PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140313  41 SMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhITQRMQGLQQFLEAVLQTPLLLSDSRLHL 120
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYNEEF-IEKRRKGLEQYLQRLLQHPELRNSEVLLE 79

                  ....*
gi 1207140313 121 FLQSQ 125
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 1207140313   3 NTSFEKreFISVWVRDPQVHKEDFWH--TYISYEICLHTNSMCFRKKTSC---VRRRYSEFVWLRHKLQDNALLIELPKL 77
Cdd:COG5391   124 HTILDY--FISSTVSNPQSLTLLVDSrdKHTSYEIITVTNLPSFQLRESRplvVRRRYSDFESLHSILIKLLPLCAIPPL 201

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1207140313  78 P--PWNPFFNLNNeFH---ITQRMQGLQQFLEAVLQTPLL 112
Cdd:COG5391   202 PskKSNSEYYGDR-FSdefIEERRQSLQNFLRRVSTHPLL 240

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 1207140313  13 SVWVRDPQVHKeDFWHTYISYEICLHTNSmcfrKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhI 92
Cdd:cd06093     1 SVSIPDYEKVK-DGGKKYVVYIIEVTTQG----GEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEF-I 74

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1207140313  93 TQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQS 124
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 1207140313  12 ISVWVRDPQVHKeDFWHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPF--FNLNNE 89
Cdd:cd06859     1 FEISVTDPVKVG-DGMSAYVVYRVTTKTNLPDFKKSEFSVLRRYSDFLWLYERLVEKYPGRIVPPPPEKQAVgrFKVKFE 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1207140313  90 FhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 125
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 1207140313  11 FISVWVRDPQVHKeDFWHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIeLPKLP--------PWNP 82
Cdd:cd06894     1 FLEIDVVNPQTHG-VGKKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSELERDSKIV-VPPLPgkalkrqlPFRG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1207140313  83 FFNLNNEFHITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 125
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 1207140313  14 VWVRDPQVHKEDFwHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNL----NNE 89
Cdd:cd06860     3 ITVDNPEKHVTTL-ETYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVKGLldrfSPE 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1207140313  90 FhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFL 122
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 1207140313  11 FISVWVRDPQVHKEDfWHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPwNPFFNLNNEF 90
Cdd:cd07295     1 FLEIEVRNPKTHGIG-RGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERESPRVMIPPLPG-KIFTNRFSDE 78

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1207140313  91 HITQRMQGLQQFLEAVLQTPLLLSDSR-LHLFLQS 124
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 1207140313  16 VRDPqvHK-EDFWHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhITQ 94
Cdd:cd06861     5 VGDP--HKvGDLTSAHTVYTVRTRTTSPNFEVSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVGRFDDNF-VEQ 81

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1207140313  95 RMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 125
Cdd:cd06861    82 RRAALEKMLRKIANHPVLQKDPDFRLFLESE 112

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 1207140313  51 VRRRYSEFVWLRHKLQD---NALLIELPKLPPWNPFF----NLNNEFhITQRMQGLQQFLEAVLQTPLL 112
Cdd:cd07280    41 AYKRYSEFVQLREALLDefpRHKRNEIPQLPPKVPWYdsrvNLNKAW-LEKRRRGLQYFLNCVLLNPVF 108

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140313  12 ISVWVRDPQVHKEDFwHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPpwNPFF------N 85
Cdd:cd07284     1 IFITVDEPESHVTAI-ETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPLP--EKFVmkgmveR 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1207140313  86 LNNEFhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 125
Cdd:cd07284    78 FNEDF-IETRRKALHKFLNRIADHPTLTFNEDFKIFLTAQ 116

The phosphoinositide binding Phox Homology domain of Sorting Nexin 4; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX4 is involved in recycling traffic from the sorting endosome (post-Golgi endosome) back to the late Golgi. It shows a similar domain architecture as SNX1-2, among others, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. SNX4 is implicated in the regulation of plasma membrane receptor trafficking and interacts with receptors for EGF, insulin, platelet-derived growth factor and the long form of the leptin receptor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140313  29 TYISYEI----CLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFF--------NLNNEFhITQRM 96
Cdd:cd06864    22 TYTVYLIetkiVEHESEEGLSKKLSSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAMFmwqklssdTFDPDF-VERRR 100

                          90       100
                  ....*....|....*....|....*..
gi 1207140313  97 QGLQQFLEAVLQTPLLLSDSRLHLFLQ 123
Cdd:cd06864   101 AGLENFLLRVAGHPELCQDKIFLEFLT 127

The phosphoinositide binding Phox Homology domain of Sorting Nexin 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX1 is both membrane associated and a cytosolic protein that exists as a tetramer in protein complexes. It can associate reversibly with membranes of the endosomal compartment, thereby coating these vesicles. SNX1 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. SNX1 contains a Bin/Amphiphysin/Rvs (BAR) domain C-terminal to the PX domain. The PX domain of SNX1 specifically binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,5)P2, while the BAR domain detects membrane curvature. Both domains help determine the specific membrane-targeting of SNX1, which is localized to a microdomain in early endosomes where it regulates cation-independent mannose-6-phosphate receptor retrieval to the trans Golgi network.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140313  12 ISVWVRDPQvHKEDFWHTYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQD----NALLIElPklPPWNPFFNLN 87
Cdd:cd07281     1 LKVSITDPE-KIGDGMNAYVVYKVTTQTSLLMFRSKHFTVKRRFSDFLGLYEKLSEkhsqNGFIVP-P--PPEKSLIGMT 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1207140313  88 N-----------EFhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 125
Cdd:cd07281    77 KvkvgkedsssaEF-LERRRAALERYLQRIVSHPSLLQDPDVREFLEKE 124

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 1207140313  14 VWVRDPQVHKEDFWH-----TYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPF---FN 85
Cdd:cd06865     2 ITVSDPKKEQEPSRVplggpPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVesqVM 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1207140313  86 LNNEFhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQSQ 125
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 1207140313  45 RKKTscVRRRYSEFVWLRHKLQDNaLLIELP-KLPP--WNpFFNLNNEFHITQRMQGLQQFLEAVLQTPlllsDSR---- 117
Cdd:cd06897    27 RSYT--VSRRYSEFVALHKQLESE-VGIEPPyPLPPksWF-LSTSSNPKLVEERRVGLEAFLRALLNDE----DSRwrns 98

                  ....*...
gi 1207140313 118 --LHLFLQ 123
Cdd:cd06897    99 paVKEFLN 106

The phosphoinositide binding Phox Homology domain of Sorting Nexin 14; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX14 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. It is expressed in the embryonic nervous system of mice, and is co-expressed in the motoneurons and the anterior pituary with Islet-1. SNX14 shows a similar domain architecture as SNX13, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207140313  50 CVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhITQRMQGLQQFLEAVLQTPLLLSDSRLHLFLQS 124
Cdd:cd06877    45 SVLRRYNEFYVLESKLTEFHGEFPDAPLPSRRIFGPKSYEF-LESKREIFEEFLQKLLQKPELRGSELLYDFLSP 118

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 1207140313  29 TYISYEIC-LHTNSMcfrkktscVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhITQRMQGLQQFLEAVL 107
Cdd:cd06862    19 SFIAYQITpTHTNVT--------VSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVTGRFEEDF-IEKRRERLELWMNRLA 89

                          90
                  ....*....|....*...
gi 1207140313 108 QTPLLLSDSRLHLFLQSQ 125
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 1207140313  29 TYISYEICLHTNSMCFRKKTSCVRRRYSEFVWLRHKLQDNalLIELPKLP-PWNPFF-NLNNEFhITQRMQGLQQFLEAV 106
Cdd:cd06873    21 TYAVYAISVTRIYPNGQEESWHVYRRYSDFHDLHMRLKEK--FPNLSKLSfPGKKTFnNLDRAF-LEKRRKMLNQYLQSL 97

                  ...
gi 1207140313 107 LQT 109
Cdd:cd06873    98 LNP 100

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.

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gi 1207140313  29 TYISYEIC-LHTNSMcfrkktscVRRRYSEFVWLRHKLQDNALLIELPKLPPWNPFFNLNNEFhITQRMQGLQQFLEAVL 107
Cdd:cd07286    19 SYISYKLVpSHTGLQ--------VHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDF-ISKRRKGLIWWMDHMC 89

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gi 1207140313 108 QTPLL 112
Cdd:cd07286    90 SHPVL 94