Phosphatidylinositol-3-phosphatase SAC1

Definition:

Phosphoinositide phosphatase which catalyzes the hydrolysis of phosphatidylinositol 4-phosphate (PtdIns(4)P). Can also catalyze the hydrolysis of phosphatidylinositol 3-phosphate (PtdIns(3)P) and has low activity towards phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2) (By similarity). Shows a very robust PtdIns(4)P phosphatase activity when it binds PtdIns(4)P in a 'cis' configuration in the cellular environment, with much less activity seen when it binds PtdIns(4)P in 'trans' configuration. PtdIns(4)P phosphatase activity (when it binds PtdIns(4)P in 'trans' configuration) is enhanced in the presence of PLEKHA3.

References:

[1]. Bruno Mesmin, et al. A four-step cycle driven by PI(4)P hydrolysis directs sterol/PI(4)P exchange by the ER-Golgi tether OSBP. Cell. 2013 Nov 7;155(4):830-43. [Content Brief]

[2]. Eamonn J Dickson, et al. Dynamic formation of ER-PM junctions presents a lipid phosphatase to regulate phosphoinositides. J Cell Biol. 2016 Apr 11;213(1):33-48. [Content Brief]

[3]. Rossella Venditti, et al. The activity of Sac1 across ER-TGN contact sites requires the four-phosphate-adaptor-protein-1. J Cell Biol. 2019 Mar 4;218(3):783-797. [Content Brief]

[4]. James P Zewe, et al. SAC1 degrades its lipid substrate PtdIns4 P in the endoplasmic reticulum to maintain a steep chemical gradient with donor membranes. Elife. 2018 Feb 20;7:e35588. [Content Brief]

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