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Protein Z, also known as PROZ, is a vitamin K-dependent plasma glycoprotein synthesized primarily in the liver and secreted into the blood. It acts as a cofactor for protein Z-dependent protease inhibitor (ZPI), greatly accelerating the inhibition of activated factor X (FXa) on phospholipid surfaces in the presence of calcium ions. This regulatory activity is critical for maintaining hemostatic balance and preventing inappropriate clot formation (thrombosis). Protein Z does not have intrinsic enzymatic activity but enhances ZPI's effect by facilitating its localization and interaction with FXa at cell membranes. Protein Z deficiency is associated with an increased risk of arterial thrombosis and adverse pregnancy outcomes. No approved drugs directly target Protein Z; its primary clinical relevance is as a supporting factor in the coagulation cascade and as a potential biomarker for thrombotic risk.
Cofactor enhancement of inhibitor: Protein Z increases the inhibitory efficiency of protein Z-dependent protease inhibitor (ZPI) against factor Xa in the presence of calcium and phospholipid membranes. The mechanism is through the formation of a ternary complex with ZPI and factor Xa at the membrane surface, leading to accelerated inhibition of Xa protease activity.
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