Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   
X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

KLK10 (Kallikrein-related peptidase 10)

Identity

Other namesNES1
PRSSL1
HGNC (Hugo) KLK10
Location 19q13.41
Location_base_pair Starts at 56207812 and ends at 56215243 bp from pter ( according to hg18-Mar_2006)  [Mapping]
Local_order Telomere to centromere.

DNA/RNA

Description Spanning 5.7 kb of genomic DNA, the KLK10 gene consists of 5 introns and six exons.
Transcription The KLK10 gene has several splice variants with different lengths of the first exon. The predominant form is 1443 bp. Since the first exon is untranslated, all splice variants encode the same protein.
Pseudogene Not identified so far.

Protein

Description KLK10 is a 30 kDa serine protease containing 276 amino acids. It consists of a signal peptide (aa 1-33), an activation peptide (aa 34-42), and a mature chain (aa 43-276).
Expression High levels of KLK10 expression are typically found in glandular epithelia in a wide variety of organs, such as salivary gland, gastrointestinal tract, prostate, lung, breast, and ovary.
Localisation KLK10 is synthesized as a precursor protein of 276 amino acids. Within the secretary pathway, its signal peptide is cleaved and it is secreted into the extracellular milieu as an inactive zymogen.
KLK10 has been identified in many biological fluids, such as blood, amniotic fluid, cerebrospinal fluid, milk, and nipple aspirate.
Function How KLK10 is activated remains undetermined. It is expected that upon activation, the peptide bond between arginine42 and lysine43 is proteolysed to release the mature chain. Mature KLK10 exhibits some typical characteristics of a trypsin-like serine protease, such as the catalytic triad (Histidine86, serine229, and aspartic acid137) and an aspartic acid in its substrate-binding pocket. However, its enzymatic activity has not been experimentally confirmed so far. Consequently, its potential physiologic substrates have not been identified.
Homology Human KLK10 shares 98.2% and 69% identity with chimpanzee and mouse/rat klk10, respectively.

Mutations

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

Implicated in

Entity Various cancers with upragulated KLK10.
Disease Epithelial ovarian carcinoma, uterine serous papillary carcinoma, head and neck squamous cell carcinoma, lung squamous cell carcinoma, and gastrointestinal tract cancer.
Prognosis In these malignancies, KLK10 has been reported to be upregulated. Among them, epithelial ovarian carcinoma is by far studied the most. KLK10 is overexpressed in ovarian tumor tissue than in normal epithelium and stromal tissues both at the mRNA and protein levels. Due to increased leakage of KLK10 into the circulation, serum concentrations of KLK10 in ovarian cancer patients are elevated. High levels of KLK10 in tumor tissue or in serum are associated with more advanced disease stages and poor survival. In particular, preoperative serum KLK10 levels can serve as a complimentary biomarker for CA125, a well-established tumor marker routinely used in ovarian cancer. It has been demonstrated that nearly all CA125-negative tumors show KLK10 immunostaining positivity and that about 35% of CA125-negative patients have increased serum levels of KLK10. In combination with CA125, KLK10 can improve the diagnostic sensitivity by about 20% compared to that of CA125 alone.
Cytogenetics No cytogenetic abnormalities are identified so far.
Hybrid/Mutated Gene Not identified so far.
  
Entity Various cancers with down regulated KLK10.
Disease Breast cancer, testicular cancer, leukemia, and prostate cancer.
Prognosis In contrast to ovarian cancer, KLK10 is down regulated in these malignancies, with breast cancer as a prototype. Several lines of evidence have demonstrated that KLK10 is progressively down regulated during breast cancer development. In a clinical study, it is observed that essentially all normal breast specimens had KLK10 expression, whereas about 46% of ductal carcinoma in situ (DCIS) and the majority of infiltrating ductal carcinoma (IDC) had no detectable KLK10 expression. More importantly, the KLK10 negative-DCIS was found to subsequently develop to IDC. In in vitro studies, it has been shown that KLK10 is expressed in normal breast epithelial cells but dramatically reduced in breast cancer cell lines. Moreover, reintroduction of KLK10 expression into these cancer cells can suppress their tumorigenecity in nude mice. KLK10 was thus considered to function as a tumor suppressor in breast cancer. The mechanisms governing the down regulation of KLK10 in breast cancer is not clear. One explanation is CpG island hypermethylation of exon 3, as demonstrated in a number of cancer cell lines. Noteworthy, expression of KLK10 is modulated by some steroid hormones and retinoid acid. They may, under certain conditions, also contribute to the aberrant expression of KLK10 in tumor tissues. However, the paradoxical expression of KLK10 in different types of tumors remains obscure.
  

External links

Nomenclature
HGNC (Hugo)KLK10   6358
Entrez_Gene (NCBI)KLK10  5655  kallikrein-related peptidase 10
Cards
AtlasKLK10ID41076ch19q13
GeneCards (Weizmann)KLK10
Ensembl (Hinxton)ENSG00000129451 [Gene_View]  KLK10 [Vega]
AceView (NCBI)KLK10
Genatlas (Paris)KLK10
euGene (Indiana)5655
SOURCE (Stanford)NM_001077500 NM_002776 NM_145888
Gene Expression (Array Express) ENSG00000129451
Genomic and cartography
GoldenPath (UCSC)KLK10  -  19q13.41   chr19:56207812-56215243 -  19q13.3-q13.4   [Description]    (hg18-Mar_2006)
EnsemblKLK10 - 19q13.3-q13.4 [CytoView]
Mapping of homologs : NCBIKLK10 [Mapview]
OMIM602673   
Gene and transcription
Gene : Genbank (Entrez)AF024605 AK292365 AK309456 AY561635 BC002710
Reference sequence (RefSeq transcript) :SRSNM_001077500 NM_002776 NM_145888
Reference transcript : EntrezNM_001077500 NM_002776 NM_145888
RefSeq genomic : SRSAC_000062 AC_000151 NC_000019 NT_011109 NW_001838498 NW_927284
RefSeq genomic : EntrezAC_000062 AC_000151 NC_000019 NT_011109 NW_001838498 NW_927284
Consensus coding sequences : CCDS NCBIKLK10
Cluster EST : UnigeneHs.275464 [ SRS ] Hs.275464 [ NCBI ]
Alternative Splicing : Fast-db (Paris)14737
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtO43240 (SRS) O43240 (Expasy) O43240 (Uniprot)
With graphics : InterProO43240
Splice isoforms : VarSplice FASTAO43240(VarSplice FASTA)
Domaine pattern : Prosite (SRS)TRYPSIN_DOM (PS50240)    TRYPSIN_HIS (PS00134)    TRYPSIN_SER (PS00135)   
Domain pattern : Prosite (Expaxy)TRYPSIN_DOM (PS50240)    TRYPSIN_HIS (PS00134)    TRYPSIN_SER (PS00135)   
Domains : Interpro (SRS)Peptidase_S1/S6_AS    Peptidase_S1_S6    Peptidase_S1A    Ser/Cys_Pept_Trypsin-like   
Domains : Interpro (EBI)Peptidase_S1/S6_AS    Peptidase_S1_S6    Peptidase_S1A    Ser/Cys_Pept_Trypsin-like   
Related proteins : CluSTrO43240
Domain families : Pfam SRSTrypsin (PF00089)   
Domain families : Pfam SangerTrypsin (PF00089)   
Domain families : Pfam NCBIpfam00089   
Domain families : Smart EMBLTryp_SPc (SM00020)  
Blocks (Seattle)O43240
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
HPRD04054
Protein Interaction databases
DIP (DOE-UCLA)O43240
IntAct (EBI)O43240
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIKLK10
SNP : GeneSNP UtahKLK10
SNP : HGBaseKLK10
Genetic variants : HAPMAPKLK10
Somatic Mutations in Cancer : COSMICKLK10 
Mutations and Diseases : HGMDKLK10
Hereditary diseases : OMIM602673   
Hereditary diseases : GENETests602673   
Diseases : Genetic AssociationKLK10
General knowledge
Homologs : HomoloGeneKLK10
Homology/Alignments : Family Browser UCSCKLK10
Phylogenetic Trees/Animal Genes : TreeFamKLK10
Catalytic activity : Enzyme3.4.21.- [ Enzyme-Expasy ]   3.4.21.- [ Enzyme-SRS ]   3.4.21.- [ IntEnz-EBI ]   3.4.21.- [ BRENDA ]   3.4.21.- [ KEGG ]   
Chemical/Protein Interactions : CTD5655
Keywords Ontology : AmiGOserine-type endopeptidase activity  extracellular region  proteolysis  cell cycle  peptidase activity  
Keywords Ontology : EGO-EBIserine-type endopeptidase activity  extracellular region  proteolysis  cell cycle  peptidase activity  
Pathways : BIOCARTA
Pathways : KEGG
Other databases
Probes
Probes : ImagenesKLK10 Related clones (RZPD - Berlin)
Literature
PubMed40 Pubmed reference(s) in Entrez
PubGeneKLK10

Bibliography

Identification of a novel serine protease-like gene, the expression of which is down-regulated during breast cancer progression.
Liu XL, Wazer DE, Watanabe K, Band V
Cancer research. 1996 ; 56 (14) : 3371-3379.
PMID 8764136
 
The role for NES1 serine protease as a novel tumor suppressor.
Goyal J, Smith KM, Cowan JM, Wazer DE, Lee SW, Band V
Cancer research. 1998 ; 58 (21) : 4782-4786.
PMID 9809976
 
Structural characterization and mapping of the normal epithelial cell-specific 1 gene.
Luo L, Herbrick JA, Scherer SW, Beatty B, Squire J, Diamandis EP
Biochemical and biophysical research communications. 1998 ; 247 (3) : 580-586.
PMID 9647736
 
Analysis of normal epithelial cell specific-1 (NES1)/kallikrein 10 mRNA expression by in situ hybridization, a novel marker for breast cancer.
Dhar S, Bhargava R, Yunes M, Li B, Goyal J, Naber SP, Wazer DE, Band V
Clinical cancer research : an official journal of the American Association for Cancer Research. 2001 ; 7 (11) : 3393-3398.
PMID 11705853
 
CpG methylation as a basis for breast tumor-specific loss of NES1/kallikrein 10 expression.
Li B, Goyal J, Dhar S, Dimri G, Evron E, Sukumar S, Wazer DE, Band V
Cancer research. 2001 ; 61 (21) : 8014-8021.
PMID 11691827
 
Immunofluorometric assay of human kallikrein 10 and its identification in biological fluids and tissues.
Luo LY, Grass L, Howarth DJ, Thibault P, Ong H, Diamandis EP
Clinical chemistry. 2001 ; 47 (2) : 237-246.
PMID 11159772
 
Expression of the normal epithelial cell-specific 1 (NES1; KLK10) candidate tumour suppressor gene in normal and malignant testicular tissue.
Luo LY, Rajpert-De Meyts ER, Jung K, Diamandis EP
British journal of cancer. 2001 ; 85 (2) : 220-224.
PMID 11461080
 
Human kallikrein 10 expression in normal tissues by immunohistochemistry.
Petraki CD, Karavana VN, Luo LY, Diamandis EP
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2002 ; 50 (9) : 1247-1261.
PMID 12185203
 
Steroid hormone regulation of the human kallikrein 10 (KLK10) gene in cancer cell lines and functional characterization of the KLK10 gene promoter.
Luo LY, Grass L, Diamandis EP
Clinica chimica acta; international journal of clinical chemistry. 2003 ; 337 (1-2) : 115-126.
PMID 14568187
 
The serum concentration of human kallikrein 10 represents a novel biomarker for ovarian cancer diagnosis and prognosis.
Luo LY, Katsaros D, Scorilas A, Fracchioli S, Bellino R, van Gramberen M, de Bruijn H, Henrik A, Stenman UH, Massobrio M, van der Zee AG, Vergote I, Diamandis EP
Cancer research. 2003 ; 63 (4) : 807-811.
PMID 12591730
 
Overexpression of kallikrein 10 in epithelial ovarian carcinomas.
Shvartsman HS, Lu KH, Lee J, Lillie J, Deavers MT, Clifford S, Wolf JK, Mills GB, Bast RC Jr, Gershenson DM, Schmandt R
Gynecologic oncology. 2003 ; 90 (1) : 44-50.
PMID 12821340
 
Loss of expression of the putative tumor suppressor NES1 gene in biopsy-proven ductal carcinoma in situ predicts for invasive carcinoma at definitive surgery.
Yunes MJ, Neuschatz AC, Bornstein LE, Naber SP, Band V, Wazer DE
International journal of radiation oncology, biology, physics. 2003 ; 56 (3) : 653-657.
PMID 12788170
 
The normal epithelial cell-specific 1 (NES1) gene, a candidate tumor suppressor gene on chromosome 19q13.3-4, is downregulated by hypermethylation in acute lymphoblastic leukemia.
Roman-Gomez J, Jimenez-Velasco A, Agirre X, Castillejo JA, Barrios M, Andreu EJ, Prosper F, Heiniger A, Torres A
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2004 ; 18 (2) : 362-365.
PMID 14628074
 
Potential markers that complement expression of CA125 in epithelial ovarian cancer.
Rosen DG, Wang L, Atkinson JN, Yu Y, Lu KH, Diamandis EP, Hellstrom I, Mok SC, Liu J, Bast RC Jr
Gynecologic oncology. 2005 ; 99 (2) : 267-277.
PMID 16061277
 
Downregulation of human kallikrein 10 (KLK10/NES1) by CpG island hypermethylation in breast, ovarian and prostate cancers.
Sidiropoulos M, Pampalakis G, Sotiropoulou G, Katsaros D, Diamandis EP
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2005 ; 26 (6) : 324-336.
PMID 16254462
 
Identification of new splice variants and differential expression of the human kallikrein 10 gene, a candidate cancer biomarker.
Yousef GM, White NM, Michael IP, Cho JC, Robb JD, Kurlender L, Khan S, Diamandis EP
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2005 ; 26 (5) : 227-235.
PMID 16103744
 
Identification of molecular targets for immunotherapy of patients with head and neck squamous cell carcinoma.
Dasgupta S, Tripathi PK, Qin H, Bhattacharya-Chatterjee M, Valentino J, Chatterjee SK
Oral oncology. 2006 ; 42 (3) : 306-316.
PMID 16321566
 
Clinical significance of human kallikrein 10 gene expression in colorectal cancer and gastric cancer.
Feng B, Xu WB, Zheng MH, Ma JJ, Cai Q, Zhang Y, Ji J, Lu AG, Qu Y, Li JW, Wang ML, Hu WG, Liu BY, Zhu ZG
Journal of gastroenterology and hepatology. 2006 ; 21 (10) : 1596-1603.
PMID 16928223
 
Overexpression of kallikrein 10 (hK10) in uterine serous papillary carcinomas.
Santin AD, Diamandis EP, Bellone S, Marizzoni M, Bandiera E, Palmieri M, Papasakelariou C, Katsaros D, Burnett A, Pecorelli S
American journal of obstetrics and gynecology. 2006 ; 194 (5) : 1296-1302.
PMID 16647913
 
The human kallikrein 10 promoter contains a functional retinoid response element.
Zeng M, Zhang Y, Bhat I, Wazer DE, Band H, Band V
Biological chemistry. 2006 ; 387 (6) : 741-747.
PMID 16800735
 
Downregulation and CpG island hypermethylation of NES1/hK10 gene in the pathogenesis of human gastric cancer.
Huang W, Zhong J, Wu LY, Yu LF, Tian XL, Zhang YF, Li B
Cancer letters. 2007 ; 251 (1) : 78-85.
PMID 17182177
 
A 10-gene classifier for distinguishing head and neck squamous cell carcinoma and lung squamous cell carcinoma.
Vachani A, Nebozhyn M, Singhal S, Alila L, Wakeam E, Muschel R, Powell CA, Gaffney P, Singh B, Brose MS, Litzky LA, Kucharczuk J, Kaiser LR, Marron JS, Showe MK, Albelda SM, Showe LC
Clinical cancer research : an official journal of the American Association for Cancer Research. 2007 ; 13 (10) : 2905-2915.
PMID 17504990
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written08-2007Liu-Ying Luo, Eleftherios P Diamandis
R and D Systems, Inc. 614 McKinley Pl. N. E. Minneapolis, MN 55413, USA (LYL); Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5, Canada (EPD)

Citation

This paper should be referenced as such :
Luo LY, Diamandis EP . KLK10 (Kallikrein-related peptidase 10). Atlas Genet Cytogenet Oncol Haematol. August 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/KLK10ID41076ch19q13.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Feb 27 10:51:15 CET 2010
Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.