Catalytic activity: Degradation of blood coagulation factors Va and VIIIa.
Subunit structure: Synthesized as a single chain precursor, which is cleaved into a light chain and a heavy chain held together by a disulfide bond. The enzyme is then activated by thrombin, which cleaves a tetradecapeptide from the amino end of the heavy chain; this reaction, which occurs at the surface of endothelial cells, is strongly promoted by thrombomodulin.
Tissue specificity: Plasma; synthesized in the liver.
Post-translational: The vitamin K-dependent, enzymatic carboxylation of some Glu residues allows the modified protein to bind calcium. N- and O-glycosylated. Partial (70%) N-glycosylation of Asn- 371 with an atypical N-X-C site produces a higher molecular weight form referred to as alpha. The lower molecular weight form, not N- glycosylated at Asn-371, is beta. O-glycosylated with core 1 or possibly core 8 glycans. The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. May be phosphorylated on a Ser or Thr in a region (AA 25-30) of the propeptide.
Involvement in disease: Thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:176860]: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency. Note=The disease is caused by mutations affecting the gene represented in this entry. Thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:612304]: A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare. Note=The disease is caused by mutations affecting the gene represented in this entry.