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Gene Review

KLKB1  -  kallikrein B, plasma (Fletcher factor) 1

Homo sapiens

Synonyms: Fletcher factor, KLK3, Kininogenin, PPK, Plasma kallikrein, ...
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Disease relevance of KLKB1


High impact information on KLKB1


Chemical compound and disease context of KLKB1


Biological context of KLKB1


Anatomical context of KLKB1


Associations of KLKB1 with chemical compounds

  • Of note were a common polymorphism (30% of the population) at position 521 of KLKB1 cDNA, which leads to the replacement of asparagine with a serine at position 124 in the heavy chain of the A2 domain of the protein [1].
  • The role of the bradykinin-generating system in the pathogenesis of cancer was explored by simultaneously measuring plasma prekallikrein (PK), the precursor of kallikrein, which is the major enzyme responsible for kinin generation, and plasma kininogens (KNG), which are precursors of kinin, in patients with various cancers [20].
  • The determination of plasma prekallikrein by direct activation with beta-XIIa in the presence of acetone offers several advantages over the use of contact activators such as dextran sulfate [21].
  • Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats [22].
  • Human plasma prekallikrein was fragmented with cyanogen bromide, and 13 homogeneous peptides were isolated and sequenced [22].

Physical interactions of KLKB1


Co-localisations of KLKB1

  • Casein autography of isolated platelets revealed a approximately 90 kDa band of activity which comigrated with plasma prekallikrein (PK)/kallikrein, a known activator of pro-UK [24].

Regulatory relationships of KLKB1


Other interactions of KLKB1


Analytical, diagnostic and therapeutic context of KLKB1

  • Exon-spanning PCR primer sets were identified by serial testing of primer pairs designed from KLKB1 cDNA sequence and DNA sequencing of PCR products [1].
  • Plasma prekallikrein was also quantitated by radial immunodiffusion, which gave results similar to those obtained by functional assay with beta-XIIa [21].
  • Recently RT-PCR studies had demonstrated the expression of plasma prekallikrein (PPK) mRNA in extrahepatic tissues [29].
  • Molecular cloning and expression of an alternative hKLK3 transcript coding for a variant protein of prostate-specific antigen [30].
  • We measured the circulating levels of plasma prekallikrein (PK) activity, factor XII, and high-molecular weight kininogen in the plasma of 636 type 1 diabetic patients from the Diabetes Control and Complications Trial/Epidemiology and Diabetes Intervention and Complications Study cohort [31].


  1. Genomic structure of the human plasma prekallikrein gene, identification of allelic variants, and analysis in end-stage renal disease. Yu, H., Anderson, P.J., Freedman, B.I., Rich, S.S., Bowden, D.W. Genomics (2000) [Pubmed]
  2. Normal plasma arginine esterase and the Hageman factor (factor XII) -prekallikrein-kininogen system in cystic fibrosis. Goldsmith, G.H., Stern, R.C., Saito, H., Ratnoff, O.D. J. Lab. Clin. Med. (1977) [Pubmed]
  3. Activation of human plasma prekallikrein by Pseudomonas aeruginosa elastase in vitro. Shibuya, Y., Tanaka, H., Nishino, N., Okabe, H., Kambara, T., Yamamoto, T. Biochim. Biophys. Acta (1991) [Pubmed]
  4. Interactions among Hageman factor (HG, Factor XII), plasma thromboplastin antecedent (PTA, Factor XI), plasma prekallikrein (PK, Fletcher factor) and high molecular weight kininogen (HMW-K, Fitzgerald factor) in blood coagulation. Saito, H., Ratnoff, O.D. Adv. Exp. Med. Biol. (1979) [Pubmed]
  5. Elevated levels of plasma prekallikrein, high molecular weight kininogen and factor XI in coronary heart disease. Merlo, C., Wuillemin, W.A., Redondo, M., Furlan, M., Sulzer, I., Kremer-Hovinga, J., Binder, B.R., Lämmle, B. Atherosclerosis (2002) [Pubmed]
  6. A prospective study of platelets and plasma proteolytic systems during the early stages of Rocky Mountain spotted fever. Rao, A.K., Schapira, M., Clements, M.L., Niewiarowski, S., Budzynski, A.Z., Schmaier, A.H., Harpel, P.C., Blackwelder, W.C., Scherrer, J.R., Sobel, E. N. Engl. J. Med. (1988) [Pubmed]
  7. Surface activation of blood coagulation, fibrinolysis and kinin formation. Heimark, R.L., Kurachi, K., Fujikawa, K., Davie, E.W. Nature (1980) [Pubmed]
  8. Streptococcal cysteine proteinase releases kinins: a virulence mechanism. Herwald, H., Collin, M., Müller-Esterl, W., Björck, L. J. Exp. Med. (1996) [Pubmed]
  9. Human neutrophils contain and bind high molecular weight kininogen. Gustafson, E.J., Schmaier, A.H., Wachtfogel, Y.T., Kaufman, N., Kucich, U., Colman, R.W. J. Clin. Invest. (1989) [Pubmed]
  10. 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]
  11. Involvement of the C-terminal end of the prostrate-specific antigen in a conformational epitope: characterization by proteolytic degradation of monoclonal antibody-bound antigen and mass spectrometry. Michel, S., Forest, E., Pétillot, Y., Deléage, G., Heuzé-Vourc'h, N., Courty, Y., Lascoux, D., Jolivet, M., Jolivet-Reynaud, C. J. Mol. Recognit. (2001) [Pubmed]
  12. Activation of plasma contact and coagulation systems and neutrophils in the active phase of ulcerative colitis. Stadnicki, A., Gonciarz, M., Niewiarowski, T.J., Hartleb, J., Rudnicki, M., Merrell, N.B., Dela Cadena, R.A., Colman, R.W. Dig. Dis. Sci. (1997) [Pubmed]
  13. The promoter and the enhancer region of the KLK 3 (prostate specific antigen) gene is frequently mutated in breast tumours and in breast carcinoma cell lines. Majumdar, S., Diamandis, E.P. Br. J. Cancer (1999) [Pubmed]
  14. Role of androgen metabolism genes CYP1B1, PSA/KLK3, and CYP11alpha in prostate cancer risk and aggressiveness. Cicek, M.S., Liu, X., Casey, G., Witte, J.S. Cancer Epidemiol. Biomarkers Prev. (2005) [Pubmed]
  15. 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]
  16. Severe Fletcher factor (plasma prekallikrein) deficiency with partial deficiency of Hageman factor (factor XII): report of a case with observation on in vivo and in vitro leukocyte chemotaxis. Poon, M.C., Moore, M.R., Castleberry, R.P., Lurie, A., Huang, S.T., Lehmeyer, J. Am. J. Hematol. (1982) [Pubmed]
  17. Assembly of contact-phase factors on the surface of the human neutrophil membrane. Henderson, L.M., Figueroa, C.D., Müller-Esterl, W., Bhoola, K.D. Blood (1994) [Pubmed]
  18. 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]
  19. Immunolocalization of plasma kallikrein in human brain. Cerf, M.E., Raidoo, D.M. Metabolic brain disease. (2000) [Pubmed]
  20. Kinin-generating cascade in advanced cancer patients and in vitro study. Matsumura, Y., Maruo, K., Kimura, M., Yamamoto, T., Konno, T., Maeda, H. Jpn. J. Cancer Res. (1991) [Pubmed]
  21. Plasma prekallikrein: quantitative determination by direct activation with Hageman factor fragment (beta-XIIa). Alving, B.M., Tankersley, D.L., Mason, B.L. J. Lab. Clin. Med. (1983) [Pubmed]
  22. Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats. Chung, D.W., Fujikawa, K., McMullen, B.A., Davie, E.W. Biochemistry (1986) [Pubmed]
  23. Binding of a monoclonal anti-human plasma prekallikrein antibody to the complexes of kallikrein with C1-inhibitor and alpha 2-macroglobulin analyzed by immunoblot and "sandwich" assays. Veloso, D., Tseng, S.Y., Craig, A.R., Colman, R.W. Adv. Exp. Med. Biol. (1989) [Pubmed]
  24. Platelet-bound prekallikrein promotes pro-urokinase-induced clot lysis: a mechanism for targeting the factor XII dependent intrinsic pathway of fibrinolysis. Loza, J.P., Gurewich, V., Johnstone, M., Pannell, R. Thromb. Haemost. (1994) [Pubmed]
  25. Recombinant prolylcarboxypeptidase activates plasma prekallikrein. Shariat-Madar, Z., Mahdi, F., Schmaier, A.H. Blood (2004) [Pubmed]
  26. Extra-hepatic transcription of plasma prekallikrein gene in human and rat tissues. Ciechanowicz, A., Bader, M., Wagner, J., Ganten, D. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  27. Human plasma prekallikrein. Studies of its activation by activated factor XII and of its inactivation by diisopropyl phosphofluoridate. Bouma, B.N., Miles, L.A., Beretta, G., Griffin, J.H. Biochemistry (1980) [Pubmed]
  28. Kallikreins and kininogens in saliva and plasma of patients presenting with rheumatoid arthritis. Hernández, C.C., Donadi, E.A., Reis, M.L. Scand. J. Rheumatol. (2002) [Pubmed]
  29. The mRNAs of prekallikrein, factors XI and XII, and kininogen, components of the contact phase cascade are differentially expressed in multiple non-hepatic human tissues. Neth, P., Arnhold, M., Nitschko, H., Fink, E. Thromb. Haemost. (2001) [Pubmed]
  30. Molecular cloning and expression of an alternative hKLK3 transcript coding for a variant protein of prostate-specific antigen. Heuzé, N., Olayat, S., Gutman, N., Zani, M.L., Courty, Y. Cancer Res. (1999) [Pubmed]
  31. Plasma prekallikrein: a risk marker for hypertension and nephropathy in type 1 diabetes. Jaffa, A.A., Durazo-Arvizu, R., Zheng, D., Lackland, D.T., Srikanth, S., Garvey, W.T., Schmaier, A.H. Diabetes (2003) [Pubmed]
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