Information on EC 3.4.21.B41 - kallikrein 10

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The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY
3.4.21.B41
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
kallikrein 10
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
proteolytic cleavage of polypeptides
show the reaction diagram
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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hydrolysis of peptide bond
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SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
human kallikrein 10
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kallikrein-like protein 1
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-
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kallikrein-related peptidase 10
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kallikrein-related peptidase 10
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kallikrein-related peptidase 10
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KLK-L1
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NES1
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prostase
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S01.246
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tissue kallikrein-related peptidase 10
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CAS REGISTRY NUMBER
COMMENTARY
334993-12-3
-
9001-01-8
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene (CANFA)KLK10
UniProt
Manually annotated by BRENDA team
gene KLK10
UniProt
Manually annotated by BRENDA team
gene KLK10
SwissProt
Manually annotated by BRENDA team
gene KLK10 or PRRSL or NES1
SwissProt
Manually annotated by BRENDA team
KLK10
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
the enzyme is a member of the human kallikrein gene family of secreted serine proteases
malfunction
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KLK10 hypermethylation is significantly associated with cirrhosis and HCV infection as well as inversely associated with HBV infection. Restoration of KLK10 expression, by 5-aza-cytidine treatment, reduces the ability of anchorage-independent growth, and sensitizes hepatocellular carcinoma cells to doxorubicin- or 5-fluorouracil-induced cytotoxicity
metabolism
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the enzyme is mplicated in the development of several types of cancer. A kallikrein cascade may play a role in the development and/or outcome of some salivary gland tumours, overview
metabolism
multiple mechanisms account for enzyme KLK10 dysregulation in cancer including hypermethylation, and the frequent inactivation and loss of KLK10 expression is a critical step towards carcinogenesis
additional information
significant correlation between KLK6 and KLK10 expression both at the invasive front and within the main tumor, indicating a collaborative effect
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
o-aminobenzoyl-FRAPR-ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
o-aminobenzoyl-FRLVR-ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
o-aminobenzoyl-SVIRRVQ-ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
o-aminobenzoyl-TSVIRRPQ-ethylenediamine + H2O
?
show the reaction diagram
-
-
-
-
?
polypeptide + H2O
peptides
show the reaction diagram
-
activity is down-regulated during oncogenic transformation
-
?
Pro-Phe-Arg-4-methylcoumarin 7-amide + H2O
Pro-Phe-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
additional information
?
-
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kallikrein 10 from asites fluid does not cleave L-Val-Pro-Arg-7-amido-4-methylcoumarin, L-Phe-Ser-Arg-7-amido-4-methylcoumarin, L-Pro-Phe-Arg-7-amido-4-methylcoumarin, L-Val-Leu-Lys-7-amido-4-methylcoumarin, L-Glu-Lys-Lys-7-amido-4-methylcoumarin, and L-Ala-Ala-Pro-Phe-7-amido-4-methylcoumarin
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
polypeptide + H2O
peptides
show the reaction diagram
-
activity is down-regulated during oncogenic transformation
-
?
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
o-aminobenzoyl-TSVIRRPQ-ethylenediamine
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
9-cis-retinoic acid
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treatment of cells with 9-cis-retinoic acid increases the levels of hK10 promoter activity and the levels of hK10 mRNA and protein
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
lung adenocarcinoma cell line
Manually annotated by BRENDA team
-
all K10 present in ovarian cancer ascites fluids are in the uncomplexed, zymogen form and have no detectable enzymatic activity
Manually annotated by BRENDA team
-
no mRNA expression, enzyme barely detectable
Manually annotated by BRENDA team
-
expression in normal cells, but no expression in breast cancer cells
Manually annotated by BRENDA team
-
KLK10 is not methylated in normal breast tissues and fibroadenomas while it is in 5 of 10 breast tumors and in 1 of 10 matching normal tissues
Manually annotated by BRENDA team
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downregulation due to hypermethylation of exon 3
Manually annotated by BRENDA team
-
KLK10 is not methylated in normal breast tissues and fibroadenomas while it is in 5 of 10 breast tumors and in 1 of 10 matching normal tissues
Manually annotated by BRENDA team
-
mRNA expression, enzyme detectable
Manually annotated by BRENDA team
-
downregulation
Manually annotated by BRENDA team
-
lower KLK10 levels in pleomorphic adenoma suggests aberrant expression in a tumour that develops primarily from myoepithelial cells
Manually annotated by BRENDA team
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gene expression
Manually annotated by BRENDA team
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significantly upregulated
Manually annotated by BRENDA team
immunohistochemic expression analysis, overview
Manually annotated by BRENDA team
the enzyme is up-regulated in colorectal cancer
Manually annotated by BRENDA team
immunohistochemic expression analysis, overview
Manually annotated by BRENDA team
Barrett esophagus with and without dysplasia
Manually annotated by BRENDA team
-
significantly upregulated
Manually annotated by BRENDA team
-
barely detectable gene expression
Manually annotated by BRENDA team
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no mRNA expression, enzyme barely detectable
Manually annotated by BRENDA team
-
hypermethylated KLK10 is frequent in hepatocellular carcinoma
Manually annotated by BRENDA team
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no mRNA expression, enzyme barely detectable
Manually annotated by BRENDA team
-
gene expression
Manually annotated by BRENDA team
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normal strain 76N and oncogenically transforming strain 76R-30
Manually annotated by BRENDA team
KLK10 expression in cancerous and noncancerous canine mammary tissues, overview
Manually annotated by BRENDA team
KLK10 expression in cancerous and noncancerous canine mammary tissues, overview
Manually annotated by BRENDA team
-
mRNA expression, enzyme detectable
Manually annotated by BRENDA team
-
no mRNA expression, enzyme barely detectable
Manually annotated by BRENDA team
KLK10 is significantly downregulated as compared to non-cancer samples. CpG island hypermethylation of KLK10 is detected in 46.2% of non-small cell lung cancer tissues
Manually annotated by BRENDA team
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kallikreins 10 is abundantly expressed in human oral squamous cell carcinoma and may be implicated in malignant progression
Manually annotated by BRENDA team
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high expression
Manually annotated by BRENDA team
-
gene expression
Manually annotated by BRENDA team
-
significantly upregulated
Manually annotated by BRENDA team
-
downregulation due to hypermethylation of exon 3
Manually annotated by BRENDA team
-
downregulation
Manually annotated by BRENDA team
-
no mRNA expression, enzyme barely detectable
Manually annotated by BRENDA team
-
significantly upregulated
Manually annotated by BRENDA team
-
coexpression of KLK10 and KLK6 plays an unfavourable role in pancreatic ductal adenocarcinoma
Manually annotated by BRENDA team
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mRNA expression, enzyme detectable
Manually annotated by BRENDA team
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immunohistochemic enzyme expression analysis in various surgically removed corticotroph adenoma subtypes: lowest enzyme expression in the silent corticotroph subtypes 1 and 2, compared with nontumorous human adenohypophysial corticotrophs, high enzyme expression in endocrinologically active subtypes, ACTH-secreting adenomas, corticotroph carcinomas, Crooke cell adenomas, Crooke cell carcinomas
Manually annotated by BRENDA team
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gene expression
Manually annotated by BRENDA team
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decreased expression compared to normal cell
Manually annotated by BRENDA team
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from malignant tumours, adenoid cystic carcinoma and mucoepidermoid carcinoma
Manually annotated by BRENDA team
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downregulation
Manually annotated by BRENDA team
-
gene expression
Manually annotated by BRENDA team
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increased mRNA expression compared to normal cells
Manually annotated by BRENDA team
-
mRNA expression, enzyme detectable
Manually annotated by BRENDA team
-
gene expression
Manually annotated by BRENDA team
-
barely detectable gene expression
Manually annotated by BRENDA team
-
increased mRNA expression compared to noncancer cells
Manually annotated by BRENDA team
-
mRNA expression, enzyme detectable
Manually annotated by BRENDA team
additional information
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gene expression is almost lost in breast cancer cell lines; no expression in fibroblasts, peripheral blood leukocytes, brain, placenta, lung, liver, skeletal muscle, and kidney
Manually annotated by BRENDA team
additional information
the enzyme shows a wide tissue distribution, and its expression level does not vary between healthy and cancer tissue
Manually annotated by BRENDA team
additional information
significantly increased enzyme expression in dysplastic lesions compared with metaplasia but not between dysplastic lesions and invasive cancers, immunohistochemic analysis, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
immunohistochemic expression analysis, overview
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
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SDS-PAGE
682961
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
reverse-phase high-performance liquid chromatography and immunoaffinity chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gene (CANFA)KLK10, DNA and amino acid sequence determination and analysis, sequence comparison with the human gene, detailed overview
DNA and amino acid sequence determination, in vitro translation
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expressed in COS-7 cells and 76R-30 cells
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expressed in Escherichia coli
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expressed in MCF-10A, MDA-MB-468 and T-47D cell lines
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expressed in Pichia pastoris
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gene KLK10, determination of frequency and functional significance of KLK10 hypermethylation in non-small cell lung cancer cells, mRNA expression and methylation status of KLK10 in 78 pairs specimens, overview
gene KLK10, located at 19q13.3-q13.4, quantitative real-time PCR expression analysis, determination of DNA hypermethylation status of KLK10 in hepatocellular carcinoma cell lines and clinical samples, DNA methylation profiles, overview. Ectopic expression of KLK10 enhances drug sensitivity of HuH7 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
frequent transcriptional inactivation of kallikrein 10 gene by CpG island hypermethylation in non-small cell lung cancer, overview. Restoration of KLK10 expression by 5-Aza-dC treatment
KLK10 expression is significantly higher in cancerous than in normal colorectal tissues
-
the enzyme is up-regulated in colorectal cancer, stepwise expression increase from metaplasia to dysplasia and invasive tumors, significantly increased enzyme expression in early invasive cancer, overview
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
DEL229S
-
extremely low protease activity
S229A
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extremely low protease activity
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
KLK10 methylation can be used as a biomarker for non-small cell lung cancer
diagnostics
-
hypermethylated KLK10 is frequent in hepatocellular carcinoma and may be useful as marker for clinical application
diagnostics
enzyme KLK10 is significantly associated with other prognostic markers in gastroesophageal junction adenocarcinoma and Barrett esophagus, including depth of invasion, indicating its potential as independent biomarker
diagnostics
KLK10 overexpression correlates with poor prognosis in colorectal cancer, being associated with liver metastases, decreased disease-free, and overall survival. Negative correlation between KLK10 expression and tumor grade, indicating that these two parameters. KLK10 expression, assessed by immunohistochemistry, is an independent indicator of poor prognosis. Assessment of KLK10 can be incorporatedto a multi-molecular prognostic model to achieve better and more accurate assessment of disease prognosis are affected by independent mechanisms
medicine
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kallikrein 10 may serve as a biomarker for uterine serous papillary carcinoma
medicine
-
high status KLK10 expression is a significant factor for disease-free survival and overall survival of colorectal cancer patients. KLK10 gene expression may be used as a marker of unfavorable prognosis for colorectal cancer