PX domain

{{Pfam_box

| Symbol = PX

| Name =

| image =1h6h.png

| width =200

| caption = PX domain of NADH oxidase (p40phox), lipid-bound

| Pfam= PF00787

| InterPro= IPR001683

| SMART= PX

| PROSITE = PDOC50195

| SCOP = 1h6h

| TCDB =

| OPM family= 57

| OPM protein= 1xte

| CDD = cd06093

| PDB=

}}

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).{{cite journal | author = Ponting CP | title = Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains? | journal = Protein Sci. | volume = 5 | issue = 11 | pages = 2353–7 |date=November 1996 | pmid = 8931154 | pmc = 2143296 | doi = 10.1002/pro.5560051122 }}{{cite journal | vauthors = Wishart MJ, Taylor GS, Dixon JE | title = Phoxy lipids: revealing PX domains as phosphoinositide binding modules | journal = Cell | volume = 105 | issue = 7 | pages = 817–20 |date=June 2001 | pmid = 11439176 | doi = 10.1016/S0092-8674(01)00414-7| s2cid = 12622490 | doi-access = free }} 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.{{cite journal | vauthors = Hiroaki H, Ago T, Ito T, Sumimoto H, Kohda D | title = Solution structure of the PX domain, a target of the SH3 domain | journal = Nat. Struct. Biol. | volume = 8 | issue = 6 | pages = 526–30 |date=June 2001 | pmid = 11373621 | doi = 10.1038/88591 | s2cid = 27416988 }} PX domains interact primarily with PtdIns(3)P lipids.{{cite journal | vauthors = Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, Williams RL | title = Binding of the PX domain of p47phox to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction | journal = EMBO J. | volume = 21 | issue = 19 | pages = 5057–68 |date=October 2002 | pmid = 12356722 | pmc = 129041 | doi = 10.1093/emboj/cdf519}}{{cite journal | vauthors = Ago T, Kuribayashi F, Hiroaki H, Takeya R, Ito T, Kohda D, Sumimoto H | title = Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 8 | pages = 4474–9 |date=April 2003 | pmid = 12672956 | pmc = 153580 | doi = 10.1073/pnas.0735712100 | bibcode = 2003PNAS..100.4474A | doi-access = free }} 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.