Kininogens are inhibitors of thiol proteases. HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; HMW-kininogen inhibits the thrombin- and plasmin-induced aggregation of thrombocytes. LMW-kininogen inhibits the aggregation of thrombocytes. LMW-kininogen is in contrast to HMW-kininogen not involved in blood clotting. The active peptide bradykinin is a potent vasodilatator that is released from HMW-kininogen shows a variety of physiological effects: (A) influence in smooth muscle contraction, (B) induction of hypotension, (C) natriuresis and diuresis, (D) decrease in blood glucose level, (E) it is a mediator of inflammation and causes (E1) increase in vascular permeability, (E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action). Secreted in plasma. T-kinin is detected in malignant ovarian, colon and breast carcinomas, but not in benign tumors. Bradykinin is inactivated by ACE, which removes the dipeptide Arg-Phe from its C-terminus. Bradykinin is released from kininogen by plasma kallikrein. Hydroxylation of Pro-383 occurs prior to the release of bradykinin. Phosphorylated by FAM20C in the extracellular medium. N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. The T-kinin peptide is missing residues 378 to 380, probably as a result of a naturally occurring variant. The complete sequence of the T-kinin peptide is therefore ISRPPGFSPFR. This peptide is associated with malignant tumors but not with benign ones. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. High molecular weight kininogen entry