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.
^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.
Boffa MC, Jackman RW, Peyri N, et al. (1992). "Thrombomodulin in the central nervous system.". Nouvelle revue française d'hématologie33 (6): 423–9. PMID1667949.
Jakubowski HV, Owen WG (1989). "Macromolecular specificity determinants on thrombin for fibrinogen and thrombomodulin.". J. Biol. Chem.264 (19): 11117–21. PMID2544585.
Jackman RW, Beeler DL, Fritze L, et al. (1987). "Human thrombomodulin gene is intron depleted: nucleic acid sequences of the cDNA and gene predict protein structure and suggest sites of regulatory control.". Proc. Natl. Acad. Sci. U.S.A.84 (18): 6425–9. doi:10.1073/pnas.84.18.6425. PMC299089. PMID2819876.
Suzuki K, Kusumoto H, Deyashiki Y, et al. (1987). "Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation.". EMBO J.6 (7): 1891–7. PMC553573. PMID2820710.
Wen DZ, Dittman WA, Ye RD, et al. (1987). "Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene.". Biochemistry26 (14): 4350–7. doi:10.1021/bi00388a025. PMID2822087.
Shirai T, Shiojiri S, Ito H, et al. (1988). "Gene structure of human thrombomodulin, a cofactor for thrombin-catalyzed activation of protein C.". J. Biochem.103 (2): 281–5. PMID2836377.
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.
Gerlitz B, Hassell T, Vlahos CJ, et al. (1993). "Identification of the predominant glycosaminoglycan-attachment site in soluble recombinant human thrombomodulin: potential regulation of functionality by glycosyltransferase competition for serine474.". Biochem. J. 295. ( Pt 1): 131–40. PMC1134829. PMID8216207.
Yasuda K, Espinosa R, Davis EM, et al. (1993). "Human somatostatin receptor genes: localization of SSTR5 to human chromosome 20p11.2.". Genomics17 (3): 785–6. doi:10.1006/geno.1993.1410. PMID8244401.
Yamamoto S, Mizoguchi T, Tamaki T, et al. (1993). "Urinary thrombomodulin, its isolation and characterization.". J. Biochem.113 (4): 433–40. PMID8390446.