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Gene Review

KNG1  -  kininogen 1

Homo sapiens

Synonyms: Alpha-2-thiol proteinase inhibitor, BDK, BK, Fitzgerald factor, HMWK, ...
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Disease relevance of KNG1


High impact information on KNG1


Chemical compound and disease context of KNG1


Biological context of KNG1


Anatomical context of KNG1


Associations of KNG1 with chemical compounds


Physical interactions of KNG1

  • High molecular weight kininogen (HK) was previously shown to interact with both GPIbalpha and Mac-1 through its domains 3 and 5, respectively [24].
  • We conclude residues Lys244-Pro254 on kininogen heavy chain is responsible for binding to thrombospondin on the surface of activated platelets [25].
  • T-kininogen did not release any immunoreactive kinins when complexed with cathepsin L, as previously observed using tissue kallikreins [26].
  • The purified light chain derived from kinin-free HMW-kininogen is shown to compete with native MHW-kininogen for binding to Hageman factor substrates and direct binding of the isolated light chain to prekalikrein and Factor XI is demonstrated [27].
  • The region Gly-486-Lys-502 from the carboxyl terminus of the domain 5 was identified as responsible for inhibition of the VN-alpha(IIb)beta(3)-integrin interaction, as this portion was also found to mediate kininogen binding to VN [28].

Enzymatic interactions of KNG1


Co-localisations of KNG1


Regulatory relationships of KNG1


Other interactions of KNG1

  • Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways [15].
  • Plasma prekallikrein, a zymogen of the contact phase system, circulates in plasma as heterodimeric complex with H-kininogen [17].
  • Although both cathepsins processed high-molecular weight kininogen under stoichiometric conditions, only cathepsin L generated significant amounts of immunoreactive kinins [40].
  • We show that the digestion of both low molecular mass (LK) and high molecular mass (HK) forms of human kininogen by HNE renders them essentially unsusceptible to processing by human urinary kallikrein (tissue-type) and also significantly quenches the kinin release from HK by plasma kallikrein [21].
  • Plasminogen activator inhibitor-1 (PAI-1) and two-chain high molecular weight kininogen (HKa) exert anti-adhesive properties in vitronectin-dependent cell adhesion [19].

Analytical, diagnostic and therapeutic context of KNG1


  1. Regulation of angiogenesis by the kallikrein-kinin system. Colman, R.W. Curr. Pharm. Des. (2006) [Pubmed]
  2. Domain 5 of kininogen inhibits proliferation of human colon cancer cell line (HCT-116) by interfering with G1/S in the cell cycle. Bior, A.D., Pixley, R.A., Colman, R.W. J. Thromb. Haemost. (2007) [Pubmed]
  3. Effect of His-Gly-Lys motif derived from domain 5 of high molecular weight kininogen on suppression of cancer metastasis both in vitro and in vivo. Kawasaki, M., Maeda, T., Hanasawa, K., Ohkubo, I., Tani, T. J. Biol. Chem. (2003) [Pubmed]
  4. Isolation of a human cDNA for alpha 2-thiol proteinase inhibitor and its identity with low molecular weight kininogen. Ohkubo, I., Kurachi, K., Takasawa, T., Shiokawa, H., Sasaki, M. Biochemistry (1984) [Pubmed]
  5. Inhibition of vitronectin-mediated haptotaxis and haptoinvasion of MG-63 cells by domain 5 (D5(H)) of human high-molecular-weight kininogen and identification of a minimal amino acid sequence. Kamiyama, F., Maeda, T., Yamane, T., Li, Y.H., Ogukubo, O., Otsuka, T., Ueyama, H., Takahashi, S., Ohkubo, I., Matsui, N. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  6. Kinin formation: mechanisms and role in inflammatory disorders. Proud, D., Kaplan, A.P. Annu. Rev. Immunol. (1988) [Pubmed]
  7. Substance P precursor and kininogen: their structures, gene organizations, and regulation. Nakanishi, S. Physiol. Rev. (1987) [Pubmed]
  8. Consumption of high-molecular-weight kininogen in hereditary angioedema. Naish, P., Hewitt, J. N. Engl. J. Med. (1983) [Pubmed]
  9. The Passovoy defect: further characterization of a hereditary hemorrhagic diathesis. Hougie, C., Mc Pherson, R.A., Brown, J.E., Lakin-Thomas, P.L., Melaragno, A., Aronson, L., Baugh, R.F. N. Engl. J. Med. (1978) [Pubmed]
  10. Plasmin-mediated activation of contact system in response to pharmacological thrombolysis. Ewald, G.A., Eisenberg, P.R. Circulation (1995) [Pubmed]
  11. Complexes between C1-inhibitor, kallikrein, high molecular weight kininogen, plasma thromboplastin antecedent, and plasmin in normal human plasma and hereditary angioneurotic edema plasmas containing dysmorphic C1-inhibitors: role of cold activation. Donaldson, V.H., Harrison, R.A. Blood (1982) [Pubmed]
  12. Activation of purified human plasma prekallikrein triggered by cell wall fractions of Escherichia coli and Staphylococcus aureus. Kalter, E.S., van Dijk, W.C., Timmerman, A., Verhoef, J., Bouma, B.N. J. Infect. Dis. (1983) [Pubmed]
  13. Augmented Hageman factor and prolactin titers, enhanced cold activation of factor VII, and spontaneous shortening of prothrombin time in survivors of myocardial infarction. Gordon, E.M., Hellerstein, H.K., Ratnoff, O.D., Arafah, B.M., Yamashita, T.S. J. Lab. Clin. Med. (1987) [Pubmed]
  14. Activation of human Hageman factor by a leukocytic protease. Newball, H.H., Revak, S.D., Cochrane, C.G., Griffin, J.H., Lichtenstein, L.M. Adv. Exp. Med. Biol. (1979) [Pubmed]
  15. Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways. Colman, R.W., Bagdasarian, A., Talamo, R.C., Scott, C.F., Seavey, M., Guimaraes, J.A., Pierce, J.V., Kaplan, A.P. J. Clin. Invest. (1975) [Pubmed]
  16. Identification of cytokeratin 1 as a binding protein and presentation receptor for kininogens on endothelial cells. Hasan, A.A., Zisman, T., Schmaier, A.H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  17. Mapping of the discontinuous H-kininogen binding site of plasma prekallikrein. Evidence for a critical role of apple domain-2. Renné, T., Dedio, J., Meijers, J.C., Chung, D., Müller-Esterl, W. J. Biol. Chem. (1999) [Pubmed]
  18. Arrangement of the disulphide bridges in human low-Mr kininogen. Kellermann, J., Thelen, C., Lottspeich, F., Henschen, A., Vogel, R., Müller-Esterl, W. Biochem. J. (1987) [Pubmed]
  19. Induction of apoptosis in vascular cells by plasminogen activator inhibitor-1 and high molecular weight kininogen correlates with their anti-adhesive properties. Al-Fakhri, N., Chavakis, T., Schmidt-Wöll, T., Huang, B., Cherian, S.M., Bobryshev, Y.V., Lord, R.S., Katz, N., Preissner, K.T. Biol. Chem. (2003) [Pubmed]
  20. High molecular weight kininogen and factor XII binding to endothelial cells and astrocytes. Fernando, L.P., Natesan, S., Joseph, K., Kaplan, A.P. Thromb. Haemost. (2003) [Pubmed]
  21. Attenuated kinin release from human neutrophil elastase-pretreated kininogens by tissue and plasma kallikreins. Dulinski, R., Suder, P., Guevara-Lora, I., Rapała-Kozik, M., Potempa, J., Silberring, J., Imamura, T., Travis, J., Kozik, A. Biol. Chem. (2003) [Pubmed]
  22. High and low molecular weight kininogen and plasma prekallikrein/plasma kallikrein in villous capillaries of human term placenta. Hermann, A., Buchinger, P., Somlev, B., Rehbock, J. Placenta (1996) [Pubmed]
  23. Different mechanisms define the antiadhesive function of high molecular weight kininogen in integrin- and urokinase receptor-dependent interactions. Chavakis, T., Kanse, S.M., Lupu, F., Hammes, H.P., Müller-Esterl, W., Pixley, R.A., Colman, R.W., Preissner, K.T. Blood (2000) [Pubmed]
  24. High molecular weight kininogen regulates platelet-leukocyte interactions by bridging Mac-1 and glycoprotein Ib. Chavakis, T., Santoso, S., Clemetson, K.J., Sachs, U.J., Isordia-Salas, I., Pixley, R.A., Nawroth, P.P., Colman, R.W., Preissner, K.T. J. Biol. Chem. (2003) [Pubmed]
  25. Expression of thrombospondin 1 on the surface of activated platelets mediates their interaction with the heavy chains of human kininogens through Lys 244-Pro 254. DeLa Cadena, R.A., Kunapuli, S.P., Walz, D.A., Colman, R.W. Thromb. Haemost. (1998) [Pubmed]
  26. Cathepsin L, but not cathepsin B, is a potential kininogenase. Desmazes, C., Gauthier, F., Lalmanach, G. Biol. Chem. (2001) [Pubmed]
  27. Studies of binding of prekallikrein and Factor XI to high molecular weight kininogen and its light chain. Thompson, R.E., Mandle, R., Kaplan, A.P. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  28. Inhibition of platelet adhesion and aggregation by a defined region (Gly-486-Lys-502) of high molecular weight kininogen. Chavakis, T., Boeckel, N., Santoso, S., Voss, R., Isordia-Salas, I., Pixley, R.A., Morgenstern, E., Colman, R.W., Preissner, K.T. J. Biol. Chem. (2002) [Pubmed]
  29. Biochemistry, regulation and potential function of kallistatin. Chao, J., Chao, L. Biol. Chem. Hoppe-Seyler (1995) [Pubmed]
  30. Bradykinin and its metabolite, Arg-Pro-Pro-Gly-Phe, are selective inhibitors of alpha-thrombin-induced platelet activation. Hasan, A.A., Amenta, S., Schmaier, A.H. Circulation (1996) [Pubmed]
  31. Interaction of human plasma kallikrein and its light chain with alpha 2-macroglobulin. van der Graaf, F., Rietveld, A., Keus, F.J., Bouma, B.N. Biochemistry (1984) [Pubmed]
  32. Interactions of human mast cell tryptase with biological protease inhibitors. Alter, S.C., Kramps, J.A., Janoff, A., Schwartz, L.B. Arch. Biochem. Biophys. (1990) [Pubmed]
  33. High molecular weight kininogen as substrate for cathepsin B. Barros, N.M., Tersariol, I.L., Oliva, M.L., Araújo, M.S., Sampaio, C.A., Juliano, L., da Motta, G. Biol. Chem. (2004) [Pubmed]
  34. Cellular localization of low-molecular-weight kininogen and bradykinin B2 receptor mRNAs in human kidney. Song, Q., Wang, D.Z., Harley, R.A., Chao, L., Chao, J. Am. J. Physiol. (1996) [Pubmed]
  35. High-Molecular-Weight Kininogen Fragments Stimulate the Secretion of Cytokines and Chemokines Through uPAR, Mac-1, and gC1qR in Monocytes. Khan, M.M., Bradford, H.N., Isordia-Salas, I., Liu, Y., Wu, Y., Espinola, R.G., Ghebrehiwet, B., Colman, R.W. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  36. Human kininogen gene is transactivated by the farnesoid X receptor. Zhao, A., Lew, J.L., Huang, L., Yu, J., Zhang, T., Hrywna, Y., Thompson, J.R., de Pedro, N., Blevins, R.A., Peláez, F., Wright, S.D., Cui, J. J. Biol. Chem. (2003) [Pubmed]
  37. High molecular mass kininogen inhibits cathepsin G-induced platelet activation by forming a complex with cathepsin G. Selim, T.E., Ghoneim, H.R., Abdel Ghaffar, H.A., Colman, R.W., Dela Cadena, R.A. Hematol. J. (2001) [Pubmed]
  38. Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2 and 3 of the urokinase receptor. Colman, R.W., Pixley, R.A., Najamunnisa, S., Yan, W., Wang, J., Mazar, A., McCrae, K.R. J. Clin. Invest. (1997) [Pubmed]
  39. Evidence for binding of the ectodomain of amyloid precursor protein 695 and activated high molecular weight kininogen. Das, A., Smalheiser, N.R., Markaryan, A., Kaplan, A. Biochim. Biophys. Acta (2002) [Pubmed]
  40. Kininogen-derived peptides for investigating the putative vasoactive properties of human cathepsins K and L. Desmazes, C., Galineau, L., Gauthier, F., Brömme, D., Lalmanach, G. Eur. J. Biochem. (2003) [Pubmed]
  41. Localization of the binding site on plasma kallikrein for high-molecular-weight kininogen to both apple 1 and apple 4 domains of the heavy chain. Page, J.D., You, J.L., Harris, R.B., Colman, R.W. Arch. Biochem. Biophys. (1994) [Pubmed]
  42. High-molecular weight kininogen. A secreted platelet protein. Schmaier, A.H., Zuckerberg, A., Silverman, C., Kuchibhotla, J., Tuszynski, G.P., Colman, R.W. J. Clin. Invest. (1983) [Pubmed]
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