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PROSITE documentation PDOC50195 [for PROSITE entry PS50195]

PX domain profile





Description

The phox homology (PX) domain is a 100-140 amino acid module that was first identified in p40-phox, p47-phox, the Cpk class of phosphatidylinositol 3-kinase, homologues of a sorting nexin (SNX1), phospholipase D, and several yeast proteins, including BEM1 and SCD2 [1]. The PX domain is found in a single copy in several eukaryotic proteins generally involved in the regulation of vesicular trafficking machinery, growth factor receptor degradation in lysosomes, signal transduction mechanisms, and NADPH oxidase activity. In addition to proteins containing only PX domains, the PX domain can coexist with other functional domains such as the lipase, the lipid kinase, the protein kinase (see <PDOC00100>), the t-SNARE domain (see <PDOC50192>), the SH3 domain (see <PDOC50002>), and the RGS domain (see <PDOC50132>). Several PX domains have been shown to bind phosphatidylinositol-3-phosphate (PtdIns(3)P), phosphatidylinositol-3,4-bisphosphate or phosphatidylinositol-4,5-bisphosphate [2,3,4,5,6]. Thus, it seems likely that PX domains fulfill a general function as phosphoinositide-binding domains in a variety of cellular processes in unicellular and multicellular organisms. Many PX domains contain a conserved proline-rich motif representing a consensus SH3-binding site and an interaction between the p47-phox PX and SH3 domains has been shown to exist [1,7]. This suggests that SH3 docking might regulate the interaction between PX domains and phosphoinositide-enriched membranes [2].

The PX domain contains several conserved positively charged and hydrophobic residues characteristic of domains known to bind to specific phosphopeptides or phospholipids. The NMR structures of the p47-phox and VAM7 PX domains have been solved and revealed that the PX domain has a flat compact shape (see <PDB:1GD5>). The p47-phox and VAM7 PX domains consist of three/four strands forming an antiparallel β-sheet structure in the N-terminal one-third of the amino-acid structure, and four/three helices in the C-terminal two-thirds, respectively [2,7]. The conserved proline-rich motif found in many PX domains and which could bind SH3 domains is located between α-helices 1 and 2 or 2 and 3, respectively [1,2,7].

Some proteins known to contain a PX domain are listed below:

  • Eukaryotic sorting nexin (SNX) proteins. They are implicated in regulating membrane traffic.
  • Animal Cpk class of phosphatidylinositol 3-kinase.
  • Mouse serine/threonine protein kinase CISK. It is implicated in IL-3- dependent cell survival.
  • Mammalian p47-phox (NCF-1) and p40-phox (NCF-4), which are cytosolic components of the phagocyte NADPH oxidase. In human, defects in the PX domain of p47-phox cause chronic granulomatous disease (CGD) with predisposition to infection by fungi and bacteria.
  • Mammalian Fish protein. It is involved in the tyrosine kinase signalling pathway.
  • Some eukaryotic phospholipases D (EC 3.1.4.4).
  • Yeast vacuolar morphogenesis protein VAM7. It helps to transport cargo such as hydrolytic enzymes to the vacuole, the yeast lysosomal counterpart.
  • Yeast BEM1 and BEM3 bud-mergence proteins.
  • Fission yeast scd2, the orthologue of BEM1.

The profile we developed covers the entire PX domain.

Last update:

May 2002 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

PX, PS50195; PX domain profile  (MATRIX)


References

1AuthorsPonting C.P.
TitleNovel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains?
SourceProtein Sci. 5:2353-2357(1996).
PubMed ID8931154

2AuthorsCheever M.L. Sato T.K. de Beer T. Kutateladze T.G. Emr S.D. Overduin M.
TitlePhox domain interaction with PtdIns(3)P targets the Vam7 t-SNARE to vacuole membranes.
SourceNat. Cell Biol. 3:613-618(2001).
PubMed ID11433291
DOI10.1038/35083000

3AuthorsXu Y. Hortsman H. Seet L. Wong S.H. Hong W.
TitleSNX3 regulates endosomal function through its PX-domain-mediated interaction with PtdIns(3)P.
SourceNat. Cell Biol. 3:658-666(2001).
PubMed ID11433298
DOI10.1038/35083051;

4AuthorsKanai F. Liu H. Field S.J. Akbary H. Matsuo T. Brown G.E. Cantley L.C. Yaffe M.B.
TitleThe PX domains of p47phox and p40phox bind to lipid products of PI(3)K.
SourceNat. Cell Biol. 3:675-678(2001).
PubMed ID11433300
DOI10.1038/35083070

5AuthorsEllson C.D. Gobert-Gosse S. Anderson K.E. Davidson K. Erdjument-Bromage H. Tempst P. Thuring J.W. Cooper M.A. Lim Z.-Y. Holmes A.B. Gaffney P.R.J. Coadwell J. Chilvers E.R. Hawkins P.T. Stephens L.R.
TitlePtdIns(3)P regulates the neutrophil oxidase complex by binding to the PX domain of p40(phox).
SourceNat. Cell Biol. 3:679-682(2001).
PubMed ID11433301
DOI10.1038/35083076

6AuthorsSong X. Xu W. Zhang A. Huang G. Liang X. Virbasius J.V. Czech M.P. Zhou G.W.
TitlePhox homology domains specifically bind phosphatidylinositol phosphates.
SourceBiochemistry 40:8940-8944(2001).
PubMed ID11467955
DOI10.1021/bi0155100

7AuthorsHiroaki H. Ago T. Ito T. Sumimoto H. Kohda D.
TitleSolution structure of the PX domain, a target of the SH3 domain.
SourceNat. Struct. Biol. 8:526-530(2001).
PubMed ID11373621
DOI10.1038/88591



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