D
IPR001683

Phox homology

InterPro entry
Short namePX_dom
Overlapping
homologous
superfamilies
 
domain relationships

Description

The PX (phox) domain
[5]
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
[10, 4, 7, 9]
. PX domains are important phosphoinositide-binding modules that have varying lipid-binding specificities
[1]
. The PX domain is approximately 120 residues long
[8]
, and folds into a three-stranded β-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
[8]
. 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
[3]
.

The PX domain is conserved from yeast to human. A multiple alignment of representative PX domain sequences from eukaryotic proteins
[2]
, 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
[6]
.

References

1.The PX domain: a new phosphoinositide-binding module. Ellson CD, Andrews S, Stephens LR, Hawkins PT. J. Cell. Sci. 115, 1099-105, (2002). View articlePMID: 11884510

2.A new method for isolating tyrosine kinase substrates used to identify fish, an SH3 and PX domain-containing protein, and Src substrate. Lock P, Abram CL, Gibson T, Courtneidge SA. EMBO J. 17, 4346-57, (1998). View articlePMID: 9687503

3.Binding of the PX domain of p47(phox) to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction. Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, Williams RL. EMBO J. 21, 5057-68, (2002). View articlePMID: 12356722

4.The Phox homology (PX) domain, a new player in phosphoinositide signalling. Xu Y, Seet LF, Hanson B, Hong W. Biochem. J. 360, 513-30, (2001). View articlePMID: 11736640

5.Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains? Ponting CP. Protein Sci. 5, 2353-7, (1996). View articlePMID: 8931154

6.The phox homology (PX) domain protein interaction network in yeast. Vollert CS, Uetz P. Mol. Cell Proteomics 3, 1053-64, (2004). View articlePMID: 15263065

7.Sorting out the cellular functions of sorting nexins. Worby CA, Dixon JE. Nat. Rev. Mol. Cell Biol. 3, 919-31, (2002). View articlePMID: 12461558

8.Solution structure of the PX domain, a target of the SH3 domain. Hiroaki H, Ago T, Ito T, Sumimoto H, Kohda D. Nat. Struct. Biol. 8, 526-30, (2001). View articlePMID: 11373621

9.The Phox (PX) domain proteins and membrane traffic. Seet LF, Hong W. Biochim. Biophys. Acta 1761, 878-96, (2006). View articlePMID: 16782399

10.Phosphoinositide signaling and the regulation of membrane trafficking in yeast. Odorizzi G, Babst M, Emr SD. Trends Biochem. Sci. 25, 229-35, (2000). View articlePMID: 10782093

GO terms

biological process

  • None

cellular component

  • None

Cross References

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