Thrombomodulin: Difference between revisions
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* {{vcite2 journal | vauthors = Van de Wouwer M, Collen D, Conway EM | title = Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 24 | issue = 8 | pages = 1374 | year = 2004 | date = Aug 2004 | pmid = 15178554 | doi = 10.1161/01.ATV.0000134298.25489.92 }} |
* {{vcite2 journal | vauthors = Van de Wouwer M, Collen D, Conway EM | title = Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 24 | issue = 8 | pages = 1374 | year = 2004 | date = Aug 2004 | pmid = 15178554 | doi = 10.1161/01.ATV.0000134298.25489.92 }} |
||
* {{vcite2 journal | vauthors = Boffa MC, Jackman RW, Peyri N, Boffa JF, George B | title = Thrombomodulin in the central nervous system | journal = Nouvelle Revue Française D'hématologie | volume = 33 | issue = 6 | pages = 423–9 | year = 1991 | pmid = 1667949 }} |
* {{vcite2 journal | vauthors = Boffa MC, Jackman RW, Peyri N, Boffa JF, George B | title = Thrombomodulin in the central nervous system | journal = Nouvelle Revue Française D'hématologie | volume = 33 | issue = 6 | pages = 423–9 | year = 1991 | pmid = 1667949 }} |
||
* {{vcite2 journal | vauthors = Jackman RW, Beeler DL, Fritze L, Soff G, Rosenberg RD | title = Human thrombomodulin gene is intron depleted: nucleic acid sequences of the cDNA and gene predict protein structure and suggest sites of regulatory control | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 84 | issue = 18 | pages = 6425–9 | year = 1987 | pmid = 2819876 | pmc = 299089 | doi = 10.1073/pnas.84.18.6425 | |
* {{vcite2 journal | vauthors = Jackman RW, Beeler DL, Fritze L, Soff G, Rosenberg RD | title = Human thrombomodulin gene is intron depleted: nucleic acid sequences of the cDNA and gene predict protein structure and suggest sites of regulatory control | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 84 | issue = 18 | pages = 6425–9 | year = 1987 | pmid = 2819876 | pmc = 299089 | doi = 10.1073/pnas.84.18.6425 | bibcode = 1987PNAS...84.6425 }} |
||
* {{vcite2 journal | vauthors = Suzuki K, Kusumoto H, Deyashiki Y, Nishioka J, Maruyama I, Zushi M, Kawahara S, Honda G, Yamamoto S, Horiguchi S | title = Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation | journal = The EMBO Journal | volume = 6 | issue = 7 | pages = 1891–7 | year = 1987 | date = Jul 1987 | pmid = 2820710 | pmc = 553573 }} |
* {{vcite2 journal | vauthors = Suzuki K, Kusumoto H, Deyashiki Y, Nishioka J, Maruyama I, Zushi M, Kawahara S, Honda G, Yamamoto S, Horiguchi S | title = Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation | journal = The EMBO Journal | volume = 6 | issue = 7 | pages = 1891–7 | year = 1987 | date = Jul 1987 | pmid = 2820710 | pmc = 553573 }} |
||
* {{vcite2 journal | vauthors = Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE | title = Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene | journal = Biochemistry | volume = 26 | issue = 14 | pages = 4350 | year = 1987 | date = Jul 1987 | pmid = 2822087 | doi = 10.1021/bi00388a025 }} |
* {{vcite2 journal | vauthors = Wen DZ, Dittman WA, Ye RD, Deaven LL, Majerus PW, Sadler JE | title = Human thrombomodulin: complete cDNA sequence and chromosome localization of the gene | journal = Biochemistry | volume = 26 | issue = 14 | pages = 4350 | year = 1987 | date = Jul 1987 | pmid = 2822087 | doi = 10.1021/bi00388a025 }} |
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Revision as of 13:26, 17 February 2015
Template:PBB 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
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
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
Thrombomodulin has been shown to interact with thrombin.[6][7]
References
- ^ IPR001491 Thrombomodulin Accessed January 19, 2012.
- ^ 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. PMID 8943899.
{{cite journal}}: CS1 maint: date and year (link) - ^ 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.
{{cite journal}}: CS1 maint: date and year (link) - ^ 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. doi:10.4049/jimmunol.165.11.6037. PMID 11086035.
{{cite journal}}: CS1 maint: date and year (link) - ^ 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. doi:10.1016/S0198-8859(02)00752-8. PMID 12480257.
{{cite journal}}: CS1 maint: date and year (link) - ^ 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.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: unflagged free DOI (link) - ^ 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.
{{cite journal}}: CS1 maint: date and year (link)
Further reading
- Esmon CT (Jul 1995). "Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface". FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. 9 (10): 946–55. PMID 7615164.
{{cite journal}}: CS1 maint: date and year (link) - Ohlin AK, Norlund L, Marlar RA (Jul 1997). "Thrombomodulin gene variations and thromboembolic disease". Thrombosis and Haemostasis. 78 (1): 396–400. PMID 9198186.
{{cite journal}}: CS1 maint: date and year (link) - Van de Wouwer M, Collen D, Conway EM (Aug 2004). "Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and inflammation". Arteriosclerosis, Thrombosis, and Vascular Biology. 24 (8): 1374. doi:10.1161/01.ATV.0000134298.25489.92. PMID 15178554.
{{cite journal}}: CS1 maint: date and year (link) - Boffa MC, Jackman RW, Peyri N, Boffa JF, George B (1991). "Thrombomodulin in the central nervous system". Nouvelle Revue Française D'hématologie. 33 (6): 423–9. PMID 1667949.
- Jackman RW, Beeler DL, Fritze L, Soff G, Rosenberg RD (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. Bibcode:1987PNAS...84.6425. doi:10.1073/pnas.84.18.6425. PMC 299089. PMID 2819876.
{{cite journal}}: Check|bibcode=length (help) - Suzuki K, Kusumoto H, Deyashiki Y, Nishioka J, Maruyama I, Zushi M, Kawahara S, Honda G, Yamamoto S, Horiguchi S (Jul 1987). "Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation". The EMBO Journal. 6 (7): 1891–7. PMC 553573. PMID 2820710.
{{cite journal}}: CS1 maint: date and year (link) - 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.
{{cite journal}}: CS1 maint: date and year (link) - Shirai T, Shiojiri S, Ito H, Yamamoto S, Kusumoto H, Deyashiki Y, Maruyama I, Suzuki K (Feb 1988). "Gene structure of human thrombomodulin, a cofactor for thrombin-catalyzed activation of protein C". Journal of Biochemistry. 103 (2): 281–5. PMID 2836377.
{{cite journal}}: CS1 maint: date and year (link) - Yonezawa S, Maruyama I, Tanaka S, Nakamura T, Sato E (Aug 1988). "Immunohistochemical localization of thrombomodulin in chorionic diseases of the uterus and choriocarcinoma of the stomach. A comparative study with the distribution of human chorionic gonadotropin". Cancer. 62 (3): 569. doi:10.1002/1097-0142(19880801)62:3<569::AID-CNCR2820620322>3.0.CO;2-T. PMID 2839283.
{{cite journal}}: CS1 maint: date and year (link) - Ishii H, Majerus PW (Dec 1985). "Thrombomodulin is present in human plasma and urine". The Journal of Clinical Investigation. 76 (6): 2178. doi:10.1172/JCI112225. PMID 3001144.
{{cite journal}}: CS1 maint: date and year (link) - Adler M, Seto MH, Nitecki DE, Lin JH, Light DR, Morser J (Oct 1995). "The structure of a 19-residue fragment from the C-loop of the fourth epidermal growth factor-like domain of thrombomodulin". The Journal of Biological Chemistry. 270 (40): 23366. doi:10.1074/jbc.270.40.23366. PMID 7559494.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: unflagged free DOI (link) - Ohlin AK, Marlar RA (Jan 1995). "The first mutation identified in the thrombomodulin gene in a 45-year-old man presenting with thromboembolic disease". Blood. 85 (2): 330–6. PMID 7811989.
{{cite journal}}: CS1 maint: date and year (link) - Srinivasan J, Hu S, Hrabal R, Zhu Y, Komives EA, Ni F (Nov 1994). "Thrombin-bound structure of an EGF subdomain from human thrombomodulin determined by transferred nuclear Overhauser effects". Biochemistry. 33 (46): 13553. doi:10.1021/bi00250a007. PMID 7947766.
{{cite journal}}: CS1 maint: date and year (link) - Gerlitz B, Hassell T, Vlahos CJ, Parkinson JF, Bang NU, Grinnell BW (Oct 1993). "Identification of the predominant glycosaminoglycan-attachment site in soluble recombinant human thrombomodulin: potential regulation of functionality by glycosyltransferase competition for serine474". The Biochemical Journal. 295 ( Pt 1) (1): 131–40. PMC 1134829. PMID 8216207.
{{cite journal}}: CS1 maint: date and year (link) - Yasuda K, Espinosa R, Davis EM, Le Beau MM, Bell GI (Sep 1993). "Human somatostatin receptor genes: localization of SSTR5 to human chromosome 20p11.2". Genomics. 17 (3): 785. doi:10.1006/geno.1993.1410. PMID 8244401.
{{cite journal}}: CS1 maint: date and year (link) - Yamamoto S, Mizoguchi T, Tamaki T, Ohkuchi M, Kimura S, Aoki N (Apr 1993). "Urinary thrombomodulin, its isolation and characterization". Journal of Biochemistry. 113 (4): 433–40. PMID 8390446.
{{cite journal}}: CS1 maint: date and year (link) - Meininger DP, Hunter MJ, Komives EA (Sep 1995). "Synthesis, activity, and preliminary structure of the fourth EGF-like domain of thrombomodulin". Protein Science : A Publication of the Protein Society. 4 (9): 1683. doi:10.1002/pro.5560040904. PMID 8528067.
{{cite journal}}: CS1 maint: date and year (link) - Maglott DR, Feldblyum TV, Durkin AS, Nierman WC (May 1996). "Radiation hybrid mapping of SNAP, PCSK2, and THBD (human chromosome 20p)". Mammalian Genome : Official Journal of the International Mammalian Genome Society. 7 (5): 400. doi:10.1007/s003359900120. PMID 8661740.
{{cite journal}}: CS1 maint: date and year (link)
External links
- GeneReviews/NCBI/NIH/UW entry on Atypical Hemolytic-Uremic Syndrome
- OMIM entries on Atypical Hemolytic-Uremic Syndrome
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