The Full Wiki

Prothrombin: Wikis


Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.


(Redirected to Thrombin article)

From Wikipedia, the free encyclopedia

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
Symbols F2; PT
External IDs OMIM176930 MGI88380 HomoloGene426 GeneCards: F2 Gene
RNA expression pattern
PBB GE F2 205754 at tn.png
More reference expression data
Species Human Mouse
Entrez 2147 14061
Ensembl ENSG00000180210 ENSMUSG00000027249
UniProt P00734 Q3TJ94
RefSeq (mRNA) NM_000506 NM_010168
RefSeq (protein) NP_000497 NP_034298
Location (UCSC) Chr 11:
46.7 - 46.72 Mb
Chr 2:
91.43 - 91.44 Mb
PubMed search [1] [2]

Thrombin (activated Factor II [IIa]) also commonly called pro-thrombin is a coagulation protein in the blood stream 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 Thrombin (prothrombin) gene is located on the eleventh chromosome (11p11-q12). The molecular weight of prothrombin is approximately 72000 gmol-1. The catalytic domain is released from prothrombin fragment 1.2 to create the active enzyme thrombin, which has a molecular weight of 36000 gmol-1.

There are an estimated 30 people in the world that have been diagnosed with the congenital form of Factor II deficiency,[1] which should not be confused with a mutation of prothrombin. The prothrombin gene mutation is called Factor II mutation. Factor II mutation is congenital.[2] 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 (1 pair), or much more rarely, homozygous (2 pairs), 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.[3]

Anchoring of bovine prothrombin to the membrane through its Gla domain




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 prothrombin 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.

In human adults the normal blood level of antithrombin activity has been measured to be around 1.1 units /ml. Newborn levels of thrombin steadily increase after birth to reach normal adult levels, from a level of around 0.5 units/ml 1 day after birth, to a level of around 0.9 units/ml after 6 months of life.[4]


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 bound to thrombomodulin 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 also known as (antiphospholipid syndrome). Hyperprothrombinemia can be caused by a mutation at 20210a.

Thrombin, a potent vasoconstrictor and mitogen, is implicated as a major factor in vasospasm following subarachnoid hemorrhage. Blood from a ruptured cerebral aneurysm clots around a cerebral artery, releasing thrombin. This can induce an acute and prolonged narrowing of the blood vessel, potentially resulting in cerebral ischemia and infarction (stroke).


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). The direct thrombin inhibitors, a newer class of medication, directly inhibit thrombin by binding to its active site.

Use in food production

Thrombin is sold under the brand name Fibrimex for use as a binding agent for meat. The thrombin in Fibrimex derives from pigs or bovine blood.[5] According to the manufacturer it can be used to new kinds of mixed meats (for example combining beef and fish seamlessly). The manufacturer also states that it can be used to combine scrap meat into whole steaks which can then be sold to a higher price, thus cutting down on production costs.[6]

Critizism against use in food production

General secretary Jan Bertoft of Sveriges Konsumenter (The Consumer Coalition of Sweden) has stated that "there is danger of misleading the consumers since there is no way to tell this reconstituted meat from real meet"[5]


After the description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converts fibrinogen into fibrin in 1872.[7]


Thrombin has been shown to interact with Thrombomodulin.[8][9]

See also

External links


  1. ^ Degen SJ, McDowell SA, et al. (1995). "Prothrombin Frankfurt: a dysfunctional prothrombin characterized by substitution of Glu-466 by Ala". Thromb. Haemost. 73 (2): 203–209. PMID 7792730. 
  2. ^ Varga EA, Moll S. (2004). "Cardiology patient pages. Prothrombin 20210 mutation (factor II mutation)". Circulation 110 (3): e15-8. PMID 15262854. 
  3. ^ Bernstein CN, Sargent M, et al. (2007). "Mutations in clotting factors and inflammatory bowel disease". Am. J. Gastroenterol. 102 (2): 338–343. PMID 17156138. 
  4. ^ Andrew M, Paes B et al. (1987). "Development of the human coagulation system in the full-term infant". Blood 70 (1): 165–172. PMID 3593964. 
  5. ^ a b "Sverige röstade ja till köttklister", Dagens nyheter, Stockholm, February 9, 2010.
  6. ^ Fibrimex website
  7. ^ Schmidt A (1872). "Neue Untersuchungen ueber die Fasserstoffesgerinnung". Pflüger's Archiv für die gesamte Physiologie 6: 413–538. doi:10.1007/BF01612263. 
  8. ^ Bajzar, L; Morser J, Nesheim M (Jul. 1996). "TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex". J. Biol. Chem. (UNITED STATES) 271 (28): 16603–8. ISSN 0021-9258. PMID 8663147. 
  9. ^ Jakubowski, H V; Owen W G (Jul. 1989). "Macromolecular specificity determinants on thrombin for fibrinogen and thrombomodulin". J. Biol. Chem. (UNITED STATES) 264 (19): 11117–21. ISSN 0021-9258. PMID 2544585. 

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/ (inactive 2008-06-28). 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/ (inactive 2008-06-28). PMID 12023853. 
  • Firth SM, Baxter RC (2003). "Cellular actions of the insulin-like growth factor binding proteins". Endocr. Rev 23 (6): 824–54. doi:10.1210/er.2001-0033. 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.


Got something to say? Make a comment.
Your name
Your email address