P4-ATPase (Phospholipid-transporting ATPase) (P4-ATPase)

P4-ATPases, also known as phospholipid-transporting ATPases, are a subfamily of P-type ATPases that function as lipid flippases.[2][3][5] These enzymes hydrolyze ATP to transport specific phospholipids from the outer to the inner leaflet of eukaryotic cell membranes, maintaining membrane lipid asymmetry, which is essential for various cellular processes including vesicle formation, trafficking, signal transduction, and apoptotic signaling.[2][3][5] P4-ATPases are highly conserved across eukaryotes and in humans comprise at least 14 distinct isoforms.[2] Defects in P4-ATPases have been associated with disorders such as progressive familial intrahepatic cholestasis (PFIC, due to ATP8B1 mutations) and certain neurological syndromes.[3] Recent studies suggest they may represent new therapeutic targets against infectious agents and multidrug-resistance phenotypes, with small-molecule inhibitors under study for such uses.[1] \n\nStructural features include three cytoplasmic domains (actuator, nucleotide-binding, and phosphorylation) and a membrane domain with multiple transmembrane helices.[1][2][3] The catalytic mechanism (Post-Albers cycle) involves sequential phosphorylation and dephosphorylation, driving conformational changes that facilitate lipid substrate translocation.[2][4][5].\n\nIn summary, P4-ATPases are crucial enzymes for maintaining membrane phospholipid distribution, with significant implications in human physiology and disease.

Other names

Phospholipid-transporting ATPaseLipid flippaseAminophospholipid translocase (historical)P-type ATPase class 4

ATP-driven translocation ("flipping") of specific phospholipids from the exoplasmic/luminal leaflet to the cytoplasmic leaflet of membranes\nDisruption of this activity may lead to defects in lipid asymmetry, cell signaling, and membrane integrity