Factor V 1557752 224258706 2008-07-08T01:08:17Z ProteinBoxBot 3991663 Replaced protein Box Template with PBB Template for easy viewing. {{PBB|geneid=2153}} '''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 is not 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 [[platelet]]s 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 in biology|calcium]]. Factor V is active as a cofactor of the thrombinase complex. The activated [[factor X]] (FXa) enzyme requires [[calcium in biology|Ca<sup>++</sup>]] 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 [[protein C|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 [[mutation]]s of factor V are associated with [[venous thrombosis]]. They are the most common hereditary causes for [[thrombophilia]] (a tendency to form [[blood clot]]s). 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.<ref name=Stormorken>{{cite journal |author=Stormorken H |title=The discovery of factor V: a tricky clotting factor |journal=J. Thromb. Haemost. |volume=1 |issue=2 |pages=206–13 |year=2003 |pmid=12871488 |doi=10.1046/j.1538-7836.2003.00043.x}}</ref> The suggestion that an additional factor might exist was made by Dr Paul Owren (1905-1990), a [[Norway|Norwegian]] physician, during his investigations into the bleeding tendency of a lady called Mary (1914-2002). She had suffered from [[epistaxis|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 [[World War II|Second World War]], and while Owren published his results in Norway in 1944, he could not publish them internationally until the war was over. They appeared finally in ''[[The Lancet]]'' in [[1947]].<ref>{{cite journal |last=Owren |first=PA |year=1947 |title=Parahaemophilia. Haemorrhagic diathesis due to absence of a previously unknown clotting factor |journal=Lancet |volume=1 |pages=446–51 |doi=10.1016/S0140-6736(47)91941-7}}</ref><ref name=Stormorken/> The possibility of an extra coagulation factor was initially resisted on methodological grounds by Drs Armand Quick and Walter Seegers, both world authorities in coagulation. Confirmatory studies from other groups led to their final approval several years later.<ref name=Stormorken/> Owren initially felt that factor V (labile factor or proaccelerin) activated another factor, which he named VI. VI was the factor that accelerated the conversion from prothrombin to thrombin. It was later discovered that factor V was "converted" (activated) by thrombin itself, and later still that factor VI was simply the activated form of factor V.<ref name=Stormorken/> The complete amino acid sequence of the protein was published in 1987.<ref>{{cite journal |author=Jenny RJ, Pittman DD, Toole JJ, ''et al'' |title=Complete cDNA and derived amino acid sequence of human factor V |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue=14 |pages=4846–50 |year=1987 |pmid=3110773 |doi=10.1073/pnas.84.14.4846}}</ref> In 1994 [[factor V Leiden]], resistant to inactivation by [[protein C]], was described; this abnormality is the most common genetic cause for [[thrombosis]].<ref>{{cite journal |author=Bertina RM, Koeleman BP, Koster T, ''et al'' |title=Mutation in blood coagulation factor V associated with resistance to activated protein C |journal=Nature |volume=369 |issue=6475 |pages=64–7 |year=1994 |pmid=8164741 |doi=10.1038/369064a0}}</ref> ==References== {{reflist}} ==Further reading== {{refbegin | 2}} {{PBB_Further_reading | citations = *{{cite journal | author=Hooper WC, De Staercke C |title=The relationship between FV Leiden and pulmonary embolism |journal=Respir. Res. |volume=3 |issue= |pages= 8 |year= 2006 |pmid= 11806843 |doi= }} *{{cite journal | author=Schrijver I, Houissa-Kastally R, Jones CD, ''et al.'' |title=Novel factor V C2-domain mutation (R2074H) in two families with factor V deficiency and bleeding |journal=Thromb. Haemost. |volume=87 |issue= 2 |pages= 294–9 |year= 2002 |pmid= 11858490 |doi= }} *{{cite journal | author=Mann KG, Kalafatis M |title=Factor V: a combination of Dr Jekyll and Mr Hyde |journal=Blood |volume=101 |issue= 1 |pages= 20–30 |year= 2003 |pmid= 12393635 |doi= 10.1182/blood-2002-01-0290 }} *{{cite journal | author=Duga S, Asselta R, Tenchini ML |title=Coagulation factor V |journal=Int. J. Biochem. Cell Biol. |volume=36 |issue= 8 |pages= 1393–9 |year= 2005 |pmid= 15147718 |doi= 10.1016/j.biocel.2003.08.002 }} *{{cite journal | author=Andreassi MG, Botto N, Maffei S |title=Factor V Leiden, prothrombin G20210A substitution and hormone therapy: indications for molecular screening |journal=Clin. Chem. Lab. Med. |volume=44 |issue= 5 |pages= 514–21 |year= 2006 |pmid= 16681418 |doi= 10.1515/CCLM.2006.103 }} *{{cite journal | author=Du X |title=Signaling and regulation of the platelet glycoprotein Ib-IX-V complex |journal=Curr. Opin. Hematol. |volume=14 |issue= 3 |pages= 262–9 |year= 2007 |pmid= 17414217 |doi= 10.1097/MOH.0b013e3280dce51a }} }} {{refend}} ==External links== * [http://macromoleculeinsights.com/coagulationfactorv.php The Coagulation Factor V Protein] {{Coagulation}} [[Category:Coagulation system]] [[de:Proaccelerin]] [[fr:Proaccélérine]] [[pl:Proakceleryna]] [[pt:Factor V]] [[sv:Faktor V]] <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. --> {{PBB_Controls | update_page = yes | require_manual_inspection = no | update_protein_box = yes | update_summary = no | update_citations = yes }}