PX domain explained

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.

Human proteins containing this domain

Sorting nexins contain this domain. Other examples include:

• HS1BP3
• KIF16B (SNX23)
• NCF1; NCF1C; NCF4; NISCH
• PIK3C2A; PIK3C2B; PIK3C2G; PLD1; PLD2; PXK
• RPS6KC1
• SGK3; SH3PXD2A; SNAG1; SNX9

Notes and References

1. Ponting CP . Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains? . Protein Sci. . 5 . 11 . 2353–7 . November 1996 . 8931154 . 2143296 . 10.1002/pro.5560051122 .
2. Wishart MJ, Taylor GS, Dixon JE . Phoxy lipids: revealing PX domains as phosphoinositide binding modules . Cell . 105 . 7 . 817–20 . June 2001 . 11439176 . 10.1016/S0092-8674(01)00414-7. 12622490 . free .
3. Hiroaki H, Ago T, Ito T, Sumimoto H, Kohda D . Solution structure of the PX domain, a target of the SH3 domain . Nat. Struct. Biol. . 8 . 6 . 526–30 . June 2001 . 11373621 . 10.1038/88591 . 27416988 .
4. Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, Williams RL . 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 . October 2002 . 12356722 . 129041 . 10.1093/emboj/cdf519.
5. Ago T, Kuribayashi F, Hiroaki H, Takeya R, Ito T, Kohda D, Sumimoto H . 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 . April 2003 . 12672956 . 153580 . 10.1073/pnas.0735712100 . 2003PNAS..100.4474A . free .