Phosphatidylinositol-4-phosphate phosphatase SAC1 (SAC1)

Phosphatidylinositol-4-phosphate phosphatase SAC1 (SAC1) is an integral membrane enzyme localized primarily to the endoplasmic reticulum, catalyzing the hydrolysis of phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 3-phosphate (PtdIns(3)P), and with minor activity toward phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2). SAC1 ensures the regulation of phosphoinositide content within the cell, impacting lipid signaling pathways, membrane trafficking, and the organization of the Golgi apparatus and mitotic spindle. The protein contains a catalytic CX5R motif (P-loop) surrounded by hydrophobic and basic residues, thought to mediate interaction with membrane bilayers and facilitate substrate access and hydrolysis. Structural studies highlight a unique active site conformation differing from other phosphatases, implying specialized regulatory mechanisms. Mouse knockout studies indicate that SAC1 is essential for early embryonic development, establishing its pivotal biological importance.

Other names

SACM1LKIAA0851Phosphatidylinositol-3-phosphatase SAC1Suppressor of actin mutations 1-like proteinSAC1 suppressor of actin mutations 1 likephosphatidylinositide phosphatase SAC1suppressor of actin 1

Hydrolysis of phosphatidylinositol 4-phosphate and 3-phosphate; drugs would, in theory, act as enzyme inhibitors or activators affecting phosphoinositide metabolism