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External IDsGeneCards: [1]
RefSeq (mRNA)



RefSeq (protein)



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Kallikrein-6 is a protein that in humans is encoded by the KLK6 gene.[1][2][3][4]


Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. The encoded enzyme is regulated by steroid hormones. In tissue culture, the enzyme has been found to generate amyloidogenic fragments from the amyloid precursor protein, suggesting a potential for involvement in Alzheimer's disease. Multiple alternatively spliced transcript variants that encode different isoforms have been identified for this gene.[4]


  1. Yamashiro K, Tsuruoka N, Kodama S, Tsujimoto M, Yamamura Y, Tanaka T, Nakazato H, Yamaguchi N (Jan 1997). "Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain". Biochimica et Biophysica Acta. 1350 (1): 11–4. doi:10.1016/s0167-4781(96)00187-x. PMID 9003450.
  2. Lundwall A, Band V, Blaber M, Clements JA, Courty Y, Diamandis EP, Fritz H, Lilja H, Malm J, Maltais LJ, Olsson AY, Petraki C, Scorilas A, Sotiropoulou G, Stenman UH, Stephan C, Talieri M, Yousef GM (Jun 2006). "A comprehensive nomenclature for serine proteases with homology to tissue kallikreins". Biological Chemistry. 387 (6): 637–41. doi:10.1515/BC.2006.082. PMID 16800724.
  3. "Proceedings of the 1st International Symposium on Kallikreins, Lausanne, Switzerland, September 1-3 , 2005". Biological Chemistry. 387 (6): 635–824. Jun 2006. doi:10.1515/BC.2006.081. PMID 16800723.
  4. 4.0 4.1 "Entrez Gene: KLK6 kallikrein-related peptidase 6".

Further reading

  • Yousef GM, Kishi T, Diamandis EP (Mar 2003). "Role of kallikrein enzymes in the central nervous system". Clinica Chimica Acta; International Journal of Clinical Chemistry. 329 (1–2): 1–8. doi:10.1016/S0009-8981(03)00004-4. PMID 12589961.
  • Menendez-Gonzalez M, Castro-Santos P, Suarez A, Calatayud MT, Perez-Pinera P, Martinez M, Ribacoba R, Gutierrez C (May 2008). "Value of measuring plasmatic levels of neurosin in the diagnosis of Alzheimer's disease". Journal of Alzheimer's Disease. 14 (1): 59–67. PMID 18525128.
  • Menendez-Gonzalez M, Castro-Santos P, Calatayud MT, Perez-Piñera P, Ribacoba R, Martinez-Rivera M, Gutierrez C, Lopez-Muñiz A, Suarez A (2008). "Plasmatic level of neurosin predicts outcome of mild cognitive impairment". International Archives of Medicine. 1 (1): 11. doi:10.1186/1755-7682-1-11. PMC 2475518. PMID 18620574.
  • Anisowicz A, Sotiropoulou G, Stenman G, Mok SC, Sager R (Sep 1996). "A novel protease homolog differentially expressed in breast and ovarian cancer". Molecular Medicine. 2 (5): 624–36. PMC 2230195. PMID 8898378.
  • Little SP, Dixon EP, Norris F, Buckley W, Becker GW, Johnson M, Dobbins JR, Wyrick T, Miller JR, MacKellar W, Hepburn D, Corvalan J, McClure D, Liu X, Stephenson D, Clemens J, Johnstone EM (Oct 1997). "Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer's disease brain". The Journal of Biological Chemistry. 272 (40): 25135–42. doi:10.1074/jbc.272.40.25135. PMID 9312124.
  • Yousef GM, Luo LY, Scherer SW, Sotiropoulou G, Diamandis EP (Dec 1999). "Molecular characterization of zyme/protease M/neurosin (PRSS9), a hormonally regulated kallikrein-like serine protease". Genomics. 62 (2): 251–9. doi:10.1006/geno.1999.6012. PMID 10610719.
  • Gan L, Lee I, Smith R, Argonza-Barrett R, Lei H, McCuaig J, Moss P, Paeper B, Wang K (Oct 2000). "Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region". Gene. 257 (1): 119–30. doi:10.1016/S0378-1119(00)00382-6. PMID 11054574.
  • Petraki CD, Karavana VN, Skoufogiannis PT, Little SP, Howarth DJ, Yousef GM, Diamandis EP (Nov 2001). "The spectrum of human kallikrein 6 (zyme/protease M/neurosin) expression in human tissues as assessed by immunohistochemistry". The Journal of Histochemistry and Cytochemistry. 49 (11): 1431–41. doi:10.1177/002215540104901111. PMID 11668196.
  • Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M (Jul 2002). "Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system". The Journal of Biological Chemistry. 277 (27): 24562–70. doi:10.1074/jbc.M202392200. PMID 11983703.
  • Gomis-Rüth FX, Bayés A, Sotiropoulou G, Pampalakis G, Tsetsenis T, Villegas V, Avilés FX, Coll M (Jul 2002). "The structure of human prokallikrein 6 reveals a novel activation mechanism for the kallikrein family". The Journal of Biological Chemistry. 277 (30): 27273–81. doi:10.1074/jbc.M201534200. PMID 12016211.
  • Scarisbrick IA, Blaber SI, Lucchinetti CF, Genain CP, Blaber M, Rodriguez M (Jun 2002). "Activity of a newly identified serine protease in CNS demyelination". Brain. 125 (Pt 6): 1283–96. doi:10.1093/brain/awf142. PMID 12023317.
  • Zarghooni M, Soosaipillai A, Grass L, Scorilas A, Mirazimi N, Diamandis EP (May 2002). "Decreased concentration of human kallikrein 6 in brain extracts of Alzheimer's disease patients". Clinical Biochemistry. 35 (3): 225–31. doi:10.1016/S0009-9120(02)00292-8. PMID 12074831.
  • Hoffman BR, Katsaros D, Scorilas A, Diamandis P, Fracchioli S, Rigault de la Longrais IA, Colgan T, Puopolo M, Giardina G, Massobrio M, Diamandis EP (Sep 2002). "Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker". British Journal of Cancer. 87 (7): 763–71. doi:10.1038/sj.bjc.6600533. PMC 2364256. PMID 12232761.
  • Mitsui S, Okui A, Uemura H, Mizuno T, Yamada T, Yamamura Y, Yamaguchi N (Nov 2002). "Decreased cerebrospinal fluid levels of neurosin (KLK6), an aging-related protease, as a possible new risk factor for Alzheimer's disease". Annals of the New York Academy of Sciences. 977: 216–23. doi:10.1111/j.1749-6632.2002.tb04818.x. PMID 12480753.
  • Hutchinson S, Luo LY, Yousef GM, Soosaipillai A, Diamandis EP (May 2003). "Purification of human kallikrein 6 from biological fluids and identification of its complex with alpha(1)-antichymotrypsin". Clinical Chemistry. 49 (5): 746–51. doi:10.1373/49.5.746. PMID 12709365.
  • Magklara A, Mellati AA, Wasney GA, Little SP, Sotiropoulou G, Becker GW, Diamandis EP (Aug 2003). "Characterization of the enzymatic activity of human kallikrein 6: Autoactivation, substrate specificity, and regulation by inhibitors". Biochemical and Biophysical Research Communications. 307 (4): 948–55. doi:10.1016/S0006-291X(03)01271-3. PMID 12878203.
  • Iwata A, Maruyama M, Akagi T, Hashikawa T, Kanazawa I, Tsuji S, Nukina N (Oct 2003). "Alpha-synuclein degradation by serine protease neurosin: implication for pathogenesis of synucleinopathies". Human Molecular Genetics. 12 (20): 2625–35. doi:10.1093/hmg/ddg283. PMID 12928483.
  • Sauter ER, Lininger J, Magklara A, Hewett JE, Diamandis EP (Feb 2004). "Association of kallikrein expression in nipple aspirate fluid with breast cancer risk". International Journal of Cancer. 108 (4): 588–91. doi:10.1002/ijc.11607. PMID 14696124.
  • Pampalakis G, Kurlender L, Diamandis EP, Sotiropoulou G (Jul 2004). "Cloning and characterization of novel isoforms of the human kallikrein 6 gene". Biochemical and Biophysical Research Communications. 320 (1): 54–61. doi:10.1016/j.bbrc.2004.04.205. PMID 15207701.

External links

  • The MEROPS online database for peptidases and their inhibitors: S01.236