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Gene Review

KLK2  -  kallikrein-related peptidase 2

Homo sapiens

Synonyms: Glandular kallikrein-1, KLK2A2, Kallikrein-2, Tissue kallikrein-2, hGK-1, ...
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Disease relevance of KLK2


Psychiatry related information on KLK2

  • Thus, hK2 may be a useful tool for more accurate prediction of tumor grade or stage and allow better clinical decision-making [6].

High impact information on KLK2

  • To determine the cellular localization of glandular kallikrein in the human pancreas, immunohistochemical studies were performed with a monospecific antibody against the antigenically identical urinary kallikrein (urokallikrein) [7].
  • Although similar increased mRNA expression and locus-wide histone acetylation were also observed at another kallikrein locus (KLK2), at a third AR target locus (TMPRSS2) increased gene expression and locus-wide histone acetylation were not seen in the absence of ligand [8].
  • A luciferase reporter gene was directed to the prostate epithelium using three composite promoters called human kallikrein 2 (hK2)-E3/P, PSA-E2/P, and ARR2PB, derived from hK2, PSA, and rat probasin regulatory elements, to generate the EZC1, EZC2, and EZC3-prostate mice, respectively [9].
  • PURPOSE: We examined the relationship between a mutant (T) for wild-type (C) allele substitution of the human kallikrein-2 gene (KLK2), circulating human kallikrein-2 (hK2) levels and prostate cancer risk [10].
  • The overall distribution of the CC, CT, and TT KLK2 genotypes was 55.1%, 38.2%, and 6.8%, respectively [10].

Chemical compound and disease context of KLK2


Biological context of KLK2

  • Unusual alternative splicing within the human kallikrein genes KLK2 and KLK3 gives rise to novel prostate-specific proteins [16].
  • Binding occurred between bp -539 and -399 and bp -349 and -224 in the PSA and KLK2 promoters respectively, which were shown previously to be necessary for AR-mediated transactivation [17].
  • CONCLUSIONS: The results verify that the PSA promoter/enhancer must be combined with KLK2 to ensure the full activity and cell specificity of the gene [18].
  • KLK5 is a newly discovered human kallikrein gene which shares a high degree of homology and is located adjacent to KLK2 and KLK3 genes on chromosome 19q13 [2].
  • The human kallikrein gene cluster, located in the chromosome band 19q13, contains several tissue-specific serine protease genes including the prostate-specific KLK2, KLK3 and prostase genes [19].

Anatomical context of KLK2


Associations of KLK2 with chemical compounds


Physical interactions of KLK2

  • N-Terminal sequencing shows that hK2 forms a covalent complex with PAI-1, PCI and ACT after cleavage at Arg346-Met347, Arg354-Ser355 and Leu358-Ser359, respectively [26].
  • Our data suggest rapid metabolism of human glandular kallikrein 2 but do not support suggestions of the significance in vivo of complex formations with alpha2-macroglobulin as a major means to eliminate PSA from plasma in patients with clinically localized prostate cancer [27].

Enzymatic interactions of KLK2

  • Free hK2 was able to hydrolyze semenogelins and fibronectin in vitro [28].
  • [Val217]hK2 also showed altered specificity on a synthetic peptide substrate compared to wild-type hK2, which exhibited partial hydrolysis at a PSA chymotrypsin-like cleavage site as well as the trypsin-like site cleaved by hK2 [29].

Co-localisations of KLK2

  • The hGK-1 mRNA was colocalized with PSA mRNA in prostatic epithelia [5].

Regulatory relationships of KLK2


Other interactions of KLK2


Analytical, diagnostic and therapeutic context of KLK2


  1. The new human kallikrein gene family: implications in carcinogenesis. Diamandis, E.P., Yousef, G.M., Luo, L.Y., Magklara, A., Obiezu, C.V. Trends Endocrinol. Metab. (2000) [Pubmed]
  2. Down-regulation of the human kallikrein gene 5 (KLK5) in prostate cancer tissues. Yousef, G.M., Scorilas, A., Chang, A., Rendl, L., Diamandis, M., Jung, K., Diamandis, E.P. Prostate (2002) [Pubmed]
  3. Immunoreactivity of recombinant human glandular kallikrein using monoclonal antibodies raised against prostate-specific antigen. Eerola, R., Piironen, T., Pettersson, K., Lövgren, J., Vehniäinen, M., Lilja, H., Dowell, B., Lövgren, T., Karp, M. Prostate (1997) [Pubmed]
  4. Robust prostate-specific expression for targeted gene therapy based on the human kallikrein 2 promoter. Xie, X., Zhao, X., Liu, Y., Young, C.Y., Tindall, D.J., Slawin, K.M., Spencer, D.M. Hum. Gene Ther. (2001) [Pubmed]
  5. Tissue-specific and hormonal regulation of human prostate-specific glandular kallikrein. Young, C.Y., Andrews, P.E., Montgomery, B.T., Tindall, D.J. Biochemistry (1992) [Pubmed]
  6. Human glandular kallikrein as a tool to improve discrimination of poorly differentiated and non-organ-confined prostate cancer compared with prostate-specific antigen. Recker, F., Kwiatkowski, M.K., Piironen, T., Pettersson, K., Huber, A., Lümmen, G., Tscholl, R. Urology (2000) [Pubmed]
  7. Identification of human glandular kallikrein in the beta cell of the pancreas. ole-MoiYoi, O.K., Pinkus, G.S., Spragg, J., Austen, K.F. N. Engl. J. Med. (1979) [Pubmed]
  8. Locus-wide chromatin remodeling and enhanced androgen receptor-mediated transcription in recurrent prostate tumor cells. Jia, L., Shen, H.C., Wantroba, M., Khalid, O., Liang, G., Wang, Q., Gentzschein, E., Pinski, J.K., Stanczyk, F.Z., Jones, P.A., Coetzee, G.A. Mol. Cell. Biol. (2006) [Pubmed]
  9. EZC-prostate models offer high sensitivity and specificity for noninvasive imaging of prostate cancer progression and androgen receptor action. Seethammagari, M.R., Xie, X., Greenberg, N.M., Spencer, D.M. Cancer Res. (2006) [Pubmed]
  10. Single nucleotide polymorphism of the human kallikrein-2 gene highly correlates with serum human kallikrein-2 levels and in combination enhances prostate cancer detection. Nam, R.K., Zhang, W.W., Trachtenberg, J., Diamandis, E., Toi, A., Emami, M., Ho, M., Sweet, J., Evans, A., Jewett, M.A., Narod, S.A. J. Clin. Oncol. (2003) [Pubmed]
  11. Dissociation between androgen responsiveness for malignant growth vs. expression of prostate specific differentiation markers PSA, hK2, and PSMA in human prostate cancer models. Denmeade, S.R., Sokoll, L.J., Dalrymple, S., Rosen, D.M., Gady, A.M., Bruzek, D., Ricklis, R.M., Isaacs, J.T. Prostate (2003) [Pubmed]
  12. Expression of human prostate-specific glandular kallikrein protein (hK2) in the breast cancer cell line T47-D. Hsieh, M.L., Charlesworth, M.C., Goodmanson, M., Zhang, S., Seay, T., Klee, G.G., Tindall, D.J., Young, C.Y. Cancer Res. (1997) [Pubmed]
  13. Concentrations of glandular kallikrein in human nasal secretions increase during experimentally induced allergic rhinitis. Baumgarten, C.R., Nichols, R.C., Naclerio, R.M., Proud, D. J. Immunol. (1986) [Pubmed]
  14. Estrogen and tamoxifen interplay with T(3) in male rats: pharmacologically distinct classes of estrogen responses affecting growth, bone, and lipid metabolism, and their relation to serum GH and IGF-I. Fitts, J.M., Klein, R.M., Powers, C.A. Endocrinology (2001) [Pubmed]
  15. Human kallikrein 11: a new biomarker of prostate and ovarian carcinoma. Diamandis, E.P., Okui, A., Mitsui, S., Luo, L.Y., Soosaipillai, A., Grass, L., Nakamura, T., Howarth, D.J., Yamaguchi, N. Cancer Res. (2002) [Pubmed]
  16. Unusual alternative splicing within the human kallikrein genes KLK2 and KLK3 gives rise to novel prostate-specific proteins. David, A., Mabjeesh, N., Azar, I., Biton, S., Engel, S., Bernstein, J., Romano, J., Avidor, Y., Waks, T., Eshhar, Z., Langer, S.Z., Lifschitz-Mercer, B., Matzkin, H., Rotman, G., Toporik, A., Savitsky, K., Mintz, L. J. Biol. Chem. (2002) [Pubmed]
  17. Androgen receptor-associated protein complex binds upstream of the androgen-responsive elements in the promoters of human prostate-specific antigen and kallikrein 2 genes. Sun, Z., Pan, J., Balk, S.P. Nucleic Acids Res. (1997) [Pubmed]
  18. Identifying the combination of the transcriptional regulatory sequences on prostate specific antigen and human glandular kallikrein genes. Tsui, K.H., Wu, L., Chang, P.L., Hsieh, M.L., Juang, H.H. J. Urol. (2004) [Pubmed]
  19. Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. Gan, L., Lee, I., Smith, R., Argonza-Barrett, R., Lei, H., McCuaig, J., Moss, P., Paeper, B., Wang, K. Gene (2000) [Pubmed]
  20. Glandular kallikreins and prostate-specific antigen are expressed in the human endometrium. Clements, J., Mukhtar, A. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  21. Expression of the kallikrein gene family in normal and Alzheimer's disease brain. Shimizu-Okabe, C., Yousef, G.M., Diamandis, E.P., Yoshida, S., Shiosaka, S., Fahnestock, M. Neuroreport (2001) [Pubmed]
  22. Expression of human glandular kallikrein, hK2, in mammalian cells. Kumar, A., Goel, A.S., Hill, T.M., Mikolajczyk, S.D., Millar, L.S., Kuus-Reichel, K., Saedi, M.S. Cancer Res. (1996) [Pubmed]
  23. Serpin-derived peptide substrates for investigating the substrate specificity of human tissue kallikreins hK1 and hK2. Bourgeois, L., Brillard-Bourdet, M., Deperthes, D., Juliano, M.A., Juliano, L., Tremblay, R.R., Dubé, J.Y., Gauthier, F. J. Biol. Chem. (1997) [Pubmed]
  24. Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor. Kang, Z., Jänne, O.A., Palvimo, J.J. Mol. Endocrinol. (2004) [Pubmed]
  25. Steroid-involved transcriptional regulation of human genes encoding prostatic acid phosphatase, prostate-specific antigen, and prostate-specific glandular kallikrein. Shan, J.D., Porvari, K., Ruokonen, M., Karhu, A., Launonen, V., Hedberg, P., Oikarinen, J., Vihko, P. Endocrinology (1997) [Pubmed]
  26. Prostatic human kallikrein 2 inactivates and complexes with plasminogen activator inhibitor-1. Mikolajczyk, S.D., Millar, L.S., Kumar, A., Saedi, M.S. Int. J. Cancer (1999) [Pubmed]
  27. Significance and metabolism of complexed and noncomplexed prostate specific antigen forms, and human glandular kallikrein 2 in clinically localized prostate cancer before and after radical prostatectomy. Lilja, H., Haese, A., Björk, T., Friedrich, M.G., Piironen, T., Pettersson, K., Huland, E., Huland, H. J. Urol. (1999) [Pubmed]
  28. Potential involvement of kallikrein hK2 in the hydrolysis of the human seminal vesicle proteins after ejaculation. Deperthes, D., Frenette, G., Brillard-Bourdet, M., Bourgeois, L., Gauthier, F., Tremblay, R.R., Dubé, J.Y. J. Androl. (1996) [Pubmed]
  29. Ala217 is important for the catalytic function and autoactivation of prostate-specific human kallikrein 2. Mikolajczyk, S.D., Millar, L.S., Marker, K.M., Grauer, L.S., Goel, A., Cass, M.M., Kumar, A., Saedi, M.S. Eur. J. Biochem. (1997) [Pubmed]
  30. Prostate-specific antigen and human glandular kallikrein: two kallikreins of the human prostate. Henttu, P., Vihko, P. Ann. Med. (1994) [Pubmed]
  31. Kininogenase activity of prostate-derived human glandular kallikrein (hK2) purified from seminal fluid. Charlesworth, M.C., Young, C.Y., Miller, V.M., Tindall, D.J. J. Androl. (1999) [Pubmed]
  32. Organization and evolution of the glandular kallikrein locus in Mus musculus. Olsson, A.Y., Lundwall, A. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  33. Kallikrein gene expression in human pituitary tissues. Clements, J.A., Mukhtar, A., Verity, K., Pullar, M., McNeill, P., Cummins, J., Fuller, P.J. Clin. Endocrinol. (Oxf) (1996) [Pubmed]
  34. Detection of metastatic prostate cancer using a splice variant-specific reverse transcriptase-polymerase chain reaction assay for human glandular kallikrein. Slawin, K.M., Shariat, S.F., Nguyen, C., Leventis, A.K., Song, W., Kattan, M.W., Young, C.Y., Tindall, D.J., Wheeler, T.M. Cancer Res. (2000) [Pubmed]
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