Factor V

A protein of the coagulation system, rarely ref2242ed to as proaccelerin or labile factor.

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.

In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor.

Deficiency leads to predisposition for hemorrhage.

Some mutations, particularly, factor V Leiden predispose for thrombosis.

Factor V protein consists of six domains: A1-A2-B-A3-C1-C2.

The B domain C-terminus acts as a cofactor for the anticoagulant protein C and activation by protein S.

Activation of factor V to factor Va is done by cleavage and release of the B domain, after which the protein no longer assists in activating protein C.

Factor V synthesis occurs in the liver, principally.

The Factor V molecule circulates in plasma as a single-chain molecule with a plasma half-life of 12–36 hours.

Factor V is able to bind to activated platelets.

It is activated by thrombin.

When activated, factor V is spliced in two chains, a heavy and light chain with molecular masses of 110000 and 73000, respectively.

These chains are noncovalently bound to each other by calcium.

The activated factor V. called FVa, is a cofactor of the prothrombinase complex.

Activated factor X (FXa) enzyme requires calcium and activated factor V to convert prothrombin to thrombin on the cell surface membrane.

Factor Va is degraded by activated protein C.

Protein C is one of the principal physiological inhibitors of coagulation.

In the presence of thrombomodulin, thrombin acts to decrease clotting by activating Protein C.

The concentration and action of protein C are important determinants in the negative feedback loop through which thrombin limits its own activation.

Deficiency of Factor V is associated with a rare mild form of hemophilia, termed parahemophilia.

The incidence of parahemophilia is about 1:1,000,000, and is inherited in an autosomal recessive fashion.

Mutations of factor V are associated with venous thrombosis, and are the most common hereditary causes for thrombophilia.

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.

Factor remains active and increases the rate of thrombin generation.

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