KNG1

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. Bradykinin also functions as an antimicrobial peptide with antibacterial and antifungal activity. 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, Nov 2014]

Kininogen 1

(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.

Antimicrobial humoral immune response mediated by antimicrobial peptideIDA:UniProtKB
Blood coagulationIEA:UniProtKB-KW
Inflammatory responseIEA:UniProtKB-KW
Killing of cells of other organismIDA:UniProtKB
Negative regulation of blood coagulationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cell adhesionManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of endopeptidase activityManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of proteolysisManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of apoptotic process1 PublicationNAS:UniProtKB
Positive regulation of cytosolic calcium ion concentrationManual Assertion Based On ExperimentIDA:UniProtKB
VasodilationIEA:UniProtKB-KW

Secreted, extracellular space

High molecular weight kininogen deficiency (HMWK deficiency):
Autosomal recessive coagulation defect. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis.

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.