KLK10 (Kallikrein-related peptidase 10)

Identity

Other names	NES1
	PRSSL1
Hugo	KLK10
Location	19q13.41
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
Hugo	KLK10
GDB	KLK10
Entrez_Gene	KLK10  5655  kallikrein-related peptidase 10
	Cards
Atlas	KLK10ID41076ch19q13
GeneCards	KLK10
Ensembl	KLK10 [Search_View]   ENSG00000129451 [Gene_View]
Genatlas	KLK10
GeneLynx	KLK10
eGenome	KLK10
euGene	5655
	Genomic and cartography
GoldenPath	KLK10  -  19q13.41   chr19:56207812-56215094 -  19q13.3-q13.4   [Description]    (hg18-Mar_2006)
Ensembl	KLK10 - 19q13.3-q13.4 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	KLK10
	Gene and transcription
Genbank	AF024605 [ ENTREZ ]
Genbank	AY561635 [ ENTREZ ]
Genbank	BC002710 [ ENTREZ ]
Genbank	BM830577 [ ENTREZ ]
Genbank	BU685208 [ ENTREZ ]
RefSeq	NM_001077500 [ SRS ]    NM_001077500 [ ENTREZ ]
RefSeq	NM_002776 [ SRS ]    NM_002776 [ ENTREZ ]
RefSeq	NM_145888 [ SRS ]    NM_145888 [ ENTREZ ]
RefSeq	AC_000062 [ SRS ]    AC_000062 [ ENTREZ ]
RefSeq	NC_000019 [ SRS ]    NC_000019 [ ENTREZ ]
RefSeq	NT_011109 [ SRS ]    NT_011109 [ ENTREZ ]
RefSeq	NW_927284 [ SRS ]    NW_927284 [ ENTREZ ]
AceView	KLK10 AceView - NCBI
Unigene	Hs.275464 [ SRS ]    Hs.275464 [ NCBI ]     HS275464 [ spliceNest ]
Fast-db	14737 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	O43240 [ SRS]    O43240 [ EXPASY ]     O43240 [ INTERPRO ]
Prosite	PS50240 TRYPSIN_DOM [ SRS ]    PS50240 TRYPSIN_DOM [ Expasy ]
Prosite	PS00134 TRYPSIN_HIS [ SRS ]    PS00134 TRYPSIN_HIS [ Expasy ]
Prosite	PS00135 TRYPSIN_SER [ SRS ]    PS00135 TRYPSIN_SER [ Expasy ]
Interpro	IPR001254 Peptidase_S1_S6 [ SRS ]    IPR001254 Peptidase_S1_S6 [ EBI ]
Interpro	IPR001314 Peptidase_S1A [ SRS ]    IPR001314 Peptidase_S1A [ EBI ]
CluSTr	O43240
Pfam	PF00089 Trypsin [ SRS ]    PF00089 Trypsin [ Sanger ]    pfam00089 [ NCBI-CDD ]
Smart	SM00020 Tryp_SPc [EMBL]
Blocks	O43240
HPRD	04054
	Protein Interaction databases
DIP	O43240
IntAct	O43240
	Polymorphism : SNP, mutations, diseases
OMIM	602673    [ map ]
GENECLINICS	602673
SNP	KLK10 [dbSNP-NCBI]
SNP	NM_001077500 [SNP-NCI]
SNP	NM_002776 [SNP-NCI]
SNP	NM_145888 [SNP-NCI]
SNP	KLK10 [GeneSNPs - Utah]  KLK10] [HGBASE - SRS]
HAPMAP	KLK10 [HAPMAP]
COSMIC	KLK10 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	KLK10
	General knowledge
Family Browser	KLK10 [UCSC Family Browser]
SOURCE	NM_001077500
SOURCE	NM_002776
SOURCE	NM_145888
SMD	Hs.275464
SAGE	Hs.275464
Enzyme	3.4.21.- [ Enzyme-SRS ]   3.4.21.- [ Brenda-SRS ]   3.4.21.- [ KEGG ]   3.4.21.- [ WIT ]
GO	serine-type endopeptidase activity [Amigo]  serine-type endopeptidase activity
GO	extracellular region [Amigo]  extracellular region
GO	proteolysis [Amigo]  proteolysis
GO	cell cycle [Amigo]  cell cycle
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
PubGene	KLK10
TreeFam	KLK10
CTD	5655 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	KLK10 Related clones (RZPD - Berlin)
	PubMed
PubMed	30 Pubmed reference(s) in LocusLink

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

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Contributor(s)

Written	08-2007	Liu-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 : Wed Jul 2 08:24:33 2008