Protein C is a plasma, vitamin κ-dependent zymogen of a serine protease that can inhibit blood coagulation by inhibiting thrombin formation, selectively inactivating Factors Va and VIIIa. The Protein C anticoagulant pathway is triggered when thrombin binds to the endothelial cell proteoglycan, thrombomodulin. This complex, which cannot clot blood, is a potent activator of the protein C zymogen. Activation involves the release of a dodecapeptide from the N-terminal domain of the heavy chain. The activated Protein C (APC) then binds to protein S on cell surfaces and inactivates the coagulation factors Va and VIIIa by proteolysis. APC has also been shown to bind to receptors on the endothelium of large blood vessels.