Thrombomodulin

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THBD
Protein THBD PDB 1adx.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases THBD, AHUS6, BDCA3, CD141, THPH12, THRM, TM, thrombomodulin
External IDs OMIM: 188040 MGI: 98736 HomoloGene: 308 GeneCards: 7056
RNA expression pattern
PBB GE THBD 203887 s at tn.png

PBB GE THBD 203888 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000361

NM_009378

RefSeq (protein)

NP_000352.1

NP_033404.1

Location (UCSC) Chr 20: 23.05 – 23.05 Mb Chr 2: 148.4 – 148.41 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

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.[1] Thrombomodulin is also expressed on human mesothelial cell,[2] monocyte and a dendritic cell subset.

Genetics and Structure[edit]

In humans, thrombomodulin is encoded by the THBD gene.[3] 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.[4]

Function[edit]

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.[citation needed]

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).[citation needed]

The antigen described as BDCA-3[5] has turned out to be identical to thrombomodulin.[6] 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.[citation needed]

Interactions[edit]

Thrombomodulin has been shown to interact with thrombin.[7][8]

References[edit]

  1. ^ IPR001491 Thrombomodulin Accessed January 19, 2012.
  2. ^ Verhagen HJ, Heijnen-Snyder GJ, Pronk A, Vroom TM, van Vroonhoven TJ, Eikelboom BC, Sixma JJ, de Groot PG (Dec 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 95 (3): 542–9. doi:10.1046/j.1365-2141.1996.d01-1935.x. PMID 8943899. 
  3. ^ Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE (Jul 1987). "Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene". Biochemistry 26 (14): 4350–7. doi:10.1021/bi00388a025. PMID 2822087. 
  4. ^ Sadler JE (Jul 1997). "Thrombomodulin structure and function". Thrombosis and haemostasis 78 (1): 392–5. PMID 9198185. 
  5. ^ Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S, Buck DW, Schmitz J (Dec 2000). "BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood". Journal of Immunology (Baltimore, Md. : 1950) 165 (11): 6037–46. doi:10.4049/jimmunol.165.11.6037. PMID 11086035. 
  6. ^ Dzionek A, Inagaki Y, Okawa K, Nagafune J, Röck J, Sohma Y, Winkels G, Zysk M, Yamaguchi Y, Schmitz J (Dec 2002). "Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions". Human Immunology 63 (12): 1133–48. doi:10.1016/S0198-8859(02)00752-8. PMID 12480257. 
  7. ^ Bajzar L, Morser J, Nesheim M (Jul 1996). "TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex". The Journal of Biological Chemistry 271 (28): 16603–8. doi:10.1074/jbc.271.28.16603. PMID 8663147. 
  8. ^ Jakubowski HV, Owen WG (Jul 1989). "Macromolecular specificity determinants on thrombin for fibrinogen and thrombomodulin". The Journal of Biological Chemistry 264 (19): 11117–21. PMID 2544585. 

Further reading[edit]

External links[edit]