Phospholipid-transporting ATPase 11C (ATP11C)

Phospholipid-transporting ATPase 11C (ATP11C) is an aminophospholipid flippase enzyme localized at the plasma membrane, particularly abundant in erythrocytes and immune cells, where it is crucial for maintaining phospholipid asymmetry by transporting phosphatidylserine from the outer to inner leaflet of the membrane[1][2]. In healthy cells, ATP11C activity conceals PS internally, preventing unwanted recognition by immune cells, while during apoptosis or upon PKC-mediated phosphorylation, ATP11C is inactivated or internalized, resulting in PS exposure and cell clearance[1][2][3]. ATP11C function relies on the accessory protein CDC50A, which is required for its proper plasma membrane localization and activity[1][2]. Genetic deficiency or loss of function mutations in ATP11C are linked to anemia, B-cell lymphopenia, and cholestasis in mice and humans due to loss of membrane lipid asymmetry and enhanced cell clearance[1]. There are no currently approved drugs that directly target ATP11C, but its modulation could have implications for therapeutic strategies targeting apoptosis, immune evasion, or red blood cell lifespan[1][2][3].

Other names

ATPase phospholipid transporting 11CATP11CPhospholipid-transporting ATPase IGATPIGATPIQATPase class VI type 11CP4-ATPase flippase complex alpha subunit ATP11CHACXLProbable phospholipid-transporting ATPase IG

Enzyme inhibition or gene knockout leads to exposure of PS on cell surface and cell recognition/clearance by macrophages. PKC activation leads to ATP11C endocytosis and downregulation of flippase activity.