Information on EC 3.4.22.64 - caspase-11

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The expected taxonomic range for this enzyme is: Euarchontoglires

EC NUMBER
COMMENTARY
3.4.22.64
-
RECOMMENDED NAME
GeneOntology No.
caspase-11
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
strict requirement for Asp at the P1 position and has a preferred cleavage sequence of (Ile/Leu/Val/Phe)-Gly-His-Asp-/-
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C14.012
-
-
-
-
caspase 11
-
-
caspase-11
-
cf 3.4.22.57
caspase-4
-
-
caspase-4
Mus musculus C57BL/6
-
-
-
Ich-3
-
-
ICH-3 protease
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
216503-96-7
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
C57BL, wild type and p53KO mice
-
-
Manually annotated by BRENDA team
strain C3H/An
SwissProt
Manually annotated by BRENDA team
strain C57BL/6 X CBA
SwissProt
Manually annotated by BRENDA team
Mus musculus C3H/An
strain C3H/An
SwissProt
Manually annotated by BRENDA team
Mus musculus C57B6
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
gene Casp11
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6 X CBA
strain C57BL/6 X CBA
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
caspase-11 is a member of the caspase family of cysteine proteases
evolution
-
inflammatory caspases all share a similar prodomain at the N-terminus responsible for protein-protein interactions: the caspase activation and recruitment domain (CARD). The genes of the inflammatory caspases are all located adjacent to the Casp1 gene on the mammalian chromosome (chromosome 9 in mouse), forming an inflammatory gene cluster. The close proximity of these genes and the high degree of similarity in the caspase protein structures might explain that the multiple inflammatory caspases arose from amplification of the Casp1 gene locus in the early stages of mammalian evolution
evolution
Mus musculus C57B6
-
caspase-11 is a member of the caspase family of cysteine proteases
-
malfunction
-
germline mutation of Casp11 in mouse strain 129 abolishes inflammasome activation by CTB. Strain 129 mice, like Casp11-/- mice, exhibits defects in IL-1beta production and harbours a mutation in the Casp11 locus that attenuates caspase-11 expression
malfunction
-
all Casp1-/- mice also lack caspase-11, due to the generation of the Casp1-/- line in the 129 mouse strain background, which express a mis-spliced and truncated version of the Casp11 messenger RNA
malfunction
-
upon infection with Salmonella typhimurium, the level of pro-interleukin-1beta maturation in bone marrow derived macrophages is reduced in the absence of caspase-11
malfunction
-
defects in the IFN-alpha/beta, but not IFN-gamma, pathways render macrophages severely impaired in processing of caspase-11 following infection with Salmonella typhimurium, EHEC or Citrobacter rodentium, while exogenous IFN-beta rescues caspase-11 processing in Trif-/- macrophages. The absence of the TRIF-IFNAR pathway abolishes both the expression and activation of caspase-11, and treatment of Trif-/- macrophages with IFN-beta or IFN-gamma restores both the precursor and cleaved forms of caspase-11
malfunction
-
Casp11-/- knockout mouse strains are resistant to developing lethal sepsis
malfunction
-
all existing caspase-1 deficient mice also lack Caspase-11 due to the backcrossing of a mutant Casp11 allele from 129 into C57BL/6 mice
malfunction
-
inhibition of caspase-11 expression with either wedelolactone or siRNAs reduces the number of methamphetamine-induced apoptotic cells. In addition, blocking caspase-11 expression inhibits methamphetamine-induced activation of caspase-3 and PARP in vitro and in vivo
malfunction
-
inhibition of caspase-11 expression with either wedelolactone or siRNAs reduces the number of methamphetamine-induced apoptotic cells, silencing of caspase-11 protects PC-12 cells from methamphetamine-induced apoptosis. In addition, blocking caspase-11 expression inhibits methamphetamine-induced activation of caspase-3 and PARP in vitro and in vivo
malfunction
Mus musculus C57BL/6
-
all existing caspase-1 deficient mice also lack Caspase-11 due to the backcrossing of a mutant Casp11 allele from 129 into C57BL/6 mice; germline mutation of Casp11 in mouse strain 129 abolishes inflammasome activation by CTB. Strain 129 mice, like Casp11-/- mice, exhibits defects in IL-1beta production and harbours a mutation in the Casp11 locus that attenuates caspase-11 expression
-
metabolism
-
Gram-negative bacteria and certain pore-forming toxins induce a caspase-11-dependent noncanonical inflammasome that contributes to NLRP3-dependent interleukin-1beta release and also triggers NLRP3- and caspase-1-independent cell death and interleukin-1alpha release
metabolism
-
apoptosis is triggered by the initiator caspases, caspase-2, -8, -9, and -10, which subsequently activate the executioner caspases, caspase-3, -6, and -7
metabolism
-
Gram-negative bacteria are specifically detected via a surveillance mechanism that involves activation of extracellular receptors such as Toll-like receptors followed by intracellular recognition and activation of pathways such as caspase-11. Extracellular LPS primarily stimulates TLR4, which can serve as a priming signal for expression of inflammasome components. Intracellular LPS can then trigger caspase-11-dependent inflammasome activation in the cytoplasm. Bacterial infection triggers caspase-11 activation and leads to two distinct signals: (i) caspase-1-dependent interleukin-1beta/interleukin-18 secretion and caspase-1-independent pyroptosis
metabolism
-
while Salmonella typhimurium and Legionella pneumophila normally reside in the vacuole, specific mutants (sifA and sdhA, respectively) that aberrantly enter the cytosol trigger Caspase-11, enhancing clearance of S. typhimurium sifA in vivo. This response does not require NLRP3, NLRC4, or ASC inflammasome pathways. Burkholderia species that naturally invade the cytosol also trigger Caspase-11, protecting mice from lethal challenge with Burkholderia thailandensis and Burkholderia pseudomallei. Caspase-11 is critical for surviving exposure to ubiquitous environmental pathogens
physiological function
-
caspase-11 mediates non-canonical inflammasome activation.Caspase-11 rather than caspase-1 is required for lipopolysaccharide-induced lethality. Interleukin-1beta secretion in response to other bacterial toxins, including adenylcyclase toxin, listeriolysin O toxin, or Clostridium difficile toxin B, is not affected by caspase-11 deficiency. Caspase-11 also is dispensable for NLRP3-dependent IL-1beta secretion in response to monosodium urate, calcium pyrophosphate, or the ionophore nigericin. In contrast, NLRP3- and ASC-dependent IL-1beta secretion from BMDMs infected with live Escherichia coli, Citrobacter rodentium and Vibriae cholerae, requires caspase-11, with or without lipopolysaccharide priming
physiological function
-
activated caspase-11 triggers cell death, caspase-11 is essential for the induction of endotoxic shock in vivo
physiological function
-
caspase-11-dependent cell death and interleukin-1beta secretion can only be detected in vitro in the absence of a NAIP/NLRC4 stimulus, e.g. flagellin. Caspase-11 is required for the release of the alarmins, interleukin-1alpha and HMGB1. The role of caspase-11 in pro-interleukin-18 and pro-interleukin-1beta maturation is dependent on NLRP3/ASC/CASP1 inflammasomes. Pro-inflammatory caspases play important roles in innate immunity, analysis of mechanisms by which caspase-11 contributes to host defense. Caspase-11 functions and mechanisms of activation, implications for human disease, overview
physiological function
-
caspase-11 is required for cofilin phosphorylation. Caspase-11-dependent cell death and interleukin-1beta secretion can only be detected in vitro in the absence of a NAIP/NLRC4 stimulus, e.g. flagellin. Caspase-11 is required for the release of the alarmins, interleukin-1alpha and HMGB1. The role of caspase-11 in pro-interleukin-18 and pro-interleukin-1beta maturation is dependent on NLRP3/ASC/CASP1 inflammasomes. Pro-inflammatory caspases play important roles in innate immunity. Caspase-11 contributes to host defenses against pathogen invasion. Caspase-11 functions and mechanisms of activation, overview
physiological function
-
caspase-11 is a highly inducible caspase that controls both inflammatory responses and cell death. Caspase-11 controls interleukin 1beta secretion by potentiating caspase-1 activation and induces caspase-1-independent pyroptosis downstream of noncanonical NLRP3 inflammasome activators such as lipopolysaccharide and Gram-negative bacteria. Caspase-11 modulates the cationic channel composition of the cell and thus regulates the unconventional secretion pathway in a manner independent of caspase-1. Caspase-11 controls the TRPC1-dependent decrease in cytosolic Ca2+ following lipopolysaccharide treatment
physiological function
-
mechanisms and implications of caspase-11-mediated noncanonical inflammasome activation, importance of this pathway in regulating host defense against intracellular bacterial pathogens. The pathway engages caspase-11 to trigger both caspase-1-dependent and -independent production of the inflammatory cytokines IL-1beta, IL-18, and IL-1alpha, as well as to promote pyroptosis, a form of genetically programmed cell death that is associated with the release of such cytokines. Caspase-11 is regulated in response to extracellular stimuli, such as lipopolysaccharide and interferons
physiological function
-
mechanisms and implications of caspase-11-mediated noncanonical inflammasome activation, importance of this pathway in regulating host defense against intracellular bacterial pathogens. The pathway engages caspase-11 to trigger both caspase-1-dependent and -independent production of the inflammatory cytokines IL-1beta, IL-18, and IL-1alpha, as well as to promote pyroptosis, a form of genetically programmed cell death that is associated with the release of such cytokines. Caspase-11 is regulated in response to extracellular stimuli, such as lipopolysaccharide and interferons. Regulation of caspase-11 expression, models of activation, and caspase-11 effector functions, overview. Role of caspase-11 in pyroptosis, caspase-11 directly controls the activation of the effector caspases 3 and 7 of the apoptotic pathway independent of caspase-1
physiological function
-
caspase-11 plays a role in the inflammasome in the cytoplasm. Activation of inflammatory caspases, e.g. caspase-11, leads to the processing and maturation of inflammatory cytokines, such as interleukin-1beta and interleukin-18, as well as a specific form of cell death termed pyroptosis. Caspase-11 can induce cell death and form hetero-complexes with caspase-1. Caspase-11 by itself inefficiently cleaves pro-interleukin-1beta, suggesting early on that caspase-11 might rely on caspase-1 for cytokine maturation. The caspase-11 non-canonical inflammasome plays a significant role in Gram-negative bacterial infections, including Escherichia coli, Citrobacter rodentium, Shigella flexneri, Salmonella typhimurium, Legionella pneumophila, and Burkholderia thailandensis, caspase-11 can restrict the replication of intracellular pathogenic bacteria (Salmonella typhimurium and Burkholderia species)
physiological function
-
caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila. NLRP3 and ASC are both required for caspase-1 activation through the caspase-11-dependent pathway induced by Legionella pneumophila, caspase-11 is required for NAIP/NLRC4-independent pyroptosis Induced by Legionella pneumophila
physiological function
-
caspase-11 is an inflammatory caspase that can also promote interleukin-1beta secretion dependent upon NLRP3, ASC, and Caspase-1. Inflammatory caspase-11 triggers pyroptosis, a form of programmed cell death. The enzyme can be detrimental in inflammatory disease,but has no protective role during infection. Caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria
physiological function
-
caspase-11 plays an essential role in methamphetamine-induced dopaminergic neuron apoptosis, the caspase-11/caspase-3 signal pathway is involved in methamphetamine-induced neurotoxicity
physiological function
Mus musculus C57B6
-
caspase-11 is a highly inducible caspase that controls both inflammatory responses and cell death. Caspase-11 controls interleukin 1beta secretion by potentiating caspase-1 activation and induces caspase-1-independent pyroptosis downstream of noncanonical NLRP3 inflammasome activators such as lipopolysaccharide and Gram-negative bacteria. Caspase-11 modulates the cationic channel composition of the cell and thus regulates the unconventional secretion pathway in a manner independent of caspase-1. Caspase-11 controls the TRPC1-dependent decrease in cytosolic Ca2+ following lipopolysaccharide treatment
-
physiological function
Mus musculus C57BL/6
-
caspase-11 is an inflammatory caspase that can also promote interleukin-1beta secretion dependent upon NLRP3, ASC, and Caspase-1. Inflammatory caspase-11 triggers pyroptosis, a form of programmed cell death. The enzyme can be detrimental in inflammatory disease,but has no protective role during infection. Caspase-11 is required for innate immunity to cytosolic, but not vacuolar, bacteria; caspase-11 mediates non-canonical inflammasome activation.Caspase-11 rather than caspase-1 is required for lipopolysaccharide-induced lethality. Interleukin-1beta secretion in response to other bacterial toxins, including adenylcyclase toxin, listeriolysin O toxin, or Clostridium difficile toxin B, is not affected by caspase-11 deficiency. Caspase-11 also is dispensable for NLRP3-dependent IL-1beta secretion in response to monosodium urate, calcium pyrophosphate, or the ionophore nigericin. In contrast, NLRP3- and ASC-dependent IL-1beta secretion from BMDMs infected with live Escherichia coli, Citrobacter rodentium and Vibriae cholerae, requires caspase-11, with or without lipopolysaccharide priming; caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila. NLRP3 and ASC are both required for caspase-1 activation through the caspase-11-dependent pathway induced by Legionella pneumophila, caspase-11 is required for NAIP/NLRC4-independent pyroptosis Induced by Legionella pneumophila
-
metabolism
Mus musculus C57BL/6
-
while Salmonella typhimurium and Legionella pneumophila normally reside in the vacuole, specific mutants (sifA and sdhA, respectively) that aberrantly enter the cytosol trigger Caspase-11, enhancing clearance of S. typhimurium sifA in vivo. This response does not require NLRP3, NLRC4, or ASC inflammasome pathways. Burkholderia species that naturally invade the cytosol also trigger Caspase-11, protecting mice from lethal challenge with Burkholderia thailandensis and Burkholderia pseudomallei. Caspase-11 is critical for surviving exposure to ubiquitous environmental pathogens
-
additional information
-
caspase-1, -2, -4, -9, and -11 have particularly long pro-domains that contain either death effector domains (DED) or caspase recruitment domains (CARD), which are thought to confer specificity of activation since they mediate interactions with other DED- and CARD-containing adaptor proteins. Association with these adaptor proteins likely nucleates caspases, increasing their local concentration. This nucleation can favor activation through dimerization
additional information
-
caspase-11 cooperatively interacts with actin-interacting protein to activate cofilin-dependent actin depolymerization leading to increased splenocyte migration, caspase-11-mediated actin depolymerization appears to be independent of its enzymatic activity. Caspase-1, -2, -4, -9, and -11 have particularly long pro-domains that contain either death effector domains (DED) or caspase recruitment domains (CARD), which are thought to confer specificity of activation since they mediate interactions with other DED- and CARD-containing adaptor proteins. Association with these adaptor proteins likely nucleates caspases, increasing their local concentration. This nucleation can favor activation through dimerization
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-VEHD-7-amido-4-methylcoumarin + H2O
acetyl-VEHD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
acetyl-VEHD-7-amido-4-methylcoumarin + H2O
acetyl-VEHD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
cationic channel subunit transient receptor potential channel 1 + H2O
?
show the reaction diagram
-
i.e. TRPC1, plays a role in regulating innate immunity by modulating channel complexes during inflammatory responses
-
-
?
procaspase-1 + H2O
?
show the reaction diagram
-
the enzyme is an upstream activator of caspase-1
-
-
?
procaspase-3 + H2O
?
show the reaction diagram
-
the enzyme is a critical initiator caspase responsible for the activation of caspase-3
-
-
?
cationic channel subunit transient receptor potential channel 1 + H2O
?
show the reaction diagram
Mus musculus C57B6
-
i.e. TRPC1, plays a role in regulating innate immunity by modulating channel complexes during inflammatory responses
-
-
?
additional information
?
-
-
-
-
-
additional information
?
-
-
optimal cleavage site is IEHD, LEHD, VEHD or PEHD
-
-
-
additional information
?
-
-
overexpression induces apoptosis
-
-
-
additional information
?
-
-
phenotype of animals deficient in caspase-11: resistant to lipopolysaccharide-induced caspase-1 processing, interleukin-1alpha and interleukin-beta secretion, and endotoxic shock
-
-
-
additional information
?
-
-
the enzyme is a critical initiator caspase responsible for the activation of caspase-3. The enzyme is an upstream activator of caspase-1. Caspase-11 deficient animals have a reduced number of apoptotic cells and a defect in caspase-3 activation after middle cerebral artery occlusion. The enzyme is A VERY IMPORTANT REGULATOR OF APOPTOSIS
-
-
-
additional information
?
-
-
enzyme is involved in cytokine activation
-
-
-
additional information
?
-
-
pro-caspase-11 physically interacts with pro-ICE in cells, the expression of casp-11 is essential for activation of ICE. Caspase-11 is a compinent of ICE complex and is required for the activation of ICE. Important role of ICE and caspase-11 in mediating apoptosis in pathological conditions
-
-
-
additional information
?
-
the enzyme may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE
-
-
-
additional information
?
-
-
the enzyme is involved in cytokine activation
-
-
-
additional information
?
-
-
C/EBP homologous protein (CHOP) is crucial for the induction of caspase-11 and the pathogenesis of lipopolysaccharide-induced inflammation
-
-
-
additional information
?
-
-
caspase-11 has a regulatory role in ethanol-induced apoptosis. Suppression of caspase-11 expression may be a mechanism by which Scutellariae radix (Chinese herbal medicine) exerts its cytoprotective effect
-
-
-
additional information
?
-
caspase-11 plays a crucial role in both inflammation and apoptosis. Caspase-11 not only activates caspase-1, that is required for the maturation of proinflammatory cytokines such as interleukin (IL)-1 and IL-18, but also activates caspase-3, leading to cellular apoptosis under pathological conditions. The expression of caspase-11 is strongly induced at both mRNA and protein levels by inflammatory stimuli such as lipopolysaccharide, interferon-Q Q, and tumor necrosis factor-K K in C6 rat glial cells as well as primary astrocytes. Induction of caspase-11 by LPS in astrocytes is mediated through the p38 MAPK pathway. Inflammatory induction of caspase-11 in astrocytes may play an important role in both inflammatory responses involving these cells and auto-regulatory apoptosis of activated astrocytes in inflammatory sites
-
-
-
additional information
?
-
-
neurotoxic effects of lipopolysaccharide on nigral dopaminergic neurons are mediated by microglial activation, interleukin-1beta, and expression of caspase-11 in mice
-
-
-
additional information
?
-
-
neurotoxicity of 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine may be mediated via activation of the caspase-11 cascade and inflammatory cascade, as well as the mitochondrial apoptotic cascade
-
-
-
additional information
?
-
-
a pathway modulating inflammatory-cell migration involve caspase-11 and actin interacting protein 1
-
-
-
additional information
?
-
-
caspase-11 may be a central regulator of multiple events, including cell migration, cytokine maturation and apoptosis, during inflammation responses. Caspase-11 interacts physically and functionally with actin interacting protein 1, an activator of cofilin-mediated actin depolymerization. Caspase-11 and actin interacting protein 1 work cooperatively to promote cofilin-mediated actin depolymerization
-
-
-
additional information
?
-
-
Flightless-I regulates the subcellular distribution of caspase-11 by promoting its localization at the cell leading edge
-
-
-
additional information
?
-
-
other caspases are substrates of caspase-11
-
-
-
additional information
?
-
Mus musculus C3H/An
-
-
-
-
additional information
?
-
Mus musculus C57BL/6 X CBA
the enzyme may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE
-
-
-
additional information
?
-
Mus musculus C57B6
-
other caspases are substrates of caspase-11
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
procaspase-1 + H2O
?
show the reaction diagram
-
-
-
-
?
procaspase-3 + H2O
?
show the reaction diagram
-
the enzyme is a critical initiator caspase responsible for the activation of caspase-3
-
-
?
cationic channel subunit transient receptor potential channel 1 + H2O
?
show the reaction diagram
Mus musculus, Mus musculus C57B6
-
i.e. TRPC1, plays a role in regulating innate immunity by modulating channel complexes during inflammatory responses
-
-
?
additional information
?
-
P70343
-
-
-
-
additional information
?
-
-
overexpression induces apoptosis
-
-
-
additional information
?
-
-
phenotype of animals deficient in caspase-11: resistant to lipopolysaccharide-induced caspase-1 processing, interleukin-1alpha and interleukin-beta secretion, and endotoxic shock
-
-
-
additional information
?
-
-
the enzyme is a critical initiator caspase responsible for the activation of caspase-3. The enzyme is an upstream activator of caspase-1. Caspase-11 deficient animals have a reduced number of apoptotic cells and a defect in caspase-3 activation after middle cerebral artery occlusion. The enzyme is A VERY IMPORTANT REGULATOR OF APOPTOSIS
-
-
-
additional information
?
-
-
enzyme is involved in cytokine activation
-
-
-
additional information
?
-
-
pro-caspase-11 physically interacts with pro-ICE in cells, the expression of casp-11 is essential for activation of ICE. Caspase-11 is a compinent of ICE complex and is required for the activation of ICE. Important role of ICE and caspase-11 in mediating apoptosis in pathological conditions
-
-
-
additional information
?
-
P70343
the enzyme may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE
-
-
-
additional information
?
-
-
the enzyme is involved in cytokine activation
-
-
-
additional information
?
-
-
C/EBP homologous protein (CHOP) is crucial for the induction of caspase-11 and the pathogenesis of lipopolysaccharide-induced inflammation
-
-
-
additional information
?
-
-
caspase-11 has a regulatory role in ethanol-induced apoptosis. Suppression of caspase-11 expression may be a mechanism by which Scutellariae radix (Chinese herbal medicine) exerts its cytoprotective effect
-
-
-
additional information
?
-
Q91XW7
caspase-11 plays a crucial role in both inflammation and apoptosis. Caspase-11 not only activates caspase-1, that is required for the maturation of proinflammatory cytokines such as interleukin (IL)-1 and IL-18, but also activates caspase-3, leading to cellular apoptosis under pathological conditions. The expression of caspase-11 is strongly induced at both mRNA and protein levels by inflammatory stimuli such as lipopolysaccharide, interferon-Q Q, and tumor necrosis factor-K K in C6 rat glial cells as well as primary astrocytes. Induction of caspase-11 by LPS in astrocytes is mediated through the p38 MAPK pathway. Inflammatory induction of caspase-11 in astrocytes may play an important role in both inflammatory responses involving these cells and auto-regulatory apoptosis of activated astrocytes in inflammatory sites
-
-
-
additional information
?
-
-
neurotoxic effects of lipopolysaccharide on nigral dopaminergic neurons are mediated by microglial activation, interleukin-1beta, and expression of caspase-11 in mice
-
-
-
additional information
?
-
-
neurotoxicity of 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine may be mediated via activation of the caspase-11 cascade and inflammatory cascade, as well as the mitochondrial apoptotic cascade
-
-
-
additional information
?
-
-
a pathway modulating inflammatory-cell migration involve caspase-11 and actin interacting protein 1
-
-
-
additional information
?
-
-
caspase-11 may be a central regulator of multiple events, including cell migration, cytokine maturation and apoptosis, during inflammation responses. Caspase-11 interacts physically and functionally with actin interacting protein 1, an activator of cofilin-mediated actin depolymerization. Caspase-11 and actin interacting protein 1 work cooperatively to promote cofilin-mediated actin depolymerization
-
-
-
additional information
?
-
-
Flightless-I regulates the subcellular distribution of caspase-11 by promoting its localization at the cell leading edge
-
-
-
additional information
?
-
-
other caspases are substrates of caspase-11
-
-
-
additional information
?
-
Mus musculus C3H/An
P70343
-
-
-
-
additional information
?
-
Mus musculus C57BL/6 X CBA
P70343
the enzyme may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE
-
-
-
additional information
?
-
Mus musculus C57B6
-
other caspases are substrates of caspase-11
-
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
wedelolactone
-
a specific inhibitor of caspase-11
Z-LEHD-fluoromethylketone
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cholera toxin B
-
a caspase-11-activating toxin
-
additional information
-
benzene, increase of caspase-4 expression after 12 days of oral benzene treatment to p53KO mice
-
additional information
-
the adaptor protein TRIF upregulates procaspase-11 expression, and this upregulation is required for caspase-11 processing and activation. Lipopolysaccharide treatment or type I IFN treatment alone does not cause caspase-11-dependent cell death
-
additional information
-
activation through dimerization. Signaling pathways involved in caspase-11 activation, overview
-
additional information
-
Bacterial infection triggers caspase-11 activation , and intracellular lipopolysaccharide triggers caspase-11 activation, Toll-like receptor 4 is dispensable for caspase-11 triggering by cytoplasmic lipopolysaccharide, mechanism, detailed overview
-
additional information
-
caspase-11 is activated by a cytosolic sensing mechanism that detects bacterial-derived signals delivered into the host cytosol through the type IV secretion apparatus. Caspase-11 activation by Legionella pneumophila has distinct kinetic and molecular parameters, overview. Caspase-11 activation requires upstream protein(s) capable of sensing a microbial or endogenous danger signal. Caspase-11 requires type I IFN production mediated by TRIF-dependent TLR signaling. And caspase-1 is dispensable for caspase-11-dependent pyroptosis induced by Legionella pneumophila
-
additional information
-
the cholera toxin B subunit and many different Gram-negative bacteria can trigger Caspase-11 activation in vitro. Cytosolic infection of cells with Burkholderia species and cytyosolic mutants of Salmonella typhimurium and Legionella pneumophila trigger the enzyme
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
-
caspase-11 is upregulated in a subpopulation of cells i brain after ischemic injury
Manually annotated by BRENDA team
Mus musculus C3H/An
-
-
-
Manually annotated by BRENDA team
Mus musculus C3H/An
-
low activity
-
Manually annotated by BRENDA team
-
caspase-11-deficient leukocytes are defective in migration
Manually annotated by BRENDA team
Mus musculus C3H/An
-
low activity
-
Manually annotated by BRENDA team
-
bone marrow-derived
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
bone marrow-derived
-
Manually annotated by BRENDA team
-
neuroblastoma cell
Manually annotated by BRENDA team
Mus musculus C3H/An
-
low activity
-
Manually annotated by BRENDA team
-
the highest expression levels of murine Casp11 gene are observed in spleens
Manually annotated by BRENDA team
Mus musculus C3H/An
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6 X CBA
-
-
-
Manually annotated by BRENDA team
additional information
no activity detected in brain
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
Flightless-I regulates the subcellular distribution of caspase-11 by promoting its localization at the cell leading edge
-
Manually annotated by BRENDA team
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
activation through dimerization
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
TRIF is required for the processing of procaspase-11 into the cleaved caspase-11 forms
proteolytic modification
-
the enzyme requires activation through proteolytic cleavage
proteolytic modification
-
procaspase-11 can autoprocess itself in vitro
proteolytic modification
-
the adaptor protein TRIF upregulates procaspase-11 expression, and this upregulation is required for caspase-11 processing and activation
proteolytic modification
-
TRIF is required for the processing of procaspase-11 into the cleaved caspase-11 forms. IFNs or lipopolyaccharides alone are not sufficient to trigger caspase-11 processing, but an unidentified factor derived from live Gram-negative bacteria is required, which is likely a mechanism to ensure that inflammatory responses do not proceed in the absence of active infection
proteolytic modification
-
the enzyme requires activation through proteolytic cleavage
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
gene Casp11
-
gene CASP11, overexpression of FLAG-tagged enzyme in HEK-293T cells, co-expression with HA-tagged cationic channel subunit transient receptor potential channel 1, i.e. TRPC1, subunits p10 and p20 of caspase-11, but not caspase recruitment domain (CARD) alone, is co-immunoprecipitated with TRPC1. FLAG-tagged caspase-11 is able to co-immunoprecipitate independently with HA-tagged TRPC1 N-terminal alone, the N-terminal domain with the transmembrane domain, and the transmembrane domain with the C-terminal domain, but not with the central transmembrane domain alone
-
overexpression in Rat-1 and HeLa cells induces apoptosis
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
poly(ADP-ribose) polymerase-1, PARP-1, regulates the expression of caspase-11 following lipopolysaccharide stimulation. PARP-1 is recruited to the caspase-11 promoter region containing predicted nuclear factor (NF)-kappaB-binding sites, but PARP-1 enzymatic activity is not required for the caspase-11 upregulation. PARP-1 can regulate the induction of caspase-11 at a transcriptional level. PARP-1 participates in the activation of caspase-11 promoter as a coactivator of NF-kappaB
-
induction of caspase-11 is dependent on NF-kappaB. PARP-1 participates in the activation of caspase-11 promoter as a coactivator of NF-kappaB. Lipopolysaccharide induce the enzyme expression
-
Lipopolysaccharide treatment or type I IFN treatment alone does not cause caspase-11-dependent cell death
-
induction of procaspase-11 expression is delayed in Myd88-/- macrophages infected with DELTAFlag Salmonella typhimurium, although procaspase-11 processing itself remains intact
-
type I IFN signaling is sufficient to induce caspase-11 upregulation and processing. The adaptor protein TRIF upregulates procaspase-11 expression, and this upregulation is required for caspase-11 processing and activation
-
bacterial lipopolysaccharide stimulation of caspase-11 expression in several mouse tissues, particularly in the spleen
-
cytosolic infection of cells with Burkholderia species and cytyosolic mutants of Salmonella typhimurium and Legionella pneumophila trigger the enzyme
-
cytosolic infection of cells with Burkholderia species and cytyosolic mutants of Salmonella typhimurium and Legionella pneumophila trigger the enzyme
Mus musculus C57BL/6
-
-
ischemia induces expression in astrocytes
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
enzyme downregulation by siRNA
additional information
-
targeting Casp11 exon 5 for deletion in C57BL/6 embryonic stem cells. Strain 129 mice, like Casp11-/- mutant mice, exhibits defects in IL-1beta production and harbours a mutation in the Casp11 locus that attenuates caspase-11 expression
additional information
-
all Casp1-/- mice also lack caspase-11, due to the generation of the Casp1-/- line in the 129 mouse strain background, which express a mis-spliced and truncated version of the Casp11 messenger RNA
additional information
-
recombination and segregation of the nonfunctional Casp11 gene away from the Casp1-/- locus is nearly impossible because Casp1 and Casp11 occur only about 1500 bp apart on chromosome 9 in mice
additional information
-
all Casp1-/- mouse strains generated from 129 embryonic stem cells also lack caspase-11 due to a 5-bp deletion in the caspase-11 locus that causes loss of the catalytic domain. As the caspase-11 and caspase-1 loci are located physically close together, the mutations do not segregate during backcrossing, leading to double mutant mice
additional information
-
generation of Casp11-/- knockout mice, overview. The common mouse knockout strategy is to inject genetically targeted 129-derived ES cells into host C57BL/6 blastocysts and then backcross the chimera with other strains, commonly C57BL/6, for over 10 generations
additional information
-
generation of Casp11-/- mice, all existing caspase-1 deficient mice also lack Caspase-11 due to the backcrossing of a mutant Casp11 allele from 129 into C57BL/6 mice
additional information
Mus musculus C57BL/6
-
generation of Casp11-/- mice, all existing caspase-1 deficient mice also lack Caspase-11 due to the backcrossing of a mutant Casp11 allele from 129 into C57BL/6 mice; targeting Casp11 exon 5 for deletion in C57BL/6 embryonic stem cells. Strain 129 mice, like Casp11-/- mutant mice, exhibits defects in IL-1beta production and harbours a mutation in the Casp11 locus that attenuates caspase-11 expression
-
additional information
-
enzyme downregulation by siRNA and shRNA sequence targeting caspase-11
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
caspase-11 has a regulatory role in ethanol-induced apoptosis. Suppression of caspase-11 may be a mechanism by which Scutellariae radix (Chineses herbal medicine) exerts its cytoprotective effect