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.
Physiology
Factor V is bound to platelets and is activated by thrombin. On activation, factor V is spliced in two chains (heavy and light chain) which are nonconvalently bound to each other by calcium.
Factor Va, the activated form, is a cofactor for factor X in its reciprocal activation of prothrombin (factor II) into thrombin.
Factor Va is degraded by activated protein C, one of the principal physiological inhibitors of coagulation.
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 (R506G). 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
It was discovered in 1947 by Dr Paul Owren (1905-1990). The complete amino acid sequence of the protein was published in 1987 by Jenny et al.
Reference
- Jenny RJ, Pittman DD, Toole JJ, Kriz RW, Aldape RA, Hewick RM, Kaufman RJ, Mann KG. Complete cDNA and derived amino acid sequence of human factor V. Proc Natl Acad Sci U S A. 1987;84:4846-50. PMID 3110773.
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