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 225543256  27 SNFLEIDVYDPQTIGVGRNRFTTYEVRMR---------ESVVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 97
Cdd:cd07294    1 SNFLEIDIFNPQTVGVGRNRFTTYEVRMRtnlpifklkESCVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 225543256  98 DEGIFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQDESIDRNYIPG 149
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 225543256  27 SNFLEIDVYDPQTIGVGRNRFTTYEVRMR---------ESVVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 97
Cdd:cd07294    1 SNFLEIDIFNPQTVGVGRNRFTTYEVRMRtnlpifklkESCVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 225543256  98 DEGIFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQDESIDRNYIPG 149
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 225543256    36 DPQTIGVGRNRFTTYEVRMR----ESVVRRRYSDFEWLKNELERD-SKIVVPPLPGKALKRQLPfrgdegIFEESFIEER 110
Cdd:smart00312   3 EPEKIGDGKHYYYVIEIETKtgleEWTVSRRYSDFLELHSKLKKHfPRSILPPLPGKKLFGRLN------NFSEEFIEKR 76

                           90       100
                   ....*....|....*....|....*....
gi 225543256   111 RAGLEQFINRIAGHP-LAQNERCLHMFLQ 138
Cdd:smart00312  77 RRGLEKYLQSLLNHPeLINHSEVVLEFLE 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 225543256  27 SNFLEIDVYDPQTIGVGRNRFTTYEVRMR---------ESVVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 97
Cdd:cd07294    1 SNFLEIDIFNPQTVGVGRNRFTTYEVRMRtnlpifklkESCVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 225543256  98 DEGIFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQDESIDRNYIPG 149
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 225543256  29 FLEIDVYDPQTIGVGRNRFTTYEVR---------MRESVVRRRYSDFEWLKNELERDSKIVVPPLPGKALKRQLPFRGDE 99
Cdd:cd07293    1 FLEIDVTNPQTVGVGRGRFTTYEIRlktnlpifkLKESTVRRRYSDFEWLRSELERESKVVVPPLPGKALFRQLPFRGDD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 225543256 100 GIFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQDESI 142
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 225543256  30 LEIDVYDPQTIGVGRNRFTTYEVRMR---------ESVVRRRYSDFEWLKNELERDSK-IVVPPLPGK-ALKRqlpFRgd 98
Cdd:cd06859    1 FEISVTDPVKVGDGMSAYVVYRVTTKtnlpdfkksEFSVLRRYSDFLWLYERLVEKYPgRIVPPPPEKqAVGR---FK-- 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 225543256  99 egiFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQDE 140
Cdd:cd06859   76 ---VKFEFIEKRRAALERFLRRIAAHPVLRKDPDFRLFLESD 114

The phosphoinositide binding Phox Homology domain of Sorting Nexin 10; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX10 may be involved in the regulation of endosome homeostasis. Its expression induces the formation of giant vacuoles in mammalian cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543256  32 IDVYDPQTIGVGR-NRFTTYEV---------RMRESVVRRRYSDFEWLKNELERDSKIV-VPPLPGKalkrQLPFRGDeg 100
Cdd:cd06898    2 VEVRDPRTHKEDDwGSYTDYEIflhtnsmcfTLKTSCVRRRYSEFVWLRNRLQKNALLIqLPSLPPK----NLFGRFN-- 75

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 225543256 101 ifEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQ 138
Cdd:cd06898   76 --NEGFIEERQQGLQDFLEKVLQTPLLLSDSRLHLFLQ 111

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 225543256  30 LEIDVYDPQTIGVGRNRFTTYEVRMR---------ESVVRRRYSDFEWLKNELERDSK-IVVPPLPGKALKrqlpfrgde 99
Cdd:cd06861    1 FEITVGDPHKVGDLTSAHTVYTVRTRttspnfevsSFSVLRRYRDFRWLYRQLQNNHPgVIVPPPPEKQSV--------- 71

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 225543256 100 GIFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQDE 140
Cdd:cd06861   72 GRFDDNFVEQRRAALEKMLRKIANHPVLQKDPDFRLFLESE 112

The phosphoinositide binding Phox Homology domain of yeast Atg24p, an autophagic degradation protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The yeast Atg24p is a sorting nexin (SNX) which is involved in membrane fusion events at the vacuolar surface during pexophagy. This is facilitated via binding of Atg24p to phosphatidylinositol 3-phosphate (PI3P) through its PX domain. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543256  30 LEIDVYDPQT-IGVGRNRFTTYEVR---------MRESVVRRRYSDFEWLKNELERD-SKIVVPPLPGKalKRQLPFRGD 98
Cdd:cd06863    1 LECLVSDPQKeLDGSSDTYISYLITtktnlpsfsRKEFKVRRRYSDFVFLHECLSNDfPACVVPPLPDK--HRLEYITGD 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 225543256  99 EgiFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQD 139
Cdd:cd06863   79 R--FSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFLES 117

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 225543256  30 LEIDVYDPQTIGVGRNRFTTYEVRMR---------ESVVRRRYSDFEWLKNELERDSK-IVVPPLPGK-ALKRQLPFRGD 98
Cdd:cd06860    1 LFITVDNPEKHVTTLETYITYRVTTKttrsefdssEYSVRRRYQDFLWLRQKLEESHPtHIIPPLPEKhSVKGLLDRFSP 80

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 225543256  99 EgifeesFIEERRAGLEQFINRIAGHPLAQNERCLHMFL 137
Cdd:cd06860   81 E------FVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

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 225543256  30 LEIDVYDPQTIGVGRNRFTTYEVRMRESV---------VRRRYSDFEWLKNELErdSK-----IVVPPLPGKALKRQLPF 95
Cdd:cd07282    1 IEIGVSDPEKVGDGMNAYMAYRVTTKTSLsmfsrsefsVRRRFSDFLGLHSKLA--SKylhvgYIVPPAPEKSIVGMTKV 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 225543256  96 R-GDEGIFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQD 139
Cdd:cd07282   79 KvGKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLES 123

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 225543256  32 IDVYDPQTIGVGRNRFTTYEVRMR---------ESVVRRRYSDFEWLKNELER-DSKIVVPPLPGKALKRQLPFRgdegi 101
Cdd:cd07284    3 ITVDEPESHVTAIETFITYRVMTKtsrsefdssEFEVRRRYQDFLWLKGRLEEaHPTLIIPPLPEKFVMKGMVER----- 77

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 225543256 102 FEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFL 137
Cdd:cd07284   78 FNEDFIETRRKALHKFLNRIADHPTLTFNEDFKIFL 113

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 225543256  50 YEV--RMRESVVRRRYSDFEWLKNEL-ERDSKIVVPPLPgkaLKRQLPFRGDEgifeesFIEERRAGLEQFINRIAGHPL 126
Cdd:cd06866   21 YEVssKRFKSTVYRRYSDFVWLHEYLlKRYPYRMVPALP---PKRIGGSADRE------FLEARRRGLSRFLNLVARHPV 91

                         90
                 ....*....|.
gi 225543256 127 AQNERCLHMFL 137
Cdd:cd06866   92 LSEDELVRTFL 102

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 225543256  48 TTYEVRMRESVVRRRYSDFEWLKNELERDSKI-VVPPLPGKALKRQLPFRgdegiFEESFIEERRAGLEQFINRIAGHPL 126
Cdd:cd07283   28 TRTEFDLPEYSVRRRYQDFDWLRNKLEESQPThLIPPLPEKFVVKGVVDR-----FSEEFVETRRKALDKFLKRIADHPV 102

                         90
                 ....*....|.
gi 225543256 127 AQNERCLHMFL 137
Cdd:cd07283  103 LSFNEHFNVFL 113

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 225543256  58 VVRRRYSDF----EWLKNELERDSKIVVPPLPGKAlkrqlPFRGDEGIFEESFIEERRAGLEQFINRIAGHPLAQNERCL 133
Cdd:cd07280   40 VAYKRYSEFvqlrEALLDEFPRHKRNEIPQLPPKV-----PWYDSRVNLNKAWLEKRRRGLQYFLNCVLLNPVFGGSPVV 114

                 ....
gi 225543256 134 HMFL 137
Cdd:cd07280  115 KEFL 118

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; 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. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543256  44 RNRFTTYEVRMRES-----VVRRRYSDFEWLKNELERDSKIVVPPLPGKAlkrqlpFRGDEgiFEESFIEERRAGLEQFI 118
Cdd:cd07276   17 RARFTVYKIRVENKvgdswFVFRRYTDFVRLNDKLKQMFPGFRLSLPPKR------WFKDN--FDPDFLEERQLGLQAFV 88

                         90
                 ....*....|....*....
gi 225543256 119 NRIAGHPLAQNERCLHMFL 137
Cdd:cd07276   89 NNIMAHKDIAKCKLVREFF 107

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 225543256  44 RNRFTTYEV----RMRESVVRRRYSDFEWLKNELERDskivvppLPGKALKrqLP---FRGDEgiFEESFIEERRAGLEQ 116
Cdd:cd06870   17 KKRFTVYKVvvsvGRSSWFVFRRYAEFDKLYESLKKQ-------FPASNLK--IPgkrLFGNN--FDPDFIKQRRAGLDE 85

                         90       100
                 ....*....|....*....|..
gi 225543256 117 FINRIAGHPLAQNERCLHMFLQ 138
Cdd:cd06870   86 FIQRLVSDPKLLNHPDVRAFLQ 107

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543256  59 VRRRYSDFEWLKNELERdSKIVVPpLPGKALKrqlpfrgdeGIFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQ 138
Cdd:cd06871   40 VIRRYNDFDLLNASLQI-SGISLP-LPPKKLI---------GNMDREFIAERQQGLQNYLNVILMNPILASCLPVKKFLD 108

                 ....*...
gi 225543256 139 DESIDRNY 146
Cdd:cd06871  109 PNNYSANF 116

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543256  59 VRRRYSDFEWLKNELE------RDSkivvpplpgkalkrQLPFRGDEGIFEESFIEERRAGLEQFINRIAGHPLAQNERC 132
Cdd:cd06877   46 VLRRYNEFYVLESKLTefhgefPDA--------------PLPSRRIFGPKSYEFLESKREIFEEFLQKLLQKPELRGSEL 111

                 ....*
gi 225543256 133 LHMFL 137
Cdd:cd06877  112 LYDFL 116

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 225543256  51 EVRMRESVVRRRYSDFEWLKNELERDSKI--VVPPLPGKALKRQLPFrgdeGIFEESFIEERRAGLEQFINRIAGHPLAQ 128
Cdd:cd06893   45 EQPLATHTVNRRFREFLTLQTRLEENPKFrkIMNVKGPPKRLFDLPF----GNMDKDKIEARRGLLETFLRQLCSIPEIS 120

                 ....*....
gi 225543256 129 NERCLHMFL 137
Cdd:cd06893  121 NSEEVQEFL 129

The phosphoinositide binding Phox Homology domain of Sorting Nexin 15-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 have similarity to sorting nexin 15 (SNX15), which contains an N-terminal PX domain and a C-terminal Microtubule Interacting and Trafficking (MIT) 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. Other members of this subfamily contain an additional C-terminal kinase domain, similar to human RPK118, which binds sphingosine kinase and the antioxidant peroxiredoxin-3 (PRDX3). RPK118 may be involved in the transport of proteins such as PRDX3 from the cytoplasm to its site of function in the mitochondria.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543256  33 DVYDPQTIGVGrnrFTTYEVR-----------MRESVVRRRYSDFEWLKNELERDSKIV-----VPPLP-GKALKRqlpf 95
Cdd:cd06881    6 TVTDTRRHKKG---YTEYKITskvfsrsvpedVSEVVVWKRYSDFKKLHRELSRLHKQLylsgsFPPFPkGKYFGR---- 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 225543256  96 rgdegiFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQ 138
Cdd:cd06881   79 ------FDAAVIEERRQAILELLDFVGNHPALYQSSAFQQFFE 115

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 225543256  34 VYDPQTIGVGrnrFTTYEVRMR-----------ESVVRRRYSDFEWLKNELERDSKIVV------PPLPgkalkRQLPFr 96
Cdd:cd07288    7 VTDPRTHPKG---YTEYKVTAQfiskkqpedvkEVVVWKRYSDLKKLHGELAYTHRNLFrrqeefPPFP-----RAQVF- 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 225543256  97 gdeGIFEESFIEERRAGLEQFINRIAGHPLAQNERCLHMFLQD 139
Cdd:cd07288   78 ---GRFEAAVIEERRNAAEAMLLFTVNIPALYNSPQLKEFFRD 117

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 225543256  26 PSNFLEidvydpqtiGVGRNRFTTYEVRMR----ESVVRRRYSDFEWLKNELERDSKIV----VPPlpGKALkrqlpfrg 97
Cdd:cd07277    6 PSVFLR---------GKGSDAHHVYQVYIRirddEWNVYRRYSEFYELHKKLKKKFPVVrsfdFPP--KKAI-------- 66

                         90       100       110
                 ....*....|....*....|....*....|...
gi 225543256  98 deGIFEESFIEERRAGLEQFINRIAGHpLAQNE 130
Cdd:cd07277   67 --GNKDAKFVEERRKRLQVYLRRVVNT-LIQTS 96

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 225543256  59 VRRRYSDF----EWLKNELERDSKIvvpPLPGKALKRQLpfrgdegifEESFIEERRAGLEQFINRI------AGHPLAQ 128
Cdd:cd06873   43 VYRRYSDFhdlhMRLKEKFPNLSKL---SFPGKKTFNNL---------DRAFLEKRRKMLNQYLQSLlnpevlDANPGLQ 110

                 ....*....
gi 225543256 129 NerCLHMFL 137
Cdd:cd06873  111 E--IVLDFL 117