Factor X

Editors-In-Chief: John Alexander, M.D. [mailto:john.h.alexander@duke.edu], Duke Clinical Research Institute;  C. Michael Gibson, M.S., M.D. Duke Clinical Research Institute  [mailto:mgibson@perfuse.org]

Overview
Factor X, also known by the eponym Stuart-Prower factor or as thrombokinase, is an enzyme of the coagulation cascade. It is a serine endopeptidase (protease group S1).

Physiology
Factor X is synthesized in the liver and requires vitamin K for its synthesis.

Factor X is activated into factor Xa by both factor IX (with its cofactor, factor VIII in a complex known as intrinsic Xase) and factor VII with its cofactor, tissue factor (a complex known as extrinsic Xase). It is therefore the first member of the final common pathway or thrombin pathway.

It acts by cleaving prothrombin in two places (an arg-thr and then an arg-ile bond), which yields the active thrombin. This process is optimized when factor Xa is complexed with activated co-factor V in the prothrombinase complex.

Factor Xa is inactivated by protein Z-dependent protease inhibitor (ZPI), a serine protease inhibitor (serpin). The affinity of this protein for factor Xa is increased 1000-fold by the presence of protein Z, while it does not require protein Z for inactivation of factor XI. Defects in protein Z lead to increased factor Xa activity and a propensity for thrombosis.

The half life of factor X is 40-45 hours.

Genetics
The human factor X gene is located on the thirteenth chromosome (13q34).

Role in disease
Inborn deficiency of factor X is very uncommon (1:500,000), and may present with epistaxis (nosebleeds), hemarthrosis (bleeding into joints) and gastrointestinal blood loss. Apart from congenital deficiency, low factor X levels may occur occasionally in a number of disease states.

Deficiency of vitamin K or antagonism by warfarin (or similar medication) leads to the production of an inactive factor X. In warfarin therapy, this is desirable to prevent thrombosis. As of late 2007, four out of five emerging anti-coagulation therapeutics targeted this enzyme.

Therapeutic use
Factor X is not commercially available as a concentrate, but is part of fresh frozen plasma and prothrombin complex.

Use in Biochemistry
The Factor Xa protease can be used in biochemistry to cleave off protein tags that improve expression or purification of a protein of interest. Its preferred cleavage site (after the arginine in ile-glu/asp-gly-arg) can easily be engineered between a tag sequence and the protein of interest. After expression and purification, the tag is then proteolytically removed by Factor Xa.

History
American and British scientists described deficiency of factor X independently in 1953 and 1956, respectively. As with some other coagulation factors, the factor was initially named after these patients, a Mr Rufus Stuart and a Miss Audrey Prower.