The phosphoinositide binding Phox Homology domain of Sorting Nexin 12; 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. The specific function of SNX12 has yet to be elucidated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 119 SNFLEIDIFNPQTVGVGRARFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 198
Cdd:cd07294     1 SNFLEIDIFNPQTVGVGRNRFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1985847024 199 DEGIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQEEAIDRNYVPG 250
Cdd:cd07294    81 DEGIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQDETIDRNYVPG 132

The phosphoinositide binding Phox Homology domain of Sorting Nexin 12; 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. The specific function of SNX12 has yet to be elucidated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 119 SNFLEIDIFNPQTVGVGRARFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 198
Cdd:cd07294     1 SNFLEIDIFNPQTVGVGRNRFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1985847024 199 DEGIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQEEAIDRNYVPG 250
Cdd:cd07294    81 DEGIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQDETIDRNYVPG 132

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 1985847024  126 IFNPQTVGVGRARFTTYEVRMRTNLpifklKESCVRRRYSDFEWLKNELERD-SKIVVPPLPGKALKRQLPfrgdegIFE 204
Cdd:smart00312   1 VVEPEKIGDGKHYYYVIEIETKTGL-----EEWTVSRRYSDFLELHSKLKKHfPRSILPPLPGKKLFGRLN------NFS 69

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1985847024  205 ESFIEERRQGLEQFINKIAGHP-LAQNERCLHMFLQ 239
Cdd:smart00312  70 EEFIEKRRRGLEKYLQSLLNHPeLINHSEVVLEFLE 105

The phosphoinositide binding Phox Homology domain of Sorting Nexin 12; 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. The specific function of SNX12 has yet to be elucidated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 119 SNFLEIDIFNPQTVGVGRARFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 198
Cdd:cd07294     1 SNFLEIDIFNPQTVGVGRNRFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1985847024 199 DEGIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQEEAIDRNYVPG 250
Cdd:cd07294    81 DEGIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQDETIDRNYVPG 132

The phosphoinositide binding Phox Homology domain of Sorting Nexin 3; 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. SNX3 associates with early endosomes through a PX domain-mediated interaction with phosphatidylinositol-3-phosphate (PI3P). It 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. SNX3 is required for the formation of multivesicular bodies, which function as transport intermediates to late endosomes. It also promotes cell surface expression of the amiloride-sensitive epithelial Na+ channel (ENaC), which is critical in sodium homeostasis and maintenance of extracellular fluid volume.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 121 FLEIDIFNPQTVGVGRARFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRGDE 200
Cdd:cd07293     1 FLEIDVTNPQTVGVGRGRFTTYEIRLKTNLPIFKLKESTVRRRYSDFEWLRSELERESKVVVPPLPGKALFRQLPFRGDD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1985847024 201 GIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQEEAI 243
Cdd:cd07293    81 GIFDDSFIEERKQGLEQFLNKVAGHPLAQNERCLHMFLQDEII 123

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 1985847024 122 LEIDIFNPQTVGVGRARFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSK-IVVPPLPGK-ALKRqlpFRgd 199
Cdd:cd06859     1 FEISVTDPVKVGDGMSAYVVYRVTTKTNLPDFKKSEFSVLRRYSDFLWLYERLVEKYPgRIVPPPPEKqAVGR---FK-- 75

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1985847024 200 egiFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQEE 241
Cdd:cd06859    76 ---VKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRLFLESD 114

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 1985847024 122 LEIDIFNPQTVGVGRARFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERDSK-IVVPPLPGKALKrqlpfrgde 200
Cdd:cd06861     1 FEITVGDPHKVGDLTSAHTVYTVRTRTTSPNFEVSSFSVLRRYRDFRWLYRQLQNNHPgVIVPPPPEKQSV--------- 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1985847024 201 GIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQEE 241
Cdd:cd06861    72 GRFDDNFVEQRRAALEKMLRKIANHPVLQKDPDFRLFLESE 112

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 1985847024  126 IFNPQTVGVGRARFTTYEVRMRTNLpifklKESCVRRRYSDFEWLKNELERD-SKIVVPPLPGKALKRQLPfrgdegIFE 204
Cdd:smart00312   1 VVEPEKIGDGKHYYYVIEIETKTGL-----EEWTVSRRYSDFLELHSKLKKHfPRSILPPLPGKKLFGRLN------NFS 69

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1985847024  205 ESFIEERRQGLEQFINKIAGHP-LAQNERCLHMFLQ 239
Cdd:smart00312  70 EEFIEKRRRGLEKYLQSLLNHPeLINHSEVVLEFLE 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 102 RRLNSKPQdLTDAYGPPSNFLEIDIFNPQTVGVG---RARFTTYEVRMRTNLPIFKLKESC---VRRRYSDFEWLKNELE 175
Cdd:COG5391   112 LPTSLQPP-LSTSHTILDYFISSTVSNPQSLTLLvdsRDKHTSYEIITVTNLPSFQLRESRplvVRRRYSDFESLHSILI 190

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1985847024 176 RDS-KIVVPPLPGKALKRQLPFRGdegiFEESFIEERRQGLEQFINKIAGHPLAQN 230
Cdd:COG5391   191 KLLpLCAIPPLPSKKSNSEYYGDR----FSDEFIEERRQSLQNFLRRVSTHPLLSN 242

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 1985847024 123 EIDIFNPQTVGVGRARFTTYEVRMRTNlpifKLKESCVRRRYSDFEWLKNELERD-SKIVVPPLPGKALKrqlpfrgdeG 201
Cdd:cd06093     1 SVSIPDYEKVKDGGKKYVVYIIEVTTQ----GGEEWTVYRRYSDFEELHEKLKKKfPGVILPPLPPKKLF---------G 67

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1985847024 202 IFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQ 239
Cdd:cd06093    68 NLDPEFIEERRKQLEQYLQSLLNHPELRNSEELKEFLE 105

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 1985847024 121 FLEIDifNPQTVGVGRARFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELER-DSKIVVPPLPGKALKRQLPFRgd 199
Cdd:cd07284     2 FITVD--EPESHVTAIETFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEaHPTLIIPPLPEKFVMKGMVER-- 77

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1985847024 200 egiFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMFL 238
Cdd:cd07284    78 ---FNEDFIETRRKALHKFLNRIADHPTLTFNEDFKIFL 113

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 1985847024 139 FTTYEVRMR---TNLPIFKLKESC-VRRRYSDFEWLKNELErDS--KIVVPPLPGKalkrQLPFRGDEGI---FEESFIE 209
Cdd:cd06864    23 YTVYLIETKiveHESEEGLSKKLSsLWRRYSEFELLRNYLV-VTypYVIVPPLPEK----RAMFMWQKLSsdtFDPDFVE 97

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1985847024 210 ERRQGLEQFINKIAGHPLAQNERCLHMFLQEE 241
Cdd:cd06864    98 RRRAGLENFLLRVAGHPELCQDKIFLEFLTHE 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 1985847024 160 VRRRYSDFEWLKNEL-ERDSKIVVPPLPGKALkrqlpfrgdEGIFEESFIEERRQGLEQFINKIAGHP-LAQNERCLHmF 237
Cdd:cd06862    34 VSRRYKHFDWLYERLvEKYSCIAIPPLPEKQV---------TGRFEEDFIEKRRERLELWMNRLARHPvLSQSEVFRH-F 103

                  ..
gi 1985847024 238 LQ 239
Cdd:cd06862   104 LT 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 1985847024 154 KLKESCVRRRYSDFEWLKNEL-ERDSKIVVPPLPgkaLKRQLPFRGDEgifeesFIEERRQGLEQFINKIAGHPLAQNER 232
Cdd:cd06866    26 KRFKSTVYRRYSDFVWLHEYLlKRYPYRMVPALP---PKRIGGSADRE------FLEARRRGLSRFLNLVARHPVLSEDE 96

                  ....*.
gi 1985847024 233 CLHMFL 238
Cdd:cd06866    97 LVRTFL 102

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 137 ARFTTYEVRMRTN----LPIFklkescVRRRYSDF----EWLKNELERDSKIVVPPLPGKAlkrqlPFRGDEGIFEESFI 208
Cdd:cd07280    20 GAYVVWKITIETKdligSSIV------AYKRYSEFvqlrEALLDEFPRHKRNEIPQLPPKV-----PWYDSRVNLNKAWL 88

                          90       100       110
                  ....*....|....*....|....*....|
gi 1985847024 209 EERRQGLEQFINKIAGHPLAQNERCLHMFL 238
Cdd:cd07280    89 EKRRRGLQYFLNCVLLNPVFGGSPVVKEFL 118

The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; 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. SNX41 and SNX42 (also called Atg20p) form dimers with SNX4, and are required in protein recycling from the sorting endosome (post-Golgi endosome) back to the late Golgi in yeast.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 154 KLKESCVRRRYSDFEWLKNELER-DSKIVVPPLPGKA-----LKRQLPFRGDEGIfeesfIEERRQGLEQFINKIAGHPL 227
Cdd:cd06867    24 RLGGSEVKRRYSEFESLRKNLTRlYPTLIIPPIPEKHslkdyAKKPSKAKNDAKI-----IERRKRMLQRFLNRCLQHPI 98

                          90
                  ....*....|....
gi 1985847024 228 AQNERCLHMFLQEE 241
Cdd:cd06867    99 LRNDIVFQKFLDPN 112

The phosphoinositide binding Phox Homology domain of Sorting Nexin 5; 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. SNX5, abundantly expressed in macrophages, regulates macropinocytosis, a process that enables cells to internalize large amounts of external solutes. It may also be a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, acting as a mammalian equivalent of yeast Vsp17p. It also binds the Fanconi anaemia complementation group A protein (FANCA). SNX5 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to other sorting nexins including SNX1-2. The PX-BAR structural unit helps determine the specific membrane-targeting of some SNXs. The PX domain of SNX5 binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,4)P2. SNX5 is localized to a subdomain of early endosome and is recruited to the plasma membrane following EGF stimulation and elevation of PI(3,4)P2 levels.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 122 LEIDIfnPQTVGV-GRARFTtyeVRMRTNLPIFKLKESCVRRRYSDFEWLKN---ELERDSKIVVPPLP------GKALK 191
Cdd:cd07291     3 LQIDI--PDALSErDKVKFT---VHTKTTLPSFQSPDFSVTRQHEDFIWLHDaliETEDYAGLIIPPAPpkpdfdGPREK 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1985847024 192 RQLPFRGDEGIFEESFiEERRQGLEQ---------------FINKIAGHPLAQNERCLHMFLQ 239
Cdd:cd07291    78 MQKLGEGEGSMTKEEF-AKMKQELEAeylavfkktvqvhevFLQRLSSHPSLSKDRNFHIFLE 139

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1985847024 160 VRRRYSDFEWLKNELERdSKIVVPpLPGKALKrqlpfrgdeGIFEESFIEERRQGLEQFINKIAGHPL 227
Cdd:cd06871    40 VIRRYNDFDLLNASLQI-SGISLP-LPPKKLI---------GNMDREFIAERQQGLQNYLNVILMNPI 96

The phosphoinositide binding Phox Homology domain of HS1BP3; 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. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 124 IDIFNPQTVGVGRARFTT---YEVRMRTNLPIFK----LKESCVR----RRYSDFEWLKNEL-ERDSKIVVPPLPGKALk 191
Cdd:cd06868     2 LDLTVPEYQEIRGKTSSGhvlYQIVVVTRLAAFKsakhKEEDVVQfmvsKKYSEFEELYKKLsEKYPGTILPPLPRKAL- 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1985847024 192 rqlpFRGdegifeESFIEERRQGLEQFINKIAGHPLAQNERCLHMFL 238
Cdd:cd06868    81 ----FVS------ESDIRERRAAFNDFMRFISKDEKLANCPELLEFL 117

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 1985847024 136 RARFTTYEVRMRTNLpifklKESCVRRRYSDFEWLKNELERDskivvppLPGKALKrqLP---FRGDEgiFEESFIEERR 212
Cdd:cd06870    17 KKRFTVYKVVVSVGR-----SSWFVFRRYAEFDKLYESLKKQ-------FPASNLK--IPgkrLFGNN--FDPDFIKQRR 80

                          90       100
                  ....*....|....*....|....*..
gi 1985847024 213 QGLEQFINKIAGHPLAQNERCLHMFLQ 239
Cdd:cd06870    81 AGLDEFIQRLVSDPKLLNHPDVRAFLQ 107

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 160 VRRRYSDFEWLKNEL--ERDSKIVVPPLPGKALKrqlpfrgdeGIFEESFIEERRQGLEQFINKIAGHPLAQNERCLHMF 237
Cdd:cd07285    34 VNHRYKHFDWLYERLlvKFGLAIPIPSLPDKQVT---------GRFEEEFIKMRMERLQAWMTRMCRHPVISESEVFQQF 104

                  .
gi 1985847024 238 L 238
Cdd:cd07285   105 L 105

The phosphoinositide binding Phox Homology domain of Sorting Nexin 6; 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. SNX6 forms a stable complex with SNX1 and may be a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi, acting as a mammalian equivalent of yeast Vsp17p. It interacts with the receptor serine/threonine kinases from the transforming growth factor-beta family. It also plays roles in enhancing the degradation of EGFR and in regulating the activity of Na,K-ATPase through its interaction with Translationally Controlled Tumor Protein (TCTP). SNX6 harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain, similar to other sorting nexins including SNX1-2. The PX-BAR structural unit helps determine the specific membrane-targeting of some SNXs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 142 YEVRMRTNLPIFKLKESCVRRRYSDFEWLKN---ELERDSKIVVPPLPGK----ALKRQLPFRGD-EGIFEESFIEERRQ 213
Cdd:cd07292    19 FTVHTKSSLPNFKQNEFSVVRQHEEFIWLHDsfvENEDYAGYIIPPAPPRpdfdASREKLQKLGEgEGSMTKEEFTKMKQ 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1985847024 214 GLEQ---------------FINKIAGHPLAQNERCLHMFLQ 239
Cdd:cd07292    99 ELEAeylaifkktvamhevFLCRVAAHPILRKDLNFHVFLE 139

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15; 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. SNX15 contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) domain. It plays a role in protein trafficking processes in the endocytic pathway and the trans-Golgi network. The PX domain of SNX15 interacts with the PDGF receptor and is responsible for the membrane association of the protein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 155 LKESCVRRRYSDFEWLKNELERDSKIVV------PPLPgkalkRQLPFrgdeGIFEESFIEERRQGLEQFINKIAGHPLA 228
Cdd:cd07288    35 VKEVVVWKRYSDLKKLHGELAYTHRNLFrrqeefPPFP-----RAQVF----GRFEAAVIEERRNAAEAMLLFTVNIPAL 105

                          90
                  ....*....|..
gi 1985847024 229 QNERCLHMFLQE 240
Cdd:cd07288   106 YNSPQLKEFFRD 117

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1985847024 163 RYSDFEWLKNELERD-SKIVVPPLPGKALKRQLPfrgdegifeeSFIEERRQGLEQFINKIAGHPLAQNERCLHMFLQ 239
Cdd:cd06885    34 RYSQLHGLNEQLKKEfGNRKLPPFPPKKLLPLTP----------AQLEERRLQLEKYLQAVVQDPRIANSDIFNSFLL 101

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 1985847024 139 FTTYEVRMRTNLPIFKLKESCVRRRYSDF----EWLKNELERDSKIvvpPLPGKALKRQLpfrgdegifEESFIEERRQG 214
Cdd:cd06873    22 YAVYAISVTRIYPNGQEESWHVYRRYSDFhdlhMRLKEKFPNLSKL---SFPGKKTFNNL---------DRAFLEKRRKM 89

                          90       100       110
                  ....*....|....*....|....*....|
gi 1985847024 215 LEQFINKI------AGHPLAQNerCLHMFL 238
Cdd:cd06873    90 LNQYLQSLlnpevlDANPGLQE--IVLDFL 117

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1985847024 139 FTTYEVRMRT---NLPIfKLKESCVRRRYSDFEWLKNELE-------RDSKIVVPPLPGKALKRqlpfrgdegiFEESFI 208
Cdd:cd07287    17 YTVYKVTARIvsrKNPE-DVQEIVVWKRYSDFKKLHKDLWqihknlcRQSELFPPFAKAKVFGR----------FDESVI 85

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1985847024 209 EERRQGLEQFINKIAGHPLAQNERCLHMFLQ 239
Cdd:cd07287    86 EERRQCAEDLLQFSANIPALYNSSQLEDFFK 116