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KLK5 (Kallikrein-related peptidase 5)

Written2008-06George M Yousef, Eleftherios P Diamandis
Department of Laboratory Medicine,St Michael's Hospital,30 Bond Street, Toronto, ON, M5B 1W8, Canada, (GMY); Department of Pathology, Laboratory Medicine, Mount Sinai Hospital, 6th Floor, Room 6-201, Box 32, 60 Murray Street, Toronto, Ontario, Canada, M5T 3L9 (EPD)

(Note : for Links provided by Atlas : click)

Identity

Other aliasEC 3.4.21
HSCTE
KLK-L2
KLKL2
SCTE
LocusID (NCBI) 25818
Atlas_Id 41085
Location 19q13.41  [Link to chromosome band 19q13]
Location_base_pair Starts at and ends at bp from pter
Local_order Telomere to centromere
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
KLK5 (19q13.41) / CDH23 (10q22.1)

DNA/RNA

Description The KLK5 gene is approximately 9.5 Kb in length, consisting of 6 exons (5 of them are coding exons) and 5 introns.
Transcription Five alternatively spliced variants have been identified for the KLK5 gene. These variants differ in the number and length of the 5' untranslated exons and/or the last two coding exons. Tissue-specific expression of these variants is regulated by multiple promoters located in the first exon of each isoform. KLK5 splice variants were found to be differentially expressed, at the mRNA level, in ovarian, breast and prostate cancers.
Pseudogene None identified.

Protein

Description Full-length KLK5 is formed of 293 amino acids. It is composed of a signal peptide (29 amino acids), followed by an activation peptide (37 amino acids) and the mature chain (227 amino acids), with 4 potential N-linked glycosylation sites. The positions of the catalytic triad of serine proteases is conserved. KLK5 is synthesized as a full-length protein intracellularly. In the secretary pathway, the signal peptide is cleaved and the zymogen is released outside the cells. Upon activation, the propeptide is removed to generate the mature active protein. In serum and ascites fluid, in addition to the free (approximately 40 kDa) form, KLK5 forms complexes with alpha(1)-antitrypsin and alpha(2)-macroglobulin.
Expression At the mRNA level, KLK5 is expressed in a variety of tissues, mainly the testis, brain, breast, thyroid and salivary glands. The KLK5 protein is expressed at higher levels in the skin, salivary gland, testis and female genital organs. KLK5 has also been identified in many biological fluids, including vaginal secretions, breast milk and seminal plasma. Many fetal tissues, including bone, skin, thymus and kidney also express KLK5.
Localisation KLK5 is a secreted protein.
Function KLK5 is a secreted serine protease. The physiological functions of KLK5 are not fully understood. The KLK5 protein was originally identified from a keratinocyte library and was purified from the stratum corneum of the human skin. It was found to have a trypsin-like enzymatic activity with strong preference for Arg over Lys in the P1 position. Evidence exists that it plays a role in skin desquamation. KLK5 can also digest extracellular matrix components, collagens type I, II, III, IV, fibronectin, and laminin, and can potentially release angiostatin from plasminogen, and "cystatin-like domain 3" from low molecular weight kininogen, and fibrinopeptide B and peptide beta15-42 from the B beta chain of fibrinogen. The KLK5 protein has been shown to activate another kallikrein, KLK7, and was found to be under steroid hormonal regulation in cancer cell lines. It has been recently shown that KLK5 is differentially expressed in a number of malignancies, including ovarian, breast and prostate cancers, but the mechanisms of its involvement in cancer have yet to be determined.
Homology The human KLK5 protein sequence shares 40-70 % homology with other members of the human tissue kallikreins, and 70% identity with that of the mouse orthologue.

Mutations

Note No germinal or somatic mutations are identified to be associated with cancer so far.

Implicated in

Note
  
Entity Ovarian cancer
Disease Higher KLK5 concentrations were found in the serum of 69% of patients with ovarian cancer. The KLK5 protein was found to be elevated in 55% of ovarian cancer tissues compared to normal. Also, KLK5 mRNA is significantly elevated in ovarian cancer, specially serous type. Ovarian cancer ascites contains higher levels, as compared to benign effusions and ascites from other cancer types. Two KLK5 splice variants are upregulated in ovarian cancer tissues compared to normal.
Prognosis The KLK5 mRNA and protein are markers of unfavorable prognosis in ovarian cancer, being overexpressed in late stage and higher grade tumors, and associated with shorter DFS and OS. In addition, the KLK5 protein was shown to be an independent indicator of poor prognosis in patients with high-grade tumors and optimal debulking success.
Cytogenetics No cytogenetic abnormalities are identified so far.
Hybrid/Mutated Gene None identified.
  
  
Entity Breast cancer
Disease Higher concentrations of KLK5 were found in the serum of 49% of patients with breast cancer. KLK5 splice variant 2 is downregulated in breast cancer compared to normal.
Prognosis The KLK5 mRNA transcript was found to be an indicator of unfavorable prognosis, being overexpressed in node-positive patients with ER-negative tumors. It is independently associated with decreased DFS and OS, and it is an independent indicator of shorter DFS and OS in node-positive patients.
Cytogenetics No cytogenetic abnormalities are identified so far.
Hybrid/Mutated Gene None identified.
  
  
Entity Prostate cancer
Disease KLK5 mRNA is downregulated in cancer vs normal prostatic tissues.
Prognosis KLK5 mRNA is a favorable prognostic maker, with higher levels associated with low grade tumors and low Gleason score.
Cytogenetics No cytogenetic abnormalities are identified so far.
Hybrid/Mutated Gene None identified.
  
  
Entity Testicular cancer
Disease KLK5 mRNA is downregulated in cancer vs normal testicular tissues.
Prognosis KLK5 mRNA is a marker of favorable prognosis, overexpressed in smaller, early stage non-seminomas.
Cytogenetics No cytogenetic abnormalities are identified so far.
Hybrid/Mutated Gene None identified.
  
  
Entity Non-small cell lung carcinoma
Disease Serum KLK5 levels are lower in lung cancer compared to normal and can be used as part of a multiparametric panel for diagnosis.
Prognosis None identified.
Cytogenetics No cytogenetic abnormalities are identified so far.
Hybrid/Mutated Gene None identified.
  
  
Entity Urinary bladder carcinoma
Disease None identified.
Prognosis Increased expression of KLK5 was frequently observed in invasive tumors (pT2-pT4) compared with superficial tumors (pTa, pT1).
Cytogenetics Copy number gain was observed in transitional cell carcinoma.
Hybrid/Mutated Gene None identified.
  

Breakpoints

Note None identified.

Bibliography

Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers.
Dong Y, Kaushal A, Brattsand M, Nicklin J, Clements JA.
Clin Cancer Res. 2003: 1710-1720.
PMID 12738725
 
Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis inovarian cancer.
Kim H, Scorilas A, Katsaros D, Yousef GM, Massobrio M, Fracchioli S, Piccinno R, Gordini G, Diamandis EP.
Br J Cancer. 2001; 84: 643-650.
PMID 11237385
 
Differential expression of a human kallikrein 5 (KLK5) splice variant in ovarian and prostate cancer.
Kurlender L, Yousef GM, Memari N, Robb JD, Michael IP, Borgoño C, Katsaros D, Stephan C, Jung K, Diamandis EP.
Tumour Biol. 2004; 25: 149-156.
PMID 15361712
 
Biochemical and enzymatic characterization of human kallikrein 5 (hK5), a novel serine protease potentially involved in cancer progression.
Michael IP, Sotiropoulou G, Pampalakis G, Magklara A, Ghosh M, Wasney G, Diamandis EP.
J Biol Chem. 2005; 280: 14628-14635.
PMID 15713679
 
A multiparametric serum kallikrein panel for diagnosis of non-small cell lung carcinoma.
Planque C, Li L, Zheng Y, Soosaipillai A, Reckamp K, Chia D, Diamandis EP, Goodglick L.
Clin Cancer Res. 2008; 14: 1355-1362.
PMID 18316555
 
KLK5 and KLK7, two members of the human tissue kallikrein family, are differentially expressed in lung cancer.
Planque C, de Monte M, Guyetant S, Rollin J, Desmazes C, Panel V, Lemarié E, Courty Y.
Biochem Biophys Res Commun. 2005; 329: 1260-1266.
PMID 15766562
 
Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells.
Prezas P, Arlt MJ, Viktorov P, Soosaipillai A, Holzscheiter L, Schmitt M, Talieri M, Diamandis EP, Krüger A, Magdolen V.
Biol Chem. 2006; 387: 807-811.
PMID 16800744
 
Distribution of 15 human kallikreins in tissues and biological fluids.
Shaw JL, Diamandis EP.
Clin Chem. 2007; 53: 1423-32.
PMID 17573418
 
Association of KLK5 overexpression with invasiveness of urinary bladder carcinoma cells.
Shinoda Y, Kozaki K, Imoto I, Obara W, Tsuda H, Mizutani Y, Shuin T, Fujioka T, Miki T, Inazawa J.
Cancer Sci. 2007; 98: 1078-1086.
PMID 17459052
 
The human kallikrein protein 5 (hK5) is enzymatically active, glycosylated and forms complexes with two protease inhibitors in ovarian cancer fluids.
Yousef GM, Kapadia C, Polymeris ME, Borgono C, Hutchinson S, Wasney GA, Soosaipillai A, Diamandis EP.
Biochim Biophys Acta. 2003; 1628(2): 88-96.
PMID 12890555
 
Differential expression of Kallikrein gene 5 in cancerous and normal testicular tissues.
Yousef GM, Obiezu CV, Jung K, Stephan C, Scorilas A, Diamandis EP.
Urology. 2002; 60: 714-718.
PMID 12385949
 
Parallel overexpression of seven kallikrein genes in ovarian cancer.
Yousef GM, Polymeris ME, Yacoub GM, Scorilas A, Soosaipillai A, Popalis C, Fracchioli S, Katsaros D, Diamandis EP.
Cancer Res. 2003; 63: 2223-2227.
PMID 12727843
 
Human kallikrein gene 5 (KLK5) expression by quantitative PCR: an independent indicator of poor prognosis in breast cancer.
Yousef GM, Scorilas A, Kyriakopoulou LG, Rendl L, Diamandis M, Ponzone R, Biglia N, Giai M, Roagna R, Sismondi P, Diamandis EP.
Clin Chem. 2002; 48: 1241-1250.
PMID 12142380
 
The kallikrein gene 5 splice variant 2 is a new biomarker for breast and ovarian cancer.
Yousef GM, White NM, Kurlender L, Michael I, Memari N, Robb JD, Katsaros D, Stephan C, Jung K, Diamandis EP.
Tumour Biol. 2004; 25: 221-227.
PMID 15627884
 
Kallikrein gene downregulation in breast cancer.
Yousef GM, Yacoub GM, Polymeris ME, Popalis C, Soosaipillai A, Diamandis EP.
Br J Cancer. 2004; 90: 167-172.
PMID 14710225
 

Citation

This paper should be referenced as such :
Yousef, GM ; Diamandis, EP
KLK5 (Kallikrein-related peptidase 5)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(5):357-359.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/KLK5ID41085ch19q13.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(10;19)(q22;q13) KLK5/CDH23


External links

Nomenclature
Cards
AtlasKLK5ID41085ch19q13.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)25818
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:40:58 CEST 2018

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