Thrombomodulin

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Thrombomodulin
Protein THBD PDB 1adx.png
PDB rendering based on 1adx.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols THBD ; AHUS6; BDCA3; CD141; THPH12; THRM; TM
External IDs OMIM188040 MGI98736 HomoloGene308 GeneCards: THBD Gene
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 7056 21824
Ensembl ENSG00000178726 ENSMUSG00000074743
UniProt P07204 P15306
RefSeq (mRNA) NM_000361 NM_009378
RefSeq (protein) NP_000352 NP_033404
Location (UCSC) Chr 20:
23.05 – 23.05 Mb
Chr 2:
148.4 – 148.41 Mb
PubMed search [1] [2]

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.

Characterization[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 5 distinct domains.

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[4] has turned out to be identical to thrombomodulin.[5] 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.[6][7]

References[edit]

  1. ^ IPR001491 Thrombomodulin Accessed January 19, 2012.
  2. ^ Verhagen HJ, Heijnen-Snyder GJ, Pronk A, Vroom TM, van Vroonhoven TJ, Eikelboom BC et al. (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. doi:10.1021/bi00388a025. PMID 2822087. 
  4. ^ Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S et al. (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. doi:10.4049/jimmunol.165.11.6037. PMID 11086035. 
  5. ^ Dzionek A, Inagaki Y, Okawa K, Nagafune J, Röck J, Sohma Y et al. (Dec 2002). "Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions". Human Immunology 63 (12): 1133. doi:10.1016/S0198-8859(02)00752-8. PMID 12480257. 
  6. ^ 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. 
  7. ^ 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]