Kininogen 1 Explained

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

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.^[2]

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 . [Kallikrein-kinin system: novel facts and concepts (literature review)] . Voprosy Meditsinskoi Khimii . 47 . 1 . 20–42 . 2001 . 11385996 .
• Matthews KW, Mueller-Ortiz SL, Wetsel RA . Carboxypeptidase N: a pleiotropic regulator of inflammation . Molecular Immunology . 40 . 11 . 785–93 . Jan 2004 . 14687935 . 10.1016/j.molimm.2003.10.002 .
• Scharfstein J, Schmitz V, Svensjö E, Granato A, Monteiro AC . 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 . 17635790 . 10.1111/j.1365-3083.2007.01983.x . 26080663 . free .
• Thompson RE, Mandle R, Kaplan AP . 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 . 291905 . 413037 . 10.1073/pnas.76.10.4862 . 1979PNAS...76.4862T . free .
• Kerbiriou DM, Griffin JH . 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 . 10.1016/S0021-9258(19)86421-9 . 500690 . free .
• Colman RW, Bagdasarian A, Talamo RC, Scott CF, Seavey M, Guimaraes JA, Pierce JV, Kaplan AP . 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 . 1202089 . 333144 . 10.1172/JCI108247 .
• Gailani D, Broze GJ . Factor XI activation in a revised model of blood coagulation . Science . 253 . 5022 . 909–12 . Aug 1991 . 1652157 . 10.1126/science.1652157 . 1991Sci...253..909G . 9262836 .
• Cheung PP, Cannizzaro LA, Colman RW . Chromosomal mapping of human kininogen gene (KNG) to 3q26----qter . Cytogenetics and Cell Genetics . 59 . 1 . 24–6 . 1992 . 1733668 . 10.1159/000133192 .
• Fong D, Smith DI, Hsieh WT . 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 . 2066106 . 10.1007/BF00204179 . 30895313 .
• Schmaier AH, Kuo A, Lundberg D, Murray S, Cines DB . The expression of high molecular weight kininogen on human umbilical vein endothelial cells . The Journal of Biological Chemistry . 263 . 31 . 16327–33 . Nov 1988 . 10.1016/S0021-9258(18)37596-3 . 2460446 . free .
• Takagaki Y, Kitamura N, Nakanishi S . 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 . 10.1016/S0021-9258(17)39515-7 . 2989293 . free .
• Kitamura N, Kitagawa H, Fukushima D, Takagaki Y, Miyata T, Nakanishi S . Structural organization of the human kininogen gene and a model for its evolution . The Journal of Biological Chemistry . 260 . 14 . 8610–7 . Jul 1985 . 10.1016/S0021-9258(17)39516-9 . 2989294 . free .
• Ishiguro H, Higashiyama S, Namikawa C, Kunimatsu M, Takano E, Tanaka K, Ohkubo I, Murachi T, Sasaki M . 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 . 3038169 . 10.1021/bi00384a030 .
• Vogel R, Assfalg-Machleidt I, Esterl A, Machleidt W, Müller-Esterl W . 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 . 10.1016/S0021-9258(18)37804-9 . 3045123 . free .
• Maeda H, Matsumura Y, Kato H . 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 . 10.1016/S0021-9258(18)37555-0 . 3182782 . free .
• Kato H, Matsumura Y, Maeda H . Isolation and identification of hydroxyproline analogues of bradykinin in human urine . FEBS Letters . 232 . 1 . 252–4 . May 1988 . 3366244 . 10.1016/0014-5793(88)80427-7 . 32363670 . free . 1988FEBSL.232..252K .
• Kellermann J, Lottspeich F, Henschen A, Müller-Esterl W . 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 . 3484703 . 10.1111/j.1432-1033.1986.tb09421.x . free .
• Kellermann J, Thelen C, Lottspeich F, Henschen A, Vogel R, Müller-Esterl W . Arrangement of the disulphide bridges in human low-Mr kininogen . The Biochemical Journal . 247 . 1 . 15–21 . Oct 1987 . 3689342 . 1148362 . 10.1042/bj2470015.
• Warn-Cramer BJ, Bajaj SP . Stoichiometry of binding of high molecular weight kininogen to factor XI/XIa . Biochemical and Biophysical Research Communications . 133 . 2 . 417–22 . Dec 1985 . 3936495 . 10.1016/0006-291X(85)90922-2 .
• Lottspeich F, Kellermann J, Henschen A, Foertsch B, Müller-Esterl W . The amino acid sequence of the light chain of human high-molecular-mass kininogen . European Journal of Biochemistry . 152 . 2 . 307–14 . Oct 1985 . 4054110 . 10.1111/j.1432-1033.1985.tb09199.x . free .

External links

• LMWK laboratory information

Notes and References

1. [UniProt]
2. Web site: Entrez Gene: kininogen 1.