeDFWHTYISYEICLHTNSmcfrKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhI 114
Cdd:cd06093   1 SVSIPDYEKVK-DGGKKYVVYIIEVTTQG----GEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEF-I 74

                        90       100       110
                ....*....|....*....|....*....|..
gi 33416413 115 TQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQS 146
Cdd:cd06093  75 EERRKQLEQYLQSLLNHPELRNSEELKEFLEL 106

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 33416413  34 ISVWVRDPQVHKeDFWHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPF--FNLNNE 111
Cdd:cd06859   1 FEISVTDPVKVG-DGMSAYVVYRVTTKTNLPDFKKSEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVgrFKVKFE 79

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 33416413 112 FhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 147
Cdd:cd06859  80 F-IEKRRAALERFLRRIAAHPVLRKDPDFRLFLESD 114

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3 and related proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily is composed of SNX3, SNX12, and fungal Grd19. Grd19 is involved in the localization of late Golgi membrane proteins in yeast. SNX3/Grp19 associates with the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, and functions as a cargo-specific adaptor for the retromer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413  33 FISVWVRDPQVHKeDFWHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIeLPKLP--------PWNP 104
Cdd:cd06894   1 FLEIDVVNPQTHG-VGKKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSELERDSKIV-VPPLPgkalkrqlPFRG 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 33416413 105 FFNLNNEFHITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 147
Cdd:cd06894  79 DDGIFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQEE 121

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 33416413  36 VWVRDPQVHKEDFwHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNL----NNE 111
Cdd:cd06860   3 ITVDNPEKHVTTL-ETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVKGLldrfSPE 81

                        90       100       110
                ....*....|....*....|....*....|...
gi 33416413 112 FhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFL 144
Cdd:cd06860  82 F-VATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413  33 FISVWVRDPQVHKEDfWHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPwNPFFNLNNEF 112
Cdd:cd07295   1 FLEIEVRNPKTHGIG-RGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERESPRVMIPPLPG-KIFTNRFSDE 78

                        90       100       110
                ....*....|....*....|....*....|....*
gi 33416413 113 HITQRMQGLQQFLEAVLQTPLLLSDSR-LHLFLQS 146
Cdd:cd07295  79 VIEERRQGLETFLQSVAGHPLLQTGSKvLAAFLQD 113

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 33416413  38 VRDPqvHK-EDFWHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhITQ 116
Cdd:cd06861   5 VGDP--HKvGDLTSAHTVYTVRTRTTSPNFEVSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNF-VEQ 81

                        90       100       110
                ....*....|....*....|....*....|.
gi 33416413 117 RMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 147
Cdd:cd06861  82 RRAALEKMLRKIANHPVLQKDPDFRLFLESE 112

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 33416413  34 ISVWVRDPQVHKEDFwHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPpwNPFF------N 107
Cdd:cd07284   1 IFITVDEPESHVTAI-ETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPLP--EKFVmkgmveR 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 33416413 108 LNNEFhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 147
Cdd:cd07284  78 FNEDF-IETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 116

The phosphoinositide binding Phox Homology domain of Sorting Nexin 30; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX30 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to the sorting nexins SNX1-2, SNX4-8, and SNX32. Both domains have been shown to determine the specific membrane-targeting of SNX1. The specific function of SNX30 has yet to be elucidated.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413  36 VWVRDPQVHKEDFwHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFH-- 113
Cdd:cd07283   3 VTVDDPKKHVCTM-ETYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRFSee 81

                        90       100       110
                ....*....|....*....|....*....|....*
gi 33416413 114 -ITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 147
Cdd:cd07283  82 fVETRRKALDKFLKRIADHPVLSFNEHFNVFLTAK 116

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33416413  73 VRRRYSEFVWLRHKLQD---NALLIELPKLPPWNPFF----NLNNEFhITQRMQGLQQFLEAVLQTPLL 134
Cdd:cd07280  41 AYKRYSEFVQLREALLDefpRHKRNEIPQLPPKVPWYdsrvNLNKAW-LEKRRRGLQYFLNCVLLNPVF 108

The phosphoinositide binding Phox Homology domain of Sorting Nexin 2; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX2 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. Similar to SNX1, SNX2 contains a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX domain of SNX2 preferentially binds phosphatidylinositol-3-phosphate (PI3P), but not PI(3,4,5)P3. Studies on mice deficient with SNX1 and/or SNX2 suggest that they provide an essential function in embryogenesis and are functionally redundant.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413  34 ISVWVRDPQvHKEDFWHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLP-PWNPFFNL---- 108
Cdd:cd07282   1 IEIGVSDPE-KVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLHVGYIVPPaPEKSIVGMtkvk 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 33416413 109 -------NNEFhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQS 146
Cdd:cd07282  80 vgkedssSTEF-VEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 123

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 33416413  36 VWVRDPQVHKEDFWH-----TYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPF---FN 107
Cdd:cd06865   2 ITVSDPKKEQEPSRVplggpPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVesqVM 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 33416413 108 LNNEFhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 147
Cdd:cd06865  82 QSAEF-IEQRRVALEKYLNRLAAHPVIGLSDELRVFLTLQ 120

The phosphoinositide binding Phox Homology domain of SNARE proteins from fungi; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. This subfamily is composed of fungal proteins similar to Saccharomyces cerevisiae Vam7p. They contain an N-terminal PX domain and a C-terminal SNARE domain. The SNARE (Soluble NSF attachment protein receptor) family of proteins are integral membrane proteins that serve as key factors for vesicular trafficking. Vam7p is anchored at the vacuolar membrane through the specific interaction of its PX domain with phosphatidylinositol-3-phosphate (PI3P) present in bilayers. It plays an essential role in vacuole fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413  67 RKKTscVRRRYSEFVWLRHKLQDNaLLIELP-KLPP--WNpFFNLNNEFHITQRMQGLQQFLEAVLQTPlllsDSR---- 139
Cdd:cd06897  27 RSYT--VSRRYSEFVALHKQLESE-VGIEPPyPLPPksWF-LSTSSNPKLVEERRVGLEAFLRALLNDE----DSRwrns 98

                ....*...
gi 33416413 140 --LHLFLQ 145
Cdd:cd06897  99 paVKEFLN 106

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413  44 HKEDFWHTY----ISYEICLH-------TNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIEL------PKLPPWNPFF 106
Cdd:cd06893  13 YKGTGTHPYtlytVQYETILDvqseqnpNAASEQPLATHTVNRRFREFLTLQTRLEENPKFRKImnvkgpPKRLFDLPFG 92

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 33416413 107 NLNNEfHITQRMQGLQQFLEAVLQTPLLLSDSRLHLFL 144
Cdd:cd06893  93 NMDKD-KIEARRGLLETFLRQLCSIPEISNSEEVQEFL 129

The phosphoinositide binding Phox Homology domain of Sorting Nexins 9 and 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX9, SNX18, and similar proteins. They contain an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis, while SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413  51 TYISYEIC-LHTNSMcfrkktscVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhITQRMQGLQQFLEAVL 129
Cdd:cd06862  19 SFIAYQITpTHTNVT--------VSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRFEEDF-IEKRRERLELWMNRLA 89

                        90
                ....*....|....*...
gi 33416413 130 QTPLLLSDSRLHLFLQSQ 147
Cdd:cd06862  90 RHPVLSQSEVFRHFLTCT 107

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33416413  51 TYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNalLIELPKLP-PWNPFF-NLNNEFhITQRMQGLQQFLEAV 128
Cdd:cd06873  21 TYAVYAISVTRIYPNGQEESWHVYRRYSDFHDLHMRLKEK--FPNLSKLSfPGKKTFnNLDRAF-LEKRRKMLNQYLQSL 97

                ...
gi 33416413 129 LQT 131
Cdd:cd06873  98 LNP 100

The phosphoinositide binding Phox Homology domain of Sorting Nexin 9; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX9, also known as SH3PX1, is a cytosolic protein that interacts with proteins associated with clathrin-coated pits such as Cdc-42-associated tyrosine kinase 2 (ACK2). It contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. Through its SH3 domain, SNX9 binds class I polyproline sequences found in dynamin 1/2 and the WASP/N-WASP actin regulators. SNX9 is localized to plasma membrane endocytic sites and acts primarily in clathrin-mediated endocytosis. Its array of interacting partners suggests that SNX9 functions at the interface between endocytosis and actin cytoskeletal organization.

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gi 33416413  51 TYISYEI-CLHTNSmcfrkktsCVRRRYSEFVWLRHKLQDN-ALLIELPKLPPWNPFFNLNNEFhITQRMQGLQQFLEAV 128
Cdd:cd07285  19 SYIEYQLtPTNTNR--------SVNHRYKHFDWLYERLLVKfGLAIPIPSLPDKQVTGRFEEEF-IKMRMERLQAWMTRM 89

                        90
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gi 33416413 129 LQTPLLLSDSRLHLFL 144
Cdd:cd07285  90 CRHPVISESEVFQQFL 105

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.

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gi 33416413  73 VRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhITQRMQGLQQFLEAVLQT 131
Cdd:cd07277  34 VYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKF-VEERRKRLQVYLRRVVNT 91