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Last Updated: 2019-08-16
Blood coagulation can be initiated by either an extrinsic or an intrinsic pathway, resulting in a cascade of serine protease activation that ultimately leads to the formation of thrombin, which converts soluble fibrinogen to an insoluble fibrin clot. The extrinsic, or tissue factor, pathway is initiated upon vascular injury, when the membrane-bound protein tissue factor (TF) comes into contact with factor VII or VIIa in plasma. The TF-VIIa complex is the strongest known activator of the coagulation cascade, and converts factors IX and X to IXa and Xa, respectively. Factors VII, IX, and X are vitamin-K-dependent proteins produced in the liver. In the intrinsic, or contact, pathway, injury exposes collagen to the bloodstream where is binds to factor XII and activates it to XIIa. Factor XIIa converts prekallikrein to kallikrein and factor XI to XIa. Both the extrinsic and intrinsic pathways result in the activation of factor IX to IXa, which forms the 'tenase' complex with factor VIIIa, calcium and phospholipids. This complex converts factor X to Xa and is important in haemostasis. Factor Xa complexes with factor Va (which functions as a non-enzymatic cofactor), calcium and a phospholipid membrane surface to form what is called the prothrombinase complex, which converts prothrombin to thrombin. Thrombin converts soluble fibrinogen to insoluble fibrin polymer, which is stabilized by cross-linking by coagulation factor XIIIa.
Kunieda M, Tsuji T, Abbasi AR, Khalaj M, Ikeda M, Miyadera K, Ogawa H, Kunieda T: An insertion mutation of the bovine Fii gene is responsible for factor XI deficiency in Japanese black cattle. Mamm Genome. 2005 May;16(5):383-9.Pubmed: 16104386
Shibuya Y, Semba U, Okabe H, Kambara T, Yamamoto T: Primary structure of bovine Hageman factor (blood coagulation factor XII): comparison with human and guinea pig molecules. Biochim Biophys Acta. 1994 May 18;1206(1):63-70. doi: 10.1016/0167-4838(94)90073-6.Pubmed: 8186251
Fujikawa K, Walsh KA, Davie EW: Isolation and characterization of bovine factor XII (Hageman factor). Biochemistry. 1977 May 17;16(10):2270-8. doi: 10.1021/bi00629a036.Pubmed: 861210
Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marcais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42. doi: 10.1186/gb-2009-10-4-r42. Epub 2009 Apr 24.Pubmed: 19393038
Katayama K, Ericsson LH, Enfield DL, Walsh KA, Neurath H, Davie EW, Titani K: Comparison of amino acid sequence of bovine coagulation Factor IX (Christmas Factor) with that of other vitamin K-dependent plasma proteins. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4990-4. doi: 10.1073/pnas.76.10.4990.Pubmed: 291916
van Dieijen G, Tans G, Rosing J, Hemker HC: The role of phospholipid and factor VIIIa in the activation of bovine factor X. J Biol Chem. 1981 Apr 10;256(7):3433-42.Pubmed: 6782101
Guinto ER, Esmon CT, Mann KG, MacGillivray RT: The complete cDNA sequence of bovine coagulation factor V. J Biol Chem. 1992 Feb 15;267(5):2971-8.Pubmed: 1737753
Xue J, Kalafatis M, Silveira JR, Kung C, Mann KG: Determination of the disulfide bridges in factor Va heavy chain. Biochemistry. 1994 Nov 8;33(44):13109-16. doi: 10.1021/bi00248a021.Pubmed: 7947716
Adams TE, Hockin MF, Mann KG, Everse SJ: The crystal structure of activated protein C-inactivated bovine factor Va: Implications for cofactor function. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8918-23. doi: 10.1073/pnas.0403072101. Epub 2004 Jun 7.Pubmed: 15184653
Irwin DM, Robertson KA, MacGillivray RT: Structure and evolution of the bovine prothrombin gene. J Mol Biol. 1988 Mar 5;200(1):31-45. doi: 10.1016/0022-2836(88)90331-2.Pubmed: 3379642
MacGillivray RT, Davie EW: Characterization of bovine prothrombin mRNA and its translation product. Biochemistry. 1984 Apr 10;23(8):1626-34. doi: 10.1021/bi00303a007.Pubmed: 6326805
Irwin DM, Ahern KG, Pearson GD, MacGillivray RT: Characterization of the bovine prothrombin gene. Biochemistry. 1985 Nov 19;24(24):6854-61. doi: 10.1021/bi00345a018.Pubmed: 3000440
This pathway was propagated using PathWhiz - Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000586
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