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Thrombin (activated Factor II [IIa]) is a coagulation protein that has many effects in the coagulation cascade. It is a serine protease (EC 3.4.21.5) 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 gmol-1; in contrast, the molecular weight of thrombin is 36000 gmol-1. Once activated, the catalytic domain of prothrombin is released from prothrombin fragment 1.2. There are an estimated 30 people in the world that 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.
In human beings the level of prothrombin in the blood stream increases after birth and typically peaks on the 8th day after which the prothrombin level lowers to normal levels.[1]
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.
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