Description: Homo sapiens kininogen 1 (KNG1), transcript variant 1, mRNA. (from RefSeq NM_001102416) RefSeq Summary (NM_001102416): 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. Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reduces or depletes angiotensin converting enzyme 2 (ACE2), which results in an increase in levels of des-Arg(9)-bradykinin, a bioactive metabolite of bradykinin that is associated with lung injury and inflammation. [provided by RefSeq, Jul 2020]. Gencode Transcript: ENST00000644859.2 Gencode Gene: ENSG00000113889.14 Transcript (Including UTRs) Position: hg38 chr3:186,717,359-186,744,410 Size: 27,052 Total Exon Count: 10 Strand: + Coding Region Position: hg38 chr3:186,717,543-186,742,331 Size: 24,789 Coding Exon Count: 10
ID:KNG1_HUMAN DESCRIPTION: RecName: Full=Kininogen-1; AltName: Full=Alpha-2-thiol proteinase inhibitor; AltName: Full=Fitzgerald factor; AltName: Full=High molecular weight kininogen; Short=HMWK; AltName: Full=Williams-Fitzgerald-Flaujeac factor; Contains: RecName: Full=Kininogen-1 heavy chain; Contains: RecName: Full=T-kinin; AltName: Full=Ile-Ser-Bradykinin; Contains: RecName: Full=Bradykinin; AltName: Full=Kallidin I; Contains: RecName: Full=Lysyl-bradykinin; AltName: Full=Kallidin II; Contains: RecName: Full=Kininogen-1 light chain; Contains: RecName: Full=Low molecular weight growth-promoting factor; Flags: Precursor; FUNCTION: (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. 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. PTM: Bradykinin is released from kininogen by plasma kallikrein. PTM: Hydroxylation of Pro-383 occurs prior to the release of bradykinin. PTM: Phosphorylation sites are present in the extracellular medium. PTM: 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. 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. SIMILARITY: Contains 3 cystatin kininogen-type domains. WEB RESOURCE: Name=Wikipedia; Note=High molecular weight kininogen entry; URL="http://en.wikipedia.org/wiki/High-molecular_weight_kininogen"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/kng/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P01042
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.