Physiology
HMWK is one of the early participants of the intrinsic pathway of coagulation, complexed with Factor XII (Hageman factor) and prekallikrein. It is 626 amino acids long, and weighs 88 to 120 kDa (dependent on glycosylation). The kininogen is not enzymatically active, and functions only as a cofactor for the activation of kallikrein and factor XII. It is also necessary for the activation of factor XI by factor XIIa. The histidine-rich region (amino acids 420 to 510) participates most strongly in coagulation. Importantly, the role of HMWK in the coagulation cascade relies on its interaction with various endothelial cell binding proteins.
In addition to its role in blood coagulation, HMWK (just as Low-molecular-weight kininogen) is a strong inhibitor of cysteine proteinases. Responsible for this activity are three related domains on its heavy chain.
HMWK is also a precursor of bradykinin; this vasodilator substance is released through positive feedback by kallikrein.
Read more about this topic: High-molecular-weight Kininogen
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