Biology:Kininogen 1

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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.

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

• "[Kallikrein-kinin system: novel facts and concepts (literature review)]". Voprosy Medit͡sinskoĭ Khimii 47 (1): 20–42. 2001. PMID 11385996. 
• "Carboxypeptidase N: a pleiotropic regulator of inflammation". Molecular Immunology 40 (11): 785–93. Jan 2004. doi:10.1016/j.molimm.2003.10.002. PMID 14687935. 
• "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. 2007. doi:10.1111/j.1365-3083.2007.01983.x. PMID 17635790. 
• "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. Oct 1979. doi:10.1073/pnas.76.10.4862. PMID 291905. Bibcode: 1979PNAS...76.4862T. 
• "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. Dec 1979. doi:10.1016/S0021-9258(19)86421-9. PMID 500690. 
• "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. Dec 1975. doi:10.1172/JCI108247. PMID 1202089. 
• "Factor XI activation in a revised model of blood coagulation". Science 253 (5022): 909–12. Aug 1991. doi:10.1126/science.1652157. PMID 1652157. Bibcode: 1991Sci...253..909G. 
• "Chromosomal mapping of human kininogen gene (KNG) to 3q26----qter". Cytogenetics and Cell Genetics 59 (1): 24–6. 1992. doi:10.1159/000133192. PMID 1733668. 
• "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. Jun 1991. doi:10.1007/BF00204179. PMID 2066106. 
• "The expression of high molecular weight kininogen on human umbilical vein endothelial cells". The Journal of Biological Chemistry 263 (31): 16327–33. Nov 1988. doi:10.1016/S0021-9258(18)37596-3. PMID 2460446. 
• "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. Jul 1985. doi:10.1016/S0021-9258(17)39515-7. PMID 2989293. 
• "Structural organization of the human kininogen gene and a model for its evolution". The Journal of Biological Chemistry 260 (14): 8610–7. Jul 1985. doi:10.1016/S0021-9258(17)39516-9. PMID 2989294. 
• "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. May 1987. doi:10.1021/bi00384a030. PMID 3038169. 
• "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. Sep 1988. doi:10.1016/S0021-9258(18)37804-9. PMID 3045123. 
• "Purification and identification of [hydroxyprolyl3]bradykinin in ascitic fluid from a patient with gastric cancer". The Journal of Biological Chemistry 263 (31): 16051–4. Nov 1988. doi:10.1016/S0021-9258(18)37555-0. PMID 3182782. 
• "Isolation and identification of hydroxyproline analogues of bradykinin in human urine". FEBS Letters 232 (1): 252–4. May 1988. doi:10.1016/0014-5793(88)80427-7. PMID 3366244. 
• "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. Jan 1986. doi:10.1111/j.1432-1033.1986.tb09421.x. PMID 3484703. 
• "Arrangement of the disulphide bridges in human low-Mr kininogen". The Biochemical Journal 247 (1): 15–21. Oct 1987. doi:10.1042/bj2470015. PMID 3689342. 
• "Stoichiometry of binding of high molecular weight kininogen to factor XI/XIa". Biochemical and Biophysical Research Communications 133 (2): 417–22. Dec 1985. doi:10.1016/0006-291X(85)90922-2. PMID 3936495. 
• "The amino acid sequence of the light chain of human high-molecular-mass kininogen". European Journal of Biochemistry 152 (2): 307–14. Oct 1985. doi:10.1111/j.1432-1033.1985.tb09199.x. PMID 4054110. 

External links

• LMWK laboratory information