Taxonomic distribution of proteins containing PX domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing PX domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

The phox homology (PX) domain protein interaction network in yeast.

Vollert CS, Uetz P
Mol Cell Proteomics. 2004; 3: 1053-64

The phox homology (PX) domain is a phosphoinositide-binding domain that is conserved from yeast to human. Here we show for the first time by genome-wide two-hybrid screens and in vitro binding assays that the PX domain is a bona fide protein interaction domain. The yeast PX domain-only proteins Grd19p (YOR357C) and Ypt35p (YHR105W), as well as the isolated PX domains from Mvp1p (YMR004W), Snx42p/Cvt20p/Atg20p (YDL113C), Vam7p (YGL212W), and Vps17p (YOR132W), yielded a total of 40 reproducible two-hybrid interactions. Thirty-five interactions were found for the full-length proteins of Bem1p (YBR200W), Snx42p, Snx4p/Cvt13p (YJL036W), Vam7p, Vps5p (YOR069W), and Vps17p, but these appear not to require the PX domain, because these interactions could not be reproduced with PX-only baits. Interactions of Grd19p, Vam7p, Vps5p, Vps17p, and Ypt35p with members of the Yip1p family of proteins were detected consistently and were verified by in vitro binding assays. The N-terminal cytoplasmic domain of Yip1p and Yif1p mediates these interactions with PX domains. A mutation in the lipid-binding pocket of Ypt35p that reduces lipid binding markedly does not affect these PX domain protein interactions, arguing that lipid binding uses a different interaction surface than protein binding.

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. 2001; 8: 526-30

The phox homology (PX) domain is a novel protein module containing aconserved proline-rich motif. We have shown that the PX domain isolatedfrom the human p47phox protein, a soluble subunit of phagocyte NADPHoxidase, binds specifically to the C-terminal SH3 domain derived from thesame protein. The solution structure of p47 PX has an alpha + betastructure with a novel folding motif topology and reveals that theproline-rich motif is presented on the molecular surface for easyrecognition by the SH3 domain. The proline-rich motif of p47 PX in thefree state adopts a distorted left-handed polyproline type II helixconformation.

Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains?

Ponting CP
Protein Sci. 1996; 5: 2353-7

Two SH3 domain-containing cytosolic components of the NADPH oxidase, p47phox and p40phox, are shown by analyses of their sequences to contain single copies of a novel class of domain, the PX (phox) domain. Homologous domains are demonstrated to be present in the Cpk class of phosphatidylinositol 3-kinase, S. cerevisiae Bem1p, and S. pombe Scd2, and a large family of human sorting nexin 1 (SNX1) homologues. The majority of these domains contains a polyproline motif, typical of SH3 domain-binding proteins. Two further findings are reported. A third NADPH oxidase subunit, p67phox, is shown to contain four tetratricopeptide repeats (TPRs) within its N-terminal RaclGTP-binding region, and a 28 residue motif in p40phox is demonstrated to be present in protein kinase C isoforms iota/lambda and zeta, and in three ZZ domain-containing proteins.