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
3.4.22.63
-
RECOMMENDED NAME
GeneOntology No.
caspase-10
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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 ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
apoptotic protease Mch-4
-
-
-
-
C14.011
-
-
-
-
CASP10
Q92851
-
caspase-10
Q92851
-
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 ACCESSION NO.
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
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
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
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
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
-
-
?
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
Q92851
-
-
-
?
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
Q92851
-
-
-
?
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
Q92851
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
Q92851
-
-
-
?
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 ACCESSION NO.
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 ACCESSION NO.
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
-
-
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
-
additional information
-
no inhibition by WEHD-CHO and YVAD-CHO
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
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
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
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]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
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
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-
reaction with acetyl-VEHD-7-amido-4-methylcoumarin
7.4
-
-
assay at
7.5
-
-
assay at
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22
-
-
assay at room temperature
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
high expression level
Manually annotated by BRENDA team
-, Q0WYJ4
strong expression
Manually annotated by BRENDA team
-, Q0WYJ4
weak expression
Manually annotated by BRENDA team
-, Q0WYJ4
weak expression
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
-, Q0WYJ4
strong expression in posterior kidney, weak expression in head kidney
Manually annotated by BRENDA team
-, Q0WYJ4
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
-, Q0WYJ4
weak expression
Manually annotated by BRENDA team
-, Q0WYJ4
strong expression
Manually annotated by BRENDA team
-, Q0WYJ4
weak expression
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 ACCESSION NO.
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
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
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
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
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
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
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 ACCESSION NO.
LITERATURE
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 ACCESSION NO.
LITERATURE
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
-
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
-, Q0WYJ4
expression in Escherichia coli
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ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
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
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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
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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
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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 ACCESSION NO.
COMMENTARY
LITERATURE
medicine
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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