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Coagulation factor II (thrombin)
Thrombin in complex with an inhibitor
Available structures: 1a2c, 1a3b, 1a3e, 1a46, 1a4w, 1a5g, 1a61, 1abi, 1abj, 1ad8, 1ae8, 1afe, 1aht, 1ai8, 1aix, 1awf, 1awh, 1ay6, 1b5g, 1b7x, 1ba8, 1bb0, 1bbr, 1bcu, 1bhx, 1bmm, 1bmn, 1bth, 1c1u, 1c1v, 1c1w, 1c4u, 1c4v, 1c4y, 1c5l, 1c5n, 1c5o, 1ca8, 1d3d, 1d3p, 1d3q, 1d3t, 1d4p, 1d6w, 1d9i, 1de7, 1dit, 1dm4, 1doj, 1dwb, 1dwc, 1dwd, 1dwe, 1dx5, 1e0f, 1eb1, 1eoj, 1eol, 1fpc, 1fph, 1g30, 1g32, 1g37, 1ghv, 1ghw, 1ghx, 1ghy, 1gj4, 1gj5, 1h8d, 1h8i, 1hag, 1hah, 1hai, 1hao, 1hap, 1hbt, 1hdt, 1hgt, 1hlt, 1hut, 1hxe, 1hxf, 1ihs, 1iht, 1jmo, 1jou, 1jwt, 1k21, 1k22, 1kts, 1ktt, 1lhc, 1lhd, 1lhe, 1lhf, 1lhg, 1mh0, 1mu6, 1mu8, 1mue, 1nm6, 1no9, 1nrn, 1nro, 1nrp, 1nrq, 1nrr, 1nrs, 1nt1, 1nu7, 1nu9, 1ny2, 1nzq, 1o0d, 1o2g, 1o5g, 1ook, 1oyt, 1p8v, 1ppb, 1qbv, 1qhr, 1qj1, 1qj6, 1qj7, 1qur, 1rd3, 1riw, 1sb1, 1sfq, 1sg8, 1sgi, 1shh, 1sl3, 1sr5, 1t4u, 1t4v, 1ta2, 1ta6, 1tb6, 1tbz, 1thp, 1thr, 1ths, 1tmb, 1tmt, 1tmu, 1tom, 1tq0, 1tq7, 1twx, 1ucy, 1uma, 1uvs, 1vit, 1vr1, 1vzq, 1w7g, 1way, 1wbg, 1xm1, 1xmn, 1ycp, 1ype, 1ypg, 1ypj, 1ypk, 1ypl, 1ypm, 1z71, 1z8i, 1z8j, 1zgi, 1zgv, 1zrb, 2a0q, 2a2x, 2a45, 2afq, 2ank, 2anm, 2b5t, 2bdy, 2bvr, 2bvs, 2bvx, 2bxt, 2bxu, 2c8w, 2c8x, 2c8y, 2c8z, 2c90, 2c93, 2cf8, 2cf9, 2cn0, 2feq, 2fes, 2gde, 2gp9, 2h9t, 2hgt, 2hnt, 2hpp, 2hpq, 2hwl, 2jh0, 2jh5, 2jh6, 2od3, 2thf, 3hat, 3htc, 4htc, 4thn, 5gds, 7kme, 8kme
Symbol(s) F2; PT
External IDs OMIM: 176930 MGI: 88380 Homologene: 426
RNA expression pattern

More reference expression data

Human Mouse
Entrez 2147 14061
Ensembl ENSG00000180210 ENSMUSG00000027249
Uniprot P00734 Q3TJ94
Refseq NM_000506 (mRNA)
NP_000497 (protein)
NM_010168 (mRNA)
NP_034298 (protein)
Location Chr 11: 46.7 - 46.72 Mb Chr 2: 91.43 - 91.44 Mb
Pubmed search [1] [2]

Thrombin (activated Factor II [IIa]) is a coagulation protein that has many effects in the coagulation cascade. It is a serine protease (EC that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions.



The prothrombin gene is located on the eleventh chromosome (11p11-q12). The molecular weight of prothrombin is approximately 72000. Once activated, the catalytic domain of prothrombin (i.e. thrombin, molecular weight 36000) is released from prothrombin fragment 1.2. There are an estimated 30 people in the world who have been diagnosed with the congenital form of Factor II deficiency (Degen, 1995)[3], which should not be confused with a mutation of prothrombin. The prothrombin gene mutation is called Factor II mutation. Factor II mutation is congenital.[4] The Factor II mutated gene is not usually accompanied by other factor mutations (i.e. the most common is Factor V Leiden). The gene may be inherited heterozygous, or much more rarely, homozygous, and is not related to gender or blood type. Homozygous mutations increase the risk of thrombosis more than heterozygous mutations, but the relative increased risk is not well documented. Other potential risks for thrombosis, such as oral contraceptives may be additive. The previously reported relationship of inflammatory bowel disease (i.e. Crohn's disease or Ulcerative Colitis) and prothrombin mutation or Factor V Leiden mutation have been contradicted by research.[5]




Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). The activity of factor Xa is greatly enhanced by binding to activated Factor V (Va), termed the prothrombinase complex. Prothrombin is produced in the liver and is post-translationally modified in a vitamin K-dependent reaction that converts ten glutamic acids on prothrombin to gamma-carboxyglutamic acid (Gla). In the presence of calcium, the Gla residues promote the binding of thrombin to phospholipid bilayers (see the picture). Deficiency of vitamin K or administration of the anticoagulant warfarin inhibits the production of gamma-carboxyglutamic acid residues, slowing the activation of the coagulation cascade.


Thrombin converts fibrinogen to an active form that assembles into fibrin. Thrombin also activates factor XI, factor V and factor VIII. This positive feedback accelerates the production of thrombin.

Factor XIII is also activated by thrombin. Factor XIIIa is a transglutaminase that catalyzes the formation of covalent bonds between lysine and glutamine residues in fibrin. The covalent bonds increase the stability of the fibrin clot.


In addition to its activity in the coagulation cascades, thrombin also promotes platelet activation, via activation of protease-activated receptors on the platelet.

Negative feedback

Thrombin activates protein C, an inhibitor of the coagulation cascade. The activation of protein C is greatly enhanced following the binding of thrombin to thrombomodulin, an integral membrane protein expressed by endothelial cells. Activated protein C inactivates factors Va and VIIIa. Binding of activated protein C to protein S leads to a modest increase in its activity.

Role in disease

Activation of prothrombin is crucial in physiological and pathological coagulation. Various rare diseases involving prothrombin have been described (e.g. hypoprothrombinemia). Anti-thrombin antibodies in autoimmune disease may be a factor in the formation of the lupus anticoagulant.

Prothrombin 20210a mutation

Substitution of adenine for guanine at position 20210 of the prothrombin gene, known as the prothrombin 20210a mutation, prothrombin 20210 mutation and less precisely just factor II mutation,[1][2] leads to hypercoagulability and may be a factor that contributes to infertility. Its prevalence is thought to be approximately 2% in caucasians and 0.5% in blacks.[2]

Position 20210 falls outside of the reading frame for the protein and is thought to play a role in promoting prothrombin production; the substitution leads to high levels of prothrombin.[3]


Due to its high proteolytic specificity thrombin is a valuable biochemical tool. The thrombin cleavage site (Leu-Val-Pro-Arg-Gly-Ser) is commonly included in linker regions of recombinant fusion protein constructs. Following purification of the fusion protein thrombin can be used to selectively cleave between the Arginine and Glycine residues of the cleavage site, effectively removing the purification tag from the protein of interest with a high degree of specificity.


Prothrombin complex concentrate and fresh frozen plasma are prothrombin-rich coagulation factor preparations that can be used to correct deficiencies (usually due to medication) of prothrombin. Indications include intractable bleeding due to warfarin.

Manipulation of prothrombin is central to the mode of action of most anticoagulants. Warfarin and related drugs inhibit vitamin K-dependent carboxylation of several coagulation factors, including prothrombin. Heparin increases the affinity of antithrombin to thrombin (as well as factor Xa). A newer class of medication, the direct thrombin inhibitors, directly inhibit thrombin by binding to its active site.


After the description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converted fibrinogen into fibrin in 1872.[4]


  1. ^ Steen CJ. Factor II. URL: Accessed on: March 11, 2007.
  2. ^ a b Varga E, Moll S (2004). "Cardiology patient pages. Prothrombin 20210 mutation (factor II mutation)". Circulation 110 (3): e15-8. PMID 15262854. Free Full Text.
  3. ^ Poort S, Rosendaal F, Reitsma P, Bertina R (1996). "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 88 (10): 3698-703. PMID 8916933.
  4. ^ Schmidt A (1872). "Neue Untersuchungen ueber die Fasserstoffesgerinnung". Pflüger's Archiv für die gesamte Physiologie 6: 413-538.

Further reading

  • Esmon CT (1995). "Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface.". FASEB J. 9 (10): 946-55. PMID 7615164.
  • Lenting PJ, van Mourik JA, Mertens K (1999). "The life cycle of coagulation factor VIII in view of its structure and function.". Blood 92 (11): 3983-96. PMID 9834200.
  • Plow EF, Cierniewski CS, Xiao Z, et al. (2002). "AlphaIIbbeta3 and its antagonism at the new millennium.". Thromb. Haemost. 86 (1): 34-40. PMID 11487023.
  • Maragoudakis ME, Tsopanoglou NE, Andriopoulou P (2002). "Mechanism of thrombin-induced angiogenesis.". Biochem. Soc. Trans. 30 (2): 173-7. doi:10.1042/. PMID 12023846.
  • Howell DC, Laurent GJ, Chambers RC (2002). "Role of thrombin and its major cellular receptor, protease-activated receptor-1, in pulmonary fibrosis.". Biochem. Soc. Trans. 30 (2): 211-6. doi:10.1042/. PMID 12023853.
  • Firth SM, Baxter RC (2003). "Cellular actions of the insulin-like growth factor binding proteins.". Endocr. Rev. 23 (6): 824-54. PMID 12466191.
  • Minami T, Sugiyama A, Wu SQ, et al. (2004). "Thrombin and phenotypic modulation of the endothelium.". Arterioscler. Thromb. Vasc. Biol. 24 (1): 41-53. doi:10.1161/01.ATV.0000099880.09014.7D. PMID 14551154.
  • De Cristofaro R, De Candia E (2004). "Thrombin domains: structure, function and interaction with platelet receptors.". J. Thromb. Thrombolysis 15 (3): 151-63. doi:10.1023/B:THRO.0000011370.80989.7b. PMID 14739624.
  • Tsopanoglou NE, Maragoudakis ME (2004). "Role of thrombin in angiogenesis and tumor progression.". Semin. Thromb. Hemost. 30 (1): 63-9. doi:10.1055/s-2004-822971. PMID 15034798.
  • Bode W (2007). "Structure and interaction modes of thrombin.". Blood Cells Mol. Dis. 36 (2): 122-30. doi:10.1016/j.bcmd.2005.12.027. PMID 16480903.
  • Wolberg AS (2007). "Thrombin generation and fibrin clot structure.". Blood Rev. 21 (3): 131-42. doi:10.1016/j.blre.2006.11.001. PMID 17208341.
  • Degen S: Prothrombin. In: High K, Roberts H, eds. Molecular Basis of Thrombosis and Hemostasis. New York, NY: Marcel Dekker; 1995:75.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Thrombin". A list of authors is available in Wikipedia.
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