Kininogen 1 (KNG1)

High molecular weight kininogen (HMWK) plays an important role in assembly of the plasma kallikrein -kinin system. The KNG1 gene generates both HMWK and low molecular weight kininogen (LMWK) through alternative splicing. Both HMWK and LMWK contain an identical heavy chain consisting of protein domains 1, 2, and 3. However, HMWK contains a 56-kD light chain that consists of domains 5 and 6H, whereas LMWK contains a unique 4-kD light chain that consists of domain 5L. In both proteins, the heavy and light chains are linked by domain 4, which contains the bradykinin (BK) nonapeptide. BK, which is released by plasma kallikrein, is a potent inflammatory mediator that causes vasodilation and enhanced capillary permeability, induces pain, and stimulates production of nitric oxide and prostacyclin from endothelial cells.