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Thrombomodulin

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THBD
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTHBD, AHUS6, BDCA3, CD141, THPH12, THRM, TM, thrombomodulin, BDCA-3
External IDsOMIM: 188040; MGI: 98736; HomoloGene: 308; GeneCards: THBD; OMA:THBD - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000361

NM_009378

RefSeq (protein)

NP_000352

NP_033404

Location (UCSC)Chr 20: 23.05 – 23.05 MbChr 2: 148.25 – 148.25 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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.[5] Thrombomodulin is also expressed on human mesothelial cell,[6] monocyte and a dendritic cell subset.

Genetics and structure

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In humans, thrombomodulin is encoded by the THBD gene.[7] 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.[8] It is a member of the C-type lectin domain (CTLD) group 14 family.[9]

Function

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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).[10]

The antigen described as BDCA-3[11] has turned out to be identical to thrombomodulin.[12] 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

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Thrombomodulin has been shown to interact with thrombin.[13][14]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000178726Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000074743Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ IPR001491 Thrombomodulin Accessed January 19, 2012.
  6. ^ Verhagen HJ, Heijnen-Snyder GJ, Pronk A, Vroom TM, van Vroonhoven TJ, Eikelboom BC, et al. (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. 95 (3): 542–549. doi:10.1046/j.1365-2141.1996.d01-1935.x. PMID 8943899. S2CID 8417511.
  7. ^ Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE (July 1987). "Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene". Biochemistry. 26 (14): 4350–4357. doi:10.1021/bi00388a025. PMID 2822087.
  8. ^ Sadler JE (July 1997). "Thrombomodulin structure and function". Thrombosis and Haemostasis. 78 (1): 392–395. doi:10.1055/s-0038-1657558. PMID 9198185. S2CID 32297505.
  9. ^ Khan KA, McMurray JL, Mohammed F, Bicknell R (September 2019). "C-type lectin domain group 14 proteins in vascular biology, cancer and inflammation". The FEBS Journal. 286 (17): 3299–3332. doi:10.1111/febs.14985. PMC 6852297. PMID 31287944.
  10. ^ Delvaeye M, Noris M, De Vriese A, Esmon CT, Esmon NL, Ferrell G, et al. (July 2009). "Thrombomodulin mutations in atypical hemolytic-uremic syndrome". The New England Journal of Medicine. 361 (4): 345–357. doi:10.1056/NEJMoa0810739. PMC 3530919. PMID 19625716.
  11. ^ Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S, et al. (December 2000). "BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood". Journal of Immunology. 165 (11): 6037–6046. doi:10.4049/jimmunol.165.11.6037. PMID 11086035.
  12. ^ Dzionek A, Inagaki Y, Okawa K, Nagafune J, Röck J, Sohma Y, et al. (December 2002). "Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions". Human Immunology. 63 (12): 1133–1148. doi:10.1016/S0198-8859(02)00752-8. PMID 12480257.
  13. ^ Bajzar L, Morser J, Nesheim M (July 1996). "TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex". The Journal of Biological Chemistry. 271 (28): 16603–16608. doi:10.1074/jbc.271.28.16603. PMID 8663147.
  14. ^ Jakubowski HV, Owen WG (July 1989). "Macromolecular specificity determinants on thrombin for fibrinogen and thrombomodulin". The Journal of Biological Chemistry. 264 (19): 11117–11121. doi:10.1016/S0021-9258(18)60437-5. PMID 2544585.

Further reading

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