High-molecular-weight kininogen (HMWK or HK) is a circulating plasma protein which participates in the initiation of blood coagulation, and in the generation of the vasodilator bradykinin via the kallikrein-kinin system.
Its current accepted name is to contrast it with low-molecular-weight kininogen (LMWK) which has a similar function to HMWK in the tissue (as opposed to serum) kinin-kallikrein system.
Domain 4 links the heavy and light chains in addition to a disulfide bond between positions close to the N- and C-termini.
[3] The resulting severed light and heavy chains remain connected by the aforementioned disulfide bond near the original N- and C-termini.
[citation needed] The existence of HMWK was hypothesised in 1975 when several patients were described with a deficiency of a class of plasma protein and a prolonged bleeding time and PTT.