PX

PhoX homologous domain, present in p47phox and p40phox.
PX
SMART accession number:SM00312
Description: Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.
Interpro abstract (IPR001683):

The PX (phox) domain [(PUBMED:8931154)] occurs in a variety of eukaryotic proteins and have been implicated in highly diverse functions such as cell signalling, vesicular trafficking, protein sorting and lipid modification [(PUBMED:10782093), (PUBMED:11736640), (PUBMED:12461558)]. PX domains are important phosphoinositide-binding modules that have varying lipid-binding specificities [(PUBMED:11884510)]. The PX domain is approximately 120 residues long [(PUBMED:11373621)], and folds into a three-stranded beta-sheet followed by three -helices and a proline-rich region that immediately preceeds a membrane-interaction loop and spans approximately eight hydrophobic and polar residues. The PX domain of p47phox binds to the SH3 domain in the same protein [(PUBMED:11373621)]. Phosphorylation of p47(phox), a cytoplasmic activator of the microbicidal phagocyte oxidase (phox), elicits interaction of p47(phox) with phoinositides. The protein phosphorylation-driven conformational change of p47(phox) enables its PX domain to bind to phosphoinositides, the interaction of which plays a crucial role in 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 of the PX domain with the C-terminal Src homology 3 (SH3) domain [(PUBMED:12356722)].

The PX domain is conserved from yeast to human. A recent multiple alignment of representative PX domain sequences can be found in [(PUBMED:9687503)], although showing relatively little sequence conservation, their structure appears to be highly conserved. Although 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 been reported as well. The PX-domain is also a protein-protein interaction domain [(PUBMED:15263065)].

GO process:cell communication (GO:0007154)
GO function:protein binding (GO:0005515), phosphatidylinositol binding (GO:0035091)
Family alignment:
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There are 3146 PX domains in 3115 proteins in SMART's nrdb database.

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