Architecture and function of yeast phosphatidate phosphatase Pah1 domains/regions.

Phosphatidate (PA) phosphatase, which catalyzes the Mg2+-dependent dephosphorylation of PA to produce diacylglycerol, provides a direct precursor for the synthesis of the storage lipid triacylglycerol and the membrane phospholipids phosphatidylcholine and phosphatidylethanolamine. The enzyme controlling the key phospholipid PA also plays a crucial role in diverse aspects of lipid metabolism and cell physiology. PA phosphatase is a peripheral membrane enzyme that is composed of multiple domains/regions required for its catalytic function and subcellular localization. In this review, we discuss the domains/regions of PA phosphatase from the yeast Saccharomyces cerevisiae with reference to the homologous enzyme from mammalian cells. • Pah1 PA phosphatase controls the DAG/PA balance to regulate the synthesis of TAG and membrane phospholipids • Pah1 requires the N-LIP and HAD-like domains with the N-terminal amphipathic helix and a C-terminal tryptophan residue • Pah1 is phosphorylated in the cytosol at sites contained within its intrinsically disordered regions and controlled by the RP domain • Phosphorylated Pah1 is recruited and dephosphorylated at the nuclear/ER membrane by the Nem1-Spo7 protein phosphatase • The catalytic and regulatory domains/regions of Pah1 control its PA phosphatase activity and roles in lipid synthesis [ABSTRACT FROM AUTHOR]