High-molecular-weight kininogen (HMWK)

High-molecular-weight kininogen is a multidomain, glycosylated plasma protein that plays a critical role in the intrinsic (contact activation) pathway of blood coagulation and in the generation of the vasoactive peptide bradykinin. It acts as an essential cofactor, facilitating the binding and activation of prekallikrein and factor XI on negatively charged surfaces, thereby promoting thrombin formation. Cleavage of HMWK by kallikrein releases bradykinin, which mediates vasodilation, increases vascular permeability, and induces pain and inflammation. HMWK and its alternative splicing forms (low-molecular-weight kininogen and T-kininogen in rodents) are encoded by the KNG1 gene. They also function as inhibitors of cysteine proteases. Deficiency of HMWK is associated with rare coagulation disorders (contact factor deficiencies), and its dysregulation is implicated in angioedema, inflammation, and cardiovascular diseases[1][3][5][6][7].

Other names

Kininogen-1KNG1high molecular weight kininogenHKlow-molecular-weight kininogen (LK)T-kininogen (rodents)Fitzgerald factorWilliams factorFlaujeac factor

Inhibition of bradykinin generation or action (via blocking kallikrein or bradykinin receptor), Reduction of vascular permeability and angioedema by interrupting the kinin–kallikrein pathway