Information on EC 3.4.22.57 - caspase-4

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The expected taxonomic range for this enzyme is: Euarchontoglires

EC NUMBER
COMMENTARY hide
3.4.22.57
-
RECOMMENDED NAME
GeneOntology No.
caspase-4
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
strict requirement for Asp at the P1 position. It has a preferred cleavage sequence of Tyr-Val-Ala-Asp-/- but also cleaves at Asp-Glu-Val-Asp-/-
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
182762-08-9
-
216503-96-7
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6 X CBA
strain C57BL/6 X CBA
SwissProt
Manually annotated by BRENDA team
no activity in Mus musculus
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
physiological function
additional information
-
elevated caspase activity in Pt1 cells is an outcome of increased caspase-4 activation
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Ac-Leu-Glu-Val-Asp-7-amido-4-trifluoro methylcoumarin + H2O
7-amino-4-trifluoromethylcoumarin + Ac-Leu-Glu-Val-Asp
show the reaction diagram
-
10 microM, 2 h, 37C, reaction stopped with HCl
-
-
?
acetyl-DEVD-4-nitroanilide + H2O
acetyl-DEVD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-DQMD-4-nitroanilide + H2O
acetyl-DQMD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-LEVDGW-amide + H2O
?
show the reaction diagram
-
preferred peptide substrate
-
-
?
acetyl-VEID-4-nitroanilide + H2O
acetyl-VEID + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-VQVD-4-nitroanilide + H2O
acetyl-VQVD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-WEHD-7-amido-4-methylcoumarin + H2O
acetyl-WEHD + 7-amino-4-methylcoumarin
show the reaction diagram
-
WEHD is the optimal tetrapeptide recognition motif
-
-
?
acetyl-YEVD-4-nitroanilide + H2O
acetyl-YEVD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-YVAD-4-nitroanilide + H2O
acetyl-YVAD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-YVAD-amido-4-methylcoumarin + H2O
acetyl-YVAD + amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
cowpox serpin CrmA + H2O
?
show the reaction diagram
-
-
-
-
?
LEVD-7-amido-4-trifluoromethylcoumarin + H2O
LEVD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
p35 + H2O
?
show the reaction diagram
-
-
-
-
?
poly(ADP-ribose)polymerase + H2O
?
show the reaction diagram
-
-
-
-
?
pro-caspase-3 + H2O
p12 + pro-p17
show the reaction diagram
-
-
-
?
procaspase-1 + H2O
caspase-1 + ?
show the reaction diagram
procaspase-9 + H2O
caspase-9 + ?
show the reaction diagram
succinyl-YVAD-4-nitroanilide + H2O
succinyl-YVAD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
succinyl-YVAD-amido-4-methylcoumarin + H2O
succinyl-YVAD + amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
LEVD-7-amido-4-trifluoromethylcoumarin + H2O
LEVD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
procaspase-1 + H2O
caspase-1 + ?
show the reaction diagram
procaspase-9 + H2O
caspase-9 + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-AEVD-aldehyde
-
-
acetyl-DEVD-aldehyde
-
-
acetyl-IETD-aldehyde
-
-
acetyl-WEHD-aldehyde
-
-
acetyl-YVAD-aldehyde
-
-
acetyl-YVD-aldehyde
-
IC50: 748 nM
benzyloxycarbonyl-VAD-fluoromethylketone
-
-
cowpox serpin CrmA
iodoacetamide
-
-
iodoacetic acid
-
-
LEVD-CHO
-
a caspase-4 inhibitor, suppresses both the apoptosis and caspase-9 activation
N-acetyl-LEVD-CHO
-
-
-
N-tert-butyloxycarbonyl-AEVD-aldehyde
-
-
N-tert-butyloxycarbonyl-IETD-aldehyde
-
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Z-LEVD-fluoromethylketone
-
caspase-4, -5, and -1 inhibitor
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
hepatocyte growth factor
-
-
-
interleukin 6
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-
Leukemia inhibitory factor
-
-
-
tunicamycin
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activates caspase-4. Activation of caspase-4 preceeds that of caspase-9
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.032
acetyl-DEVD-4-nitroanilide
-
pH 7.5, 30C
0.35
acetyl-DQMD-4-nitroanilide
-
pH 7.5, 30C
0.044
acetyl-LEVD-4-nitroanilide
-
pH 7.5, 30C
0.43
acetyl-LEVDGW-amide
-
pH 7.5, 30C
0.681
acetyl-Tyr-Val-Ala-Asp-4-nitroanilide
-
pH 7.0, 30C
0.205
acetyl-VEID-4-nitroanilide
-
pH 7.5, 30C
0.72
acetyl-VQVD-4-nitroanilide
-
pH 7.5, 30C
0.031 - 0.079
acetyl-WEHD-7-amido-4-methylcoumarin
0.874
acetyl-YVAD-4-nitroanilide
-
pH 7.5, 30C
0.035
acetyl-YVAD-amido-4-methylcoumarin
-
pH 7.5
0.048 - 0.09
succinyl-YVAD-4-nitroanilide
0.09
succinyl-YVAD-7-amido-4-methylcoumarin
-
pH 7.5, 37C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.2
acetyl-WEHD 7-amido-4-methylcoumarin
Homo sapiens
-
at pH 7.0 and pH 7.5
0.5
acetyl-YVAD-amido-4-methylcoumarin
Homo sapiens
-
pH 7.5
1.07 - 1.1
succinyl-YVAD-4-nitroanilide
0.4
succinyl-YVAD-amido-4-methylcoumarin
Homo sapiens
-
pH 7.5, 37C
additional information
additional information
Homo sapiens
-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000375
acetyl-AEVD-aldehyde
-
pH 7.5, 25C
0.000132 - 0.00015
acetyl-DEVD-aldehyde
0.0004
acetyl-IETD-aldehyde
-
pH 7.5, 25C
0.000097
acetyl-WEHD-aldehyde
-
pH 7.5, 25C
0.00002 - 0.000362
acetyl-YVAD-aldehyde
0.0000011
cowpox serpin CrmA
-
pH 7.5, 25C
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000748
acetyl-YVD-aldehyde
Homo sapiens
-
IC50: 748 nM
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
reaction with acetyl-WEHD-7-amido-4-methylcoumarin
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
2 h incubation time
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
primary, activated
Manually annotated by BRENDA team
-
caspase-4 is upregulated in lymphoblastoid cells
Manually annotated by BRENDA team
-
neuroblastoma cell
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 35000, active enzyme, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged enzyme
-
recombinant T7-tagged enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Mus musculus
-
expression in baculovirus-infected insect cells as 30000 Da proteins lacking the propeptide. Automaturation into p20 and p10 subunits occurs within the cells
-
expression in Escherichia coli
-
expression in Escherichia coli; full-length clones are originally transfected into various host cells, including COS-M6, RAT-1 and HeLa
-
expression of wild-type, native caspase-4, of C-terminal Myc-tagged wild-type vcaspase-4, and of caspase-4 mutant C285A in COS-1 cells, co-expression with caspase-1
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
apoptosis-independent cell death is accompanied by increased expression of the inflammatory marker, caspase-4. Caspase-4 is upregulated in Pt1 cells and induced by interferons
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c-Rel as well as other endoplasmic reticulum stress genes directly modulate expression of caspase-4
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c-Rel is a negative regulator of caspase-4, e.g. in EBV lymphoblastoid cells
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caspase-4 protein expression is strongly induced in the lesional stratum corneum of patients suffering from psoriasis, a common chronic inflammatory disease
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enhancement of nuclear factor-kappaB activity by p65 (RelA) overexpression increases the expression of caspase-4 at both mRNA and protein levels
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mRNA expression of the pro-form of caspase-4 is up-regulated 2fold after poly-I:C stimulation
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the dominant negative form of IkappaBalpha suppresses the expression of caspase-4
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tunicamycin and thapsigargin induce caspase-4 mRNA expression and protein activation
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
knockdown expression of caspase-4 with siRNA in keratinocytes, overexpression of active caspase-4 rescues UVB-induced secretion of IL-1b by caspase-4 knockdown keratinocytes
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine