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Gene Review

F2  -  coagulation factor II

Mus musculus

Synonyms: Cf-2, Cf2, Coagulation factor II, FII, Prothrombin, ...
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Disease relevance of F2


High impact information on F2


Chemical compound and disease context of F2


Biological context of F2

  • Characterization of the cDNA coding for mouse prothrombin and localization of the gene on mouse chromosome 2 [12].
  • The complete prothrombin cDNA is 1,987 bp in length [excluding the poly(A) tail] and codes for 18 bp of 5' untranslated sequence, an open reading frame coding for 618 amino acids, a stop codon, and a 3' untranslated region of 112 bp followed by a poly(A) tail [12].
  • A series of overlapping cDNAs coding for mouse prothrombin (coagulation factor II) have been isolated and the composite DNA sequence has been determined [12].
  • The conversion of prothrombin (FII) to the serine protease, thrombin (FIIa), is a key step in the coagulation cascade because FIIa triggers platelet activation, converts fibrinogen to fibrin, and activates regulatory pathways that both promote and ultimately suppress coagulation [13].
  • The predicted posttranslational modifications, including disulfide bonds, N-glycosylation, phosphorylation, and sulfation, in pseutarin C are significantly different compared with bovine factor V. Thus, our data demonstrate that the nonenzymatic subunit of group C prothrombin activators is structurally similar to mammalian FV [14].

Anatomical context of F2


Associations of F2 with chemical compounds

  • Chymotrypsin digestion of prothrombin and isolation on QAE-Sephadex of the peptide representing amino-terminal residues 1-44 of prothrombin further localized the antigenic site recognized by the monoclonal antibody to the highly conserved gamma-carboxyglutamic acid-containing domain [19].
  • We monitored neuromuscular behavior, correlated with acetylcholinesterase and silver nitrate histochemistry at endplates, for changes in the timecourse of in vivo synapse elimination and assayed both thrombin activity and prothrombin expression in developing muscle [20].
  • Processing was facilitated by CaCl2 but prevented by a thrombin inhibitor and did not occur in prothrombin-depleted plasma [21].
  • Recent experiments showing that thrombin is released from myotubes in culture under the influence of acetylcholine suggest that locally-synthesized prothrombin may be the source of this Hebbian synaptic interaction [18].
  • Following protein adsorption to the column, prothrombin was washed out using a sodium phosphate buffer containing 2 mM imidazole and protein C was recovered with 15 mM imidazole in the buffer [4].

Physical interactions of F2

  • All three antibodies bound to the light chain of protein C on immunoblots and also bound to the homologous proteins factor X and prothrombin in solid-phase radioimmunoassays [22].
  • Differently from platelets, B16F10-assembled prothrombinase complex was inhibited by prothrombin fragment 1 but not by fragment 2 [23].
  • The three-dimensional structure of prothrombin predicted by homology modeling also revealed that the prothrombin fragment 1 and the catalytic domain structures are well conserved except for the insertion of an extra 7-amino-acid loop in the connecting region (CR) between the Gla and kringle I domain of fragment 1 [24].

Enzymatic interactions of F2


Regulatory relationships of F2


Other interactions of F2

  • In contrast to the thrombin receptor, prothrombin mRNA was limited to the embryonic liver and was not detected until E12.5, well after the onset of receptor expression. mRNA for tissue factor, one important trigger for thrombin generation in the adult, was detected in embryonic epithelia from E9.5-12 [26].
  • The prothrombin locus lies on mouse chromosome 2, 1.8 +/- 1.3 map units proximal to the catalase locus [12].
  • Anti-TF or anti-FVII/VIIa (but not inhibited factor IXa) delayed the burst in thrombin production by gel-filtered platelets suspended in prothrombin and CVX by 14 min and 40 min, respectively [28].
  • As compared with WT mice, MT (-/-) mice revealed significant prolongation of prothrombin and activated partial thromboplastin time, a significant increase in the levels of fibrinogen and fibrinogen/fibrin degradation products, and a significant decrease in activated protein C, after LPS treatment [29].
  • Factor IX is proposed to have branched off early on, followed by protein C and prothrombin and finally factors VII and X [30].

Analytical, diagnostic and therapeutic context of F2


  1. A recombinant murine meizothrombin precursor, prothrombin R157A/R268A, inhibits thrombosis in a model of acute carotid artery injury. Shim, K., Zhu, H., Westfield, L.A., Sadler, J.E. Blood (2004) [Pubmed]
  2. The PB1-F2 protein of Influenza A virus: increasing pathogenicity by disrupting alveolar macrophages. Coleman, J.R. Virol. J. (2007) [Pubmed]
  3. Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice. Xue, J., Wu, Q., Westfield, L.A., Tuley, E.A., Lu, D., Zhang, Q., Shim, K., Zheng, X., Sadler, J.E. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Homologous human blood protein separation using immobilized metal affinity chromatography: protein C separation from prothrombin with application to the separation of factor IX and prothrombin. Wu, H., Bruley, D.F. Biotechnol. Prog. (1999) [Pubmed]
  5. Generation of C5a in the absence of C3: a new complement activation pathway. Huber-Lang, M., Sarma, J.V., Zetoune, F.S., Rittirsch, D., Neff, T.A., McGuire, S.R., Lambris, J.D., Warner, R.L., Flierl, M.A., Hoesel, L.M., Gebhard, F., Younger, J.G., Drouin, S.M., Wetsel, R.A., Ward, P.A. Nat. Med. (2006) [Pubmed]
  6. Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V. Cui, J., O'Shea, K.S., Purkayastha, A., Saunders, T.L., Ginsburg, D. Nature (1996) [Pubmed]
  7. Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life. Nagashima, M., Yin, Z.F., Zhao, L., White, K., Zhu, Y., Lasky, N., Halks-Miller, M., Broze, G.J., Fay, W.P., Morser, J. J. Clin. Invest. (2002) [Pubmed]
  8. Regulation of factor IXa in vitro in human and mouse plasma and in vivo in the mouse. Role of the endothelium and the plasma proteinase inhibitors. Fuchs, H.E., Trapp, H.G., Griffith, M.J., Roberts, H.R., Pizzo, S.V. J. Clin. Invest. (1984) [Pubmed]
  9. A Ca++ activated serine protease (LOPAP) could be responsible for the haemorrhagic syndrome caused by the caterpillar Lonomia obliqua. L obliqua Prothrombin Activator Protease. Reis, C.V., Kelen, E.M., Farsky, S.H., Portaro, F.C., Sampaio, C.A., Fernandes, B.L., Camargo, A.C., Chudzinski-Tavassi, A.M. Lancet (1999) [Pubmed]
  10. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Price, P.A., Faus, S.A., Williamson, M.K. Arterioscler. Thromb. Vasc. Biol. (1998) [Pubmed]
  11. Antihaemostatic and antithrombotic effect of some antiplatelet agents isolated from Chinese herbs. Teng, C.M., Ko, F.N., Wang, J.P., Lin, C.N., Wu, T.S., Chen, C.C., Huang, T.F. J. Pharm. Pharmacol. (1991) [Pubmed]
  12. Characterization of the cDNA coding for mouse prothrombin and localization of the gene on mouse chromosome 2. Degen, S.J., Schaefer, L.A., Jamison, C.S., Grant, S.G., Fitzgibbon, J.J., Pai, J.A., Chapman, V.M., Elliott, R.W. DNA Cell Biol. (1990) [Pubmed]
  13. Prothrombin deficiency results in embryonic and neonatal lethality in mice. Sun, W.Y., Witte, D.P., Degen, J.L., Colbert, M.C., Burkart, M.C., Holmbäck, K., Xiao, Q., Bugge, T.H., Degen, S.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  14. The nonenzymatic subunit of pseutarin C, a prothrombin activator from eastern brown snake (Pseudonaja textilis) venom, shows structural similarity to mammalian coagulation factor V. Rao, V.S., Swarup, S., Kini, R.M. Blood (2003) [Pubmed]
  15. Activated factor X and thrombin formation triggered by tissue factor on endothelial cell matrix in a flow model: effect of the tissue factor pathway inhibitor. van 't Veer, C., Hackeng, T.M., Delahaye, C., Sixma, J.J., Bouma, B.N. Blood (1994) [Pubmed]
  16. Transcriptional regulation of the prothrombin gene in muscle. Kim, S., Nelson, P.G. J. Biol. Chem. (1998) [Pubmed]
  17. Antiangiogenic property of human thrombin. Chan, B., Merchan, J.R., Kale, S., Sukhatme, V.P. Microvasc. Res. (2003) [Pubmed]
  18. Quantitative PCR analysis reveals novel expression of prothrombin mRNA and regulation of its levels in developing mouse muscle. Citron, B.A., Smirnova, I.V., Zoubine, M.N., Festoff, B.W. Thromb. Res. (1997) [Pubmed]
  19. A conserved epitope on several human vitamin K-dependent proteins. Location of the antigenic site and influence of metal ions on antibody binding. Church, W.R., Messier, T., Howard, P.R., Amiral, J., Meyer, D., Mann, K.G. J. Biol. Chem. (1988) [Pubmed]
  20. A molecular mechanism for synapse elimination: novel inhibition of locally generated thrombin delays synapse loss in neonatal mouse muscle. Zoubine, M.N., Ma, J.Y., Smirnova, I.V., Citron, B.A., Festoff, B.W. Dev. Biol. (1996) [Pubmed]
  21. Thrombin-mediated in vitro processing of pro-von Willebrand factor. Váradi, K., Turecek, P.L., Mitterer, A., Dorner, F., Schwarz, H.P. Thromb. Haemost. (2001) [Pubmed]
  22. Conformational changes in an epitope localized to the NH2-terminal region of protein C. Evidence for interaction of protein C domains. Orthner, C.L., Madurawe, R.D., Velander, W.H., Drohan, W.N., Battey, F.D., Strickland, D.K. J. Biol. Chem. (1989) [Pubmed]
  23. Assembly and regulation of prothrombinase complex on B16F10 melanoma cells. Kirszberg, C., Rumjanek, V.M., Monteiro, R.Q. Thromb. Res. (2005) [Pubmed]
  24. Characterization of zebrafish full-length prothrombin cDNA and linkage group mapping. Jagadeeswaran, P., Gregory, M., Zhou, Y., Zon, L., Padmanabhan, K., Hanumanthaiah, R. Blood Cells Mol. Dis. (2000) [Pubmed]
  25. Cellular and metabolic requirements for induction of macrophage procoagulant activity by murine hepatitis virus strain 3 in vitro. Chung, S., Sinclair, S., Leibowitz, J., Skamene, E., Fung, L.S., Levy, G. J. Immunol. (1991) [Pubmed]
  26. Disparate temporal expression of the prothrombin and thrombin receptor genes during mouse development. Soifer, S.J., Peters, K.G., O'Keefe, J., Coughlin, S.R. Am. J. Pathol. (1994) [Pubmed]
  27. Suppression of infection-induced endotoxin shock in mice by a citrus flavanone naringin. Kawaguchi, K., Kikuchi, S., Hasunuma, R., Maruyama, H., Ryll, R., Kumazawa, Y. Planta Med. (2004) [Pubmed]
  28. Factor VIIa-mediated tenase function on activated platelets under flow. Goel, M.S., Diamond, S.L. J. Thromb. Haemost. (2004) [Pubmed]
  29. Role of metallothionein in coagulatory disturbance and systemic inflammation induced by lipopolysaccharide in mice. Inoue, K., Takano, H., Shimada, A., Wada, E., Yanagisawa, R., Sakurai, M., Satoh, M., Yoshikawa, T. FASEB J. (2006) [Pubmed]
  30. Molecular reconstruction and homology modelling of the catalytic domain of the common ancestor of the haemostatic vitamin-K-dependent serine proteinases. Krawczak, M., Wacey, A., Cooper, D.N. Hum. Genet. (1996) [Pubmed]
  31. Partial characterization of vertebrate prothrombin cDNAs: amplification and sequence analysis of the B chain of thrombin from nine different species. Banfield, D.K., MacGillivray, R.T. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  32. Regulation of prothrombin, thrombin receptor, and protease nexin-1 expression during development and after denervation in muscle. Kim, S., Buonanno, A., Nelson, P.G. J. Neurosci. Res. (1998) [Pubmed]
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