KLK-4

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Kallikrein-related peptidase 4
Kallikrein-related peptidase 4

Existing structure data : 2BDG , 2BDH , 2BDI , 4K1E , 4K8Y , 4KEL , 4KGA

Properties of human protein
Mass / length primary structure 224 amino acids
Cofactor Zn 2+
Identifier
Gene name KLK4
External IDs
Enzyme classification
EC, category 3.4.21. ,  Serine protease
MEROPS S01.251
Orthologue
human mouse
Entrez 9622 56640
Ensemble ENSG00000167749 ENSMUSG00000006948
UniProt Q9Y5K2
Refseq (mRNA) XM_001134318 NM_019928
Refseq (protein) XP_001134318 NP_064312
Gene locus Chr chr19: 56.1 - 56.11 Mb Chr chr7: 43.75 - 43.75 Mb
PubMed search 9622 56640

Kallikrein-related peptidase 4 , also known as KLK4 or EMSP1 , is a human protein .

Nomenclature and Genetics

Kallikreins are a subgroup of the serine proteases and have different biological functions. The kallikrein group includes the tumor marker prostate-specific antigen , which is referred to as KLK-3 in the kallikrein nomenclature. KLK4 is one of the 15 known members of the kallikrein family located on chromosome 19 in humans. The exact number of mouse genes is not known and is estimated to be 13 to 26.

Tumor biological aspects

Recently, there has been increasing evidence that other kallikreines, in addition to PSA, also play a role in the development of cancer. KLK-4 seems to be able to activate the PSA precursor pro-PSA and the urokinase-like plasmin activator uPA. It is therefore believed that it is involved in the development of prostate carcinoma. In addition, the expression of KLK-4 is hormonally regulated in prostate and mammary gland tissue. This observation also supports the assumption that it plays a role in tumor development in these tissues. Based on the tissue-specific expression of the KLK-4 protein, it was investigated whether it is suitable for a tumor vaccine against prostate carcinoma.

Tooth development

The mouse homologue of KLK4 is expressed in the tooth systems. It could be detected in odontoblasts and ameloblasts. This supports the assumption that KLK4 plays a role in the degradation of tooth enamel proteins, as it shows 78% sequence homology with the porcine enamel matrix serine protease I, which performs such a function. Mutations in the KLK4 gene can be the cause of amelogenesis imperfecta (AIPH).

Further reading on chromosome 19

  • RL Strausberg, EA Feingold, LH Grouse et al .: Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. In: Proc. Natl. Acad. Sci. USA Vol. 99, 26, 2003, pp. 16899-16903. PMID 12477932 .
  • J. Grimwood, LA Gordon, A. Olsen et al.: The DNA sequence and biology of human chromosome 19. In: Nature Volume 428, 6982, 2004, pp. 529-535. PMID 15057824 .
  • DS Gerhard, L. Wagner, EA Feingold et al .: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). In: Genome Res. Volume 14, 10B, 2004, pp. 2121-2127. PMID 15489334 .

Individual evidence

  1. ↑ Entrez Gene: KLK4 kallikrein-related peptidase 4. Retrieved January 7, 2011 .
  2. ↑ JP Simmer, M. Fukae, T. Tanabe et al: Purification, characterization, and cloning of enamel matrix serine proteinase 1. In: J. Dent. Res. Volume 77,2, 1998, pp. 377-386. PMID 9465170 .
  3. ↑ L. Gan, I. Lee, R. Smith et al .: Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. In: Genes. Volume 257,1, 2001, pp. 119-130. PMID 11054574 .
  4. ↑ SA Stephenson, K. Verity, LK Ashworth, JA Clements: 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. In: J. Biol. Chem. Vol. 274,33, 1999, pp. 23210-23214. PMID 10438493 .
  5. ^ BR DuPont, CC Hu, X. Reveles, JP Simmer: Assignment of serine protease 17 (PRSS17) to human chromosome bands 19q13.3 → q13.4 by in situ hybridization. In: Cytogenet. Cell Genet. Volume 86, 3-4, 2000, pp. 212-213. PMID 10575207 .
  6. ^ A b J. Clements, J. Hooper, Y. Dong, T. Harvey: The expanded human kallikrein (KLK) gene family: genomic organization, tissue-specific expression and potential functions. In: Biol. Chem. Vol. 382,1, 2001, pp. 5-14. PMID 11258672 .
  7. ↑ TL Veveris-Lowe, MG Lawrence, RL Collard et al .: 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. In: Endocr-Relat Cancer Volume 12.3, 2005, pp. 631-643. PMID 16172196 .
  8. ↑ Z. Xi, TI Klokk, K. Korkmaz et al.: Kallikrein 4 is a predominantly nuclear protein and is overexpressed in prostate cancer. In: Cancer Res . Volume 64, 7, 2004, pp. 2365-2370. PMID 15059887 .
  9. ↑ TK Takayama, BA McMullen, PS Nelson et al .: 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. In: Biochemistry Vol. 40, 50, 2002, pp. 15341-15348. PMID 11735417 .
  10. ↑ TK Takayama, CA Carter, T. Deng: Activation of prostate-specific antigen precursor (pro-PSA) by prostin, a novel human prostatic serine protease identified by degenerate PCR. In: Biochemistry. Volume 40, 6, 2001, pp. 1679-1687. PMID 11327827 .
  11. ↑ GM Yousef, CV Obiezu, LY Luo et al .: Prostase / KLK-L1 is a new member of the human kallikrein gene family, is expressed in prostate and breast tissues, and is hormonally regulated. In: Cancer Res. Vol. 59, 17, 1999, pp. 4252-4256. PMID 10485467 .
  12. ↑ KS Korkmaz, CG Korkmaz, TG Pretlow, F. Saatcioglu: 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. In: DNA Cell Biol. Vol. 20, 7, 2001, pp. 435-445. PMID 11506707 .
  13. ↑ JA Hural, RS Friedman, A. McNabb et al: Identification of naturally processed CD4 T cell epitopes from the prostate-specific antigen kallikrein 4 using peptide-based in vitro stimulation. In: J. Immunol. Volume 169.1, 2002, pp. 557-565. PMID 12077288 .
  14. ↑ JC Hu, C. Zhang, X. Sun et al .: Characterization of the mouse and human PRSS17 genes, their relationship to other serine proteases, and the expression of PRSS17 in developing mouse incisors. In: Genes. Volume 251, 1, 2000, pp. 1-8. PMID 10863090 .
  15. ↑ PS Nelson, L. Gan, C. Ferguson et al: Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression. In: Proc. Natl. Acad. Sci. USA Vol. 96,6, 1999, pp. 3114-3119. PMID 10077646 .
  16. ↑ AIPH.  In: Online Mendelian Inheritance in Man . (English).
  17. ↑ PS Hart, TC Hart, MD Michalec et al: Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. In: J. Med. Genet. Volume 41.7, 2004, pp. 545-549. PMID 15235027 .