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 1371977046  12 SVWVRDPRIQKEDFWHSYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLFFNMNNRQHV 91
Cdd:cd06898     1 SVEVRDPRTHKEDDWGSYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRFNNEGFI 80

                          90
                  ....*....|....*...
gi 1371977046  92 DQRRQGLEDFLRKVLQNA 109
Cdd:cd06898    81 EERQQGLQDFLEKVLQTP 98

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 1371977046  12 SVWVRDPRIQKEDFWHSYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLFFNMNNRQHV 91
Cdd:cd06898     1 SVEVRDPRTHKEDDWGSYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRFNNEGFI 80

                          90
                  ....*....|....*...
gi 1371977046  92 DQRRQGLEDFLRKVLQNA 109
Cdd:cd06898    81 EERQQGLQDFLEKVLQTP 98

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 1371977046   27 HSYIDYEICIHTNSmcftmKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLF--FNMNNRQHVDQRRQGLEDFLRK 104
Cdd:smart00312  12 HYYYVIEIETKTGL-----EEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFgrLNNFSEEFIEKRRRGLEKYLQS 86

                   ....
gi 1371977046  105 VLQN 108
Cdd:smart00312  87 LLNH 90

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 1371977046  12 SVWVRDPRIQKEDFWHSYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLFFNMNNRQHV 91
Cdd:cd06898     1 SVEVRDPRTHKEDDWGSYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQKNALLIQLPSLPPKNLFGRFNNEGFI 80

                          90
                  ....*....|....*...
gi 1371977046  92 DQRRQGLEDFLRKVLQNA 109
Cdd:cd06898    81 EERQQGLQDFLEKVLQTP 98

PX domain; PX domains bind to phosphoinositides.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1371977046  40 SMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLFFNMnNRQHVDQRRQGLEDFLRKVLQN 108
Cdd:pfam00787   1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRY-NEEFIEKRRKGLEQYLQRLLQH 68

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 1371977046   27 HSYIDYEICIHTNSmcftmKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLF--FNMNNRQHVDQRRQGLEDFLRK 104
Cdd:smart00312  12 HYYYVIEIETKTGL-----EEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFgrLNNFSEEFIEKRRRGLEKYLQS 86

                   ....
gi 1371977046  105 VLQN 108
Cdd:smart00312  87 LLNH 90

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977046  10 FVSVWVRDPRIQKEDfWHSYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKnLFFNMNNRQ 89
Cdd:cd07295     1 FLEIEVRNPKTHGIG-RGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERESPRVMIPPLPGK-IFTNRFSDE 78

                          90
                  ....*....|....*.
gi 1371977046  90 HVDQRRQGLEDFLRKV 105
Cdd:cd07295    79 VIEERRQGLETFLQSV 94

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 1371977046  28 SYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLFFNMNNR---QHVDQRRQGLEDFLRK 104
Cdd:cd06860    17 TYITYRVTTKTTRSEFDSSEYSVRRRYQDFLWLRQKLEESHPTHIIPPLPEKHSVKGLLDRfspEFVATRMRALHKFLNR 96

                  ...
gi 1371977046 105 VLQ 107
Cdd:cd06860    97 IVE 99

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 1371977046  15 VRDPrIQKEDFWHSYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLF--FNMNnrqHVD 92
Cdd:cd06861     5 VGDP-HKVGDLTSAHTVYTVRTRTTSPNFEVSSFSVLRRYRDFRWLYRQLQNNHPGVIVPPPPEKQSVgrFDDN---FVE 80

                          90
                  ....*....|....*.
gi 1371977046  93 QRRQGLEDFLRKVLQN 108
Cdd:cd06861    81 QRRAALEKMLRKIANH 96

The phosphoinositide binding Phox Homology domain of SNX-like proteins; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. This subfamily is composed of uncharacterized proteins, predominantly from plants, with similarity to sorting nexins. A few members show a similar domain architecture as a subfamily of sorting nexins, containing a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit is known to determine specific membrane localization.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977046  13 VWVRDPRIQKEDFWH-----SYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLF--FNM 85
Cdd:cd06865     2 ITVSDPKKEQEPSRVplggpPYISYKVTTRTNIPSYTHGEFTVRRRFRDVVALADRLAEAYRGAFVPPRPDKSVVesQVM 81

                          90       100
                  ....*....|....*....|
gi 1371977046  86 NNRQHVDQRRQGLEDFLRKV 105
Cdd:cd06865    82 QSAEFIEQRRVALEKYLNRL 101

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 1371977046  28 SYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLFFNMNNR---QHVDQRRQGLEDFLRK 104
Cdd:cd07283    17 TYITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEESQPTHLIPPLPEKFVVKGVVDRfseEFVETRRKALDKFLKR 96

                  .
gi 1371977046 105 V 105
Cdd:cd07283    97 I 97

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977046  29 YIDYEICIHTNSMCFTMKTSC---VRRRYREFVWLRQRLQSNALLVQLPELPSK----NLFFNMNNRQHVDQRRQGLEDF 101
Cdd:COG5391   151 HTSYEIITVTNLPSFQLRESRplvVRRRYSDFESLHSILIKLLPLCAIPPLPSKksnsEYYGDRFSDEFIEERRQSLQNF 230

                  ....
gi 1371977046 102 LRKV 105
Cdd:COG5391   231 LRRV 234

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1371977046  37 HTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLFF--------NMNnRQHVDQRRQGLEDFLRKV 105
Cdd:cd06864    35 HESEEGLSKKLSSLWRRYSEFELLRNYLVVTYPYVIVPPLPEKRAMFmwqklssdTFD-PDFVERRRAGLENFLLRV 110

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 1371977046  28 SYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQLPELPSKNLFFNMNNR---QHVDQRRQGLEDFLRK 104
Cdd:cd07284    17 TFITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEAHPTLIIPPLPEKFVMKGMVERfneDFIETRRKALHKFLNR 96

                  .
gi 1371977046 105 V 105
Cdd:cd07284    97 I 97

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 1371977046  11 VSVWVRDPRiQKEDFWHSYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQSNALLVQL--PELPSKNLFF----- 83
Cdd:cd07282     1 IEIGVSDPE-KVGDGMNAYMAYRVTTKTSLSMFSRSEFSVRRRFSDFLGLHSKLASKYLHVGYivPPAPEKSIVGmtkvk 79

                          90       100
                  ....*....|....*....|....*....
gi 1371977046  84 ----NMNNRQHVDQRRQGLEDFLRKVLQN 108
Cdd:cd07282    80 vgkeDSSSTEFVEKRRAALERYLQRTVKH 108

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977046  11 VSVWVRDPRiQKEDFWHSYIDYEICIHTNSMCFTMKTSCVRRRYREFVWLRQRLQ----SNALLVQLPelPSKNLFF--- 83
Cdd:cd07281     1 LKVSITDPE-KIGDGMNAYVVYKVTTQTSLLMFRSKHFTVKRRFSDFLGLYEKLSekhsQNGFIVPPP--PEKSLIGmtk 77

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1371977046  84 ------NMNNRQHVDQRRQGLEDFLRKVLQN 108
Cdd:cd07281    78 vkvgkeDSSSAEFLERRRAALERYLQRIVSH 108

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 1371977046  28 SYIDYEIC-IHTNSMcftmktscVRRRYREFVWLRQRLQSNALLVQLPELPSKNL---FfnmnNRQHVDQRRQGLEDFLR 103
Cdd:cd06862    19 SFIAYQITpTHTNVT--------VSRRYKHFDWLYERLVEKYSCIAIPPLPEKQVtgrF----EEDFIEKRRERLELWMN 86

                  ....
gi 1371977046 104 KVLQ 107
Cdd:cd06862    87 RLAR 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1371977046  50 VRRRYREFVWLRQRLQSNALLVQLPELPSKNLFFNMNnRQHVDQRRQGLEDFLRKVLQN 108
Cdd:cd07277    34 VYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKD-AKFVEERRKRLQVYLRRVVNT 91

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; 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. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1371977046  49 CVRRRYREFVWLRQRLQSnalLVQLPELPSKNLffnMNNRQHV-DQRRQGLEDFLRKVL 106
Cdd:cd06880    34 TVEKRYSEFHALHKKLKK---SIKTPDFPPKRV---RNWNPKVlEQRRQGLEAYLQGLL 86

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1371977046  50 VRRRYREFVWLRQRLQSNALLVQLPELPSKNLFFnmnNRQHVDQRRQGLEDFLRKVLQNA 109
Cdd:cd06868    49 VSKKYSEFEELYKKLSEKYPGTILPPLPRKALFV---SESDIRERRAAFNDFMRFISKDE 105

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.

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gi 1371977046  50 VRRRYREFVWLrqrlqSNALLVQLP----ELPSKNLFFNMNNRQHVDQRRQGLEDFLRKVL 106
Cdd:cd06870    36 VFRRYAEFDKL-----YESLKKQFPasnlKIPGKRLFGNNFDPDFIKQRRAGLDEFIQRLV 91