Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. It reduces blood coagulation by converting thrombin to an anticoagulant enzyme from a procoagulant enzyme. Thrombomodulin is also expressed on human mesothelial cell, monocyte and a dendritic cell subset.
Thrombomodulin functions as a cofactor in the thrombin-induced activation of protein C in the anticoagulant pathway by forming a 1:1 stoichiometric complex with thrombin. This raises the speed of protein C activation thousandfold. Thrombomodulin-bound thrombin has procoagulant effect at the same time by inhibiting fibrinolysis by cleaving thrombin-activatable fibrinolysis inhibitor (TAFI,aka carboxypeptidase B2) into its active form.
Thrombomodulin is a glycoprotein on the surface of endothelial cells that, in addition to binding thrombin, regulates C3b inactivation by factor I. Mutations in the thrombomodulin gene (THBD) have also been reported to be associated with atypical hemolytic-uremic syndrome (aHUS).
The antigen described as BDCA-3 has turned out to be identical to thrombomodulin. Thus, it was revealed that this molecule also occurs on a very rare (0.02%) subset of human dendritic cells called MDC2. Its function on these cells is unknown.
^Dzionek A, Inagaki Y, Okawa K, Nagafune J, Röck J, Sohma Y, Winkels G, Zysk M, Yamaguchi Y, Schmitz J (December 2002). "Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions". Hum. Immunol.63 (12): 1133–48. doi:10.1016/S0198-8859(02)00752-8. PMID12480257.
^Bajzar, L; Morser J, Nesheim M (Jul 1996). "TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex". J. Biol. Chem. (UNITED STATES) 271 (28): 16603–8. doi:10.1074/jbc.271.28.16603. ISSN0021-9258. PMID8663147.Cite uses deprecated parameters (help)
^Jakubowski, H V; Owen W G (Jul 1989). "Macromolecular specificity determinants on thrombin for fibrinogen and thrombomodulin". J. Biol. Chem. (UNITED STATES) 264 (19): 11117–21. ISSN0021-9258. PMID2544585.Cite uses deprecated parameters (help)
Adler M, Seto MH, Nitecki DE, et al. (1995). "The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin.". J. Biol. Chem.270 (40): 23366–72. doi:10.1074/jbc.270.40.23366. PMID7559494.
Ohlin AK, Marlar RA (1995). "The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease.". Blood85 (2): 330–6. PMID7811989.
Srinivasan J, Hu S, Hrabal R, et al. (1994). "Thrombin-bound structure of an EGF subdomain from human thrombomodulin determined by transferred nuclear Overhauser effects.". Biochemistry33 (46): 13553–60. doi:10.1021/bi00250a007. PMID7947766.