Thrombomodulin

Genetics and structure

In humans, thrombomodulin is encoded by the gene. The protein has a molecular mass of 74kDa, and consists of a single chain with six tandemly repeated EGF-like domains, a Serine/Threonine-rich spacer and a transmembrane domain. It is a member of the C-type lectin domain (CTLD) group 14 family.

Function

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.

Interactions

Thrombomodulin has been shown to interact with thrombin.

References

References

1. [http://www.ebi.ac.uk/interpro/IEntry?ac=IPR001491 IPR001491 Thrombomodulin] Accessed January 19, 2012.
2. (December 1996). "Thrombomodulin activity on mesothelial cells: perspectives for mesothelial cells as an alternative for endothelial cells for cell seeding on vascular grafts". British Journal of Haematology.
3. (July 1987). "Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene". Biochemistry.
4. (July 1997). "Thrombomodulin structure and function". Thrombosis and Haemostasis.
5. (September 2019). "C-type lectin domain group 14 proteins in vascular biology, cancer and inflammation". The FEBS Journal.
6. (July 2009). "Thrombomodulin mutations in atypical hemolytic-uremic syndrome". The New England Journal of Medicine.
7. (December 2000). "BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood". Journal of Immunology.
8. (December 2002). "Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions". Human Immunology.
9. (July 1996). "TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex". The Journal of Biological Chemistry.
10. (July 1989). "Macromolecular specificity determinants on thrombin for fibrinogen and thrombomodulin". The Journal of Biological Chemistry.