Factor V

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, 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-lifes 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. Protein C itself is activated by thrombin, and concentration and action of protein C are therefore 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

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.

External link

Coagulation system