Kininogen, Single Chain HMW, Human Plasma (KNG1) Protein

This gene uses alternative splicing to generate two different proteins- high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK). HMWK is essential for blood coagulation and assembly of the kallikrein-kinin system. Also, bradykinin, a peptide causing numerous physiological effects, is released from HMWK. In contrast to HMWK, LMWK is not involved in blood coagulation. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

KNG1: (1) Kininogens are inhibitors of thiol proteases; (2) HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin- induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects: (4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW- kininogen is in contrast to HMW-kininogen not involved in blood clotting. Defects in KNG1 are the cause of high molecular weight kininogen deficiency (HMWK deficiency). HMWK deficiency is an autosomal recessive coagulation defect. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Motility/polarity/chemotaxis; Cell adhesion; Contractile; Secreted, signal peptide; Secreted; Inhibitor

Chromosomal Location of Human Ortholog: 3q27

Cellular Component: extracellular space; plasma membrane; extracellular region

Molecular Function: heparin binding; protein binding; zinc ion binding; cysteine protease inhibitor activity; receptor binding

Biological Process: negative regulation of proteolysis; platelet activation; elevation of cytosolic calcium ion concentration; platelet degranulation; smooth muscle contraction; positive regulation of apoptosis; negative regulation of blood coagulation; negative regulation of cell adhesion; blood coagulation; inflammatory response; vasodilation; blood coagulation, intrinsic pathway

Disease: High Molecular Weight Kininogen Deficiency