The PX domain is a phosphoinositide -binding structural domain involved in targeting of proteins to cell membranes.
This domain was first found in P40phox and p47phox domains of NADPH oxidase (phox stands for phagocytic oxidase).[ 1] [ 2] It was also identified in many other proteins involved in membrane trafficking, including nexins, Phospholipase D , and phosphoinositide -3-kinases .
The PX domain is structurally conserved in eukaryotes , although amino acid sequences show little similarity.[ 3] PX domains interact primarily with PtdIns(3)P lipids.[ 4] [ 5] However some of them bind to phosphatidic acid , PtdIns(3,4)P2 , PtdIns(3,5)P2 , PtdIns(4,5)P2 , and PtdIns(3,4,5)P3 . The PX-domain can also interact with other domains and proteins.
^ Ponting CP (November 1996). "Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains?" . Protein Sci . 5 (11): 2353–7. doi :10.1002/pro.5560051122 . PMC 2143296 . PMID 8931154 .
^ Wishart MJ, Taylor GS, Dixon JE (June 2001). "Phoxy lipids: revealing PX domains as phosphoinositide binding modules" . Cell . 105 (7): 817–20. doi :10.1016/S0092-8674(01)00414-7 . PMID 11439176 . S2CID 12622490 .
^ Hiroaki H, Ago T, Ito T, Sumimoto H, Kohda D (June 2001). "Solution structure of the PX domain, a target of the SH3 domain". Nat. Struct. Biol . 8 (6): 526–30. doi :10.1038/88591 . PMID 11373621 . S2CID 27416988 .
^ Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, Williams RL (October 2002). "Binding of the PX domain of p47phox to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction" . EMBO J . 21 (19): 5057–68. doi :10.1093/emboj/cdf519 . PMC 129041 . PMID 12356722 .
^ Ago T, Kuribayashi F, Hiroaki H, Takeya R, Ito T, Kohda D, Sumimoto H (April 2003). "Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation" . Proc. Natl. Acad. Sci. U.S.A . 100 (8): 4474–9. Bibcode :2003PNAS..100.4474A . doi :10.1073/pnas.0735712100 . PMC 153580 . PMID 12672956 .