KLK14

Kallikrein-14 is a protein that in humans is encoded by the KLK14 gene.[5][6][7]

KLK14
Identifiers
AliasesKLK14, KLK-L6, kallikrein related peptidase 14
External IDsOMIM: 606135 MGI: 2447564 HomoloGene: 69348 GeneCards: KLK14
Gene location (Human)
Chr.Chromosome 19 (human)[1]
Band19q13.41Start51,077,495 bp[1]
End51,084,245 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

43847

317653

Ensembl

ENSG00000129437

ENSMUSG00000044737

UniProt

Q9P0G3

Q8CGR5

RefSeq (mRNA)

NM_001311182
NM_022046
NM_001369775

NM_174866

RefSeq (protein)

NP_001298111
NP_071329
NP_001356704

NP_777355

Location (UCSC)Chr 19: 51.08 – 51.08 MbChr 7: 43.69 – 43.7 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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, skin disorders and other disease biomarkers.[8] This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Apart from its common transcript, an additional transcript variant has been described but its difference in function and full length nature has not been determined.[7]

KLK14 displays optimal trypsin-like activity at an alkaline pH of 8.0 and remains active in the pH ranges of 5.0 - 9.0 and is produced as a zymogen, but can function also in a chymotrypsin-like fashion.[9] Activation of KLK14 is mediated by KLK5 and after KLK14 activation, it further amplifies the activity of KLK proteases by a positive feedback loop via cleavage of pro-KLK5, which is a central player in KLK cascade.[10][11] KLK14 function has not yet been fully elucidated, but its most notable substrate is PAR2.[12][13] Its activity is inhibited by a wide variety of proteins, like macroglobulins, serpins, and the serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI) and also micro-environmental pH; and single-metal-ion inhibitors of KLKs among others.[14]

References
  1. GRCh38: Ensembl release 89: ENSG00000129437 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000044737 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Lundwall A, Band V, Blaber M, Clements JA, Courty Y, Diamandis EP, et al. (June 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. S2CID 436200.
  6. "Proceedings of the 1st International Symposium on Kallikreins, Lausanne, Switzerland, September 1-3 , 2005". Biological Chemistry. 387 (6): 635–824. June 2006. doi:10.1515/BC.2006.081. PMID 16800723. S2CID 83910246.
  7. "Entrez Gene: KLK14 kallikrein-related peptidase 14".
  8. Prassas I, Eissa A, Poda G, Diamandis EP (March 2015). "Unleashing the therapeutic potential of human kallikrein-related serine proteases". Nature Reviews. Drug Discovery. 14 (3): 183–202. doi:10.1038/nrd4534. PMID 25698643. S2CID 38090565.
  9. Emami N, Diamandis EP (December 2007). "New insights into the functional mechanisms and clinical applications of the kallikrein-related peptidase family". Molecular Oncology. 1 (3): 269–87. doi:10.1016/j.molonc.2007.09.003. PMC 5543873. PMID 19383303.
  10. Brattsand M, Stefansson K, Lundh C, Haasum Y, Egelrud T (January 2005). "A proteolytic cascade of kallikreins in the stratum corneum". The Journal of Investigative Dermatology. 124 (1): 198–203. doi:10.1111/j.0022-202x.2004.23547.x. PMID 15654974.
  11. Eissa A, Diamandis EP (June 2008). "Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions". Biological Chemistry. 389 (6): 669–80. doi:10.1515/bc.2008.079. PMID 18627299. S2CID 30602024.
  12. Hachem JP, Man MQ, Crumrine D, Uchida Y, Brown BE, Rogiers V, et al. (September 2005). "Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity". The Journal of Investigative Dermatology. 125 (3): 510–20. doi:10.1111/j.0022-202x.2005.23838.x. PMID 16117792.
  13. Hachem JP, Wagberg F, Schmuth M, Crumrine D, Lissens W, Jayakumar A, et al. (July 2006). "Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome". The Journal of Investigative Dermatology. 126 (7): 1609–21. doi:10.1038/sj.jid.5700288. PMID 16601670.
  14. Swedberg JE, Veer SJ, Harris JM (2012). "Natural, engineered and synthetic inhibitors of kallikrein-related peptidases.". In Magdolen V, Sommerhoff CP, Fritz H, Schmitt M (eds.). Kallikrein-Related Peptidases. 1: Characterization, regulation, and interactions within the proteas e. Walter de Gruyter GmbH. pp. 141–160. doi:10.1515/9783110260373.141. ISBN 978-3-11-026037-3.

Further reading
  • The MEROPS online database for peptidases and their inhibitors: S01.029
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