Factor XII: Proteins and Enzymes

Coagulation factor XII, also called Hageman factor, circulates in blood as a zymogen. This single chain zymogen is activated by contact with negatively charged polyanions,to form a two chain serine protease containing alpha factor XIIa. The heavy chain contains two fibronectin type domains, two epidermal growth factor (EGF) like domains, a kringle domain and a proline rich domain, whereas the light chain contains only a catalytic domain. On activation, further cleavages takes place in the heavy chain, resulting in the production of beta factor XIIa light chain and the alpha factor XIIa light chain becomes beta factor XIIa heavy chain. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha factor XIIa and then to beta factor XIIa. The active factor XIIa participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. It activates coagulation factors VII and XI. Defects in Factor XII gene do not cause any clinical symptoms and the sole effect is that whole blood clotting time is prolonged.