Information on EC 3.4.22.63 - caspase-10

New: Word Map on EC 3.4.22.63
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY
3.4.22.63
-
RECOMMENDED NAME
GeneOntology No.
caspase-10
-
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
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
apoptotic protease Mch-4
-
-
-
-
C14.011
-
-
-
-
caspase-10
-
caspase-10
no activity in Mus musculus
-
-
caspase-10/b
-
-
caspase-10beta
-
-
FAS-associated death domain protein interleukin-1B-converting enzyme 2
-
-
-
-
FLICE2
-
-
-
-
FLICE2
-
-
ICE-like apoptotic protease 4
-
-
-
-
Mch4
-
-
-
-
Mch4
-
-
CAS REGISTRY NUMBER
COMMENTARY
189088-85-5
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
-
mutations or deficiencies in caspase-10 are associated with autoimmune lymphoproliferative syndrome
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
-
addition of a caspase-10 inhibitor totally blocks PTK7-knockdown-induced apoptosis
malfunction
-
apoptosis is totally prevented when caspase-10 is specifically inhibited in the cells
physiological function
-
flunarizine triggers apoptosis in Jurkat cells via FADD-independent activation of caspase-10
physiological function
-
caspase-10 activation is important in the initiation phase of apoptosis
physiological function
-
prodeath role for both cleaved and uncleaved caspase-10
physiological function
-
individual caspase-10 isoforms play distinct and opposing roles in the initiation of death receptor-mediated tumour cell apoptosis in several tumour cell types. Distinct caspase-10 isoforms induce opposed apoptotic signals in NB cells. Isozymes caspase-10A and -10D strongly increase tumour necrosis factor-related apoptosis-inducing ligand, i.e. TRAIL, and FasL sensitivity, whereas caspase-10B or -10G have no effect or are weakly anti-apoptotic. The unique C-terminal end of caspase-10B is responsible for its degradation by the ubiquitin-proteasome pathway and for its lack of pro-apoptotic activity compared with caspase-10A and -10D. Functional comparison to caspase-8, EC 3.4.22.61, overview. Caspase-10A or -10D isoforms can substitute for caspase-8 in the initiation extrinsic apoptosis
physiological function
-
caspase-10 is an initiator caspase of proinflammatory and apoptotic pathways induced by vaccinia infection. The processing of a short vaccinia virus-encoded antigen can take place by a proteasome-independent pathway involving initiator caspase-5 and -10, which generate antigenic peptides recognized by CD8+ T lymphocytes. Each enzyme can use the degradation products of the other as substrate for new cleavages, indicating concerted endoproteolytic activity of caspase-5 and -10, EC 3.4.22.58 and EC 3.4.22.63
physiological function
-
activation of caspase-10 in apoptosis is induced by PTK7 knockdown. Caspase-10 may play a critical role in PTK7-knockdown-induced apoptosis, downstream of mitochondria. The intrinsic pathway, i.e. mitochondria pathway, involves a decrease in mitochondrial membrane potential and release of cytochrome, overview
physiological function
-
Smac mimetic-induced cell death is associated with caspase-10 activation and is Bid-independent, suggesting that in the absence of caspase-8, caspase-10 mediates response to Smac mimetics, overview
physiological function
the enzyme is involved in immunity reactions against infection by Aphanomyces invadans and bacteria Aeromonas hydrophila
physiological function
-
caspase-10 is the key initiator caspase involved in tributyltin-mediated apoptosis in immune cells. Caspase-10 is recruited by the TRAIL-R2 receptor
physiological function
-
apoptosis is dependent on caspase-10 in association with the formation of the death-inducing signaling complex (DISC) incorporating pro-caspase-10 and tumor necrosis factor receptor 1 (TNF-R1), the process is ligand-independent
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
additional information
-
residue D297 is essential for autocleavage, while even though the sequence surrounding D319 is compatible for cleavage by caspase-10, its location close to the compact core makes it unavailable for cleavage
additional information
-
the heterodimer of caspase-10 with FLIPL still can cleave Bid and induce intrinsic apoptosis
additional information
-
isozymes caspase-10B and -10A/B are protected from CHX-mediated degradation by lactacystin treatment
additional information
-
autophagy is associated to human caspase-10-induced cell death in yeast, a specific process that depends on an intact MAPK pathway, the Factor-arrest (Far) protein family, and the autophagy machinery, overview. Far11 coordinates a death-promoting signal and regulates both autophagy and the DNA damage response. The expression of human caspase-10 in Saccharomyces cerevisiae activates an intracellular death signal that depends on the Far protein complex. Expression of initiator caspase-10 is toxic in yeast and induces a lethal phenotype with most of the principal hallmarks of apoptosis and autophagy, which include the production of ROS, chromatin condensation, phosphatidylserine externalization, and increased vacuolization. The MAP kinases Fus3, Kss1, and Slt2 are activated after the expression of caspase-10 in yeast cells
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
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-amino-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
-
-
-
-
?
B cell lymphoma-2-interacting domain + H2O
?
show the reaction diagram
-
-
-
-
?
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
-
-
?
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
-
-
?
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
-
-
?
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
-
-
?
YVAD-7-amido-4-methylcoumarin + H2O
YVAD + 7-amino-4-methylcoumarin
show the reaction diagram
-
less efficient cleavage than DEVD-7-amido-4-methylcoumarin
-
?
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
?
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
?
-
-
the enzyme acts as initiator of apoptosis
-
-
-
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 is involved in the early phase of advanced glycation end-product-induced pericyte apoptosis
-
-
-
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
?
-
-
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
-
-
-
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
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
procaspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
?
RIPK1 + H2O
?
show the reaction diagram
-
-
-
-
?
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
-
-
?
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
?
-
-
the enzyme acts as initiator of apoptosis
-
-
-
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 is involved in the early phase of advanced glycation end-product-induced pericyte apoptosis
-
-
-
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
?
-
-
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
-
-
-
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
-
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acetyl-AEVD-aldehyde
-
-
acetyl-DEVD-aldehyde
-
-
acetyl-IETD-aldehyde
-
-
acetyl-WEHD-aldehyde
-
-
acetyl-YVAD-aldehyde
-
-
benzyloxycarbonyl-AEVD-fluoromethylketone
-
-
benzyloxycarbonyl-AEVD-fluoromethylketone
-
specific caspase-10 inhibitor
benzyloxycarbonyl-AEVD-fluoromethylketone
-
caspase-10 inhibitor
benzyloxycarbonyl-IETD-fluoromethylketone
-
caspase-8/caspase-10 inhibitor
benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone
-
-
benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone
-
-
CBZ-VAD-trifluoromethylketone
-
pancaspase inhibitor
-
cowpox serpin CrmA
-
-
-
cowpox serpin CrmA
-
poorly inhibited
-
CrmA
-
caspase-10 is more resistant than caspase-8, EC 3.4.22.61, to the caspase inhibitor
-
DEVD-aldehyde
-
-
Z-AEVD-fluoromethylketone
-
a caspase-10 inhibitor
-
Z-VAD-fluoromethylketone
-
caspase-10 is more resistant than caspase-8, EC 3.4.22.61, to the caspase inhibitor
Z-VAD-fluoromethylketone
-
a caspase-family inhibitor
DEVD-CHO
-
-
additional information
-
no inhibition by WEHD-CHO and YVAD-CHO
-
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
-
caspase-8
-
caspase-8 cleaves and activates caspase-10 directly
-
FLICE-like inhibitory protein
-
i.e. FLIPL, activation occurs independently of cleavage of either the caspase or FLIPL
-
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
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
-
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
-
caspase-10 is activated at the DISC, downstream of death-receptor signaling
-
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
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.042
acetyl-VEHD-7-amido-4-methylcoumarin
-
at pH 7.0 and pH 7.5
0.071
DEVD-7-amido-4-methylcoumarin
-
-
0.13
DEVD-7-amido-4-methylcoumarin
-
pH 7.5
0.15
YVAD-7-amido-4-methylcoumarin
-
pH 7.5
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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
-
pH 7.5, 25C
0.000017
cowpox serpin CrmA
-
pH 7.5
-
0.000014
DEVD-aldehyde
-
pH 7.5
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0025
purified recombinant enzyme, pH not specified in the publication, 37C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7
-
reaction with acetyl-VEHD-7-amido-4-methylcoumarin
7.4
-
assay at
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
-
assay at room temperature
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.2
sequence calculation, mature enzyme
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
high expression level
Manually annotated by BRENDA team
high exxpression level
Manually annotated by BRENDA team
-
nine different cell lines, caspase-10 fragments are specifically detected in Smac mimetic-sensitive HSC3 cells
Manually annotated by BRENDA team
low exxpression level
Manually annotated by BRENDA team
-
low expression level
Manually annotated by BRENDA team
-
fetal, activity is undetectable in the adult
Manually annotated by BRENDA team
strong expression in posterior kidney, weak expression in head kidney
Manually annotated by BRENDA team
peripheral blood leukocyte. Strong expression
Manually annotated by BRENDA team
-
fetal, activity is undetectable in the adult
Manually annotated by BRENDA team
-
breast cancer cell line
Manually annotated by BRENDA team
-
low expression level
Manually annotated by BRENDA team
-
polymorphonuclear
Manually annotated by BRENDA team
-
neuroblastoma cells
Manually annotated by BRENDA team
-
neuroblastoma cells
Manually annotated by BRENDA team
-
fetal, activity is undetectable in the adult
Manually annotated by BRENDA team
-
low expression level
Manually annotated by BRENDA team
-
from peripheral blood, high expression level
Manually annotated by BRENDA team
additional information
-
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
GeneOntology No.
LITERATURE
SOURCE
-
caspase-10/c is insoluble and localizes to filamentous perinuclear structures
-
Manually annotated by BRENDA team
-
caspase-10/a and caspase-10/d are soluble proteins
-
Manually annotated by BRENDA team
additional information
the enzyme's amino acid sequence does not have either signal peptide region or transmembrane region
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
61000
recombinant enzyme cleaved from maltose-binding protein-fusion protein, gel filtration
731832
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 40000, caspase-10/c, SDS-PAGE
?
-
x * 58900 Da, calculated, not proteolytically activated
dimer
-
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
dimer
-
caspases can only be active as dimers, since neither the active site dyad nor the substrate pocket can be formed in the monomeric form
monomer
1 * 61000, about, sequence calculation, mature enzyme, 1 * 103500, recombinant maltose-binding protein-fusion enzyme, SDS-PAGE
additional information
-
proMch4 can autoprocess after Asp-219 and Asp-372 to generate the two subunits of the mature enzyme: P17, the large subunit and p12, the small subunit
additional information
-
homology modelling of caspase-10, structural modeling based on the structure of procaspase-8, PDB ID 2K7Z
additional information
the enzyme contains two death effector domains (DED) in the N-terminal at 2-77 and 87-154 and it contains caspase family p20 domain (large subunit) and caspase family p10 domain (small subunit) in the C-terminal at 299-425 and 449-536 respectively
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
Mch4 is derived from a single chain proenzym, granzyme B cleaves proMch4 at a IXXD-A processing sequence to produce mature Mch4
proteolytic modification
-
proMch4 can autoprocess after Asp-219 and Asp-372 to generate the two subunits of the mature enzyme : P17, the large subunit and p12, the small subunit
proteolytic modification
-
caspase-10/c and caspase-10/d are splice isoforms. Caspase-10/c is a truncated protein that is essentially a prodomain-only form of the caspase. Caspase-10/d is a hybrid of caspase-10/a (Mch4) and caspase-10/b (FLICE2), as it is identical to FLICE2 except for the small p12 catalytic subunit, which is identical to Mch4
proteolytic modification
-
autoprocessing, the wild-type 55000 Da GST fusion protein is cleaved to the 43000 Da active form
proteolytic modification
-
procaspase-10 is 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
proteolytic modification
-
caspase-10 is activated at the DISC, downstream of death-receptor signaling. Caspases-8 and -10 are recruited to the DISC as intact monomers and recruitment of the caspases to the DISC subsequently leads to their dimerization and activation through induced proximity, mechanism, overview
proteolytic modification
-
procaspase-10 is activated to caspase-10. Activation of caspase-10 is induced in apoptosis
proteolytic modification
-
the enzyme is activated by proteoltic cleavage
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
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant maltose-binding protein-fused enzyme from Escherichia coli strain BL21(DE3) by amylose affinity chromatography
recombinant His-tagged truncated mutant, with and without the D279A mutation, from Escherichia coli strain BL21 (DE3) by nickel affinity chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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)
cloning of caspase-10/c and caspase-10/d isoforms
-
expression in Escherichia coli
-
expression in NIH-3T3 cells
-
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
-
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
-
proMch4 lacking the two N-terminal FADD-like domains is subcloned in the bacterial expression vector pET21b
-
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
-
the caspase-10 gene is linked to the caspase-8 gene, EC 3.4.22.61, at the human chromosome locus 2q33-34
-
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)
-
the over-expression analysis of JF-caspase-10 in Japanese flounder cell line HINAE induces apoptosis 24 h post-transfection
expression in Escherichia coli
-
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
LITERATURE
C401G
-
active site, essential for CASP10-induced cell death
D219A
-
involved in proteolytic activation, essential for CASP10-induced cell death
D297A
-
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
-
involved in proteolytic activation, essential for CASP10-induced cell death
I406L
-
impairs apoptosis when transfected alone and dominantly inhibits apoptosis mediated by wild-type caspase-10 in a co-transfection assay
L285F
-
impairs apoptosis when transfected alone and dominantly inhibits apoptosis mediated by wild-type caspase-10 in a co-transfection assay
R21C
-
the mutation may contribute to the pathogenesis of factions of T-acute lymphoblastic leukemia and multiple myeloma
V410I
-
no dominant negative effect in co-transfection assay into H9 lymphocytic cell line. Protection from severe disease by caspase-10 V410I in 63 families with autoimmune lymphoproliferative syndrome Ia due to dominant Fas mutation
V410I
-
the mutation in caspase-10, that is associated with autoimmune lymphoproliferative syndrome, ALPS, is a common polymorphism in the healthy Danish population
Y446C
-
no dominant negative effect in co-transfection assay into H9 lymphocytic cell line
L285P
-
the mutation may contribute to the pathogenesis of factions of T-acute lymphoblastic leukemia and multiple myeloma
additional information
-
somatic mutation of caspase-10 is rare in colon, breast, lung, and hepatocellular carcinomas, caspase-10 mutation may contribute to the pathogenesis of some colon carcinomas
additional information
-
construction of a truncated mutant lacking the first 202 residues, and of the truncation mutant with a substitution D297A in the catalytic site, cloning into a vector with chimeric protein with an N-terminal His-tag followed by the Fv-domain. Chemically inducible dimerization fusions activate the wild-type but not the cleavage site mutant caspase-10
additional information
-
caspase-10 isoforms are transiently downregulated using siRNAs targeting all caspase-10 isoforms, or siRNAs specific for individual caspase-10 isoforms. Downregulation of individual or all caspase-10 isoforms in SH-EP cells does not affect TRAIL sensitivity
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
two patients that are combined heterozygous for single nucleotide substitutions in the Fas and caspase-10 genes. The first patient carries a splice site defect suppressing allele expression in the Fas gene and the P501L substitution in caspase-10. The second has a mutation causing a premature stop codon (Q47X) in the Fas gene and the Y446C substitution in caspase-10. Fas expression is reduced and caspase-10 activity is decreased in both patients. In both patients, the mutations are inherited from distinct healthy parents. Co-transmission of these mutation is responsible for autoimmune lymphoproliferative syndrome
medicine
-
silencer of death domain and caspase-10 are frequently over-expressed in ALL. Interfering with these proteins may provide another strategy for the treatment of this and potentially other cancers
pharmacology
-
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