Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa. Selective cleavage of Arg-|-Ile bonds in factor VII to form factor VIIa and factor XI to form factor XIa. Interacts with HRG; the interaction, which is enhanced in the presence of zinc ions and inhibited by heparin-binding, inhibits factor XII autoactivation and contact-initiated coagulation. Factor XII is activated by kallikrein in alpha-factor XIIa, which is further converted by trypsin into beta-factor XIIa. Alpha-factor XIIa is composed of an NH2-terminal heavy chain, called coagulation factor XIIa heavy chain, and a COOH-terminal light chain, called coagulation factor XIIa light chain, connected by a disulfide bond. Beta-factor XIIa is composed of 2 chains linked by a disulfide bond, an N-terminal nonapeptide, called beta-factor XIIa part 1, and coagulation factor XIIa light chain, also known in this context as beta-factor XIIa part 2. O- and N-glycosylated. The O-linked polysaccharides were not identified, but are probably the mucin type linked to GalNAc. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Belongs to the peptidase S1 family. Factor XII entry