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 21357265  32 FLEIDVVNPLTTMAaGKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELERDSKIVVPPLPGKAWKRQMPFRGD 111
Cdd:cd06894   1 FLEIDVVNPQTHGV-GKKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSELERDSKIVVPPLPGKALKRQLPFRGD 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 21357265 112 EGIFDESFIEERRKGLEAFINKIAGHPLAQNERCLHMFLQENVI 155
Cdd:cd06894  80 DGIFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQEETI 123

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 21357265  32 FLEIDVVNPLTTMAaGKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELERDSKIVVPPLPGKAWKRQMPFRGD 111
Cdd:cd06894   1 FLEIDVVNPQTHGV-GKKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSELERDSKIVVPPLPGKALKRQLPFRGD 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 21357265 112 EGIFDESFIEERRKGLEAFINKIAGHPLAQNERCLHMFLQENVI 155
Cdd:cd06894  80 DGIFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQEETI 123

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21357265  19 KQTLDDAYAVPANFLEIDVVNPLTTM--AAGKKRYTDYEVRMRTNLPVF---KVKESSVRRRYSDFEWLRNELERDS-KI 92
Cdd:COG5391 117 QPPLSTSHTILDYFISSTVSNPQSLTllVDSRDKHTSYEIITVTNLPSFqlrESRPLVVRRRYSDFESLHSILIKLLpLC 196

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 21357265  93 VVPPLPGKAWKRQMPFRGdegiFDESFIEERRKGLEAFINKIAGHPLAQN 142
Cdd:COG5391 197 AIPPLPSKKSNSEYYGDR----FSDEFIEERRQSLQNFLRRVSTHPLLSN 242

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 21357265  32 FLEIDVVNPLTTMAaGKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELERDSKIVVPPLPGKAWKRQMPFRGD 111
Cdd:cd06894   1 FLEIDVVNPQTHGV-GKKRFTDYEVRMRTNLPVFKKKESSVRRRYSDFEWLRSELERDSKIVVPPLPGKALKRQLPFRGD 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 21357265 112 EGIFDESFIEERRKGLEAFINKIAGHPLAQNERCLHMFLQENVI 155
Cdd:cd06894  80 DGIFEEEFIEERRKGLETFINKVAGHPLAQNEKCLHMFLQEETI 123

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 21357265  32 FLEIDVVNPlTTMAAGKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELERDSKIVVPPLPGKAWKRQMPFRGD 111
Cdd:cd07293   1 FLEIDVTNP-QTVGVGRGRFTTYEIRLKTNLPIFKLKESTVRRRYSDFEWLRSELERESKVVVPPLPGKALFRQLPFRGD 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 21357265 112 EGIFDESFIEERRKGLEAFINKIAGHPLAQNERCLHMFLQENVI 155
Cdd:cd07293  80 DGIFDDSFIEERKQGLEQFLNKVAGHPLAQNERCLHMFLQDEII 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 21357265  33 LEIDVVNPlTTMAAGKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELERDSK-IVVPPLPGKawkrQMPfrgd 111
Cdd:cd06859   1 FEISVTDP-VKVGDGMSAYVVYRVTTKTNLPDFKKSEFSVLRRYSDFLWLYERLVEKYPgRIVPPPPEK----QAV---- 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 21357265 112 eGIFDES--FIEERRKGLEAFINKIAGHPLAQNERCLHMFLQ 151
Cdd:cd06859  72 -GRFKVKfeFIEKRRAALERFLRRIAAHPVLRKDPDFRLFLE 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 21357265  33 LEIDVVNPLTTMAAGKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELERD-SKIVVPPLPGKawKRQMPFRGD 111
Cdd:cd06863   1 LECLVSDPQKELDGSSDTYISYLITTKTNLPSFSRKEFKVRRRYSDFVFLHECLSNDfPACVVPPLPDK--HRLEYITGD 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 21357265 112 EgiFDESFIEERRKGLEAFINKIAGHPLAQNERCLHMFLQEN 153
Cdd:cd06863  79 R--FSPEFITRRAQSLQRFLRRISLHPVLSQSKILHQFLESS 118

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 21357265  33 LEIDVVNPlTTMAAGKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELERDSK-IVVPPLPGK-AWKRqmpfrg 110
Cdd:cd06861   1 FEITVGDP-HKVGDLTSAHTVYTVRTRTTSPNFEVSSFSVLRRYRDFRWLYRQLQNNHPgVIVPPPPEKqSVGR------ 73

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 21357265 111 degiFDESFIEERRKGLEAFINKIAGHPLAQNERCLHMFLQ 151
Cdd:cd06861  74 ----FDDNFVEQRRAALEKMLRKIANHPVLQKDPDFRLFLE 110

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 21357265     47 GKKRYTDYEVRMRTNLpvfkvKESSVRRRYSDFEWLRNELERD-SKIVVPPLPGKAWKrqmpfrGDEGIFDESFIEERRK 125
Cdd:smart00312  10 GKHYYYVIEIETKTGL-----EEWTVSRRYSDFLELHSKLKKHfPRSILPPLPGKKLF------GRLNNFSEEFIEKRRR 78

                           90       100
                   ....*....|....*....|....*..
gi 21357265    126 GLEAFINKIAGHP-LAQNERCLHMFLQ 151
Cdd:smart00312  79 GLEKYLQSLLNHPeLINHSEVVLEFLE 105

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 21357265  33 LEIDVVNP---LTTMAAgkkrYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELERDSK-IVVPPLPGKAWKRQMPF 108
Cdd:cd06860   1 LFITVDNPekhVTTLET----YITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPtHIIPPLPEKHSVKGLLD 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 21357265 109 RgdegiFDESFIEERRKGLEAFINKIAGHPLAQNERCLHMFL 150
Cdd:cd06860  77 R-----FSPEFVATRMRALHKFLNRIVEHPVLSFNEHLKVFL 113

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 21357265  51 YTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELER-DSKIVVPPLPGKAWKRQMPFRgdegiFDESFIEERRKGLEA 129
Cdd:cd07284  18 FITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEaHPTLIIPPLPEKFVMKGMVER-----FNEDFIETRRKALHK 92

                        90       100
                ....*....|....*....|.
gi 21357265 130 FINKIAGHPLAQNERCLHMFL 150
Cdd:cd07284  93 FLNRIADHPTLTFNEDFKIFL 113

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 21357265  51 YTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELERDSKI-VVPPLPGKawkrqMPFRGDEGIFDESFIEERRKGLEA 129
Cdd:cd07283  18 YITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEESQPThLIPPLPEK-----FVVKGVVDRFSEEFVETRRKALDK 92

                        90       100
                ....*....|....*....|.
gi 21357265 130 FINKIAGHPLAQNERCLHMFL 150
Cdd:cd07283  93 FLKRIADHPVLSFNEHFNVFL 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 21357265  50 RYTDYEVrmrtnlpVFKVKESSVRRRYSDFEWLRNEL-ERDSKIVVPPLPGKawkRQMpfrgdeGIFDESFIEERRKGLE 128
Cdd:cd06866  17 KHVEYEV-------SSKRFKSTVYRRYSDFVWLHEYLlKRYPYRMVPALPPK---RIG------GSADREFLEARRRGLS 80

                        90       100
                ....*....|....*....|..
gi 21357265 129 AFINKIAGHPLAQNERCLHMFL 150
Cdd:cd06866  81 RFLNLVARHPVLSEDELVRTFL 102

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 21357265  48 KKRYTDYEVRMRtnlpvFKVKESSVRRRYSDFEWLRNELERDSKIVVP-PLPGKAWKRQmpfrgdeGIFDESFIEERRKG 126
Cdd:cd06897  12 PKPYTVYNIQVR-----LPLRSYTVSRRYSEFVALHKQLESEVGIEPPyPLPPKSWFLS-------TSSNPKLVEERRVG 79

                        90       100
                ....*....|....*....|....*..
gi 21357265 127 LEAFINKIAGHPLA--QNERCLHMFLQ 151
Cdd:cd06897  80 LEAFLRALLNDEDSrwRNSPAVKEFLN 106

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 21357265  33 LEIDVVNPlTTMAAGKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNELErdSK-----IVVPPLPGKAWKRQMP 107
Cdd:cd07282   1 IEIGVSDP-EKVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLA--SKylhvgYIVPPAPEKSIVGMTK 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 21357265 108 FR-GDEGIFDESFIEERRKGLEAFINKIAGHPLAQNERCLHMFLQEN 153
Cdd:cd07282  78 VKvGKEDSSSTEFVEKRRAALERYLQRTVKHPTLLQDPDLRQFLESS 124

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 21357265  33 LEIDVVNPLTtmaagKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRN---ELERDSKIVVPPLP------GKAWK 103
Cdd:cd07291   3 LQIDIPDALS-----ERDKVKFTVHTKTTLPSFQSPDFSVTRQHEDFIWLHDaliETEDYAGLIIPPAPpkpdfdGPREK 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21357265 104 RQMPFRGDEGIFDESFIEERRKgLEA---------------FINKIAGHPLAQNERCLHMFLQ 151
Cdd:cd07291  78 MQKLGEGEGSMTKEEFAKMKQE-LEAeylavfkktvqvhevFLQRLSSHPSLSKDRNFHIFLE 139

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 21357265  47 GKKRYTDYEVRMRT-----------NLPVFKVKESSVRRRYSDFEWLRNELERDSKI--VVPPLPGKAWKRQMPFrgdeG 113
Cdd:cd06893  17 GTHPYTLYTVQYETildvqseqnpnAASEQPLATHTVNRRFREFLTLQTRLEENPKFrkIMNVKGPPKRLFDLPF----G 92

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 21357265 114 IFDESFIEERRKGLEAFINKIAGHPLAQNERCLHMFL 150
Cdd:cd06893  93 NMDKDKIEARRGLLETFLRQLCSIPEISNSEEVQEFL 129

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 21357265  35 IDVVNPLTTMAAGKKR--YTDYEVRMRTNLPVFK--------VKESSVRRRYSDFEWLRNEL-ERDSKIVVPPLPGKAWk 103
Cdd:cd06868   2 LDLTVPEYQEIRGKTSsgHVLYQIVVVTRLAAFKsakhkeedVVQFMVSKKYSEFEELYKKLsEKYPGTILPPLPRKAL- 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 21357265 104 rqmpFRGdegifdESFIEERRKGLEAFINKIAGHPLAQNERCLHMFL 150
Cdd:cd06868  81 ----FVS------ESDIRERRAAFNDFMRFISKDEKLANCPELLEFL 117

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 21357265  34 EIDVVNPLT---TMAAGKKRYTDYEVRMRTNlpVFKVKESSVRRRYSDFEWLRNELERdSKIVVPpLPGKAWKRQMpfrg 110
Cdd:cd06871   1 LLDDTVPLTcviEASQNIQSHTEYIIRVQRG--PSPENSWQVIRRYNDFDLLNASLQI-SGISLP-LPPKKLIGNM---- 72

                        90       100
                ....*....|....*....|....*....
gi 21357265 111 degifDESFIEERRKGLEAFINKIAGHPL 139
Cdd:cd06871  73 -----DREFIAERQQGLQNYLNVILMNPI 96

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 21357265  33 LEIDVVNPLTtmaagKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRN---ELERDSKIVVPPLPGK----AWKRQ 105
Cdd:cd07292   3 LQVDISDALS-----ERDKVKFTVHTKSSLPNFKQNEFSVVRQHEEFIWLHDsfvENEDYAGYIIPPAPPRpdfdASREK 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 21357265 106 MPFRGD-EGIFDESFIEERRKGLEA---------------FINKIAGHPLAQNERCLHMFLQEN 153
Cdd:cd07292  78 LQKLGEgEGSMTKEEFTKMKQELEAeylaifkktvamhevFLCRVAAHPILRKDLNFHVFLEYN 141

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 21357265  48 KKRYTDYEVrmrtnlpVFKVKESS--VRRRYSDFEWLRNELERDSKIVVPPLPGKAwkrqmpFRGDEgiFDESFIEERRK 125
Cdd:cd06870  17 KKRFTVYKV-------VVSVGRSSwfVFRRYAEFDKLYESLKKQFPASNLKIPGKR------LFGNN--FDPDFIKQRRA 81

                        90       100
                ....*....|....*....|....*...
gi 21357265 126 GLEAFINKIAGHPLAQNERCLHMFLQEN 153
Cdd:cd06870  82 GLDEFIQRLVSDPKLLNHPDVRAFLQMD 109

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 21357265  47 GKKRYTDYEVRMRTNlpvfkvkESSVRRRYSDFEWLRNEL--ERDSKIVVPPLPGKAWKrqmpfrgdeGIFDESFIEERR 124
Cdd:cd07285  16 GLKSYIEYQLTPTNT-------NRSVNHRYKHFDWLYERLlvKFGLAIPIPSLPDKQVT---------GRFEEEFIKMRM 79

                        90       100
                ....*....|....*....|....*.
gi 21357265 125 KGLEAFINKIAGHPLAQNERCLHMFL 150
Cdd:cd07285  80 ERLQAWMTRMCRHPVISESEVFQQFL 105

The phosphoinositide binding Phox Homology domain of Sorting Nexins 20 and 21; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. This subfamily consists of SNX20, SNX21, and similar proteins. SNX20 interacts with P-Selectin glycoprotein ligand-1 (PSGL-1), a surface-expressed mucin that acts as a ligand for the selectin family of adhesion proteins. It may function in the sorting and cycling of PSGL-1 into endosomes. SNX21, also called SNX-L, is distinctly and highly-expressed in fetal liver and may be involved in protein sorting and degradation during embryonic liver development.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21357265  43 TMAAGKKRYTDYEVRMRTNlPVFKVKESSVRRRYSDFEWLRNELERDskivvppLPGKAWKRQMPFRGDEGIFDESFIEE 122
Cdd:cd07279  10 TVKEGEKKYVVYQLAVVQT-GDPDTQPAFIERRYSDFLKLYKALRKQ-------HPQLMAKVSFPRKVLMGNFSSELIAE 81

                        90       100
                ....*....|....*....|....*....
gi 21357265 123 RRKGLEAFINKIAGHPLAQNERCLHMFLQ 151
Cdd:cd07279  82 RSRAFEQFLGHILSIPNLRDSKAFLDFLQ 110

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 21357265  47 GKKRYTDYEVRMRTNLPVFKVKESSVRRRYSDFEWLRNEL-ERDSKIVVPPLPGKAWKRQMpfrgdegifDESFIEERRK 125
Cdd:cd06873  18 HGKTYAVYAISVTRIYPNGQEESWHVYRRYSDFHDLHMRLkEKFPNLSKLSFPGKKTFNNL---------DRAFLEKRRK 88

                        90       100       110
                ....*....|....*....|....*....|.
gi 21357265 126 GLEAFINKI------AGHPLAQNerCLHMFL 150
Cdd:cd06873  89 MLNQYLQSLlnpevlDANPGLQE--IVLDFL 117

The phosphoinositide binding Phox Homology domain of Phospholipase D1; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Phospholipase D (PLD) catalyzes the hydrolysis of the phosphodiester bond of phosphatidylcholine to generate membrane-bound phosphatidic acid and choline. PLDs are implicated in many cellular functions like signaling, cytoskeletal reorganization, vesicular transport, stress responses, and the control of differentiation, proliferation, and survival. PLD1 contains PX and Pleckstrin Homology (PH) domains in addition to the catalytic domain. It acts as an effector of Rheb in the signaling of the mammalian target of rapamycin (mTOR), a serine/threonine protein kinase that transduces nutrients and other stimuli to regulate many cellular processes. PLD1 also regulates the secretion of the procoagulant von Willebrand factor (VWF) in endothelial cells. 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 PLD1 specifically binds to phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3], which enables PLD1 to mediate signals via the ERK1/2 pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21357265  72 VRRRYSDFEWLRNELERDSKIVVPPLPGKAW-----------KRQMPF--RGDEGIFDESFIEERRKGLEAFINKIAGHP 138
Cdd:cd07296  41 VKRKFKHFQELHRELLRYKAFIRIPIPTRSHtvrrqtikrgePRHMPSlpRGAEEEAREEQFSSRRKQLEDYLSKLLKMP 120

                ....
gi 21357265 139 LAQN 142
Cdd:cd07296 121 MYRN 124