Information on EC 3.4.22.63 - caspase-10

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY hide
3.4.22.63
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RECOMMENDED NAME
GeneOntology No.
caspase-10
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp-/-Gly
show the reaction diagram
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
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-
-
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CAS REGISTRY NUMBER
COMMENTARY hide
189088-85-5
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
-
apoptosis is a form of programmed cell death that requires members of a family of aspartate-specific cysteine proteases, called caspases, to both initiate and execute the apoptotic phenotype
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Ac-IETD-4-trifluoromethylcoumarin-7-amide + H2O
Ac-IETD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
acetyl-Ala-Glu(OMe)-Val-Asp(OMe)-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Ala-Glu-Val-Asp-4-trifluoromethylcoumarin-7-amide + H2O
acetyl-Ala-Glu-Val-Asp + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
acetyl-aspartyl-glutamyl-valinyl-aspartyl-aminofluorocoumarin + H2O
?
show the reaction diagram
-
-
-
-
-
acetyl-VEHD-7-amido-4-methylcoumarin + H2O
acetyl-VEHD + 7-amino-4-methylcoumarin
show the reaction diagram
-
the optimal tetrapeptide recognition motif is LEXD
-
-
?
AEVD-4-nitroanilide + H2O
AEVD + 4-nitroaniline
show the reaction diagram
-
-
-
?
B cell lymphoma-2-interacting domain + H2O
?
show the reaction diagram
BID + H2O
?
show the reaction diagram
-
cleavage at sites LQTD/G and IEPD/S, for apical caspases
-
-
?
CPP32 + H2O
?
show the reaction diagram
-
-
-
?
DEVD-4-nitroanilide + H2O
DEVD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
DEVD-7-amido-4-methylcoumarin + H2O
DEVD + 7-amino-4-methylcoumarin
show the reaction diagram
Hsp90beta + H2O
?
show the reaction diagram
-
Hsp90beta is cleaved by activated caspase-10 under UV-B irradiation at D278, P293, and D294
-
-
?
MDIGAYPHFMPTNLAGDPY + H2O
YPHFMPTNL + AYPHFMPTNL + YPHFMPTNLA + AYPHFMPTNLAG + AYPHFMPTNLAGD + DIGAYPHFMPTNLA + DIGAYPHFMPTNLAG + YPHFMPTNLAGDPY + IGAYPHFMPTNLAGD + MDIG + MDIGA + Met-Asp + Met + Tyr + Pro-Tyr + GDPY + DPY
show the reaction diagram
-
-
quantitative product mass spectrometric analysis, overview
-
?
pro-Mch3 + H2O
?
show the reaction diagram
cleaves the propeptide of Mch3 to generate a 33000 Da protein which is further processed to the 20000 Da band and the 12000 Da protein
-
-
?
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
-
?
procaspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
-
?
RIPK1 + H2O
?
show the reaction diagram
-
-
-
-
?
YVAD-7-amido-4-methylcoumarin + H2O
YVAD + 7-amino-4-methylcoumarin
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
B cell lymphoma-2-interacting domain + H2O
?
show the reaction diagram
-
caspase-10 can serve as an initiator caspase in Fas signaling leading to Bid processing, caspase cascade activation, and apoptosis
-
-
?
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
-
?
procaspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
-
?
RIPK1 + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-AEVD-aldehyde
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acetyl-DEVD-aldehyde
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acetyl-IETD-aldehyde
-
-
acetyl-WEHD-aldehyde
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acetyl-YVAD-aldehyde
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benzyloxycarbonyl-AEVD-fluoromethylketone
benzyloxycarbonyl-IETD-fluoromethylketone
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caspase-8/caspase-10 inhibitor
benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone
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benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
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CBZ-VAD-trifluoromethylketone
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pancaspase inhibitor
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cowpox serpin CrmA
CrmA
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caspase-10 is more resistant than caspase-8, EC 3.4.22.61, to the caspase inhibitor
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DEVD-aldehyde
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DEVD-CHO
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Z-AEVD-fluoromethylketone
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a caspase-10 inhibitor
Z-VAD-fluoromethylketone
additional information
-
no inhibition by WEHD-CHO and YVAD-CHO
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-(acetyloxy)benzoic acid 4-(nitrooxymethyl)-phenyl ester
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i.e. para-NO-ASA, activates proteolytic enzyme activation. The compund inhibits the proliferation and induces cell death in acute lymphoblastic leukemia cell lines and patient samples
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caspase-8
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caspase-8 cleaves and activates caspase-10 directly
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FLICE-like inhibitory protein
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i.e. FLIPL, activation occurs independently of cleavage of either the caspase or FLIPL
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FLIPL protein
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heterodimerization with the long isoform of cFLIP, FLIPL, leads to activation of caspase-10. The heterodimer of caspase-10 with FLIPL still can cleave Bid and induce intrinsic apoptosis
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Sodium citrate
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activates the wild-type enzyme up to 500fold and the D297A mutant 100fold at up to 1.0 M, is inhibitory above probably due to precipitation
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.042
acetyl-VEHD-7-amido-4-methylcoumarin
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at pH 7.0 and pH 7.5
0.071 - 0.13
DEVD-7-amido-4-methylcoumarin
0.15
YVAD-7-amido-4-methylcoumarin
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pH 7.5
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00032
acetyl-AEVD-aldehyde
-
pH 7.5, 25C
0.000012
acetyl-DEVD-aldehyde
-
pH 7.5, 25C
0.000027
acetyl-IETD-aldehyde
-
pH 7.5, 25C
0.00033
acetyl-WEHD-aldehyde
-
pH 7.5, 25C
0.000408
acetyl-YVAD-aldehyde
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pH 7.5, 25C
0.000017
cowpox serpin CrmA
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pH 7.5
-
0.000014
DEVD-aldehyde
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pH 7.5
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0025
purified recombinant enzyme, pH not specified in the publication, 37C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
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reaction with acetyl-VEHD-7-amido-4-methylcoumarin
7.4
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assay at
7.5
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
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assay at room temperature
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.2
sequence calculation, mature enzyme
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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high expression level
Manually annotated by BRENDA team
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nine different cell lines, caspase-10 fragments are specifically detected in Smac mimetic-sensitive HSC3 cells
Manually annotated by BRENDA team
weak expression
Manually annotated by BRENDA team
peripheral blood leukocyte. Strong expression
Manually annotated by BRENDA team
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fetal, activity is undetectable in the adult
Manually annotated by BRENDA team
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breast cancer cell line
Manually annotated by BRENDA team
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low expression level
Manually annotated by BRENDA team
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polymorphonuclear
Manually annotated by BRENDA team
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retinal
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
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neuroblastoma cells
Manually annotated by BRENDA team
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neuroblastoma cells
Manually annotated by BRENDA team
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fetal, activity is undetectable in the adult
Manually annotated by BRENDA team
weak expression
Manually annotated by BRENDA team
weak expression
Manually annotated by BRENDA team
-
low expression level
Manually annotated by BRENDA team
additional information
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the expression levels of caspase-10-related mRNAs are generally higher in fetal than in adult tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
caspase-10/c is insoluble and localizes to filamentous perinuclear structures
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Manually annotated by BRENDA team
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caspase-10/a and caspase-10/d are soluble proteins
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Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
61000
recombinant enzyme cleaved from maltose-binding protein-fusion protein, gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
1 * 61000, about, sequence calculation, mature enzyme, 1 * 103500, recombinant maltose-binding protein-fusion enzyme, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
caspase-10B is a highly unstable caspase-10 isoform, while isozymes caspase-10A, -D and and -G are remarkably stable
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged truncated mutant, with and without the D279A mutation, from Escherichia coli strain BL21 (DE3) by nickel affinity chromatography
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recombinant maltose-binding protein-fused enzyme from Escherichia coli strain BL21(DE3) by amylose affinity chromatography
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of caspase-10/c and caspase-10/d isoforms
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expression in Escherichia coli
expression in NIH-3T3 cells
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expression of both the long and short isoforms of the wild-type or the caspase-10 mutants are transfected into Hela or MCF-7 cells together with a bet-gal reporter construct
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gene CASP10, recombinant expression of human caspase-10 in Saccharomyces cerevisiae strain strain BY4741 and derivatives, phenotypes, overview. Identification of 46 suppressors whose coexpression abolishes caspase-10 function and leads to cell curvaival and growth
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gene CsCasp10, cDNA library construction, DNA and amino acid sequence determination and analysis, phylogenetic analysis and tree, quantitative real time PCR expression analysis, recombinant expression of enzyme fused to maltose-binding protein in Escherichia coli strain BL21(DE3)
proMch4 lacking the two N-terminal FADD-like domains is subcloned in the bacterial expression vector pET21b
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splice variant caspase-10g (comprising five exons including exons 2-5 and a specific exon between exons 5 and 6 of the caspase-10 gene), expression in HeLa and JURKAT cells
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the caspase-10 gene is linked to the caspase-8 gene, EC 3.4.22.61, at the human chromosome locus 2q33-34
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the caspase-10 gene is linked to the caspase-8 gene, EC 3.4.22.61, at the human chromosome locus 2q33-34. Expression of His-tagged truncated mutant, with and without the D279A mutation, in Escherichia coli strain BL21 (DE3)
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the over-expression analysis of JF-caspase-10 in Japanese flounder cell line HINAE induces apoptosis 24 h post-transfection
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the CsCasp10 gene expression in Channa striata is upregulated in gills by fungus Aphanomyces invadans and bacteria Aeromonas hydrophila induction
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C401G
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active site, essential for CASP10-induced cell death
D219A
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involved in proteolytic activation, essential for CASP10-induced cell death
D297A
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site-directed mutagenesis, the single mutation D297A completely abrogates autocleavage between the subunits, the purified mutant is a single chain of 35 kDa. The cleavage site mutant has restricted specificity and highly reduced activity on protein substrates, overview
D416A
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involved in proteolytic activation, essential for CASP10-induced cell death
I406L
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impairs apoptosis when transfected alone and dominantly inhibits apoptosis mediated by wild-type caspase-10 in a co-transfection assay
L285F
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impairs apoptosis when transfected alone and dominantly inhibits apoptosis mediated by wild-type caspase-10 in a co-transfection assay
L285P
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the mutation may contribute to the pathogenesis of factions of T-acute lymphoblastic leukemia and multiple myeloma
R21C
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the mutation may contribute to the pathogenesis of factions of T-acute lymphoblastic leukemia and multiple myeloma
Y446C
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no dominant negative effect in co-transfection assay into H9 lymphocytic cell line
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
pharmacology
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tumour necrosis factor-related apoptosis-inducing ligand and SMs effectively kill head and neck squamous cancer cell lines and therefore represent potential targeted therapeutics for head and neck cancer. Distinct molecular mechanisms determine the sensitivity to each agent, with levels of TNF-alpha, caspase-8, Bid and caspase-10 providing important predictive biomarkers of response to these agents