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KLK11 (Kallikrein-related peptidase 11)

Written2008-03Liu-Ying Luo, Eleftherios P Diamandis
R&D Systems, Inc. 614 McKinley Place, N. E. Minneapolis, MN 55413, USA (LYL); Department of Pathology, Laboratory Medicine, Mount Sinai Hospital, 600 University Ave. Toronto, ON M5G 1X5, Canada (EPD)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPRSS20
kallikrein 11
Alias_symbol (synonym)TLSP
Other aliasHippostasin
hK11
HGNC (Hugo) KLK11
LocusID (NCBI) 11012
Atlas_Id 41077
Location 19q13.41  [Link to chromosome band 19q13]
Location_base_pair Starts at 51022231 and ends at 51026616 bp from pter ( according to hg19-Feb_2009)  [Mapping KLK11.png]
Local_order Telomere to centromere
Fusion genes
(updated 2016)
CIC (19q13.2) / KLK11 (19q13.41)

DNA/RNA

Description The KLK11 gene is about 5.8 Kb in length, consisting of 6 exons and 5 introns.
Transcription Three alternatively spliced variants have been described in the literature: including isoform 1, isoform 2, and isoform 3. Isoform 1 is preferentially expressed in the brain and it encodes a protein of 250 amino acids. Isoform 2 and isoform 3 are mainly expressed in the prostate. Compared to isoform 1, isoform 2 has additional 32 amino acids at the N-terminus and isoform 3 contains extra 25 amino acids inserted in the catalytic triad. Tissue-specific expression of these isoforms is regulated by multiple promoters that locate in the first exon of each isoform.
Pseudogene Not identified so far

Protein

Description Full-length KLK11 is composed of a signal peptide (aa 1-50), a propeptide (aa 51-53), and a mature chain (aa 54-282). KLK11 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 propetide is removed to generate the mature active protein.
Expression KLK11 is mainly expressed in epithelial tissues, such as stomach, trachea, and skin, with high levels in the brain and the prostate. KLK11 has also been identified in many biological fluids. Seminal plasma, containing an average of 15 μg/mL of KLK11, is the biological fluid reported to have the most abundant KLK11 so far. Other specimens, including serum, lactating milk, cerebrospinal fluid, and amniotic fluid, all have detectable amounts of KLK11.
Localisation Secreted.
Function The physiology functions of KLK11 and the mechanisms of its involvement in cancer have yet to be determined. Using positional scanning combinatorial tetrapeptide substrate library, it has revealed that KLK11 preferentially cleaves peptide bonds after methionine, arginine, and lysine. However, its physiology substrates remain unidentified. One hypothesis is that KLK11 may be part of a proteolytic cascade consisting of multiple kallikreins (KLKs). Since KLK11 is unable to autoactivate, in the cascade, it is likely that KLK11 is activated by upstream KLKs, then subsequently activate/inactaivate other downstream KLKs or other proteins. Accumulating experimental evidence is in accord with this hypothesis. It has been shown in in vitro experiments that, both KLK12 and KLK14 are able to activate KLK11. Another hypothesis is that KLK11 may be involved in the homeostasis of insulin growth factor. This hypothesis comes from the observation that KLK11 is able to degrade insulin growth factor binding protein 3 (IGFBP3) to facilitate the release of insulin growth factor. KLK11 enzymatic activity is mainly regulated by internal cleavage. In seminal plasma, about half the KLK11 is in the cleaved inactive form. Some abundant serine protease inhibitors present in the circulation or in seminal plasma, such as α1-antitrypsin, protein C inhibitor, α2-antiplasmin, and C1 inhibitor, fail to show rapid inhibition of KLK11.
Homology Human KLK11 protein sequence shares 98% and 82% identity with that of chimpanzee and dog/bovine/mouse/rat, respectively.

Mutations

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

Implicated in

Note
  
Entity Prostate cancer
Disease A number of investigations have been reported concerning the role of KLK11 as a potential diagnostic biomarker for prostate cancer (CaP). Prostate specific antigen (PSA) is currently the most widely used diagnostic marker for CaP. However, measuring PSA alone is lack of specificity, since some benign prostatic diseases, such as benign prostatic hyperplasia (BPH) and prostatitis, can also have increased serum PSA levels, whereas some CaP patients may have only mild elevation of PSA (4-10 ng/mL). To improve the specificity, a number of additional analyses, such as measuring the molecular forms of PSA, have been proposed. Patients with low free to total PSA ratios are considered to have higher risk of developing CaP. In spite of these efforts, false positive and false negative still occur and doctors frequently need to rely on prostate biopsy to make the final diagnosis. Some investigations have shown that measuring serum KLK11 concentrations may help discriminate CaP from BPH and reduce the number of unnecessary biopsies. Similar to PSA, serum KLK11 concentrations are elevated in the majority of CaP patients. However, compared to the BPH patients, the CaP patients tend to have lower serum KLK11 concentrations and lower KLK11 to total PSA ratios. In those patients that have less than 20% free PSA, measuring KLK11 to total PSA ratio identified 54% to have BPH. As such, it seems that KLK11 to total PSA ratio might be a complementary marker for free PSA percentage and combination of these two markers results in better specificity for CaP. KLK11 might not be superior to PSA in population screening. In a retrospective study, serum KLK11 or KLK11 to PSA ratio showed no advantage over PSA alone to differentiate CaP patients from noncancer individuals whose total PSA levels are in the range of 2.5 to 10 ng/mL.
Prognosis Tissue expression levels of KLK11 may be used as a prognostic indicator for prostate cancer. Lower KLK11 mRNA levels have been found to be associated with higher tumor grade, tumor stage, and Gleason score, suggesting that KLK11 might be able to indicate the aggressiveness of prostate tumors.
Cytogenetics No cytogenetic abnormalities are identified so far.
Hybrid/Mutated Gene Not identified so far.
  
  
Entity Ovarian cancer
Disease KLK11 has shown promise as a diagnostic biomarker for ovarian cancer. Earlier studies have revealed that serum KLK11 concentrations are elevated in the majority of ovarian cancer patients. Subsequent investigations further demonstrate that KLK11 is able to distinguish ovarian cancer cases from healthy controls. More importantly, it is less sensitive to benign ovarian diseases than is CA125, the most widely used diagnostic marker for ovarian cancer. Moreover, it has high temporal stability, which implies that it could be used in a longitudinal screening program for early detection.
Prognosis Many investigations have clearly demonstrated that KLK11 has elevated protein levels in primary ovarian tumors than in normal tissue, benign or nonovarian metastatic tumors. In general, higher levels of KLK11 in ovarian tumor extracts are predictive of favorable outcome. They are more likely to be associated with early stage, responsive to chemotherapy, and longer progression free survival.
Cytogenetics No cytogenetic abnormalities are identified so far.
Hybrid/Mutated Gene Not identified so far.
  
  
Entity Lung cancer
Prognosis The prognostic role of KLK11 has also been explored in lung cancer both at the mRNA and protein levels. With quantitative PCR, it has shown that KLK11 mRNA levels are lower in tumor tissues in comparison with adjacent normal counterparts. No significant correlation is identified with clinical stages, tumor status, and lymph node status. However, those patients with low KLK11 mRNA expression seem to have a significantly worse prognosis than those with high levels. At the protein level, serum KLK11 concentrations in non-small cell lung cancer patients are higher than in healthy controls and they are positively correlated with tumor stages.
Cytogenetics No cytogenetic abnormalities are identified so far.
Hybrid/Mutated Gene Not identified so far.
  

Breakpoints

Note Not described so far.

Bibliography

Favorable prognostic value of tissue human kallikrein 11 (hK11) in patients with ovarian carcinoma.
Borgoño CA, Fracchioli S, Yousef GM, Rigault de la Longrais IA, Luo LY, Soosaipillai A, Puopolo M, Grass L, Scorilas A, Diamandis EP, Katsaros D.
Int J Cancer 2003; 106: 605-610.
PMID 12845660
 
Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences.
Debela M, Magdolen V, Schechter N, Valachova M, Lottspeich F, Craik CS, Choe Y, Bode W, Goettig P.
J Biol Chem 2006; 281: 25678-25688.
PMID 16740631
 
Human kallikrein 11: a new biomarker of prostate and ovarian carcinoma.
Diamandis EP, Okui A, Mitsui S, Luo LY, Soosaipillai A, Grass L, Nakamura T, Howarth DJ, Yamaguchi N.
Cancer Res 2002; 62(1): 295-300.
PMID 11782391
 
Primary tumor levels of human tissue kallikreins affect surgical success and survival in ovarian cancer patients.
Dorn J, Schmitt M, Kates R, Schmalfeldt B, Kiechle M, Scorilas A, Diamandis EP, Harbeck N.
Clin Cancer Res 2007; 13: 1742-1748.
PMID 17363527
 
Human kallikrein-related peptidase 14 (KLK14) is a new activator component of the KLK proteolytic cascade. Possible function in seminal plasma and skin.
Emami N, Diamandis EP.
J Biol Chem 2008; 283: 3031-304.
PMID 18056261
 
Inhibition profiles of human tissue kallikreins by serine protease inhibitors.
Luo LY, Jiang W.
Biol Chem 2006; 387: 813-816.
PMID 16800745
 
Purification and characterization of human kallikrein 11, a candidate prostate and ovarian cancer biomarker, from seminal plasma.
Luo LY, Shan SJ, Elliott MB, Soosaipillai A, Diamandis EP.
Clin Cancer Res 2006; 12: 742-750.
PMID 16467084
 
Validation and characterization of human kallikrein 11 as a serum marker for diagnosis of ovarian carcinoma.
McIntosh MW, Liu Y, Drescher C, Urban N, Diamandis EP.
Clin Cancer Res 2007; 13: 4422-4428.
PMID 17671125
 
Enzymatic properties of human kallikrein-related peptidase 12 (KLK12).
Memari N, Jiang W, Diamandis EP, Luo LY.
Biol Chem 2007; 388: 427-435.
PMID 17391064
 
Multiple promoters regulate tissue-specific alternative splicing of the human kallikrein gene, KLK11/hippostasin
Mitsui S, Nakamura T, Okui A, Kominami K, Uemura H, Yamaguchi N.
FEBS J 2006; 273: 3678-3686.
PMID 16911518
 
A novel isoform of a kallikrein-like protease, TLSP/hippostasin, (PRSS20), is expressed in the human brain and prostate.
Mitsui S, Yamada T, Okui A, Kominami K, Uemura H, Yamaguchi N.
Biochem Biophys Res Commun 2000; 272: 205-211.
PMID 10872828
 
Quantitative analysis of hippostasin/KLK11 gene expression in cancerous and noncancerous prostatic tissues.
Nakamura T, Stephan C, Scorilas A, Yousef GM, Jung K, Diamandis EP.
Urology 2003; 61: 1042-1046.
PMID 12736044
 
Is there a role for serum human tissue kallikrein in detection of prostate cancer?
Ochiai A, Shukla A, Davis JW, Fritsche HA, Bhadkamkar V, Babaian RJ.
Urology 2007; 70: 519-522.
PMID 17905108
 
Expression of the human kallikrein genes 10 (KLK10) and 11 (KLK11) in cancerous and non-cancerous lung tissues.
Planque C, Aïnciburu M, Heuzé-Vourc'h N, Régina S, de Monte M, Courty Y.
Biol Chem 2006; 387: 783-788.
PMID 16800740
 
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
 
Kallikrein 11 expressed in human breast cancer cells releases insulin-like growth factor through degradation of IGFBP-3.
Sano A, Sangai T, Maeda H, Nakamura M, Hasebe T, Ochiai A.
Int J Oncol 2007; 30: 1493-1498.
PMID 17487371
 
Decreased kallikrein 11 messenger RNA expression in lung cancer.
Sasaki H, Kawano O, Endo K, Suzuki E, Haneda H, Yukiue H, Kobayashi Y, Yano M, Fujii Y.
Clin Lung Cancer 2006; 8: 45-48.
PMID 16870045
 
mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy.
Scorilas A, Gregorakis AK.
Biol Chem 2006; 387: 789-793.
PMID 16800741
 
Human kallikrein gene 11 (KLK11) mRNA overexpression is associated with poor prognosis in patients with epithelial ovarian cancer.
Shigemasa K, Gu L, Tanimoto H, O'Brien TJ, Ohama K.
Clin Cancer Res 2004; 10: 2766-2770.
PMID 15102682
 
Expression analysis and prognostic significance of human kallikrein 11 in prostate cancer.
Stavropoulou P, Gregorakis AK, Plebani M, Scorilas A.
Clin Chim Acta 2005; 357: 190-195.
PMID 15893744
 
Improved prostate cancer detection with a human kallikrein 11 and percentage free PSA-based artificial neural network.
Stephan C, Meyer HA, Cammann H, Nakamura T, Diamandis EP, Jung K.
Biol Chem 2006; 387: 801-805.
PMID 16800743
 
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
 
A multiparametric panel for ovarian cancer diagnosis, prognosis, and response to chemotherapy.
Zheng Y, Katsaros D, Shan SJ, de la Longrais IR, Porpiglia M, Scorilas A, Kim NW, Wolfert RL, Simon I, Li L, Feng Z, Diamandis EP.
Clin Cancer Res 2007; 13: 6984-6992.
PMID 18056174
 

Citation

This paper should be referenced as such :
Luo, LY ; Diamandis, EP
KLK11 (Kallikrein-related peptidase 11)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(1):15-17.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/KLK11ID41077ch19q13.html


External links

Nomenclature
HGNC (Hugo)KLK11   6359
Cards
AtlasKLK11ID41077ch19q13
Entrez_Gene (NCBI)KLK11  11012  kallikrein related peptidase 11
AliasesPRSS20; TLSP
GeneCards (Weizmann)KLK11
Ensembl hg19 (Hinxton)ENSG00000167757 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000167757 [Gene_View]  chr19:51022231-51026616 [Contig_View]  KLK11 [Vega]
ICGC DataPortalENSG00000167757
TCGA cBioPortalKLK11
AceView (NCBI)KLK11
Genatlas (Paris)KLK11
WikiGenes11012
SOURCE (Princeton)KLK11
Genetics Home Reference (NIH)KLK11
Genomic and cartography
GoldenPath hg38 (UCSC)KLK11  -     chr19:51022231-51026616 -  19q13.41   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)KLK11  -     19q13.41   [Description]    (hg19-Feb_2009)
EnsemblKLK11 - 19q13.41 [CytoView hg19]  KLK11 - 19q13.41 [CytoView hg38]
Mapping of homologs : NCBIKLK11 [Mapview hg19]  KLK11 [Mapview hg38]
OMIM604434   
Gene and transcription
Genbank (Entrez)AB012917 AB013730 AB041036 AB078780 AB259014
RefSeq transcript (Entrez)NM_001136032 NM_001167605 NM_006853 NM_144947
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)KLK11
Cluster EST : UnigeneHs.57771 [ NCBI ]
CGAP (NCI)Hs.57771
Alternative Splicing GalleryENSG00000167757
Gene ExpressionKLK11 [ NCBI-GEO ]   KLK11 [ EBI - ARRAY_EXPRESS ]   KLK11 [ SEEK ]   KLK11 [ MEM ]
Gene Expression Viewer (FireBrowse)KLK11 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)11012
GTEX Portal (Tissue expression)KLK11
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UBX7   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UBX7  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UBX7
Splice isoforms : SwissVarQ9UBX7
Catalytic activity : Enzyme3.4.21.- [ Enzyme-Expasy ]   3.4.21.-3.4.21.- [ IntEnz-EBI ]   3.4.21.- [ BRENDA ]   3.4.21.- [ KEGG ]   
PhosPhoSitePlusQ9UBX7
Domaine pattern : Prosite (Expaxy)TRYPSIN_DOM (PS50240)    TRYPSIN_HIS (PS00134)    TRYPSIN_SER (PS00135)   
Domains : Interpro (EBI)Peptidase_S1_PA    Peptidase_S1A    Trypsin_dom    TRYPSIN_HIS    TRYPSIN_SER   
Domain families : Pfam (Sanger)Trypsin (PF00089)   
Domain families : Pfam (NCBI)pfam00089   
Domain families : Smart (EMBL)Tryp_SPc (SM00020)  
Conserved Domain (NCBI)KLK11
DMDM Disease mutations11012
Blocks (Seattle)KLK11
SuperfamilyQ9UBX7
Human Protein AtlasENSG00000167757
Peptide AtlasQ9UBX7
HPRD05114
IPIIPI00002818   IPI00218137   IPI00217503   
Protein Interaction databases
DIP (DOE-UCLA)Q9UBX7
IntAct (EBI)Q9UBX7
FunCoupENSG00000167757
BioGRIDKLK11
STRING (EMBL)KLK11
ZODIACKLK11
Ontologies - Pathways
QuickGOQ9UBX7
Ontology : AmiGOserine-type endopeptidase activity  extracellular space  Golgi apparatus  proteolysis  serine-type peptidase activity  extracellular exosome  
Ontology : EGO-EBIserine-type endopeptidase activity  extracellular space  Golgi apparatus  proteolysis  serine-type peptidase activity  extracellular exosome  
NDEx NetworkKLK11
Atlas of Cancer Signalling NetworkKLK11
Wikipedia pathwaysKLK11
Orthology - Evolution
OrthoDB11012
GeneTree (enSembl)ENSG00000167757
Phylogenetic Trees/Animal Genes : TreeFamKLK11
HOVERGENQ9UBX7
HOGENOMQ9UBX7
Homologs : HomoloGeneKLK11
Homology/Alignments : Family Browser (UCSC)KLK11
Gene fusions - Rearrangements
Fusion : MitelmanCIC/KLK11 [19q13.2/19q13.41]  [t(19;19)(q13;q13)]  
Fusion: TCGACIC 19q13.2 KLK11 19q13.41 LUAD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerKLK11 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)KLK11
dbVarKLK11
ClinVarKLK11
1000_GenomesKLK11 
Exome Variant ServerKLK11
ExAC (Exome Aggregation Consortium)KLK11 (select the gene name)
Genetic variants : HAPMAP11012
Genomic Variants (DGV)KLK11 [DGVbeta]
DECIPHERKLK11 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisKLK11 
Mutations
ICGC Data PortalKLK11 
TCGA Data PortalKLK11 
Broad Tumor PortalKLK11
OASIS PortalKLK11 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICKLK11  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDKLK11
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch KLK11
DgiDB (Drug Gene Interaction Database)KLK11
DoCM (Curated mutations)KLK11 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)KLK11 (select a term)
intoGenKLK11
NCG5 (London)KLK11
Cancer3DKLK11(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604434   
Orphanet
MedgenKLK11
Genetic Testing Registry KLK11
NextProtQ9UBX7 [Medical]
TSGene11012
GENETestsKLK11
Target ValidationKLK11
Huge Navigator KLK11 [HugePedia]
snp3D : Map Gene to Disease11012
BioCentury BCIQKLK11
ClinGenKLK11
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD11012
Chemical/Pharm GKB GenePA30148
Clinical trialKLK11
Miscellaneous
canSAR (ICR)KLK11 (select the gene name)
Probes
Litterature
PubMed42 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineKLK11
EVEXKLK11
GoPubMedKLK11
iHOPKLK11
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Sep 18 17:06:22 CEST 2017

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