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 40889191  35 FLEIEVHNPKTHIPNgmdsKGMFTDYEIICRTNLPSFHKRVSKVRRRYSDFEFFRK*LIKEIsmlnhPKVMVPHLPGKIL 114
Cdd:cd07295   1 FLEIEVRNPKTHGIG----RGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERES-----PRVMIPPLPGKIF 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 40889191 115 LsNRFSNEVIEERRQGLNTWMQSVAGHPLLQSGSKVLVRFIEAEKF 160
Cdd:cd07295  72 T-NRFSDEVIEERRQGLETFLQSVAGHPLLQTGSKVLAAFLQDPKF 116

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 40889191  35 FLEIEVHNPKTHIPNgmdsKGMFTDYEIICRTNLPSFHKRVSKVRRRYSDFEFFRK*LIKEIsmlnhPKVMVPHLPGKIL 114
Cdd:cd07295   1 FLEIEVRNPKTHGIG----RGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERES-----PRVMIPPLPGKIF 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 40889191 115 LsNRFSNEVIEERRQGLNTWMQSVAGHPLLQSGSKVLVRFIEAEKF 160
Cdd:cd07295  72 T-NRFSDEVIEERRQGLETFLQSVAGHPLLQTGSKVLAAFLQDPKF 116

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 40889191     51 MDSKGMFTDYEIICRTNLPSFHkrvskVRRRYSDFEFFRK*LIKEismlnHPKVMVPHLPGKILLS--NRFSNEVIEERR 128
Cdd:smart00312   8 GDGKHYYYVIEIETKTGLEEWT-----VSRRYSDFLELHSKLKKH-----FPRSILPPLPGKKLFGrlNNFSEEFIEKRR 77

                           90       100
                   ....*....|....*....|....*...
gi 40889191    129 QGLNTWMQSVAGHPLLQSGSKVLVRFIE 156
Cdd:smart00312  78 RGLEKYLQSLLNHPELINHSEVVLEFLE 105

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 40889191  35 FLEIEVHNPKTHIPNgmdsKGMFTDYEIICRTNLPSFHKRVSKVRRRYSDFEFFRK*LIKEIsmlnhPKVMVPHLPGKIL 114
Cdd:cd07295   1 FLEIEVRNPKTHGIG----RGMFTDYEIVCRTNIPAFKLRVSSVRRRYSDFEYFRDILERES-----PRVMIPPLPGKIF 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 40889191 115 LsNRFSNEVIEERRQGLNTWMQSVAGHPLLQSGSKVLVRFIEAEKF 160
Cdd:cd07295  72 T-NRFSDEVIEERRQGLETFLQSVAGHPLLQTGSKVLAAFLQDPKF 116

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40889191   1 MPREFKSFGSTEKSLLSKGHGEPSYSEIYAEPENFLEIEVHNPKTHIPNgMDSKGMFTDYEIICRTNLPSFHKRVS---K 77
Cdd:COG5391  96 SRASEFRSLRDMLSLLLPTSLQPPLSTSHTILDYFISSTVSNPQSLTLL-VDSRDKHTSYEIITVTNLPSFQLRESrplV 174

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40889191  78 VRRRYSDFEFFRK*LIKeismlNHPKVMVPHLPGKILLSN----RFSNEVIEERRQGLNTWMQSVAGHPLL--------- 144
Cdd:COG5391 175 VRRRYSDFESLHSILIK-----LLPLCAIPPLPSKKSNSEyygdRFSDEFIEERRQSLQNFLRRVSTHPLLsnyknsksw 249

                       170
                ....*....|....*...
gi 40889191 145 QSGSKVLVRFIEAEKFVG 162
Cdd:COG5391 250 ESHSTLLSSFIENRKSVP 267

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 40889191     51 MDSKGMFTDYEIICRTNLPSFHkrvskVRRRYSDFEFFRK*LIKEismlnHPKVMVPHLPGKILLS--NRFSNEVIEERR 128
Cdd:smart00312   8 GDGKHYYYVIEIETKTGLEEWT-----VSRRYSDFLELHSKLKKH-----FPRSILPPLPGKKLFGrlNNFSEEFIEKRR 77

                           90       100
                   ....*....|....*....|....*...
gi 40889191    129 QGLNTWMQSVAGHPLLQSGSKVLVRFIE 156
Cdd:smart00312  78 RGLEKYLQSLLNHPELINHSEVVLEFLE 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 40889191  34 NFLEIEVHNPKThIPNGmdsKGMFTDYEIICRTNLPSFHKRVSKVRRRYSDFEFFRK*LIKEismlnhPKVMVPHLPGKI 113
Cdd:cd07294   2 NFLEIDIFNPQT-VGVG---RNRFTTYEVRMRTNLPIFKLKESCVRRRYSDFEWLKNELERD------SKIVVPPLPGKA 71

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 40889191 114 L---LSNR-----FSNEVIEERRQGLNTWMQSVAGHPLLQSgSKVLVRFIEAE 158
Cdd:cd07294  72 LkrqLPFRgdegiFEESFIEERRQGLEQFINKIAGHPLAQN-ERCLHMFLQDE 123

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 40889191  38 IEVHNPKTHIPngmDSKGMFTDYEIICRTNLPSFHKRVSKVRRRYSDFEFFRK*LIKeismlNHPKVMVPHLPGKILLSn 117
Cdd:cd06898   2 VEVRDPRTHKE---DDWGSYTDYEIFLHTNSMCFTLKTSCVRRRYSEFVWLRNRLQK-----NALLIQLPSLPPKNLFG- 72

                        90       100       110
                ....*....|....*....|....*....|..
gi 40889191 118 RFSNE-VIEERRQGLNTWMQSVAGHPLLQSGS 148
Cdd:cd06898  73 RFNNEgFIEERQQGLQDFLEKVLQTPLLLSDS 104

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 40889191  37 EIEVHNPKTHIpngmDSKGMFTDYEIICRTNlpsfHKRVSKVRRRYSDFEFFRK*LIKeismlNHPKVMVPHLPGKILLS 116
Cdd:cd06093   1 SVSIPDYEKVK----DGGKKYVVYIIEVTTQ----GGEEWTVYRRYSDFEELHEKLKK-----KFPGVILPPLPPKKLFG 67

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 40889191 117 NrFSNEVIEERRQGLNTWMQSVAGHPLLQSgSKVLVRFIE 156
Cdd:cd06093  68 N-LDPEFIEERRKQLEQYLQSLLNHPELRN-SEELKEFLE 105

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 40889191  39 EVHNPKTHIPNGMDSKGMFTDYEIICRTNlPSFHKRVSkVRRRYSDFEFFRK*LIKEISmlNHPKVMVPHLPGKILLSN- 117
Cdd:cd07280   4 DVNVGDYTIVGGDTGGGAYVVWKITIETK-DLIGSSIV-AYKRYSEFVQLREALLDEFP--RHKRNEIPQLPPKVPWYDs 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 40889191 118 --RFSNEVIEERRQGLNTWMQSVAGHPLLQsGSKVLVRFIEA 157
Cdd:cd07280  80 rvNLNKAWLEKRRRGLQYFLNCVLLNPVFG-GSPVVKEFLLP 120

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 40889191  38 IEVHNPKTHIpNGMDSkgmFTDYEIICRTNLPSFHKRVSKVRRRYSDFEFFRK*LIKEismlnHPKVMVPHLPGKILLS- 116
Cdd:cd07284   3 ITVDEPESHV-TAIET---FITYRVMTKTSRSEFDSSEFEVRRRYQDFLWLKGRLEEA-----HPTLIIPPLPEKFVMKg 73

                        90       100       110
                ....*....|....*....|....*....|..
gi 40889191 117 --NRFSNEVIEERRQGLNTWMQSVAGHPLLQS 146
Cdd:cd07284  74 mvERFNEDFIETRRKALHKFLNRIADHPTLTF 105

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40889191  36 LEIEVHNP-KTHIPNGMDSKGMFTDYEIICR----TNLPSFHKRVSKVRRRYSDFEFFRK*LIkeismLNHPKVMVPHLP 110
Cdd:cd06864   1 MEITVTEAeKRTGGSAMNLKETYTVYLIETKivehESEEGLSKKLSSLWRRYSEFELLRNYLV-----VTYPYVIVPPLP 75

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 40889191 111 GK-------ILLSNRFSNEVIEERRQGLNTWMQSVAGHPLL 144
Cdd:cd06864  76 EKramfmwqKLSSDTFDPDFVERRRAGLENFLLRVAGHPEL 116

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 40889191  36 LEIEVHNPKTHIPNgMDSkgmFTDYEIICRTNLPSFHKRVSKVRRRYSDFEFFRK*LIKeismlNHPKVMVPHLPGKILL 115
Cdd:cd07283   1 LFVTVDDPKKHVCT-MET---YITYRVTTKTTRTEFDLPEYSVRRRYQDFDWLRNKLEE-----SQPTHLIPPLPEKFVV 71

                        90       100       110
                ....*....|....*....|....*....|..
gi 40889191 116 S---NRFSNEVIEERRQGLNTWMQSVAGHPLL 144
Cdd:cd07283  72 KgvvDRFSEEFVETRRKALDKFLKRIADHPVL 103

The phosphoinositide binding Phox Homology domain of Sorting Nexin 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 40889191  76 SKVRRRYSDFEFFRK*LIKEIsmlnhPKVMVPHLPGKiLLSNRFSNEVIEERRQGLNTWMQSVAGHPLL 144
Cdd:cd07286  32 LQVHRRYKHFDWLYARLAEKF-----PVISVPHIPEK-QATGRFEEDFISKRRKGLIWWMDHMCSHPVL 94

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 40889191  36 LEIEVHNPKThIPNGMDSkgmFTDYEIICRTNLPSFHKRVSKVRRRYSDFEFFRK*LIKEISmlnHPKVMVPHLPGKILL 115
Cdd:cd07281   1 LKVSITDPEK-IGDGMNA---YVVYKVTTQTSLLMFRSKHFTVKRRFSDFLGLYEKLSEKHS---QNGFIVPPPPEKSLI 73

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 40889191 116 ---------SNRFSNEVIEERRQGLNTWMQSVAGHPLLQSGSKVLvRFIEAE 158
Cdd:cd07281  74 gmtkvkvgkEDSSSAEFLERRRAALERYLQRIVSHPSLLQDPDVR-EFLEKE 124

The phosphoinositide binding Phox Homology domain of fungal Sorting Nexins 41 and 42; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Some SNXs are localized in early endosome structures such as clathrin-coated pits, while others are located in late structures of the endocytic pathway. SNX41 and SNX42 (also called Atg20p) form dimers with SNX4, and are required in protein recycling from the sorting endosome (post-Golgi endosome) back to the late Golgi in yeast.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 40889191  76 SKVRRRYSDFEFFRK*LIKEismlnHPKVMVPHLPGK--IL------LSNRFSNEVIEERRQGLNTWMQSVAGHPLLqSG 147
Cdd:cd06867  28 SEVKRRYSEFESLRKNLTRL-----YPTLIIPPIPEKhsLKdyakkpSKAKNDAKIIERRKRMLQRFLNRCLQHPIL-RN 101

                        90
                ....*....|.
gi 40889191 148 SKVLVRFIEAE 158
Cdd:cd06867 102 DIVFQKFLDPN 112

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 40889191  46 HIPNGMDSKGMFTDYEIICRTNLpsfhkRVSKVRRRYSDFEFFRK*LIKEISmlnhpkVMVPH-LPGKILLSNRFSN-EV 123
Cdd:cd06897   4 SIPTTSVSPKPYTVYNIQVRLPL-----RSYTVSRRYSEFVALHKQLESEVG------IEPPYpLPPKSWFLSTSSNpKL 72

                        90
                ....*....|....
gi 40889191 124 IEERRQGLNTWMQS 137
Cdd:cd06897  73 VEERRVGLEAFLRA 86

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 40889191  52 DSKGMFTDYEIICRTNLPSFHkrvskVRRRYSDFEFFRK*LIKEISMLNHpkvmvpHLPGKILLSNRFSNEVIEERRQGL 131
Cdd:cd06870  15 EKKKRFTVYKVVVSVGRSSWF-----VFRRYAEFDKLYESLKKQFPASNL------KIPGKRLFGNNFDPDFIKQRRAGL 83

                        90
                ....*....|....*....
gi 40889191 132 NTWMQSVAGHPLLQSGSKV 150
Cdd:cd06870  84 DEFIQRLVSDPKLLNHPDV 102

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.

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gi 40889191  76 SKVRRRYSDFEFFRK*LIKEismlnHPKVMVP-HLPGKILLSNrFSNEVIEERRQGLNTWMQSVAGHPLLQSgSKVLVRF 154
Cdd:cd07279  36 AFIERRYSDFLKLYKALRKQ-----HPQLMAKvSFPRKVLMGN-FSSELIAERSRAFEQFLGHILSIPNLRD-SKAFLDF 108

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

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gi 40889191  40 VHNPKTHiPNGmdskgmFTDYE----IICRTNLPSFHKRVskVRRRYSDFEFFRK*LIK-EISMLNHPKVMVPHLPGKIL 114
Cdd:cd07287   7 VTDPRRH-PKG------YTVYKvtarIVSRKNPEDVQEIV--VWKRYSDFKKLHKDLWQiHKNLCRQSELFPPFAKAKVF 77

                        90       100       110
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gi 40889191 115 lsNRFSNEVIEERRQGLNTWMQSVAGHPLLQSGSKV 150
Cdd:cd07287  78 --GRFDESVIEERRQCAEDLLQFSANIPALYNSSQL 111

The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; 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. SNX27 contains an N-terminal PDZ domain followed by a PX domain and a Ras-Associated (RA) domain. It binds G protein-gated potassium (Kir3) channels, which play a role in neuronal excitability control, through its PDZ domain. SNX27 downregulates Kir3 channels by promoting their movement in the endosome, reducing surface expression and increasing degradation. SNX27 also associates with 5-hydroxytryptamine type 4 receptor (5-HT4R), cytohesin associated scaffolding protein (CASP), and diacylglycerol kinase zeta, and may play a role in their intracellular trafficking and endocytic recycling. The SNX27 PX domain preferentially binds to phosphatidylinositol-3-phosphate (PI3P) and is important for targeting to the early endosome.

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gi 40889191  80 RRYSDFEFFRK*LIKEISMLNHPKvmvphLPGKILLSnrFSNEVIEERRQGLNTWMQSV 138
Cdd:cd06886  36 RRYREFANLHQNLKKEFPDFQFPK-----LPGKWPFS--LSEQQLDARRRGLEQYLEKV 87

The phosphoinositide binding Phox Homology domain of the Imidazoline Receptor Antisera-Selected; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Imidazoline Receptor Antisera-Selected (IRAS), also called nischarin, contains an N-terminal PX domain, leucine rich repeats, and a predicted coiled coil domain. The PX domain of IRAS binds to phosphatidylinositol-3-phosphate in membranes. Together with the coiled coil domain, it is essential for the localization of IRAS to endosomes. IRAS has been shown to interact with integrin and inhibit cell migration. Its interaction with alpha5 integrin causes a redistribution of the receptor from the cell surface to endosomal structures, suggesting that IRAS may function as a sorting nexin (SNX) which regulates the endosomal trafficking of integrin. 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. 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.

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gi 40889191  77 KVRRRYSDFEFFRK*LIKEIsmlnhpKVMVPHLPGKILLSNRfSNEVIEERRQGLNTWMQSVAGhpLLQSG-SKVLVRFI 155
Cdd:cd06875  32 TVKHRYSDFAELHDKLVAEH------KVDKDLLPPKKLIGNK-SPSFVEKRRKELEIYLQTLLS--FFQKTmPRELAHFL 102

                ....*
gi 40889191 156 EAEKF 160
Cdd:cd06875 103 DFHKY 107