KNG1 (Kininogen 1)

Kininogens are inhibitors of thiol proteases; (2) KNG1 plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) KNG1 inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from KNG1 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 KNG1 not involved in blood clotting.

KNG1 (Kininogen 1) Related Areas

Immunology>>Innate Immunity>>Coagulation>>KNG1/Kininogen 1

Cardiovascular>>Coagulation>>KNG1/Kininogen 1

KNG1 (Kininogen 1) Alternative Names

KNG1, kininogen 1, BDK, KNG, HMWK [Homo sapiens]

Kng1, kininogen 1, Kng, MGC123437 [Mus musculus]

Summaries for KNG1 (Kininogen 1)

Entrez Gene summary for KNG1:

This KNG1 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]

OMIM - description for KNG1:

High molecular weight kininogen (HMWK) plays an important role in assembly of the plasma kallikrein (see 147910)-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 (see 601699) from endothelial cells. During vascular damage, BK stimulates smooth muscle proliferation and intimal hypertrophy. Release of BK from HMWK generates a 2-chain HMWK, termed HMWKa, containing the heavy and light chains joined by a disulfide bond (Merkulov et al., 2008).

Wikipedia summary for KNG1:

High-molecular-weight kininogen (HMWK or HK), also known as the Williams-Fitzgerald-Flaujeac factor or the Fitzgerald factor or the HMWK-kallikrein factor, is a protein from the blood coagulation system as well as the kinin-kallikrein system. KNG1 is a protein that adsorbs to the surface of biomaterials that come in contact with blood in vivo. KNG1 circulates throughout the blood and quickly adsorbs to the material surfaces.[clarification needed]

Human KNG1 (Kininogen 1) Protein General Information

 

• Protein names: High molecular weight kininogen, Short name=HMWK
• Sequence length: 644 AA.
• Sequence similarities: KNG1 contains 3 cystatin domains.
• Post-translational modification: 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.
• Polymorphism: 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.
• Subcellular location: Secreted › extracellular space.
• Tissue specificity: 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]. KNG1 deficiency is an autosomal recessive coagulation defect. Patients with KNG1 deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis.

General information above from UniProt

Function for KNG1 (Kininogen 1) Protein

UniProtKB:

Kininogens are inhibitors of thiol proteases; (2) KNG1 plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) KNG1 inhibits the thrombin- and plasmin-induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from KNG1 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 KNG1 not involved in blood clotting.

Genatlas:

• KNG1 contacts activation pathway
• KNG1 is cysteine proteinase inhibitor
• inhibits endothelial cell proliferation and angiogenesis through domain D5
• KNG1 may be involved in smooth muscle contraction, natriuresis, diuresis, inflammatory response, positive regulation of apoptosis
• antimicrobial activity of the heparin-binding and cell-binding domain 5 of high molecular weight kininogen
• KNG1 plays an essential role in prevention of metastasis of cancer cells
• KNG1 inhibits ERK-dependent T cell proliferation, and these observations may have a possible role in immunosenescence (Acuna-Castillo 2005)
• KNG1 acts as an important signal directing the invasion of glioma cells toward blood vessels (Pubmed 21451024)

Homology for human KNG1 (Kininogen 1)

• ortholog to kng1, Mus musculus
• ortholog to kng1, Rattus norvegicus

Phenotype Information for KNG1 (Kininogen 1)

• Gene/Locus: KNG1, KNG
• Phenotype: [High molecular weight kininogen deficiency]
  [Kininogen deficiency]

Phenotype Information for KNG1 from OMIM (Online Mendelian Inheritance in Man)