In vitro and in silico characterization of human PHOSPHO2 reveals its phospholipid phosphatase activity

Purified human PHOSPHO2 shows Mg2+-dependent, NEM-sensitive phosphatase activity toward phosphatidic acid (PA) and other lipids in vitro, with strong membrane lipid enhancement.

• Why it matters: Mammalian PAPs regulate lipid signaling by controlling PA and diacylglycerol levels, but the specific properties of PHOSPHO2 and its role among PAP types were unclear.
• What they did: The authors purified PHOSPHO2 and measured enzymological activity in vitro against PA, LPA, S1P, C1P, and G3P, testing lipid substrate selectivity and effects of phosphatidylcholine/phosphatidylethanolamine.
• The result: PHOSPHO2 preferentially acts on PA species with shorter saturated or polyunsaturated fatty acids, and its PAP activity—but not other phosphatase activities—is strongly enhanced by phosphatidylcholine and phosphatidylethanolamine, implying cytoplasm-facing membrane PAP function.