Human Thrombomodulin (THBD) (THBD)

Human Thrombomodulin (hTM) is a type I transmembrane glycoprotein that acts as a critical natural anticoagulant by serving as a cofactor for thrombin (UniProt P07204). When thrombin binds to hTM, its substrate specificity shifts from fibrinogen to Protein C, leading to the generation of activated Protein C (APC), which subsequently inactivates coagulation factors Va and VIIIa (PubMed: 26033515). In the field of xenotransplantation, the expression of a human Thrombomodulin transgene on porcine endothelium is a primary strategy to overcome the molecular incompatibility between porcine thrombomodulin and human Protein C. This incompatibility otherwise leads to rapid thrombin generation, platelet activation, and thrombotic microangiopathy, resulting in graft failure (PubMed: 27043368). By expressing hTM, the porcine vascular surface is rendered thromboresistant to human blood, significantly reducing the risk of both hyperacute and delayed vascular rejection. This transgenic approach is often combined with other genetic modifications, such as the knockout of alpha-1,3-galactosyltransferase, to ensure long-term survival of porcine-to-human xenografts.

Other names

CD141TMTHRMFetomodulinAntigen CD141BDCA-3

Binds to thrombin to form a complex that activates protein C; activated protein C then proteolytically inactivates coagulation factors Va and VIIIa, thereby inhibiting further thrombin generation and promoting an anticoagulant state.