Thrombomodulin(TM) is an endothelial specific receptor that forms a complex with thrombin, a protein with procoagulant, inflammatory and anticoagulant effects. The TM/thrombin complex activates protein C (PC) to generate activated protein C (APC) and initiate the APC anticoagulant pathway. APC attenuates thrombin formation through the inactivation, by limited proteolysis, of two significant cofactors of blood clot formation, Factor Va and Factor VIIIa. This process is augmented by the activity of the endothelial cell Protein C receptor (EPCR), which binds both PC and APC with high affinity. The EPCR gene maps to human chromosome 20q11.22 and encodes an anticoagulant that is preferentially expressed on large blood vessel endothelium in the heart and lung with some expression in capillaries in the lung and skin. EPCR, also designated CCD41 in mouse, is a member of the major histocompatibility complex and displays significant homology to CD1. Soluble plasma EPCR is thought to inhibit the membrane-bound EPCR activation of the APC pathway.
