Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. It is a serine protease (EC 3.4.21.5) that converts fibrinogen into fibrin. The coagulation of blood is a complex process during which blood forms solid clots. ... The coagulation of blood is a complex process during which blood forms solid clots. ... In biochemistry, serine proteases or serine endopeptidases (newer name) are a class of peptidases (enzymes that cleave peptide bonds in proteins) that are characterised by the presence of a serine residue in the active center of the enzyme. ... EC numbers (Enzyme Commission numbers) are a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Fibrin is a protein involved in the clotting of blood. ... Fibrin is a protein involved in the clotting of blood. ...

Generation

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 gamma-carboxyglutamic acid residues promote the binding of thrombin to phospholipid bilayers. 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 (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. ... Factor X, also known by the eponym Stuart-Prower factor or as thrombokinase, is an enzyme ( EC 3. ... Factor V is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. ... Vitamin K denotes a group of 2-methilo-naphthoquinone derivatives. ... Warfarin (also known under the brand names of Coumadin® and Marevan®) is an anticoagulant medication that is administered orally. ...

Action

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 XI or plasma thromboplastin antecent is one of the enzymes ( EC 3. ... Factor V is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. ... Factor VIII (FVIII) is an essential clotting factor. ...

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. Factor XIII or fibrin stabilizing factor is an enzyme (EC 2. ...

Platelets

In addition to its activity in the coagulation cascades, thrombin also promotes platelet activation, via activation of protease-activated receptors on the platelet. A 250 ml bag of newly collected platelets. ... A protease-activated receptor is a cell receptor that is activated by cleavage of part of its extracellular domain. ...

Inhibitors and fibrinolysis

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. Protein C is a major physiological anticoagulant. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ...

Role in disease

Activation of prothrombin is crucial in physiological and pathological coagulation. Various rare diseases involving prothrombin have been described.

An apparently quite common disorder (up to 5% in Western patients) is the substitution of adenine for guanine at position 20210 of the prothrombin gene. Although this falls outside the reading frame for the protein, it leads to high levels of prothrombin and a possibly increased risk of thrombosis (Poort et al 1996). Adenine is one of the two purine nucleobases used in forming nucleotides of the nucleic acids DNA and RNA. In DNA, adenine (A) binds to thymine (T) via two hydrogen bonds to assist in stabilizing the nucleic acid structures. ... Guanine is one of the five main nucleobases found in nucleic acids (, DNA and RNA). ... In biology, a reading frame is a contiguous and non-overlapping set of three-nucleotide codons in DNA or RNA. There are 3 possible reading frames in a strand. ... Thrombosis is the formation of a clot or thrombus inside a blood vessel, obstructing the flow of blood through the circulatory system. ...

Gene

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. This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Figure 1: Chromosome. ...

References

• Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. 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. PMID 8916933.