Phox homologous domain (IPR001683)

Short name: Phox

Overlapping homologous superfamilies

Domain relationships


The PX (phox) domain [PMID: 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 [PMID: 10782093, PMID: 11736640, PMID: 12461558]. PX domains are important phosphoinositide-binding modules that have varying lipid-binding specificities [PMID: 11884510]. The PX domain is approximately 120 residues long [PMID: 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 neutrophil cytosol factor 1 (p47phox) binds to the SH3 domain in the same protein [PMID: 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 [PMID: 12356722].

The PX domain is conserved from yeast to human. A multiple alignment of representative PX domain sequences from eukaryotic proteins [PMID: 9687503], shows relatively little sequence conservation, although 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 [PMID: 15263065].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0035091 phosphatidylinositol binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles