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Information on EC 3.4.22.63 - caspase-10
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3.4.22.63 caspase-10Specify your search results
Word Map
- 3.4.22.63
- caspase-8
- necrosis
- fadd
-
trail
-
apoptosis-inducing
- bid
-
lymphoproliferative
-
factor-related
-
death-inducing
-
fas-associated
-
casp11
-
fas-mediated
-
trail-induced
- c-flips
-
tnf-related
- lymphadenopathy
-
faslg
-
caspase-8-deficient
-
trail-mediated
-
cflar
- apaf-1
-
z-ietd-fmk
-
tnf-r1
-
trail-resistant
-
template-based
- medicine
- pharmacology
The enzyme appears in viruses and cellular organisms
Reaction Schemes
strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp-/-Gly
Synonyms
caspase-10, casp10, caspase 10, flice2, caspase-10/b, 
more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
apoptotic protease Mch-4
-
-
-
-
C14.011
-
-
-
-
CASP10
caspase-10
FAS-associated death domain protein interleukin-1B-converting enzyme 2
-
-
-
-
FLICE2
ICE-like apoptotic protease 4
-
-
-
-
Mch4
FLICE2
-
-
-
-
Mch4
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp-/-Gly
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
189088-85-5
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Ac-IETD-4-trifluoromethylcoumarin-7-amide + H2O
Ac-IETD + 7-amino-4-trifluoromethylcoumarin
-
-
-
?
acetyl-Ala-Glu-Val-Asp-4-trifluoromethylcoumarin-7-amide + H2O
acetyl-Ala-Glu-Val-Asp + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
acetyl-VEHD-7-amido-4-methylcoumarin + H2O
acetyl-VEHD + 7-amino-4-methylcoumarin
-
the optimal tetrapeptide recognition motif is LEXD
-
-
?
BID + H2O
?
cleavage at sites LQTD/G and IEPD/S, for apical caspases
-
-
?
Hsp90beta + H2O
?
-
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
-
-
quantitative product mass spectrometric analysis, overview
-
?
pro-Mch3 + H2O
?
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
-
-
?
B cell lymphoma-2-interacting domain + H2O
?
-
caspase-10 can serve as an initiator caspase in Fas signaling leading to Bid processing, caspase cascade activation, and apoptosis
-
-
?
DEVD-7-amido-4-methylcoumarin + H2O
DEVD + 7-amino-4-methylcoumarin
-
-
-
?
YVAD-7-amido-4-methylcoumarin + H2O
YVAD + 7-amino-4-methylcoumarin
-
-
-
?
YVAD-7-amido-4-methylcoumarin + H2O
YVAD + 7-amino-4-methylcoumarin
less efficient cleavage than DEVD-7-amido-4-methylcoumarin
-
-
?
additional information
?
-
-
caspase-10 is involved in the early phase of advanced glycation end-product-induced pericyte apoptosis
-
-
?
additional information
?
-
-
broad specificity towards pro-aspartate-specific cysteine proteases
-
-
?
additional information
?
-
FLICE2 is a signaling caspase able to interact with the cell death receptors p55 and CD95 through the adapter molecule FADD
-
-
?
additional information
?
-
caspase-10/c is a truncated protein that is essentially a prodomain-only form of the caspase that lacks proteolytic activity in vitro but efficiently induces the formation of perinuclear filamentous structures and cell death in vivo, potential role of caspase-10/c in amplifying the apoptotic response to extracellular stimuli such as cytokines. Caspase-10/d is proteolytically active in vitro and also induces cell death ion vivo, although it is less active than Mch4. Possible role of caspase-10 family in the fetal development
-
-
?
additional information
?
-
inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II, caspase-10 mutations in Pt 11 and Pt 36 affect TRAIL-induced death of dendritic cells
-
-
?
additional information
?
-
-
inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II, caspase-10 mutations in Pt 11 and Pt 36 affect TRAIL-induced death of dendritic cells
-
-
?
additional information
?
-
-
caspase-8 has a role in a non-apoptotic or anti-apoptotic signaling pathway leading to NF-kappaB activation through RIP, NIK and IKKalpha
-
-
?
additional information
?
-
-
Mch4 mediates the CrmA-insensitive apoptotic pathways, such as the DNA-damaging agents and staurosporine pathways
-
-
?
additional information
?
-
-
caspase-10 actively contributes to cytotoxic drug-induced apoptosis in leukemic cells. Caspase-10 activation does not occur at the level of a death-inducing signaling complex, nor in a Fas-associated death domain-dependent manner, but requires cytochrome c release from the mitochondria and the adapter molecule Apaf-1. Caspase-10 is activated downstream of caspase-9 and amplifies the caspase cascade by activating caspase-9 and caspase-3 in a feedback loop. Caspase-10 plays a role in cytotoxic drug-induced apoptosis downstream of the mitochondria
-
-
?
additional information
?
-
-
caspase-10 is involved in RIG-I/Mda5-dependent antiviral immune responses, particularly inflammatory responses
-
-
?
additional information
?
-
-
caspase-10 sensitizes breast carcinoma cells to TNF-related apoptosis-inducing ligand-induced but not tumor necrosis factor-induced apoptosis in a caspase-3-dependent manner
-
-
?
additional information
?
-
-
genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome
-
-
?
additional information
?
-
-
spontaneous apoptosis requires the activation of caspase-10/b
-
-
?
additional information
?
-
-
caspase-10 mRNA level is increased by the treatment with sodium butyrate. Sodium butyrate may trigger apoptosis via the induction of the caspase-10 expression
-
-
?
additional information
?
-
the 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), a prodomain-only isoform of caspase-10, may play a regulatory role preferentially in the NF-kappaB pathway. Caspase-10g induces low level of apoptosis and has no effect on the caspase-10a-mediated cell apoptosis
-
-
?
additional information
?
-
-
the 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), a prodomain-only isoform of caspase-10, may play a regulatory role preferentially in the NF-kappaB pathway. Caspase-10g induces low level of apoptosis and has no effect on the caspase-10a-mediated cell apoptosis
-
-
?
additional information
?
-
-
xCaspase-10beta can interact with other Xenopus initiator caspases via the conformational activity of its DED, xCaspase-10beta is involved in the early development of Xenopus embryos
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
B cell lymphoma-2-interacting domain + H2O
?
-
caspase-10 can serve as an initiator caspase in Fas signaling leading to Bid processing, caspase cascade activation, and apoptosis
-
-
?
additional information
?
-
-
caspase-10 is involved in the early phase of advanced glycation end-product-induced pericyte apoptosis
-
-
?
additional information
?
-
FLICE2 is a signaling caspase able to interact with the cell death receptors p55 and CD95 through the adapter molecule FADD
-
-
?
additional information
?
-
caspase-10/c is a truncated protein that is essentially a prodomain-only form of the caspase that lacks proteolytic activity in vitro but efficiently induces the formation of perinuclear filamentous structures and cell death in vivo, potential role of caspase-10/c in amplifying the apoptotic response to extracellular stimuli such as cytokines. Caspase-10/d is proteolytically active in vitro and also induces cell death ion vivo, although it is less active than Mch4. Possible role of caspase-10 family in the fetal development
-
-
?
additional information
?
-
inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II, caspase-10 mutations in Pt 11 and Pt 36 affect TRAIL-induced death of dendritic cells
-
-
?
additional information
?
-
-
inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II, caspase-10 mutations in Pt 11 and Pt 36 affect TRAIL-induced death of dendritic cells
-
-
?
additional information
?
-
-
caspase-8 has a role in a non-apoptotic or anti-apoptotic signaling pathway leading to NF-kappaB activation through RIP, NIK and IKKalpha
-
-
?
additional information
?
-
-
Mch4 mediates the CrmA-insensitive apoptotic pathways, such as the DNA-damaging agents and staurosporine pathways
-
-
?
additional information
?
-
-
caspase-10 actively contributes to cytotoxic drug-induced apoptosis in leukemic cells. Caspase-10 activation does not occur at the level of a death-inducing signaling complex, nor in a Fas-associated death domain-dependent manner, but requires cytochrome c release from the mitochondria and the adapter molecule Apaf-1. Caspase-10 is activated downstream of caspase-9 and amplifies the caspase cascade by activating caspase-9 and caspase-3 in a feedback loop. Caspase-10 plays a role in cytotoxic drug-induced apoptosis downstream of the mitochondria
-
-
?
additional information
?
-
-
caspase-10 is involved in RIG-I/Mda5-dependent antiviral immune responses, particularly inflammatory responses
-
-
?
additional information
?
-
-
caspase-10 sensitizes breast carcinoma cells to TNF-related apoptosis-inducing ligand-induced but not tumor necrosis factor-induced apoptosis in a caspase-3-dependent manner
-
-
?
additional information
?
-
-
genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome
-
-
?
additional information
?
-
-
spontaneous apoptosis requires the activation of caspase-10/b
-
-
?
additional information
?
-
-
caspase-10 mRNA level is increased by the treatment with sodium butyrate. Sodium butyrate may trigger apoptosis via the induction of the caspase-10 expression
-
-
?
additional information
?
-
the 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), a prodomain-only isoform of caspase-10, may play a regulatory role preferentially in the NF-kappaB pathway. Caspase-10g induces low level of apoptosis and has no effect on the caspase-10a-mediated cell apoptosis
-
-
?
additional information
?
-
-
the 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), a prodomain-only isoform of caspase-10, may play a regulatory role preferentially in the NF-kappaB pathway. Caspase-10g induces low level of apoptosis and has no effect on the caspase-10a-mediated cell apoptosis
-
-
?
additional information
?
-
-
xCaspase-10beta can interact with other Xenopus initiator caspases via the conformational activity of its DED, xCaspase-10beta is involved in the early development of Xenopus embryos
-
-
?
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
CrmA
-
caspase-10 is more resistant than caspase-8, EC 3.4.22.61, to the caspase inhibitor
-
Z-VAD-fluoromethylketone
-
caspase-10 is more resistant than caspase-8, EC 3.4.22.61, to the caspase inhibitor
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-(acetyloxy)benzoic acid 4-(nitrooxymethyl)-phenyl ester
-
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
FLICE-like inhibitory protein
-
i.e. FLIPL, activation occurs independently of cleavage of either the caspase or FLIPL
-
FLIPL protein
-
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
-
Sodium citrate
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
-
caspase-10 is activated at the DISC, downstream of death-receptor signaling
-
additional information
procaspase-10 is proteolytically activated to caspase-10, mechanism of activation and the role of the inter-subunit cleavage, overview. Caspase-10 follows the proximity-induced dimerization model for apical caspases. Chemically inducible dimerization fusions activate the wild-type but not the cleavage site mutant caspase-10
-
additional information
-
procaspase-10 is proteolytically activated to caspase-10, mechanism of activation and the role of the inter-subunit cleavage, overview. Caspase-10 follows the proximity-induced dimerization model for apical caspases. Chemically inducible dimerization fusions activate the wild-type but not the cleavage site mutant caspase-10
-
additional information
-
proteolytic activation of caspase-10 is induced in apoptosis
-
additional information
-
in head and neck squamous cancer cell lines with low caspase-8 levels, Smac mimetics treatment induced caspase-10 activation
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0025
purified recombinant enzyme, pH not specified in the publication, 37°C
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
markedly expressed in blood tissues under physiological conditions
brenda
-
nine different cell lines, caspase-10 fragments are specifically detected in Smac mimetic-sensitive HSC3 cells
brenda
additional information
strong expression in posterior kidney, weak expression in head kidney
brenda
additional information
the expression levels of caspase-10-related mRNAs are generally higher in fetal than in adult tissues
brenda
additional information
ubiquitously transcribed in the tissues examined. Abundant transcription in blood, and, in descending order, in gill, spleen, and intestine tissues, compared to the least abundant transcript level in muscle tissue
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
caspase-10/c is insoluble and localizes to filamentous perinuclear structures
-
brenda
additional information
additional information
the enzyme's amino acid sequence does not have either signal peptide region or transmembrane region
-
brenda
additional information
-
the enzyme's amino acid sequence does not have either signal peptide region or transmembrane region
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
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
evolution
human caspase-10 and caspase-8, EC 3.4.22.61, are highly homologous in their protein sequence, 46% identical in the catalytic domain, and their genes are on the same region of human chromosome 2q33-34 suggesting that they have a common ancestor
evolution
-
initiator and executioner caspases, the pro-apoptotic members of the caspase family are subdivided in the initiators of apoptosis, i.e. caspases-8, -9 and -10 in humans, and the executioners of apoptosis, caspase-3, -6 and -7, phylogenetic tree of all the human caspases, overview. The initiators have a relatively large N-terminal dimerization domain, either a death effector domain, caspases-8 and -10, or a structurally related caspase recruitment domain, caspase-9. Caspase-18 and the ancestor of -8 and -10 called caspase-810 in this schematic are still found in fishes. Later on in evolution, caspase-8 and -10 branched off from caspase-810
malfunction
-
addition of a caspase-10 inhibitor totally blocks PTK7-knockdown-induced apoptosis
malfunction
-
caspase-10 silencing in neuroblastoma is cell-type related. Downregulation of individual or all caspase-10 isoforms in SH-EP cells does not affect TRAIL sensitivity
malfunction
-
mutations or deficiencies in caspase-10 are associated with autoimmune lymphoproliferative syndrome
malfunction
-
apoptosis is totally prevented when caspase-10 is specifically inhibited in the cells