Gene Symbol: F2
Description: coagulation factor II, thrombin
Alias: RPRGL2, THPH1, prothrombin, prepro-coagulation factor II, prothrombin B-chain, serine protease, thrombin factor II
Species: human
Products:     F2

Top Publications

  1. Poort S, Rosendaal F, Reitsma P, Bertina R. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996;88:3698-703 pubmed
    We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia...
  2. Miyawaki Y, Suzuki A, Fujita J, Maki A, Okuyama E, Murata M, et al. Thrombosis from a prothrombin mutation conveying antithrombin resistance. N Engl J Med. 2012;366:2390-6 pubmed publisher
    ..Arg596Leu) in the gene encoding prothrombin (called prothrombin Yukuhashi)...
  3. Marrero J, Feng Z, Wang Y, Nguyen M, Befeler A, Roberts L, et al. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. Gastroenterology. 2009;137:110-8 pubmed publisher
    ..Des-gamma carboxy-prothrombin (DCP) and lectin-bound AFP (AFP-L3%) are potential surveillance tests for HCC...
  4. Hu L, Ibrahim S, Liu C, Skaar J, Pagano M, Karpatkin S. Thrombin induces tumor cell cycle activation and spontaneous growth by down-regulation of p27Kip1, in association with the up-regulation of Skp2 and MiR-222. Cancer Res. 2009;69:3374-81 pubmed publisher
    ..04). Repetitive hirudin, a specific potent antithrombin, decreased tumor volume 13- to 24-fold (P < 0.04). Thus, thrombin stimulates tumor cell growth in vivo by down-regulation of p27(Kip1). ..
  5. Chon Y, Choi G, Lee M, Kim S, Kim D, Ahn S, et al. Combined measurement of preoperative ?-fetoprotein and des-?-carboxy prothrombin predicts recurrence after curative resection in patients with hepatitis-B-related hepatocellular carcinoma. Int J Cancer. 2012;131:2332-41 pubmed publisher
    Alpha-fetoprotein (AFP) and des-?-carboxy prothrombin (DCP) are widely used complementary tumor markers for hepatocellular carcinoma (HCC)...
  6. Lee M, Kim S, Kim D, Ahn S, Choi E, Lee K, et al. Early on-treatment predictions of clinical outcomes using alpha-fetoprotein and des-gamma-carboxy prothrombin responses in patients with advanced hepatocellular carcinoma. J Gastroenterol Hepatol. 2012;27:313-22 pubmed publisher
    The clinical utility of alpha-fetoprotein (AFP) and des-?-carboxy prothrombin (DCP) as a predictor of treatment outcome in patients with advanced hepatocellular carcinoma (HCC) receiving hepatic artery infusional chemotherapy (HAIC) or ..
  7. Danckwardt S, Gantzert A, Macher Goeppinger S, Probst H, Gentzel M, Wilm M, et al. p38 MAPK controls prothrombin expression by regulated RNA 3' end processing. Mol Cell. 2011;41:298-310 pubmed publisher
    ..Although induced in many (patho-)physiological conditions, the underlying mechanisms controlling prothrombin expression remained enigmatic...
  8. Ng N, Quinsey N, Matthews A, Kaiserman D, Wijeyewickrema L, Bird P, et al. The effects of exosite occupancy on the substrate specificity of thrombin. Arch Biochem Biophys. 2009;489:48-54 pubmed publisher
    ..Thus, exosite I ligands do affect the activity and specificity of thrombin, but not greatly enough to explain the altered substrate profile of the enzyme when complexed with thrombomodulin. ..
  9. Murata K, Suzuki H, Okano H, Oyamada T, Yasuda Y, Sakamoto A. Hypoxia-induced des-gamma-carboxy prothrombin production in hepatocellular carcinoma. Int J Oncol. 2010;36:161-70 pubmed
    Des-gamma-carboxy prothrombin (DCP) is an established HCC tumor marker, but the precise mechanism of its production is still unclear...

More Information


  1. Olivieri O, Martinelli N, Girelli D, Pizzolo F, Friso S, Beltrame F, et al. Apolipoprotein C-III predicts cardiovascular mortality in severe coronary artery disease and is associated with an enhanced plasma thrombin generation. J Thromb Haemost. 2010;8:463-71 pubmed publisher
    ..Such concentrations were associated with an enhanced plasma endogenous thrombin generation, suggesting a complex interplay between TG-rich particles and the coagulation cascade as well as a new 'thrombogenetic' role for apo C-III. ..
  2. Rungroj N, Sritippayawan S, Thongnoppakhun W, Paemanee A, Sawasdee N, Nettuwakul C, et al. Prothrombin haplotype associated with kidney stone disease in Northeastern Thai patients. Urology. 2011;77:249.e17-23 pubmed publisher
    ..including trefoil factor 1, calgranulin (A, B, and C), bikunin, osteopontin, tamm-Horsfall protein, and prothrombin, respectively, were initially genotyped in 112 individuals each and in additional subjects to consist of 164 ..
  3. Said J, Higgins J, Moses E, Walker S, Borg A, Monagle P, et al. Inherited thrombophilia polymorphisms and pregnancy outcomes in nulliparous women. Obstet Gynecol. 2010;115:5-13 pubmed publisher
    ..Genotyping for factor V Leiden, prothrombin gene mutation, methylenetetrahydrofolate reductase enzyme (MTHFR) C677T, MTHFR A1298C, and thrombomodulin ..
  4. Silver R, Zhao Y, Spong C, Sibai B, Wendel G, Wenstrom K, et al. Prothrombin gene G20210A mutation and obstetric complications. Obstet Gynecol. 2010;115:14-20 pubmed publisher
    To estimate whether maternal carriage of the prothrombin gene G20210A mutation is associated with pregnancy loss, preeclampsia, placental abruption, or small for gestational age (SGA) neonates in a low-risk, prospective cohort.
  5. Gissel M, Undas A, Slowik A, Mann K, Brummel Ziedins K. Plasma factor and inhibitor composition contributes to thrombin generation dynamics in patients with acute or previous cerebrovascular events. Thromb Res. 2010;126:262-9 pubmed publisher
    ..Augmented thrombin generation in acute stroke/TIA is to some extent determined by altered plasma levels of coagulation factors. ..
  6. Yin X, Wright J, Wall T, Grammas P. Brain endothelial cells synthesize neurotoxic thrombin in Alzheimer's disease. Am J Pathol. 2010;176:1600-6 pubmed publisher
  7. Seremak Mrozikiewicz A, Drews K, Wender Ozegowska E, Mrozikiewicz P. The significance of genetic polymorphisms of factor V Leiden and prothrombin in the preeclamptic Polish women. J Thromb Thrombolysis. 2010;30:97-104 pubmed publisher
    ..Inherited thrombophilias, like polymorphism of factor V (FV) Leiden and prothrombin (PTM) are considered to be involved in the PE development...
  8. Kamath P, Huntington J, Krishnaswamy S. Ligand binding shuttles thrombin along a continuum of zymogen- and proteinase-like states. J Biol Chem. 2010;285:28651-8 pubmed publisher
    ..These interconversions, reciprocally regulated by different ligands, cast new light on the problem of thrombin allostery and provide a thermodynamic framework to explain the regulation of thrombin by different ligands. ..
  9. Houston D, Timson D. Interaction of prothrombin with a phospholipid surface: evidence for a membrane-induced conformational change. Mol Cell Biochem. 2011;348:109-15 pubmed publisher
    b>Prothrombin interacts with phosphatidylserine containing platelet membranes via its N-terminal, ?-carboxyglutamate (gla) residue-rich domain. Once bound it is cleaved to form the active protease, thrombin (factor IIa)...
  10. Beijers H, Ferreira I, Spronk H, Bravenboer B, Dekker J, Nijpels G, et al. Body composition as determinant of thrombin generation in plasma: the Hoorn study. Arterioscler Thromb Vasc Biol. 2010;30:2639-47 pubmed publisher
    ..This association may partially be explained by adiposity-related low-grade inflammation, but this hypothesis needs to be further investigated in mechanistic/prospective studies. ..
  11. Ceelie H, Bertina R, Van Hylckama Vlieg A, Rosendaal F, Vos H. Polymorphisms in the prothrombin gene and their association with plasma prothrombin levels. Thromb Haemost. 2001;85:1066-70 pubmed
    To find genetic causes of high plasma prothrombin levels, an established prothrombotic risk factor. we searched for sequence variations in the prothrombin gene...
  12. D Elia A, Driul L, Giacomello R, Colaone R, Fabbro D, Di Leonardo C, et al. Frequency of factor V, prothrombin and methylenetetrahydrofolate reductase gene variants in preeclampsia. Gynecol Obstet Invest. 2002;53:84-7 pubmed
    The association between thrombophilic variants (Leiden mutation of the factor V gene, G20210A mutation of the prothrombin gene and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene) with preeclampsia was ..
  13. Pollak E, Lam H, Russell J. The G20210A mutation does not affect the stability of prothrombin mRNA in vivo. Blood. 2002;100:359-62 pubmed
    The activated form of prothrombin plays pivotal roles in the regulation of crucial coagulation, fibrinolytic, and cellular processes...
  14. Kumar S, Kumar A, Srivastava S, Saraswat V, Aggarwal R. Low frequency of factor V Leiden and prothrombin G20210A mutations in patients with hepatic venous outflow tract obstruction in northern India: a case-control study. Indian J Gastroenterol. 2005;24:211-5 pubmed
    Factor V Leiden (FVL) and prothrombin gene (G20210A) mutations are known to be associated with venous thromboembolism. Several studies have shown an association of these mutations with hepatic venous outflow tract obstruction (HVOTO)...
  15. Butenas S, Orfeo T, Gissel M, Brummel K, Mann K. The significance of circulating factor IXa in blood. J Biol Chem. 2004;279:22875-82 pubmed
  16. Lin G, Xu P, Qi H, Lian J, Zheng H, Dang X. Relations of Budd-Chiari syndrome to prothrombin gene mutation. Hepatobiliary Pancreat Dis Int. 2004;3:214-8 pubmed
    ..This study was to explore whether prothrombin gene mutation (FII G20210A) takes part in the pathogenesis of BCS and to investigate their correlativity...
  17. Pineda A, Carrell C, Bush L, Prasad S, Caccia S, Chen Z, et al. Molecular dissection of Na+ binding to thrombin. J Biol Chem. 2004;279:31842-53 pubmed
    ..The role of the water network uncovered in this study establishes a new paradigm for the allosteric regulation of thrombin and other Na(+)-activated enzymes involved in blood coagulation and the immune response. ..
  18. Frances F, Portoles O, Gabriel F, Corella D, Sorlí J, Sabater A, et al. [Factor V Leiden (G1691A) and prothrombin-G20210A alleles among patients with deep venous thrombosis and in the general population from Spain]. Rev Med Chil. 2006;134:13-20 pubmed
    Factor V leiden and the -G20210A variant of prothrombin gene are associated to a higher risk of deep venous thrombosis...
  19. Colak Y, Karasu Z, Oruc N, Can C, Balým Z, Akarca U, et al. Hyperhomocysteinaemia and factor V Leiden mutation are associated with Budd-Chiari syndrome. Eur J Gastroenterol Hepatol. 2006;18:917-20 pubmed
    ..We aimed to study the role of hyperhomocysteinaemia, factor V Leiden mutation and G20210A prothrombin gene mutation in the pathogenesis of the syndrome...
  20. Kim H, Park J, Jang J, Kim H, Shin W, Kim K, et al. Prognostic values of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in hepatitis B virus-related hepatocellular carcinoma: a prospective study. J Clin Gastroenterol. 2009;43:482-8 pubmed publisher
    ..258, 95% confidence interval: 2.418-8.445, P<0.001). Serum PIVKA-II level, not serum AFP, was a valuable independent prognostic factor in HBV-related HCC. ..
  21. Dentali F, Galli M, Gianni M, Ageno W. Inherited thrombophilic abnormalities and risk of portal vein thrombosis. a meta-analysis. Thromb Haemost. 2008;99:675-82 pubmed publisher
    ..It was the purpose of this study to assess the risk of PVT associated with factor V Leiden (FVL) and G20210A prothrombin mutation (PTM)...
  22. Rosendaal F, Siscovick D, Schwartz S, Psaty B, Raghunathan T, Vos H. A common prothrombin variant (20210 G to A) increases the risk of myocardial infarction in young women. Blood. 1997;90:1747-50 pubmed
    ..These results, in which the effect of major coronary risk factors is enhanced fourfold to sixfold by the prothrombin variant, are similar to those previously reported for another genetic clotting abnormality, factor V Leiden...
  23. Lima L, Zingali R, Foguel D, Monteiro R. New insights into conformational and functional stability of human alpha-thrombin probed by high hydrostatic pressure. Eur J Biochem. 2004;271:3580-7 pubmed
    ..5 m urea was also present. Altogether, analysis of urea and HHP effects on thrombin structure and activity indicates the formation of dissimilar intermediate states during denaturation by these agents. ..
  24. Dudding T, Heron J, Thakkinstian A, Nurk E, Golding J, Pembrey M, et al. Factor V Leiden is associated with pre-eclampsia but not with fetal growth restriction: a genetic association study and meta-analysis. J Thromb Haemost. 2008;6:1869-75 pubmed publisher
    ..V gene, the 1691G to A change (rs6025) located on chromosome 1q23 (factor V Leiden, FVL), and the other in the prothrombin gene, 20210G to A change (rs1799963) on chromosome 11p11-q12 (PT). These results, however, are conflicting...
  25. Lin J, August P. Genetic thrombophilias and preeclampsia: a meta-analysis. Obstet Gynecol. 2005;105:182-92 pubmed
    ..single nucleotide polymorphism (SNP), the methylene tetrahydrofolate reductase (MTHFR) 677 C-T SNP, and the prothrombin 20210 G-A SNP and the risk of preeclampsia, by conducting a meta-analysis of all case-control studies with data ..
  26. Rydel T, Ravichandran K, Tulinsky A, Bode W, Huber R, Roitsch C, et al. The structure of a complex of recombinant hirudin and human alpha-thrombin. Science. 1990;249:277-80 pubmed
    ..In all, 27 of the 65 residues of hirudin have contacts less than 4.0 A with thrombin (10 ion pairs and 23 hydrogen bonds). Such abundant interactions may account for the high affinity and specificity of hirudin. ..
  27. Huntington J, Esmon C. The molecular basis of thrombin allostery revealed by a 1.8 A structure of the "slow" form. Structure. 2003;11:469-79 pubmed
    ..These residues constitute an allosteric switch, which is flipped directly through sodium binding, resulting in the fast form with an open active site. ..
  28. van der Putten H, Spaargaren van Riel C, Bertina R, Vos H. Functional analysis of two prothrombin 3'-untranslated region variants: the C20209T variant, mainly found among African-Americans, and the C20209A variant. J Thromb Haemost. 2006;4:2285-7; author reply 2288-9 pubmed
  29. Danckwardt S, Kaufmann I, Gentzel M, Foerstner K, Gantzert A, Gehring N, et al. Splicing factors stimulate polyadenylation via USEs at non-canonical 3' end formation signals. EMBO J. 2007;26:2658-69 pubmed
    The prothrombin (F2) 3' end formation signal is highly susceptible to thrombophilia-associated gain-of-function mutations...
  30. Dusse L, Carvalho M, Bragança W, Paiva S, Godoi L, Guimarães D, et al. Inherited thrombophilias and pre-eclampsia in Brazilian women. Eur J Obstet Gynecol Reprod Biol. 2007;134:20-3 pubmed
    ..Differences in the mutation frequencies detected in the two groups were not statistically significant. No correlation was observed between pre-eclampsia and presence of G1691A, G20210A and C677T mutations in Brazilian women. ..
  31. Brummel K, Paradis S, Butenas S, Mann K. Thrombin functions during tissue factor-induced blood coagulation. Blood. 2002;100:148-52 pubmed
    ..time with inhibitors, the soluble phases were analyzed for thrombin-antithrombin III (TAT) complex formation, prothrombin fragments, platelet activation (osteonectin release), factor Va generation, fibrinopeptide (FP) A and FPB ..
  32. Webber D, Rodgers A, Sturrock E. Glycosylation of prothrombin fragment 1 governs calcium oxalate crystal nucleation and aggregation, but not crystal growth. Urol Res. 2007;35:277-85 pubmed
    ..In several cases, this has been attributed to glycosylation of the proteins as evidenced by urinary prothrombin fragment 1 where there is a correlation between sialylation and calcium oxalate kidney stone disease...
  33. Yalinkaya A, Erdemoglu M, Akdeniz N, Kale A, Kale E. The relationship between thrombophilic mutations and preeclampsia: a prospective case-control study. Ann Saudi Med. 2006;26:105-9 pubmed
    ..two months after delivery for mutations of factor V Leiden, methylenetetrahydrofolate reductase (MTHFR), and prothrombin gene mutation as well as for deficiencies of protein C, protein S, and antithrombin III...
  34. . No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age. Circulation. 2003;107:1117-22 pubmed
    ..This study provides no evidence supporting an association between 9 polymorphisms of genes encoding proteins involved in hemostasis and the occurrence of premature myocardial infarction or protection against it. ..
  35. Russo C, Girelli D, Olivieri O, Guarini P, Manzato F, Pizzolo F, et al. G20210A prothrombin gene polymorphism and prothrombin activity in subjects with or without angiographically documented coronary artery disease. Circulation. 2001;103:2436-40 pubmed
    G20210A prothrombin mutation has been associated with high prothrombin levels and an increased risk of venous thrombosis...
  36. Wu O, Robertson L, Twaddle S, Lowe G, Clark P, Greaves M, et al. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study. Health Technol Assess. 2006;10:1-110 pubmed
    ..FVL); deficiencies of antithrombin, protein C, or protein S, elevated levels of factor VIIIc; and FVL and prothrombin G20210A. For hormone replacement therapy (HRT), a significant association was found in women with FVL...
  37. Weger M, Renner W, Pinter O, Stanger O, Temmel W, Fellner P, et al. Role of factor V Leiden and prothrombin 20210A in patients with retinal artery occlusion. Eye (Lond). 2003;17:731-4 pubmed
    ..Numerous studies have shown that two genetic variants, factor V Leiden and prothrombin 20210A, cause a procoagulant state...
  38. Radjabi A, Sawada K, Jagadeeswaran S, Eichbichler A, Kenny H, Montag A, et al. Thrombin induces tumor invasion through the induction and association of matrix metalloproteinase-9 and beta1-integrin on the cell surface. J Biol Chem. 2008;283:2822-34 pubmed
    The procoagulatory serine protease, thrombin, is known to induce invasion and metastasis in various cancers, but the mechanisms by which it promotes tumorigenesis are poorly understood...
  39. Esmon C. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem. 1989;264:4743-6 pubmed
  40. Tang W, Miki K, Kokudo N, Sugawara Y, Imamura H, Minagawa M, et al. Des-gamma-carboxy prothrombin in cancer and non-cancer liver tissue of patients with hepatocellular carcinoma. Int J Oncol. 2003;22:969-75 pubmed
    Des-gamma-carboxy prothrombin (DCP), also known as protein induced by vitamin K absence or antagonist II absence (PIVKA-II), has been considered as a useful serum tumor marker for hepatocellular carcinoma (HCC)...
  41. Kupferminc M, Peri H, Zwang E, Yaron Y, Wolman I, Eldor A. High prevalence of the prothrombin gene mutation in women with intrauterine growth retardation, abruptio placentae and second trimester loss. Acta Obstet Gynecol Scand. 2000;79:963-7 pubmed
    ..investigate the association between pregnancy complications and the guanine 20210 adenine (G20210A) mutation in prothrombin gene...
  42. Leung A, Huang C, Muto R, Liu Y, Pan Q. CYP2C9 and VKORC1 genetic polymorphism analysis might be necessary in patients with Factor V Leiden and prothrombin gene G2021A mutation(s). Diagn Mol Pathol. 2007;16:184-6 pubmed
    ..Factor V Leiden gene (most common) and the prothrombin G20210A gene mutation are inherited mild to moderate risk factors for hypercoagulability...
  43. Almawi W, Ameen G, Tamim H, Finan R, Irani Hakime N. Factor V G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T gene polymorphism in angiographically documented coronary artery disease. J Thromb Thrombolysis. 2004;17:199-205 pubmed
    Single point mutations in the genes coding for factor V [G1691A; Leiden], prothrombin [PRT; G20210A], and methylenetetrahydrofolate reductase [MTHFR, C677T] were shown to be major inherited predisposing factors for venous thromboembolism...
  44. Celikel R, McClintock R, Roberts J, Mendolicchio G, Ware J, Varughese K, et al. Modulation of alpha-thrombin function by distinct interactions with platelet glycoprotein Ibalpha. Science. 2003;301:218-21 pubmed
    ..These interactions may modulate alpha-thrombin function by mediating GpIbalpha clustering and cleavage of protease-activated receptors, which promote platelet activation, while limiting fibrinogen clotting through blockade of exosite I. ..
  45. Ceelie H, Spaargaren van Riel C, Bertina R, Vos H. G20210A is a functional mutation in the prothrombin gene; effect on protein levels and 3'-end formation. J Thromb Haemost. 2004;2:119-27 pubmed
    The prothrombin G20210A mutation is associated with increased plasma prothrombin levels and risk of thrombosis...
  46. Doggen C, Cats V, Bertina R, Rosendaal F. Interaction of coagulation defects and cardiovascular risk factors: increased risk of myocardial infarction associated with factor V Leiden or prothrombin 20210A. Circulation. 1998;97:1037-41 pubmed
    A genetic variation located in the 3'-untranslated region of the prothrombin gene (prothrombin 20210 G-->A) was recently described as a risk factor for venous thrombosis...
  47. Lu Y, Zhao Y, Liu G, Wang X, Liu Z, Chen B, et al. Factor V gene G1691A mutation, prothrombin gene G20210A mutation, and MTHFR gene C677T mutation are not risk factors for pulmonary thromboembolism in Chinese population. Thromb Res. 2002;106:7-12 pubmed
    A mutation in coagulant factor V gene, a substitution in the 3' untranslated region of prothrombin gene, and a variant in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have been reported to be related to venous thromboembolism in ..
  48. Dumas J, Kumar R, Seehra J, Somers W, Mosyak L. Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation. Science. 2003;301:222-6 pubmed
    ..The details of these interactions reconcile GpIbalpha-thrombin binding modes that are presently controversial,highlighting two distinct interfaces that are potential targets for development of novel antithrombotic drugs. ..
  49. Burzotta F, Paciaroni K, De Stefano V, Crea F, Maseri A, Leone G, et al. G20210A prothrombin gene polymorphism and coronary ischaemic syndromes: a phenotype-specific meta-analysis of 12 034 subjects. Heart. 2004;90:82-6 pubmed
    To investigate the possible link between the G20210A prothrombin gene variant and different forms of ischaemic heart disease...
  50. Orfeo T, Brufatto N, Nesheim M, Xu H, Butenas S, Mann K. The factor V activation paradox. J Biol Chem. 2004;279:19580-91 pubmed
    ..factor Xa and a positive effector of factor Xa catalytic efficiency and thus is key to efficient conversion of prothrombin to thrombin...
  51. Karakantza M, Androutsopoulos G, Mougiou A, Sakellaropoulos G, Kourounis G, Decavalas G. Inheritance and perinatal consequences of inherited thrombophilia in Greece. Int J Gynaecol Obstet. 2008;100:124-9 pubmed
    ..To investigate the impact of inherited thrombophilic factors on the gestational outcome of unselected pregnant women...
  52. Vu T, Hung D, Wheaton V, Coughlin S. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991;64:1057-68 pubmed
    ..These data reveal a novel signaling mechanism in which thrombin cleaves its receptor's amino-terminal extension to create a new receptor amino terminus that functions as a tethered ligand and activates the receptor. ..
  53. Bode W, Mayr I, Baumann U, Huber R, Stone S, Hofsteenge J. The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J. 1989;8:3467-75 pubmed
    ..The narrow active site cleft, with a more polar base and hydrophobic rims, extends towards the arginine-rich surface of loop Lys70-Glu80 that probably represents part of the anionic binding region for hirudin and fibrinogen. ..
  54. Degen S, Davie E. Nucleotide sequence of the gene for human prothrombin. Biochemistry. 1987;26:6165-77 pubmed
    A human genomic DNA library was screened for the gene coding for human prothrombin with a cDNA coding for the human protein. Eighty-one positive lambda phage were identified, and three were chosen for further characterization...
  55. Ozdag H, Egin Y, Akar N. Prothrombin gene 20209 C >T along with the first description of a homozygous polymorphism at the 3' downstream region +4 C >T in the Turkish population. Lab Hematol. 2006;12:131-3 pubmed
    Mutation screening studies related with thrombosis revealed that prothrombin 20210A allele of the prothrombin gene leads to an increase in plasma prothrombin levels...
  56. Danckwardt S, Gehring N, Neu Yilik G, Hundsdoerfer P, Pforsich M, Frede U, et al. The prothrombin 3'end formation signal reveals a unique architecture that is sensitive to thrombophilic gain-of-function mutations. Blood. 2004;104:428-35 pubmed
    The functional analysis of the common prothrombin 20210 G>A(F2 20210(*)A) mutation has recently revealed gain of function of 3'end processing as a novel genetic mechanism predisposing to human disease...
  57. Jun Z, Ping T, Lei Y, Li L, Ming S, Jing W. Prevalence of factor V Leiden and prothrombin G20210A mutations in Chinese patients with deep venous thrombosis and pulmonary embolism. Clin Lab Haematol. 2006;28:111-6 pubmed
    ..Several genetic risk factors, especially factor V Leiden and prothrombin G20210A mutations have been reported to be related to VTE in Caucasians, but the relationship remains ..
  58. Dizon Townson D, Miller C, Sibai B, Spong C, Thom E, Wendel G, et al. The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstet Gynecol. 2005;106:517-24 pubmed
    ..antithrombin III deficiency, activated protein C resistance, or lupus anticoagulant-positive, heterozygous for prothrombin G20210A or homozygous for the 5,10 methylenetetrahydrofolate reductase mutations...
  59. Almawi W, Tamim H, Kreidy R, Timson G, Rahal E, Nabulsi M, et al. A case control study on the contribution of factor V-Leiden, prothrombin G20210A, and MTHFR C677T mutations to the genetic susceptibility of deep venous thrombosis. J Thromb Thrombolysis. 2005;19:189-96 pubmed
    Insofar as the inherited prothrombotic single nucleotide polymorphisms (SNPs) factor V G1691A (FV-Leiden), prothrombin (PRT) G20210A, and methylenetetrahydrofolate reductase (MTHFR), C677T are inherited risk factors of venous ..
  60. Carter A, Sachchithananthan M, Stasinopoulos S, Maurer F, Medcalf R. Prothrombin G20210A is a bifunctional gene polymorphism. Thromb Haemost. 2002;87:846-53 pubmed
    The G20210A polymorphism has been shown to alter the efficiency of prothrombin mRNA processing. Here we show that the G20210A mutation also alters prothrombin mRNA stability...
  61. Li C, Vindigni A, Sadler J, Wardell M. Platelet glycoprotein Ib alpha binds to thrombin anion-binding exosite II inducing allosteric changes in the activity of thrombin. J Biol Chem. 2001;276:6161-8 pubmed
  62. Heller C, Schobess R, Kurnik K, Junker R, Gunther G, Kreuz W, et al. Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors - a multicentre case-control study. For the Childhood Thrombophilia Study Group. Br J Haematol. 2000;111:534-9 pubmed
    The factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, the methylenetetrahydrofolate reductase (MTHFR) T677T genotype, together with fasting homocysteine (HCY) concentration, lipoprotein (Lp)(a), anti-thrombin (AT), ..
  63. Huang Y, Li J, Hu L, Lee M, Karpatkin S. Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells. Blood. 2002;99:1646-50 pubmed
    ..Thus, thrombin-induced tumorigenesis and metastasis is associated with enhanced Ang-2 protein synthesis and secretion via enhanced transcription of Ang-2. This could help explain how thrombin promotes angiogenesis. ..
  64. von Ahsen N, Oellerich M. The intronic prothrombin 19911A>G polymorphism influences splicing efficiency and modulates effects of the 20210G>A polymorphism on mRNA amount and expression in a stable reporter gene assay system. Blood. 2004;103:586-93 pubmed
    The common prothrombin gene cleavage site mutation 20210G>A is associated with elevated prothrombin levels and thrombosis...
  65. Stubbs M, Oschkinat H, Mayr I, Huber R, Angliker H, Stone S, et al. The interaction of thrombin with fibrinogen. A structural basis for its specificity. Eur J Biochem. 1992;206:187-95 pubmed
    ..The multiple interactions between thrombin and fibrinogen provide an explanation for the narrow specificity of thrombin. Structural grounds can be put forward for certain congenital clotting disorders. ..
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    The gene for human prothrombin, or factor II (F2) has been assigned to 11p11-q12 by the combined use of a panel of somatic cell hybrid DNAs and in situ hybridization, using both cDNA and genomic probes...
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    ..Two recently identified prothrombin gene mutations (20209C>T and 20221C>T) have been observed in non-Caucasian patients with thrombosis...
  72. Colucci M, Binetti B, Tripodi A, Chantarangkul V, Semeraro N. Hyperprothrombinemia associated with prothrombin G20210A mutation inhibits plasma fibrinolysis through a TAFI-mediated mechanism. Blood. 2004;103:2157-61 pubmed
    The prothrombin gene mutation G20210A is a common risk factor for thrombosis and is associated with increased prothrombin levels. However, the mechanism whereby hyperprothrombinemia predisposes to thrombosis remains unclear...
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    ..the frequency and type of vascular lesions and to study the association of factor V gene G1691A (Leiden) and prothrombin gene G20210A polymorphisms with venous thrombosis in Italian patients with Behçet's disease (BD)...
  74. Casas J, Hingorani A, Bautista L, Sharma P. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch Neurol. 2004;61:1652-61 pubmed
    ..33; 95% CI, 1.12-1.58), methylenetetrahydrofolate reductase C677T (OR, 1.24; 95% CI, 1.08-1.42), prothrombin G20210A (OR, 1.44; 95% CI, 1.11-1.86), and angiotensin-converting enzyme insertion/deletion (OR, 1...
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    ..The allelic prevalence of the factor V Leiden and 20210 G/A prothrombin variants in this population was 2.1% and 0.5% respectively...
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    ..In summary, fibrinogen gamma' chain binds with high affinity to thrombin and inhibits with combined mechanisms the platelet response to thrombin. Thus, its variations in vivo may affect the hemostatic balance in arterial circulation. ..
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    ..9, 95% confidence interval (CI) 0.4, 2.2; prothrombin mutation, OR 1.9, 95% CI 0.5, 7.0; methylentetrahydrofolate reductase 677TT genotype, OR 0.8, 95% CI 0.4, 1...
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    ..9-fold increased risk (OR(adj) 7.86, 95% CI 4.70-13.15); for prothrombin 20210A this was a 6.6-fold increased risk (OR(adj) 6.58, 95% CI 2.31-18.69)...
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    ..puerperium is predisposed to by polymorphisms G1691A in the factor V gene (F5) (F5G1691A) and G20210A in the prothrombin gene (F2) (F2G20210A)...
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    ..The polymorphisms studied were: G1691A in Factor V (Factor V Leiden; FVL), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, plasminogen activator inhibitor-1 4G/5G and the ..
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