3.4.22.63: caspase-10
This is an abbreviated version!
For detailed information about caspase-10, go to the full flat file.
Word Map on EC 3.4.22.63
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3.4.22.63
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caspase-8
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necrosis
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fadd
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trail
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apoptosis-inducing
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bid
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lymphoproliferative
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factor-related
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death-inducing
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fas-associated
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casp11
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fas-mediated
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trail-induced
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c-flips
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tnf-related
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lymphadenopathy
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faslg
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caspase-8-deficient
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trail-mediated
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cflar
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apaf-1
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z-ietd-fmk
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tnf-r1
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trail-resistant
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template-based
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medicine
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pharmacology
- 3.4.22.63
- caspase-8
- necrosis
- fadd
-
trail
-
apoptosis-inducing
- bid
-
lymphoproliferative
-
factor-related
-
death-inducing
-
fas-associated
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casp11
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fas-mediated
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trail-induced
- c-flips
-
tnf-related
- lymphadenopathy
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faslg
-
caspase-8-deficient
-
trail-mediated
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cflar
- apaf-1
-
z-ietd-fmk
-
tnf-r1
-
trail-resistant
-
template-based
- medicine
- pharmacology
Reaction
strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp-/-Gly =
Synonyms
apoptotic protease Mch-4, C14.011, CASP10, caspase 10, caspase-10, caspase-10/b, caspase-10beta, FAS-associated death domain protein interleukin-1B-converting enzyme 2, FLICE2, ICE-like apoptotic protease 4, Mch4
ECTree
3.4.22.63 caspase-10Advanced search results
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results (General Information
General Information on EC 3.4.22.63 - caspase-10
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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
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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
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addition of a caspase-10 inhibitor totally blocks PTK7-knockdown-induced apoptosis
malfunction
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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
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mutations or deficiencies in caspase-10 are associated with autoimmune lymphoproliferative syndrome
malfunction
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apoptosis is totally prevented when caspase-10 is specifically inhibited in the cells
physiological function
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caspase-10 activation is important in the initiation phase of apoptosis
physiological function
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flunarizine triggers apoptosis in Jurkat cells via FADD-independent activation of caspase-10
physiological function
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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
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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
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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
prodeath role for both cleaved and uncleaved caspase-10
physiological function
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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
physiological function
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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
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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 negatively regulates caspase-8-mediated cell death. Caspase-10 reduces death-inducing signaling complex DISC association and activation of caspase-8. Caspase-10 does not compete with caspase-8 for binding to adaptor protein FADD. Caspase-8 is required upstream of both regulator cFLIP and caspase-10 and DISC formation critically depends on the scaffold function of caspase-8. Caspase-10 rewires DISC signaling to NF-kappaB activation/cell survival and the catalytic activity of caspase-10, and caspase-8, is redundant in gene induction
physiological function
the apoptosis-inducing complex FADDosome is driven by ATR-dependent caspase-10 upregulation. During FADDosome-induced apoptosis, FLICE-inhibitory protein cFLIPL is ubiquitinated by TRAF2, leading to its degradation and subsequent adaptor protein FADD-dependent caspase-8 activation. Cancer cells lacking caspase-10, TRAF2 or ATR switch from this cell-autonomous suicide to a more effective, autocrine/paracrine mode of apoptosis initiated by a different complex, the FLIPosome. It leads to processing of cFLIPL to cFLIPp43, TNF-alpha production and consequently, contrary to the FADDosome, p53-independent apoptosis
additional information
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isozymes caspase-10B and -10A/B are protected from CHX-mediated degradation by lactacystin treatment
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
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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
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the heterodimer of caspase-10 with FLIPL still can cleave Bid and induce intrinsic apoptosis
additional information
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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
