PX Domain
Class:Phospholipid binding

No ImageThe structural basis for PX domain interactions with phosphoinositides have been determined from the structures of the PX domains of p40phox and Vmp7p in a complex with PI(3)P. Interactions between all PX domains and their bound phosphoinositides involve the 1-phosphate and the inositol ring. A hydrogen bond between a well-conserved residue, K92 (in p40phox), and the 1-phosphate is the most important interaction with this group. Y59 (in p40phox) forms the floor of the lipid-binding pocket in the PX domain, allowing the inositol ring of PI(3)P to stack tightly against it. This carbohydrate-aromatic stacking is likely to be a common feature of binding, since all PX domains have either Y or F at the analogous position.

Structure Reference:
Bravo, J. et al. (2001) Mol. Cell. 8(4): 829-839. PDB: 1H6H.

Domain binding and function:
The Phox homology (PX) domain is a phospholipid-binding domain consisting of ~120 amino acids. The PX domain is found in more than 250 proteins, including the p40phox and p47phox components of the NADPH oxidase complex, sorting nexins, phospholipases D1 and 2 and the kinases PI3K and CISK.  PX domains show an N-terminal three-stranded β-sheet, followed by a helical subdomain made up of four α-helices.  PX domains preferentially bind to PtdIns(3)P, although some have been reported to bind other phosphoinositides.  Proteins containing PX domains have been implicated in a wide spectrum of functions, including protein sorting, vesicular trafficking and phospholipids metabolism.
Examples of Proteins: 
PX Domain Proteins
Binding Partners
p40phox PI(3)P
p47phox PI(3,4)P2,  PI(3)P
Vmp7 PI(3)P

PI(3,5)P2, PI(4)P, PI(5)P


PI3K    (Class II)


No Image