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{
"metadata": {
"accession": "IPR036871",
"entry_id": null,
"type": "homologous_superfamily",
"go_terms": [
{
"identifier": "GO:0035091",
"name": "phosphatidylinositol binding",
"category": {
"code": "F",
"name": "molecular_function"
}
}
],
"source_database": "interpro",
"member_databases": {
"cathgene3d": {
"G3DSA:3.30.1520.10": "Phox-like domain"
},
"ssf": {
"SSF64268": "PX domain"
}
},
"integrated": null,
"hierarchy": {
"accession": "IPR036871",
"name": "PX domain superfamily",
"type": "Homologous_superfamily",
"children": []
},
"name": {
"name": "PX domain superfamily",
"short": "PX_dom_sf"
},
"description": [
{
"text": "<p>The PX (phox) domain [[cite:PUB00005042]] occurs in a variety of eukaryotic proteins and has been implicated in highly diverse functions, including cell signalling, vesicular trafficking, protein sorting and lipid modification [[cite:PUB00020791], [cite:PUB00020788], [cite:PUB00010010], [cite:PUB00084390]]. PX domains are important phosphoinositide-binding modules that exhibit varying lipid-binding specificities [[cite:PUB00007152]]. The PX domain is approximately 120 residues in length [[cite:PUB00008032]] and folds into a three-stranded β-sheet followed by three α-helices and a proline-rich region. This region immediately precedes a membrane-interaction loop and spans approximately eight hydrophobic and polar residues. The PX domain of neutrophil cytosol factor 1 (p47phox) binds to the SH3 domain within the same protein [[cite:PUB00008032]]. Phosphorylation of p47(phox), a cytoplasmic activator of the microbicidal phagocyte oxidase (phox), triggers interaction of p47(phox) with phosphoinositides. This phosphorylation-driven conformational change enables the PX domain to bind phosphoinositides, an interaction that plays a crucial role in the recruitment of p47(phox) from the cytoplasm to membranes and subsequent activation of the phagocyte oxidase. The lipid-binding activity of this protein is normally suppressed by intramolecular interaction between the PX domain and the C-terminal Src homology 3 (SH3) domain [[cite:PUB00011220]].</p>\n\n<p>The PX domain is conserved from yeast to humans. Multiple alignment of representative PX domain sequences from eukaryotic proteins [[cite:PUB00006581]] reveals relatively little sequence conservation, although the overall structure appears to be highly conserved. While phosphatidylinositol-3-phosphate (PtdIns(3)P) is the primary target of PX domains, binding to phosphatidic acid, phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2), phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2), phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) has also been reported. The PX domain additionally functions as a protein-protein interaction domain [[cite:PUB00020786]].</p>",
"llm": false,
"checked": false,
"updated": false
},
{
"text": "<p>This domain is found in Sorting nexin and related proteins. Sorting nexins (SNXs) are a diverse family of proteins characterised by the presence of a phosphoinositide-binding PX domain, which mediates their association with endosomal membranes. They play essential roles in membrane trafficking, endosomal sorting and signal transduction across eukaryotes.</p>\n\n<p>SNX1 functions in retrograde transport from endosomes to the trans-Golgi network as a core component of the retromer complex, facilitating the retrieval of cargo receptors such as the cation-independent mannose-6-phosphate receptor [[cite:PUB00068936]].</p>\n\n<p>SNX2 shares functional similarity with SNX1 and also participates in retromer-mediated retrograde trafficking, with partial redundancy between the two proteins in endosome-to-Golgi transport [[cite:PUB00068936]].</p>\n\n<p>SNX3 is a smaller sorting nexin that regulates the recycling of specific cargo proteins, including Wntless, which is essential for Wnt secretion [[cite:PUB00163290], [cite:PUB00163291]], and transferrin receptor, thereby contributing to iron homeostasis [[cite:PUB00163292]].</p>\n\n<p>SNX4 is involved in endosomal recycling pathways, where it promotes transferrin receptor recycling and prevents its degradation [[cite:PUB00084407]], and additionally participates in autophagosome assembly by regulating the trafficking of the phospholipid scramblase ATG9A [[cite:PUB00101856], [cite:PUB00163293]].</p>",
"llm": false,
"checked": false,
"updated": false
}
],
"wikipedia": null,
"literature": {
"PUB00084390": {
"PMID": 16782399,
"ISBN": null,
"volume": "1761",
"issue": "8",
"year": 2006,
"title": "The Phox (PX) domain proteins and membrane traffic.",
"URL": null,
"raw_pages": "878-96",
"medline_journal": "Biochim Biophys Acta",
"ISO_journal": "Biochim. Biophys. Acta",
"authors": [
"Seet LF",
"Hong W."
],
"DOI_URL": "http://dx.doi.org/10.1016/j.bbalip.2006.04.011"
},
"PUB00020788": {
"PMID": 11736640,
"ISBN": null,
"volume": "360",
"issue": "Pt 3",
"year": 2001,
"title": "The Phox homology (PX) domain, a new player in phosphoinositide signalling.",
"URL": null,
"raw_pages": "513-30",
"medline_journal": "Biochem J",
"ISO_journal": "Biochem. J.",
"authors": [
"Xu Y",
"Seet LF",
"Hanson B",
"Hong W."
],
"DOI_URL": "http://dx.doi.org/10.1042/0264-6021:3600513"
},
"PUB00020786": {
"PMID": 15263065,
"ISBN": null,
"volume": "3",
"issue": "11",
"year": 2004,
"title": "The phox homology (PX) domain protein interaction network in yeast.",
"URL": null,
"raw_pages": "1053-64",
"medline_journal": "Mol Cell Proteomics",
"ISO_journal": "Mol. Cell Proteomics",
"authors": [
"Vollert CS",
"Uetz P."
],
"DOI_URL": "http://dx.doi.org/10.1074/mcp.M400081-MCP200"
},
"PUB00020791": {
"PMID": 10782093,
"ISBN": null,
"volume": "25",
"issue": "5",
"year": 2000,
"title": "Phosphoinositide signaling and the regulation of membrane trafficking in yeast.",
"URL": null,
"raw_pages": "229-35",
"medline_journal": "Trends Biochem Sci",
"ISO_journal": "Trends Biochem. Sci.",
"authors": [
"Odorizzi G",
"Babst M",
"Emr SD."
],
"DOI_URL": "http://dx.doi.org/10.1016/S0968-0004(00)01543-7"
},
"PUB00007152": {
"PMID": 11884510,
"ISBN": null,
"volume": "115",
"issue": "Pt 6",
"year": 2002,
"title": "The PX domain: a new phosphoinositide-binding module.",
"URL": null,
"raw_pages": "1099-105",
"medline_journal": "J Cell Sci",
"ISO_journal": "J. Cell. Sci.",
"authors": [
"Ellson CD",
"Andrews S",
"Stephens LR",
"Hawkins PT."
],
"DOI_URL": "http://jcs.biologists.org/cgi/content/abstract/115/6/1099"
},
"PUB00006581": {
"PMID": 9687503,
"ISBN": null,
"volume": "17",
"issue": "15",
"year": 1998,
"title": "A new method for isolating tyrosine kinase substrates used to identify fish, an SH3 and PX domain-containing protein, and Src substrate.",
"URL": null,
"raw_pages": "4346-57",
"medline_journal": "EMBO J",
"ISO_journal": "EMBO J.",
"authors": [
"Lock P",
"Abram CL",
"Gibson T",
"Courtneidge SA."
],
"DOI_URL": "http://dx.doi.org/10.1093/emboj/17.15.4346"
},
"PUB00010010": {
"PMID": 12461558,
"ISBN": null,
"volume": "3",
"issue": "12",
"year": 2002,
"title": "Sorting out the cellular functions of sorting nexins.",
"URL": null,
"raw_pages": "919-31",
"medline_journal": "Nat Rev Mol Cell Biol",
"ISO_journal": "Nat. Rev. Mol. Cell Biol.",
"authors": [
"Worby CA",
"Dixon JE."
],
"DOI_URL": "http://dx.doi.org/10.1038/nrm974"
},
"PUB00011220": {
"PMID": 12356722,
"ISBN": null,
"volume": "21",
"issue": "19",
"year": 2002,
"title": "Binding of the PX domain of p47(phox) to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction.",
"URL": null,
"raw_pages": "5057-68",
"medline_journal": "EMBO J",
"ISO_journal": "EMBO J.",
"authors": [
"Karathanassis D",
"Stahelin RV",
"Bravo J",
"Perisic O",
"Pacold CM",
"Cho W",
"Williams RL."
],
"DOI_URL": "http://dx.doi.org/10.1093/emboj/cdf519"
},
"PUB00008032": {
"PMID": 11373621,
"ISBN": null,
"volume": "8",
"issue": "6",
"year": 2001,
"title": "Solution structure of the PX domain, a target of the SH3 domain.",
"URL": null,
"raw_pages": "526-30",
"medline_journal": "Nat Struct Biol",
"ISO_journal": "Nat. Struct. Biol.",
"authors": [
"Hiroaki H",
"Ago T",
"Ito T",
"Sumimoto H",
"Kohda D."
],
"DOI_URL": "http://dx.doi.org/10.1038/88591"
},
"PUB00005042": {
"PMID": 8931154,
"ISBN": null,
"volume": "5",
"issue": "11",
"year": 1996,
"title": "Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains?",
"URL": null,
"raw_pages": "2353-7",
"medline_journal": "Protein Sci",
"ISO_journal": "Protein Sci.",
"authors": [
"Ponting CP."
],
"DOI_URL": "http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=EBI&pubmedid=8931154&action=stream&blobtype=pdf"
},
"PUB00068936": {
"PMID": 17101778,
"ISBN": null,
"volume": "27",
"issue": "3",
"year": 2007,
"title": "Interchangeable but essential functions of SNX1 and SNX2 in the association of retromer with endosomes and the trafficking of mannose 6-phosphate receptors.",
"URL": null,
"raw_pages": "1112-24",
"medline_journal": "Mol Cell Biol",
"ISO_journal": "Mol. Cell. Biol.",
"authors": [
"Rojas R",
"Kametaka S",
"Haft CR",
"Bonifacino JS."
],
"DOI_URL": "http://dx.doi.org/10.1128/MCB.00156-06"
},
"PUB00084407": {
"PMID": 17994011,
"ISBN": null,
"volume": "9",
"issue": "12",
"year": 2007,
"title": "SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment.",
"URL": null,
"raw_pages": "1370-80",
"medline_journal": "Nat Cell Biol",
"ISO_journal": "Nat. Cell Biol.",
"authors": [
"Traer CJ",
"Rutherford AC",
"Palmer KJ",
"Wassmer T",
"Oakley J",
"Attar N",
"Carlton JG",
"Kremerskothen J",
"Stephens DJ",
"Cullen PJ."
],
"DOI_URL": "http://dx.doi.org/10.1038/ncb1656"
},
"PUB00101856": {
"PMID": 32513819,
"ISBN": null,
"volume": "133",
"issue": "14",
"year": 2020,
"title": "A heterodimeric SNX4--SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly.",
"URL": null,
"raw_pages": "jcs246306",
"medline_journal": "J Cell Sci",
"ISO_journal": "J Cell Sci",
"authors": [
"Anton Z",
"Betin VMS",
"Simonetti B",
"Traer CJ",
"Attar N",
"Cullen PJ",
"Lane JD."
],
"DOI_URL": null
},
"PUB00163290": {
"PMID": 21725319,
"ISBN": null,
"volume": "13",
"issue": "8",
"year": 2011,
"title": "A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion.",
"URL": null,
"raw_pages": "914-923",
"medline_journal": "Nat Cell Biol",
"ISO_journal": "Nat Cell Biol",
"authors": [
"Harterink M",
"Port F",
"Lorenowicz MJ",
"McGough IJ",
"Silhankova M",
"Betist MC",
"van Weering JRT",
"van Heesbeen RGHP",
"Middelkoop TC",
"Basler K",
"Cullen PJ",
"Korswagen HC."
],
"DOI_URL": "https://doi.org/10.1038/ncb2281"
},
"PUB00163291": {
"PMID": 22041890,
"ISBN": null,
"volume": "21",
"issue": "12",
"year": 2011,
"title": "SNX3 controls Wingless/Wnt secretion through regulating retromer-dependent recycling of Wntless.",
"URL": null,
"raw_pages": "1677-90",
"medline_journal": "Cell Res",
"ISO_journal": "Cell Res",
"authors": [
"Zhang P",
"Wu Y",
"Belenkaya TY",
"Lin X."
],
"DOI_URL": "https://doi.org/10.1038/cr.2011.167"
},
"PUB00163292": {
"PMID": 23416069,
"ISBN": null,
"volume": "17",
"issue": "3",
"year": 2013,
"title": "Snx3 regulates recycling of the transferrin receptor and iron assimilation.",
"URL": null,
"raw_pages": "343-52",
"medline_journal": "Cell Metab",
"ISO_journal": "Cell Metab",
"authors": [
"Chen C",
"Garcia-Santos D",
"Ishikawa Y",
"Seguin A",
"Li L",
"Fegan KH",
"Hildick-Smith GJ",
"Shah DI",
"Cooney JD",
"Chen W",
"King MJ",
"Yien YY",
"Schultz IJ",
"Anderson H",
"Dalton AJ",
"Freedman ML",
"Kingsley PD",
"Palis J",
"Hattangadi SM",
"Lodish HF",
"Ward DM",
"Kaplan J",
"Maeda T",
"Ponka P",
"Paw BH."
],
"DOI_URL": "https://doi.org/10.1016/j.cmet.2013.01.013"
},
"PUB00163293": {
"PMID": 33468622,
"ISBN": null,
"volume": "134",
"issue": "3",
"year": 2021,
"title": "The phosphatidylinositol 3-phosphate-binding protein SNX4 controls ATG9A recycling and autophagy.",
"URL": null,
"raw_pages": "jcs250670",
"medline_journal": "J Cell Sci",
"ISO_journal": "J Cell Sci",
"authors": [
"Ravussin A",
"Brech A",
"Tooze SA",
"Stenmark H."
],
"DOI_URL": "https://doi.org/10.1242/jcs.250670"
}
},
"set_info": null,
"overlaps_with": [
{
"accession": "IPR001683",
"name": "Phox homology",
"type": "domain"
},
{
"accession": "IPR035550",
"name": "Bem1/Scd2, PX domain",
"type": "domain"
},
{
"accession": "IPR035704",
"name": "SNX8/Mvp1, PX domain",
"type": "domain"
},
{
"accession": "IPR034902",
"name": "Sorting nexin 4, PX domain",
"type": "domain"
},
{
"accession": "IPR034909",
"name": "Neutrophil cytosol factor 1, PX domain",
"type": "domain"
},
{
"accession": "IPR001655",
"name": "Neutrophil cytosol factor 1",
"type": "family"
},
{
"accession": "IPR034912",
"name": "Neutrophil cytosol factor 4, PX domain",
"type": "domain"
},
{
"accession": "IPR000919",
"name": "Neutrophil cytosol factor P40",
"type": "family"
},
{
"accession": "IPR035703",
"name": "SNX18, PX domain",
"type": "domain"
},
{
"accession": "IPR034901",
"name": "Sorting Nexin 1, PX domain",
"type": "domain"
},
{
"accession": "IPR037907",
"name": "Vps17, PX domain",
"type": "domain"
},
{
"accession": "IPR042138",
"name": "Fungal SNX3, PX domain",
"type": "domain"
},
{
"accession": "IPR051074",
"name": "Sorting Nexin",
"type": "family"
},
{
"accession": "IPR044106",
"name": "Snx41 /Atg20, PX domain",
"type": "domain"
},
{
"accession": "IPR037833",
"name": "SNX27, PX domain",
"type": "domain"
},
{
"accession": "IPR037917",
"name": "Ypt35, PX domain",
"type": "domain"
},
{
"accession": "IPR037868",
"name": "Vacuolar protein sorting-associated protein 5, PX domain",
"type": "domain"
},
{
"accession": "IPR037437",
"name": "Sorting nexin-13, PX domain",
"type": "domain"
},
{
"accession": "IPR037916",
"name": "SNX29, PX domain",
"type": "domain"
},
{
"accession": "IPR043544",
"name": "Sorting nexin-10/11",
"type": "family"
},
{
"accession": "IPR037911",
"name": "SNX16, PX domain",
"type": "domain"
},
{
"accession": "IPR037900",
"name": "CISK, PX domain",
"type": "domain"
},
{
"accession": "IPR037899",
"name": "SNX25, PX domain",
"type": "domain"
},
{
"accession": "IPR052467",
"name": "Sorting nexin PX domain-containing protein",
"type": "family"
},
{
"accession": "IPR037904",
"name": "Nischarin, PX domain",
"type": "domain"
},
{
"accession": "IPR037903",
"name": "MONaKA, PX domain",
"type": "domain"
},
{
"accession": "IPR037436",
"name": "Sorting nexin-14, PX domain",
"type": "domain"
},
{
"accession": "IPR040288",
"name": "PX domain-containing protein 1",
"type": "family"
},
{
"accession": "IPR037961",
"name": "SH3PXD2, PX domain",
"type": "domain"
},
{
"accession": "IPR042136",
"name": "SNX6, PX domain",
"type": "domain"
},
{
"accession": "IPR037426",
"name": "Sorting nexin-9, PX domain",
"type": "domain"
},
{
"accession": "IPR037909",
"name": "SNX19, PX domain",
"type": "domain"
},
{
"accession": "IPR037901",
"name": "HCLS1-binding protein 3, PX domain",
"type": "domain"
},
{
"accession": "IPR042133",
"name": "Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha, PX domain",
"type": "domain"
},
{
"accession": "IPR042130",
"name": "SNX7, PX domain",
"type": "domain"
},
{
"accession": "IPR037918",
"name": "SNX2, PX domain",
"type": "domain"
},
{
"accession": "IPR042134",
"name": "Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta, PX domain",
"type": "domain"
},
{
"accession": "IPR042139",
"name": "Rho GTPase-activating protein 32, PX domain",
"type": "domain"
},
{
"accession": "IPR042132",
"name": "Ribosomal protein S6 kinase delta-1, PX domain",
"type": "domain"
},
{
"accession": "IPR042135",
"name": "SNX5, PX domain",
"type": "domain"
},
{
"accession": "IPR042137",
"name": "Vertebrate SNX3, PX domain",
"type": "domain"
}
],
"counters": {
"subfamilies": 0,
"domain_architectures": 0,
"interactions": 0,
"matches": 122702,
"pathways": 116,
"proteins": 122265,
"proteomes": 3395,
"sets": 0,
"structural_models": {
"alphafold": 101259,
"bfvd": 0
},
"structures": 87,
"taxa": 14506
},
"entry_annotations": {},
"cross_references": {},
"is_llm": false,
"is_reviewed_llm": false,
"is_updated_llm": false,
"representative_structure": {
"accession": "1kq6",
"name": "p47phox PX domain"
}
}
}
