Factor V Totally Explained

Everything about Factor V totally explained

,, | Name = Coagulation factor V (proaccelerin, labile factor) | HGNCid = 3542 | Symbol = F5 | AltSymbols =; FVL; PCCF; factor V | OMIM = 227400 | ECnumber = | Homologene = 104 | MGIid = 88382 | GeneAtlas_image1 = PBB_GE_F5_204714_s_at_tn.png | GeneAtlas_image2 = PBB_GE_F5_204713_s_at_tn.png | Function = | Component = | Process = | Orthologs = }} Factor V is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it isn't enzymatically active but functions as a cofactor. Deficiency leads to predisposition for hemorrhage, while some mutations (most notably factor V Leiden) predispose for thrombosis.

Genetics

The gene for factor V is located on the first chromosome (1q23). It is genomically related to the family of multicopper oxidases, and is homologous to coagulation factor VIII. The gene spans 70 kb, consists of 25 exons, and the resulting protein has a relative molecular mass of approximately 330000.

Physiology

Factor V circulates in plasma as a single-chain molecule with a plasma half-life of about 12 hours. Half-lives up to 36 hours have been reported, though.
Factor V is able to bind to activated platelets and is activated by thrombin. On activation, factor V is spliced in two chains (heavy and light chain with molecular masses of 110000 and 73000, respectively) which are nonconvalently bound to each other by calcium. Factor V is active as a cofactor of the thrombinase complex. The activated factor X (FXa) enzyme requires Ca⁺⁺ and activated factor V to convert prothrombin to thrombin on the cell surface membrane. This is considered part of the common pathway in the coagulation cascade.
Factor Va is degraded by activated protein C, one of the principal physiological inhibitors of coagulation. In the presence of thrombomodulin, thrombin acts to decrease clotting by activating Protein C; therefore, the concentration and action of protein C are important determinants in the negative feedback loop through which thrombin limits its own activation.

Role in disease

Various hereditary disorders of factor V are known. Deficiency is associated with a rare mild form of hemophilia (termed parahemophilia or Owren parahemophilia), the incidence of which is about 1:1,000,000. It inherits in an autosomal recessive fashion.
Other mutations of factor V are associated with venous thrombosis. They are the most common hereditary causes for thrombophilia (a tendency to form blood clots). The most common one of these, factor V Leiden, is due to the replacement of an arginine residue with glutamine at amino acid position 506 (R506Q). All prothrombotic factor V mutations (factor V Leiden, factor V Cambridge, factor V Hong Kong) make it resistant to cleavage by activated protein C ("APC resistance"). It therefore remains active and increases the rate of thrombin generation.

History

Until the discovery of factor V, coagulation was regarded as a product of four factors: calcium (IV) and thrombokinase (III) together acting on prothrombin (II) to produce fibrinogen (I); this model had been outlined by Paul Morawitz in 1905.
The suggestion that an additional factor might exist was made by Dr Paul Owren (1905-1990), a Norwegian physician, during his investigations into the bleeding tendency of a lady called Mary (1914-2002). She had suffered from nosebleeds and menorrhagia (excessive menstrual blood loss) for most her life, and was found to have a prolonged prothrombin time, suggesting either vitamin K deficiency or chronic liver disease leading to prothrombin deficiency. However, neither were the case, and Owren demonstrated this by correcting the abnormality with plasma from which prothrombin had been removed. Using Mary's serum as index, he found that the "missing" factor, which he labeled V (I-IV having been used in Morawitz' model), had particular characteristics. Most investigations were performed during the Second World War, and while Owren published his results in Norway in 1944, he couldn't publish them internationally until the war was over. They appeared finally in The Lancet in 1947. In 1994 factor V Leiden, resistant to inactivation by protein C, was described; this abnormality is the most common genetic cause for thrombosis.

Further Information

Get more info on 'Factor V'.

External Link Exchanges

Do you know how hard it is to get a link from a large encyclopaedia? Well we're different and will prove it. To get a link from us just add the following HTML to your site on a relevant page:

<a href="http://factor_v.totallyexplained.com">Factor V Totally Explained</a>

Then simply click through this link from your web page. Our crawlers will verify your link, extract the title of your web page and instantly add a link back to it. If you like you can remove the words Totally Explained and embed the link in article text.
As long as your link remains in place, we'll keep our link to you right here. Please play fair - our crawlers are watching. Your site must be closely related to this one's topic. Any kind of spamming, dubious practises or removing the link will result in your link from us being dropped and, potentially, your whole site being banned.