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 . 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
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
- 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
- Some eukaryotic phospholipases D (EC 184.108.40.206).
- 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.
PROSITE is copyright. It is produced by the SIB Swiss Institute
Bioinformatics. There are no restrictions on its use by non-profit
institutions as long as its content is in no way modified. Usage by and
for commercial entities requires a license agreement. For information
about the licensing scheme send an email to