(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.
Secreted in plasma. T-kinin is detected in malignant ovarian, colon and breast carcinomas, but not in benign tumors.
Involvement in disease
Defects in KNG1 are the cause of high molecular weight kininogen deficiency (HMWK deficiency) [MIM:228960]. 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.
Contains 3 cystatin domains.
Bradykinin is released from kininogen by plasma kallikrein. Hydroxylation of Pro-383 occurs prior to the release of bradykinin. Phosphorylation sites are present in the extracelllular medium. N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans.
Flow cytometric analysis of Ramos cells labeling Kininogen 1 with ab170475 at 1/10 dilution (right hoistogram) ompared to a negative control cell (left histogram).FITC-conjugated goat-anti-rabbit secondary antibodies were used for the analysis.
Immunohistochemical analysis of formalin-fixed, paraffin-embedded Human breast carcinoma tissue labeling Kininogen 1 with ab170475 at 1/50 dilution, followed by peroxidase-conjugated secondary antibody and DAB staining.
Western blot - Anti-Kininogen 1 antibody (ab170475)
All lanes : Anti-Kininogen 1 antibody (ab170475) at 1/100 dilution
Lane 1 : 293 cell lysate, non-transfected Lane 2 : 293 cell lysate, transiently transfected with Kininogen 1