KLK4 explained

Kallikrein-related peptidase 4 is a protein which in humans is encoded by the KLK4 gene.^{[1] [2] [3]}

Kallikreins are a subgroup of serine proteases having diverse physiological functions.^[4] Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. In particular, they may serve as biomarkers for both prostate cancer and breast cancer.

This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins.^[5] Alternate splice variants for this gene have been described, but their biological validity has not been determined.^[6]

Further reading

• Clements J, Hooper J, Dong Y, Harvey T . The expanded human kallikrein (KLK) gene family: genomic organisation, tissue-specific expression and potential functions. . Biol. Chem. . 382 . 1 . 5–14 . 2001 . 11258672 . 10.1515/BC.2001.002 . 5864448 .
• Simmer JP, Fukae M, Tanabe T, etal . Purification, characterization, and cloning of enamel matrix serine proteinase 1. . J. Dent. Res. . 77 . 2 . 377–86 . 1998 . 9465170 . 10.1177/00220345980770020601 . 21816663 .
• Nelson PS, Gan L, Ferguson C, etal . Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression. . Proc. Natl. Acad. Sci. U.S.A. . 96 . 6 . 3114–9 . 1999 . 10077646 . 10.1073/pnas.96.6.3114 . 15904 . 1999PNAS...96.3114N . free .
• Stephenson SA, Verity K, Ashworth LK, Clements JA . Localization of a new prostate-specific antigen-related serine protease gene, KLK4, is evidence for an expanded human kallikrein gene family cluster on chromosome 19q13.3-13.4. . J. Biol. Chem. . 274 . 33 . 23210–4 . 1999 . 10438493 . 10.1074/jbc.274.33.23210 . free .
• Yousef GM, Obiezu CV, Luo LY, etal . Prostase/KLK-L1 is a new member of the human kallikrein gene family, is expressed in prostate and breast tissues, and is hormonally regulated. . Cancer Res. . 59 . 17 . 4252–6 . 1999 . 10485467 .
• DuPont BR, Hu CC, Reveles X, Simmer JP . Assignment of serine protease 17 (PRSS17) to human chromosome bands 19q13.3→q13.4 by in situ hybridization. . Cytogenet. Cell Genet. . 86 . 3–4 . 212–3 . 2000 . 10575207 . 10.1159/000015340 . 42446073 .
• Hu JC, Zhang C, Sun X, etal . Characterization of the mouse and human PRSS17 genes, their relationship to other serine proteases, and the expression of PRSS17 in developing mouse incisors . Gene . 251 . 1 . 1–8 . 2000 . 10863090 . 10.1016/S0378-1119(00)00203-1 .
• Gan L, Lee I, Smith R, etal . Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region . Gene . 257 . 1 . 119–30 . 2001 . 11054574 . 10.1016/S0378-1119(00)00382-6 .
• Obiezu CV, Diamandis EP . An alternatively spliced variant of KLK4 expressed in prostatic tissue . Clin. Biochem. . 33 . 7 . 599–600 . 2001 . 11124349 . 10.1016/S0009-9120(00)00178-8 .
• Takayama TK, Carter CA, Deng T . Activation of prostate-specific antigen precursor (pro-PSA) by prostin, a novel human prostatic serine protease identified by degenerate PCR . Biochemistry . 40 . 6 . 1679–87 . 2001 . 11327827 . 10.1021/bi002129r .
• Korkmaz KS, Korkmaz CG, Pretlow TG, Saatcioglu F . Distinctly different gene structure of KLK4/KLK-L1/prostase/ARM1 compared with other members of the kallikrein family: intracellular localization, alternative cDNA forms, and Regulation by multiple hormones . DNA Cell Biol. . 20 . 7 . 435–45 . 2001 . 11506707 . 10.1089/104454901750361497 .
• Takayama TK, McMullen BA, Nelson PS, etal . Characterization of hK4 (prostase), a prostate-specific serine protease: activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase . Biochemistry . 40 . 50 . 15341–8 . 2002 . 11735417 . 10.1021/bi015775e .
• Hural JA, Friedman RS, McNabb A, etal . Identification of naturally processed CD4 T cell epitopes from the prostate-specific antigen kallikrein 4 using peptide-based in vitro stimulation . J. Immunol. . 169 . 1 . 557–65 . 2002 . 12077288 . 10.4049/jimmunol.169.1.557. free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Grimwood J, Gordon LA, Olsen A, etal . The DNA sequence and biology of human chromosome 19 . Nature . 428 . 6982 . 529–35 . 2004 . 15057824 . 10.1038/nature02399 . 2004Natur.428..529G . free .
• Xi Z, Klokk TI, Korkmaz K, etal . Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer . Cancer Res. . 64 . 7 . 2365–70 . 2004 . 15059887 . 10.1158/0008-5472.CAN-03-2025 . 301169 .
• Hart PS, Hart TC, Michalec MD, etal . Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta . J. Med. Genet. . 41 . 7 . 545–9 . 2004 . 15235027 . 10.1136/jmg.2003.017657 . 1735847 .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Veveris-Lowe TL, Lawrence MG, Collard RL, etal . Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells . Endocr. Relat. Cancer . 12 . 3 . 631–43 . 2005 . 16172196 . 10.1677/erc.1.00958 . free . 2027.42/152955 . free .

External links

• The MEROPS online database for peptidases and their inhibitors: S01.251

Notes and References

1. Simmer JP, Fukae M, Tanabe T, Yamakoshi Y, Uchida T, Xue J, Margolis HC, Shimizu M, DeHart BC, Hu CC, Bartlett JD . Purification, characterization, and cloning of enamel matrix serine proteinase 1 . Journal of Dental Research . 77 . 2 . 377–86 . February 1998 . 9465170 . 10.1177/00220345980770020601 . 21816663 . 2008-10-20 . https://web.archive.org/web/20080821181950/http://jdr.iadrjournals.org/cgi/content/abstract/77/2/377 . 2008-08-21 . dead .
2. Nelson PS, Gan L, Ferguson C, Moss P, Gelinas R, Hood L, Wang K . Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression . Proceedings of the National Academy of Sciences of the United States of America . 96 . 6 . 3114–9 . March 1999 . 10077646 . 15904 . 10.1073/pnas.96.6.3114. 1999PNAS...96.3114N . free .
3. Stephenson SA, Verity K, Ashworth LK, Clements JA . Localization of a new prostate-specific antigen-related serine protease gene, KLK4, is evidence for an expanded human kallikrein gene family cluster on chromosome 19q13.3-13.4 . The Journal of Biological Chemistry . 274 . 33 . 23210–4 . August 1999 . 10438493 . 10.1074/jbc.274.33.23210 . free .
4. 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 . A comprehensive nomenclature for serine proteases with homology to tissue kallikreins . Biological Chemistry . 387 . 6 . 637–41 . June 2006 . 16800724 . 10.1515/BC.2006.082 . 436200 .
5. Simmer JP, Fukae M, Tanabe T, Yamakoshi Y, Uchida T, Xue J, Margolis HC, Shimizu M, DeHart BC, Hu CC, Bartlett JD . Characterization of the mouse and human PRSS17 genes, their relationship to other serine proteases, and the expression of PRSS17 in developing mouse incisors . Gene . 251 . 1 . 1–8 . June 2000 . 10863090 . 10.1016/S0378-1119(00)00203-1 . 2008-10-20 . https://web.archive.org/web/20080821181950/http://jdr.iadrjournals.org/cgi/content/abstract/77/2/377 . 2008-08-21 . dead .
6. Web site: Entrez Gene: KLK4 kallikrein-related peptidase 4.