The first cupredoxin domain of coagulation factor VIII and similar proteins
Factor V is an essential coagulation protein with both pro- and anti-coagulant functions. Aberrant expression of human factor V can lead to bleeding or thromboembolic disease, which may be life-threatening. Bovine factor Va serves as the cofactor in the prothrombinase complex that results in a 300,000-fold increase in the rate of thrombin generation. Factor V is synthesized as a single polypeptide with six cupredoxin domains and a domain structure of 1-2-3-4-B-5-6-C1-C2, where 1-6 are cupredoxin domains, B is a domain with no known structural homologs and is dispensible for coagulant activity, and C are domains distantly related to discoidin protein-fold family members. Factor V has little activity prior to proteolytic cleavage by thrombin or FXa upon secretion. The resulting Factor Va is a heterodimer consisting of a heavy chain (1-2-3-4) and a light chain (5-6-C1-C2). This model represents the cupredoxin domain 1 of unprocessed Factor V or the heavy chain of Factor Va, and similar proteins including pseutarin C non-catalytic subunit. Pseutarin C is a prothrombin activator from Pseudonaja textilis venom.
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