Kininogen 1

Kininogen-1 (KNG1), also known as alpha-2-thiol proteinase inhibitor, Williams-Fitzgerald-Flaujeac factor or the HMWK-kallikrein factor is a protein that in humans is encoded by the KNG1 gene. Kininogen-1 is the precursor protein to high-molecular-weight kininogen (HMWK), low-molecular-weight kininogen (LMWK), and bradykinin.

KNG1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1NY2, 2WOK, 4ASQ, 4ASR, 4ECB, 4ECC, 5I25
Identifiers
Aliases	KNG1, BDK, BK, KNG, Kininogen 1, HMWK, HAE6, HK
External IDs	OMIM: 612358 MGI: 3027157 HomoloGene: 88343 GeneCards: KNG1
Gene location (Human) Chr. Chromosome 3 (human) Band 3q27.3 Start 186,717,348 bp End 186,744,410 bp
Gene location (Mouse) Chr. Chromosome 16 (mouse) Band 16|16 B1 Start 22,804,604 bp End 22,848,232 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in renal medulla liver right lobe of liver kidney tubule kidney metanephric glomerulus pancreatic ductal cell rectum prefrontal cortex tibialis anterior muscle Top expressed in kidney renal cortex proximal tubule liver bone marrow morula placenta esophagus quadriceps femoris muscle zone of skin More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase inhibitor activity heparin binding zinc ion binding protein binding signaling receptor binding cysteine-type endopeptidase inhibitor activity Cellular component blood microparticle plasma membrane extracellular exosome platelet alpha granule lumen extracellular space endoplasmic reticulum lumen extracellular matrix extracellular region collagen-containing extracellular matrix Biological process hemostasis blood coagulation, intrinsic pathway negative regulation of proteolysis negative regulation of cell adhesion negative regulation of peptidase activity negative regulation of blood coagulation positive regulation of cytosolic calcium ion concentration platelet degranulation vasodilation positive regulation of apoptotic process inflammatory response blood coagulation negative regulation of endopeptidase activity post-translational protein modification G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3827 385643 Ensembl ENSG00000113889 ENSMUSG00000060459 UniProt P01042 n/a RefSeq (mRNA) NM_001166451 NM_000893 NM_001102416 NM_001102409 NM_001102410 NM_201375 RefSeq (protein) NP_000884 NP_001095886 NP_001159923 n/a Location (UCSC) Chr 3: 186.72 – 186.74 Mb Chr 16: 22.8 – 22.85 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Expression

The KNG1 gene uses alternative splicing to generate two different proteins: high-molecular-weight kininogen (HMWK) and low-molecular-weight kininogen (LMWK). HMWK in turn is cleaved by the enzyme kallikrein to produce bradykinin.

• KNG1 gene → low-molecular-weight kininogen (LMWK) protein (contains 427 amino acids) or high-molecular-weight kininogen (HMWK) protein (644 amino acids)
• HMWK protein → bradykinin peptide (9 amino acids)

Function

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.

Kininogen-1 is a constituent of the blood coagulation system as well as the kinin-kallikrein system.

See also

• high-molecular-weight kininogen
• low-molecular-weight kininogen
• bradykinin

Further reading

• Iarovaia GA (2001). "[Kallikrein-kinin system: novel facts and concepts (literature review)]". Voprosy Medit͡sinskoĭ Khimii. 47 (1): 20–42. PMID 11385996.
• Matthews KW, Mueller-Ortiz SL, Wetsel RA (Jan 2004). "Carboxypeptidase N: a pleiotropic regulator of inflammation". Molecular Immunology. 40 (11): 785–93. doi:10.1016/j.molimm.2003.10.002. PMID 14687935.
• Scharfstein J, Schmitz V, Svensjö E, Granato A, Monteiro AC (2007). "Kininogens coordinate adaptive immunity through the proteolytic release of bradykinin, an endogenous danger signal driving dendritic cell maturation". Scandinavian Journal of Immunology. 66 (2–3): 128–36. doi:10.1111/j.1365-3083.2007.01983.x. PMID 17635790. S2CID 26080663.
• Thompson RE, Mandle R, Kaplan AP (Oct 1979). "Studies of binding of prekallikrein and Factor XI to high molecular weight kininogen and its light chain". Proceedings of the National Academy of Sciences of the United States of America. 76 (10): 4862–6. Bibcode:1979PNAS...76.4862T. doi:10.1073/pnas.76.10.4862. PMC 413037. PMID 291905.
• Kerbiriou DM, Griffin JH (Dec 1979). "Human high molecular weight kininogen. Studies of structure-function relationships and of proteolysis of the molecule occurring during contact activation of plasma". The Journal of Biological Chemistry. 254 (23): 12020–7. doi:10.1016/S0021-9258(19)86421-9. PMID 500690.
• Colman RW, Bagdasarian A, Talamo RC, Scott CF, Seavey M, Guimaraes JA, Pierce JV, Kaplan AP (Dec 1975). "Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways". The Journal of Clinical Investigation. 56 (6): 1650–62. doi:10.1172/JCI108247. PMC 333144. PMID 1202089.
• Gailani D, Broze GJ (Aug 1991). "Factor XI activation in a revised model of blood coagulation". Science. 253 (5022): 909–12. Bibcode:1991Sci...253..909G. doi:10.1126/science.1652157. PMID 1652157. S2CID 9262836.
• Cheung PP, Cannizzaro LA, Colman RW (1992). "Chromosomal mapping of human kininogen gene (KNG) to 3q26----qter". Cytogenetics and Cell Genetics. 59 (1): 24–6. doi:10.1159/000133192. PMID 1733668.
• Fong D, Smith DI, Hsieh WT (Jun 1991). "The human kininogen gene (KNG) mapped to chromosome 3q26-qter by analysis of somatic cell hybrids using the polymerase chain reaction". Human Genetics. 87 (2): 189–92. doi:10.1007/BF00204179. PMID 2066106. S2CID 30895313.
• Schmaier AH, Kuo A, Lundberg D, Murray S, Cines DB (Nov 1988). "The expression of high molecular weight kininogen on human umbilical vein endothelial cells". The Journal of Biological Chemistry. 263 (31): 16327–33. doi:10.1016/S0021-9258(18)37596-3. PMID 2460446.
• Takagaki Y, Kitamura N, Nakanishi S (Jul 1985). "Cloning and sequence analysis of cDNAs for human high molecular weight and low molecular weight prekininogens. Primary structures of two human prekininogens". The Journal of Biological Chemistry. 260 (14): 8601–9. doi:10.1016/S0021-9258(17)39515-7. PMID 2989293.
• Kitamura N, Kitagawa H, Fukushima D, Takagaki Y, Miyata T, Nakanishi S (Jul 1985). "Structural organization of the human kininogen gene and a model for its evolution". The Journal of Biological Chemistry. 260 (14): 8610–7. doi:10.1016/S0021-9258(17)39516-9. PMID 2989294.
• Ishiguro H, Higashiyama S, Namikawa C, Kunimatsu M, Takano E, Tanaka K, Ohkubo I, Murachi T, Sasaki M (May 1987). "Interaction of human calpains I and II with high molecular weight and low molecular weight kininogens and their heavy chain: mechanism of interaction and the role of divalent cations". Biochemistry. 26 (10): 2863–70. doi:10.1021/bi00384a030. PMID 3038169.
• Vogel R, Assfalg-Machleidt I, Esterl A, Machleidt W, Müller-Esterl W (Sep 1988). "Proteinase-sensitive regions in the heavy chain of low molecular weight kininogen map to the inter-domain junctions". The Journal of Biological Chemistry. 263 (25): 12661–8. doi:10.1016/S0021-9258(18)37804-9. PMID 3045123.
• Maeda H, Matsumura Y, Kato H (Nov 1988). "Purification and identification of [hydroxyprolyl3]bradykinin in ascitic fluid from a patient with gastric cancer". The Journal of Biological Chemistry. 263 (31): 16051–4. doi:10.1016/S0021-9258(18)37555-0. PMID 3182782.
• Kato H, Matsumura Y, Maeda H (May 1988). "Isolation and identification of hydroxyproline analogues of bradykinin in human urine". FEBS Letters. 232 (1): 252–4. doi:10.1016/0014-5793(88)80427-7. PMID 3366244. S2CID 32363670.
• Kellermann J, Lottspeich F, Henschen A, Müller-Esterl W (Jan 1986). "Completion of the primary structure of human high-molecular-mass kininogen. The amino acid sequence of the entire heavy chain and evidence for its evolution by gene triplication". European Journal of Biochemistry. 154 (2): 471–8. doi:10.1111/j.1432-1033.1986.tb09421.x. PMID 3484703.
• Kellermann J, Thelen C, Lottspeich F, Henschen A, Vogel R, Müller-Esterl W (Oct 1987). "Arrangement of the disulphide bridges in human low-Mr kininogen". The Biochemical Journal. 247 (1): 15–21. doi:10.1042/bj2470015. PMC 1148362. PMID 3689342.
• Warn-Cramer BJ, Bajaj SP (Dec 1985). "Stoichiometry of binding of high molecular weight kininogen to factor XI/XIa". Biochemical and Biophysical Research Communications. 133 (2): 417–22. doi:10.1016/0006-291X(85)90922-2. PMID 3936495.
• Lottspeich F, Kellermann J, Henschen A, Foertsch B, Müller-Esterl W (Oct 1985). "The amino acid sequence of the light chain of human high-molecular-mass kininogen". European Journal of Biochemistry. 152 (2): 307–14. doi:10.1111/j.1432-1033.1985.tb09199.x. PMID 4054110.

External links

• LMWK laboratory information