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 23238248 105 DRPSTPTILGYEVMEERAKFT-----------------------------LKEMFPGFRLALPPKRWFKDNYNADFLEDR 155
Cdd:cd07276   1 DRPIRPPILGYEVMEERARFTvykirvenkvgdswfvfrrytdfvrlndkLKQMFPGFRLSLPPKRWFKDNFDPDFLEER 80

                        90       100       110
                ....*....|....*....|....*....|
gi 23238248 156 QLGLQAFLQNLVAHKDIANCLAVREFLCLD 185
Cdd:cd07276  81 QLGLQAFVNNIMAHKDIAKCKLVREFFCLD 110

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23238248 105 DRPSTPTILGYEVMEERAKFT-----------------------------LKEMFPGFRLALPPKRWFKDNYNADFLEDR 155
Cdd:cd07276   1 DRPIRPPILGYEVMEERARFTvykirvenkvgdswfvfrrytdfvrlndkLKQMFPGFRLSLPPKRWFKDNFDPDFLEER 80

                        90       100       110
                ....*....|....*....|....*....|
gi 23238248 156 QLGLQAFLQNLVAHKDIANCLAVREFLCLD 185
Cdd:cd07276  81 QLGLQAFVNNIMAHKDIAKCKLVREFFCLD 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 23238248    126 LKEMFPGFRL-ALPPKRWF--KDNYNADFLEDRQLGLQAFLQNLVAHKDIAN-CLAVREFL 182
Cdd:smart00312  44 LKKHFPRSILpPLPGKKLFgrLNNFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFL 104

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23238248 105 DRPSTPTILGYEVMEERAKFT-----------------------------LKEMFPGFRLALPPKRWFKDNYNADFLEDR 155
Cdd:cd07276   1 DRPIRPPILGYEVMEERARFTvykirvenkvgdswfvfrrytdfvrlndkLKQMFPGFRLSLPPKRWFKDNFDPDFLEER 80

                        90       100       110
                ....*....|....*....|....*....|
gi 23238248 156 QLGLQAFLQNLVAHKDIANCLAVREFLCLD 185
Cdd:cd07276  81 QLGLQAFVNNIMAHKDIAKCKLVREFFCLD 110

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 23238248 125 TLKEMFPGFRLALPPKRWFKDNYNADFLEDRQLGLQAFLQNLVAHKDIANCLAVREFLCLD 185
Cdd:cd06870  49 SLKKQFPASNLKIPGKRLFGNNFDPDFIKQRRAGLDEFIQRLVSDPKLLNHPDVRAFLQMD 109

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 23238248 125 TLKEMFPGFRLA----LPPKRWFKD---NYNADFLEDRQLGLQAFLQNLVAHKDIANCLAVREFL 182
Cdd:cd07280  54 ALLDEFPRHKRNeipqLPPKVPWYDsrvNLNKAWLEKRRRGLQYFLNCVLLNPVFGGSPVVKEFL 118

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 23238248    126 LKEMFPGFRL-ALPPKRWF--KDNYNADFLEDRQLGLQAFLQNLVAHKDIAN-CLAVREFL 182
Cdd:smart00312  44 LKKHFPRSILpPLPGKKLFgrLNNFSEEFIEKRRRGLEKYLQSLLNHPELINhSEVVLEFL 104

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. 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. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 23238248 120 ERAKFTLKEMfPGFRLALPPKRWFKDNYNADFLEDRQLGLQAFLQNLVAHKDIANCLAVREFL 182
Cdd:cd06872  43 ETLHRRLKEV-PKYNLELPPKRFLSSSLDGAFIEERCKLLDKYLKDLLVIEKVAESHEVWSFL 104

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 23238248 126 LKEMFPGFR-LALPPKRWFKdNYNADFLEDRQLGLQAFLQNLVAHKDIANCLAVREFLC 183
Cdd:cd06873  57 LKEKFPNLSkLSFPGKKTFN-NLDRAFLEKRRKMLNQYLQSLLNPEVLDANPGLQEIVL 114

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23238248   202 ETLEETNYRLQKELLEKQKEMESLKKLLSEKQLHIDTLENRIRTLSLEPEESLDVSETEGEQILKVESSALEVDQDVLD- 280
Cdd:TIGR04523 352 TNSESENSEKQRELEEKQNEIEKLKKENQSYKQEIKNLESQINDLESKIQNQEKLNQQKDEQIKKLQQEKELLEKEIERl 431

                          90       100
                  ....*....|....*....|....*..
gi 23238248   281 EESRADNKPCLSFSEPENAVSEIEVAE 307
Cdd:TIGR04523 432 KETIIKNNSEIKDLTNQDSVKELIIKN 458

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23238248 123 KFTLKEMFPGFRLALPPKRWF----------KDNYNADFLEDRQLGLQAFLQNLVAHKDIANCLAVREFL 182
Cdd:cd07281  52 KLSEKHSQNGFIVPPPPEKSLigmtkvkvgkEDSSSAEFLERRRAALERYLQRIVSHPSLLQDPDVREFL 121

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 23238248 126 LKEMFPGFRLALPPKRwfkdnyNADFLEDRQLGLQAFLQNLVAHKDIANCLAVREFL 182
Cdd:cd06869  66 LKKEFPGKKLPKLPHK------DKLPREKLRLSLRQYLRSLLKDPEVAHSSILQEFL 116