Information on EC 3.4.22.62 - caspase-9

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The expected taxonomic range for this enzyme is: Euteleostomi

EC NUMBER
COMMENTARY hide
3.4.22.62
-
RECOMMENDED NAME
GeneOntology No.
caspase-9
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
strict requirement for an Asp residue at position P1 and with a marked preference for His at position P2. It has a preferred cleavage sequence of Leu-Gly-His-Asp-/-Xaa
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
180189-96-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
gene CSP9
-
-
Manually annotated by BRENDA team
gene Lyccasp9
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6J
-
-
-
Manually annotated by BRENDA team
Wistar
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Ac-LEDH-4-nitroanilide + H2O
Ac-LEDH + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-Asp-Glu-Val-Asp-p-nitroanilide + H2O
acetyl-Asp-Glu-Val-Asp + p-nitroanilide
show the reaction diagram
-
i.e. Ac-DEVD-pNA, caspase-9/-3 activation in differentiated cells can be prevented by protein kinase C (PKC) and the mitogen activated protein kinase (MEK) signaling pathways
-
-
?
acetyl-DEVD-7-amido-4-methylcoumarin + H2O
acetyl-DEVD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
acetyl-DEVD-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-DEVD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
acetyl-Ile-Glu-Thr-Asp-p-nitroanilide + H2O
acetyl-Ile-Glu-Thr-Asp + p-nitroaniline
show the reaction diagram
-
13% of the activity with acetyl-Leu-Glu-His-Asp-p-nitroanilide
-
-
?
acetyl-LEHD-7-amido-4-trifluoromethyl coumarin + H2O
acetyl-LEHD + 7-amino-4-trifluoromethyl coumarin
show the reaction diagram
acetyl-LEHD-7-amido-4-trifluoromethylcoumarin + H2O
acetyl-LEHD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
acetyl-Leu-Glu-His-Asp-p-nitroanilide + H2O
acetyl-Leu-Glu-His-Asp + p-nitroaniline
show the reaction diagram
acetyl-Trp-Glu-His-Asp-p-nitroanilide + H2O
acetyl-Trp-Glu-His-Asp + p-nitroaniline
show the reaction diagram
-
49% of the activity with acetyl-Leu-Glu-His-Asp-p-nitroanilide
-
-
?
acetyl-Val-Glu-Ile-Asp-p-nitroanilide + H2O
acetyl-Val-Glu-Ile-Asp + p-nitroaniline
show the reaction diagram
-
19% of the activity with acetyl-Leu-Glu-His-Asp-p-nitroanilide
-
-
?
acetyl-VEHD-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
Bcl-2 + H2O
?
show the reaction diagram
-
-
-
-
?
BclxL + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Leu-Glu-His-Asp-7-amido-4-trifluoromethylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Leu-Glu-His-Asp-7-amino-4-trifluoromethylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
inactive Bid + H2O
active tBid + ?
show the reaction diagram
inactive procaspase-7 variant C186A + H2O
active caspase-7 variant C186A + ?
show the reaction diagram
-
-
-
-
?
L-histidine decarboxylase precursor + H2O
?
show the reaction diagram
LEDH-4-nitroanilide + H2O
LEDH + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
LEHD-7-amido-4-methylcoumarin + H2O
LEHD + 7-amino-4-methylcoumarin
show the reaction diagram
N-acetyl-LEHD-4-trifluoromethylcoumarin 7-amide + H2O
N-acetyl-LEHD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
N-acetyl-Leu-Glu-His-Asp-7-amido-4-fluorocoumarin + H2O
N-acetyl-Leu-Glu-His-Asp + 7-amino-4-fluorocoumarin
show the reaction diagram
-
-
-
-
?
poly (ADP-ribose) polymerase + H2O
?
show the reaction diagram
-
i.e. PARP
-
-
?
poly(ADP-ribose) polymerase + H2O
?
show the reaction diagram
-
-
-
?
pro-caspase-2L + H2O
caspase-2L + ?
show the reaction diagram
pro-caspase-3 + H2O
?
show the reaction diagram
pro-caspase-3 + H2O
active caspase-3 + caspase-3 propeptide
show the reaction diagram
-
-
-
-
?
pro-caspase-3 + H2O
caspase-3
show the reaction diagram
-
modification at Ser196 results in alterations of proteolytic cleavage of procaspase-9 and caspase-9 activity
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
pro-caspase-3 + H2O
caspase-3 + caspase-3 propeptide
show the reaction diagram
-
-
-
-
?
pro-caspase-7 + H2O
caspase-7 + ?
show the reaction diagram
pro-caspase-9 + H2O
caspase-9
show the reaction diagram
-
modification at Ser196 results in alterations of proteolytic cleavage of procaspase-9 and caspase-9 activity
-
-
?
pro-caspase-9 + H2O
caspase-9 + ?
show the reaction diagram
-
auto-processing, apoptosis induced by tumor necrosis factor (TNF)-alpha promotes dephosphorylation of caspase-9 by casein kinase 2 (CK2), phosphorylation by casein kinase 2 decreases susceptibility of caspase-9 to cleavage by active caspase-8
-
-
?
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
-
?
procaspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
-
?
retinoblastoma protein Rb + H2O
p76Rb + ?
show the reaction diagram
-
caspase-9 interferes, upstream of the mitochondrion, with P53-induced apoptosis in both immortalized and primary fibroblasts. The involvement of caspase-9 in a premitochondrial protective pathway results from the cleavage of retinoblastoma protein Rb (tumor suppressor), at a LExD site, into a p76Rb form, which antagonizes p53-induced apoptosis
-
-
?
additional information
?
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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
Bcl-2 + H2O
?
show the reaction diagram
-
-
-
-
?
BclxL + H2O
?
show the reaction diagram
-
-
-
-
?
inactive Bid + H2O
active tBid + ?
show the reaction diagram
-
cleavage at amino acid 59
-
-
?
inactive procaspase-7 variant C186A + H2O
active caspase-7 variant C186A + ?
show the reaction diagram
-
-
-
-
?
L-histidine decarboxylase precursor + H2O
?
show the reaction diagram
poly (ADP-ribose) polymerase + H2O
?
show the reaction diagram
-
i.e. PARP
-
-
?
pro-caspase-2L + H2O
caspase-2L + ?
show the reaction diagram
Q9R0T0
mechanisms of apoptotic pathways controlling fragmentation of unfertilized ovulated oocyte, caspase-3 and caspase-2L (long isoform) transcripts and proteins present in oocytes during ealy stages of meiosis, zymogen and cleaved forms
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
pro-caspase-3 + H2O
active caspase-3 + caspase-3 propeptide
show the reaction diagram
-
-
-
-
?
pro-caspase-3 + H2O
caspase-3
show the reaction diagram
-
modification at Ser196 results in alterations of proteolytic cleavage of procaspase-9 and caspase-9 activity
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
pro-caspase-3 + H2O
caspase-3 + caspase-3 propeptide
show the reaction diagram
-
-
-
-
?
pro-caspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
mechanisms of cordycepin-induced apoptosis, activation of caspase-9, caspase-3 and caspase-7
-
-
?
pro-caspase-9 + H2O
caspase-9
show the reaction diagram
-
modification at Ser196 results in alterations of proteolytic cleavage of procaspase-9 and caspase-9 activity
-
-
?
pro-caspase-9 + H2O
caspase-9 + ?
show the reaction diagram
-
auto-processing, apoptosis induced by tumor necrosis factor (TNF)-alpha promotes dephosphorylation of caspase-9 by casein kinase 2 (CK2), phosphorylation by casein kinase 2 decreases susceptibility of caspase-9 to cleavage by active caspase-8
-
-
?
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
-
?
procaspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
-
?
retinoblastoma protein Rb + H2O
p76Rb + ?
show the reaction diagram
-
caspase-9 interferes, upstream of the mitochondrion, with P53-induced apoptosis in both immortalized and primary fibroblasts. The involvement of caspase-9 in a premitochondrial protective pathway results from the cleavage of retinoblastoma protein Rb (tumor suppressor), at a LExD site, into a p76Rb form, which antagonizes p53-induced apoptosis
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
slight activation
NaF
-
NaF-induced apoptosis of osteoblasts
Pb2+
-
slight activation
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(3S,6S,10aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide
-
-
(3S,6S,8aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxooctahydroindolizine-3-carboxamide
-
-
(3S,6S,9aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepine-3-carboxamide
-
-
acetyl-AEVD-CHO
-
-
acetyl-DEVD-CHO
-
-
acetyl-DVAD fluoromethyl ketone
-
prediction of the tertiary structure of a caspase-9/inhibitor complex
acetyl-IETD-CHO
-
-
acetyl-WEHD-CHO
-
-
acetyl-YVAD-CHO
-
-
ATP
-
enzyme activity is inhibited in both normoxic and hypoxic groups. The IC50 increases 5fold following hypoxia, suggesting a hypoxia-induced modification of the ATP binding site. 70% inhibition by 1 mM
benzyloxycarbonyl-Ile-Glu-Thr-Asp-fluoromethylketone
-
-
benzyloxycarbonyl-LEHD-fluoromethylketone
benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone
benzyloxycarbonyl-VAD-fluoromethylketone
benzyloxycarbonyl-VAE-fluoromethylketone
-
-
benzyloxycarbonyl-Val-Asp-Val-Ala-Asp-fluoromethylketone
-
-
biotin-Val-Ala-Asp-fluoromethyl ketone
-
i.e. biotin-VAD-fmk, presence or absence of 50 microM inhibitor, caspase-9 activation analyzed by affinity labelling and immunoblotting
cadmium
-
anti-apoptotic cell survival function of cadmium, cadmium inhibits apoptosis induced by benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) at non-cytotoxic concentrations, 40% and 52% inhibition at 10 and 20 microM cadmium chloride, respectively
caspase-9S
-
transfection of renal epithelial cells with the dominant-negative inhibitor caspase-9S
-
cowpox serpin CrmA
-
the Ki-value is below 2.3 nM
-
cytochrome c
-
enzyme activity is inhibited in both normoxic and hypoxic groups. The IC50 increases 1.5fold following hypoxia, suggesting a hypoxia-induced modification of the cytochrome binding site. 70% inhibition by 0.003 mM
L-alanyl-L-valyl-L-prolyl-L-isoleucinamide
-
-
Mn2+
-
slight inhibition
N-(2-amino-2-oxoethyl)-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-N-[2-(2-fluorophenyl)ethyl]-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h, 51% inhibition of caspase-3 activity in SAOS-2 cells
N-(2-amino-2-oxoethyl)-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-N-[2-(2-methoxyphenyl)ethyl]-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h, 1% inhibition of caspase-3 activity in SAOS-2 cells
N-(2-amino-2-oxoethyl)-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-N-[2-(4-fluorophenyl)ethyl]-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72, 34% inhibition of caspase-3 activity in SAOS-2 cells
N-(2-amino-2-oxoethyl)-N-(2-cyclopropylethyl)-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h, 16% inhibition of caspase-3 activity in SAOS-2 cells
N-(2-amino-2-oxoethyl)-N-butyl-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h for caspase activity assay, 45% inhibition of caspase-3 activity in SAOS-2 cells
N-(2-amino-2-oxoethyl)-N-[2-(4-chlorophenyl)ethyl]-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h, 2% inhibition of caspase-3 activity in SAOS-2 cells
N-benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone
-
i.e. Z-VAD-FMK, treatment with 100 microM caspase inhibitor in combination with 100 microM cordycepin for 24 h suppresses sub-G1 phase in MA-10 cells
N-Fmoc-S-2-(2'-octyl)alanine
-
-
-
N-Fmoc-S-2-(2'-pentyl)alanine
-
-
-
N-[2-(acetylamino)ethyl]-N-(2-amino-2-oxoethyl)-1-[2-(2,4-dichlorophenyl)ethyl]-4-(3,3-diphenylpropyl)-3,7-dioxo-1,4-diazepane-5-carboxamide
-
5 microM for cell treatment, cells harvested after 24, 48, and 72 h, 22% inhibition of caspase-3 activity in SAOS-2 cells
NO32-
-
slight inhibition
-
Pen-1-XBIR3
-
caspase-9 is inhibited by unilateral intravitreal injection of highly specific X-linked inhibitor of apoptosis (IAP) baculoviral IAP repeat 3 (XBIR3) domain linked to the cell transduction peptide penetratin 1 (Pen-1) after ballistic injury
-
Q-VD-OPH
-
i.e. (3S)-5-(2,6-difluorophenoxy)-3-[[(2S)-2-(isoquinoline-3-carbonylamino)-3-methylbutanoyl]amino]-4-oxopentanoic acid, cell treatment with the broad-spectrum caspase inhibitor Q-VD-OPH (concentration 30 microM) prior to induction of differentiation
RQIKIWFQNRRMKWKKGG-N-[2-(2,4-dichlorophenyl)ethyl]glycyl-N-(3,3-diphenylpropyl)glycyl-N2-[2-(2,4-dichlorophenyl)ethyl]glycinamide
-
i.e. PEN-1, modified compound with peptide bridge, 5 microM for cell treatment, shows low inhibitory activity of caspase-3
XIAP
-
can antagonise caspase-9 activity and stabilises its interaction with the apoptosome. Caspase-3 cleaves XIAP into fragments that retain their inhibitory potential towards caspases-3 or -9, thereby eliminating sterical hindrance that may prevent parallel inhibition of caspases-3 and -9 by XIAP
-
XIAP-BIR3
-
a natural caspase-9 inhibitor that binds at the dimer interface keeping the enzyme in an inactive monomeric state, binding to the enzyme involves the alpha5 helix of XIAP-BIR3
-
Z-IETD-fluoromethylketone
-
a caspase-8 specific inhibitor, delays the activation of caspase-3 and caspase-9 significantly
Z-LEHD-fluoromethylketone
Z-VAD-fluoromethylketone
-
a pan-caspase inhibitor
Zn2+
-
mixed-tpe inhibition, kinetics and mechanism of zinc-mediated inhibition of caspase-9, overview. Two distinct zinc-binding sites on caspase-9, the first site, composed of H237, C239, and C287, includes the active site dyad and is primarily responsible for zinc-mediated inhibition. The second binding site at C272 is distal from the active site. EDTA can hinder enzyme inhibition by Zn2+. Zinc-mediated inhibition does not influence the overall structure of caspase-9 monomers. Each wild-type caspase-9 monomer binds two zinc ions. Caspase-9 variants in which the active-site residues are replaced, C287A or H237A, bind just one zinc
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2S)-1-([2-[(2S)-2-aminopropanoyl]-1-(prop-2-en-1-yl)hydrazinyl]carbonyl)-N-(diphenylmethyl)pyrrolidine-2-carboxamide (non-preferred name)
-
-
(2S)-1-([2-[(2S)-2-aminopropanoyl]-1-(prop-2-yn-1-yl)hydrazinyl]carbonyl)-N-(diphenylmethyl)pyrrolidine-2-carboxamide (non-preferred name)
-
-
(2S)-1-([2-[(2S)-2-aminopropanoyl]-1-benzylhydrazinyl]carbonyl)-N-(diphenylmethyl)pyrrolidine-2-carboxamide (non-preferred name)
-
-
(2S)-1-([2-[(2S)-2-aminopropanoyl]-1-methylhydrazinyl]carbonyl)-N-(diphenylmethyl)pyrrolidine-2-carboxamide (non-preferred name)
-
-
(2S)-1-([2-[(2S)-2-aminopropanoyl]hydrazinyl]carbonyl)-N-(diphenylmethyl)pyrrolidine-2-carboxamide (non-preferred name)
-
-
adenosine
-
extracellular adenosine induces apoptosis by activating caspase-9 and caspase-3 in association with mitochondrial damage via A2a adenosine receptors, induction dose-dependent (1-20 mM) and time-dependent (24-72 h)
APAF-1
apoptosome
-
activates caspase-9 by dimerization
-
cordycepin
-
i.e. 3'-deoxyadenosine, cells treated with 100 mM and 1 mM for 24 h, expression of caspase-9, Western blot analysis
NO
-
NO generated during hypoxia leads to activation of caspase-9 and results in initiation of caspase-cascade-dependent hypoxic neuronal death
staurosporine
-
initiates apoptosis, 25% of the cells are apoptotic in staurosporine-treated cultures, 1 microM for 4 h, used as a positive control for caspase-9 activation in C2C12 cells, mitochondrial changes in apoptotic but not in differentiating cells
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.466 - 0.686
acetyl-LEHD-7-amido-4-trifluoromethyl coumarin
0.686
acetyl-LEHD-7-amido-4-trifluoromethylcoumarin
-
caspase-9 holoenzyme
0.408 - 0.78
acetyl-VEHD-7-amido-4-methylcoumarin
0.139
procaspase-3
-
caspase-9 holoenzyme
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1 - 0.2
acetyl-VEHD-7-amido-4-methylcoumarin
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000014
(3S,6S,10aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamide
-
pH and temperature not specified in the publication
0.00233
(3S,6S,8aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxooctahydroindolizine-3-carboxamide
-
pH and temperature not specified in the publication
0.00006
(3S,6S,9aS)-6-(L-alanylamino)-N-(diphenylmethyl)-5-oxooctahydro-1H-pyrrolo[1,2-a]azepine-3-carboxamide
-
pH and temperature not specified in the publication
0.000048
acetyl-AEVD-CHO
-
pH 7.5, 25C
0.00006
acetyl-DEVD-CHO
-
pH 7.5, 25C
0.000108
acetyl-IETD-CHO
-
pH 7.5, 25C
0.000508
acetyl-WEHD-CHO
-
pH 7.5, 25C
0.00097
acetyl-YVAD-CHO
-
pH 7.5, 25C
0.0171
benzyloxycarbonyl-VAD-fluoromethylketone
-
-
0.0142
benzyloxycarbonyl-VAE-fluoromethylketone
-
-
0.00058
L-alanyl-L-valyl-L-prolyl-L-isoleucinamide
-
pH and temperature not specified in the publication
0.0002 - 0.0018
Zn2+
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2
-
mutant DELTA1-111
6.5 - 7
-
reaction with acetyl-VEHD-7-amido-4-methylcoumarin
6.5
-
assay at
7.2
-
mutant DELTA1-111/E306A/D315A
7.5
-
caspase activity assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
10C9
Manually annotated by BRENDA team
-
high expression level
Manually annotated by BRENDA team
-
caspase-9 is highly expressed in tadpole brain during metamorphosis. Caspase-9 mRNA is expressed mainly in the ventricular area, a site of neuroblast proliferation. Caspase-9, a key members of the mitochondrial death pathway, is implicated in controlling the proliferative status of neuroblasts in the metamorphosing Xenopus brain. Modification of the expression during the critical period of metamorphosis alters the outcome of metamorphic neurogenesis, resulting in a modified brain phenotype in juvenile Xenopus
Manually annotated by BRENDA team
-
mouse embryonic fibroblast cell oncogenically transformed with both E1A and ras, and containing wild-type p53
Manually annotated by BRENDA team
-
mouse embryonic fibroblast cell oncogenically transformed with both E1A and ras, and containing p53-/-
Manually annotated by BRENDA team
-
hypoxic conditions
Manually annotated by BRENDA team
-
caspase-9 is released into the cerebrospinal fluid after severe traumatic brain injury
Manually annotated by BRENDA team
-
inhibition of caspase-9 enhances the viability of the CHO cells in both batch and fed-batch suspension cultures. Caspase-9 is possible involved in the apoptotic cell death in batch and fed-batch cultures of CHO cells
Manually annotated by BRENDA team
-
cochlear cell line HEI-OC1
Manually annotated by BRENDA team
-
caspase-9 mutations in the tumors are detected, the frequency of the mutations is very low and all the mutations are silent mutations that may not alter the function of the caspase protein. Caspase-9 gene mutation may not contribute to the pathogenesis of this cancer
Manually annotated by BRENDA team
-
from cecum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum. Caspase-9 mutations in the tumors are detected, the frequency of the mutations is very low and all the mutations are silent mutations that may not alter the function of the caspase protein. Caspase-9 gene mutation may not contribute to the pathogenesis of this cancer
Manually annotated by BRENDA team
-
mouse embryonic fibroblast cell oncogenically transformed with both E1A and ras, and containing p53-/-; mouse embryonic fibroblast cell oncogenically transformed with both E1A and ras, and containing wild-type p53
Manually annotated by BRENDA team
-
human fibroblast GM03349
Manually annotated by BRENDA team
-
cell line HF1A3, wild-type, dominant negative caspase-9 overexpressing
Manually annotated by BRENDA team
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cell line HF1A3, wild-type, dominant negative caspase-9 overexpressing
Manually annotated by BRENDA team
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caspase-9 mutations in the tumors are detected, the frequency of the mutations is very low and all the mutations are silent mutations that may not alter the function of the caspase protein. Caspase-9 gene mutation may not contribute to the pathogenesis of this cancer
Manually annotated by BRENDA team
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caspase-9 mutations in the tumors are detected, the frequency of the mutations is very low and all the mutations are silent mutations that may not alter the function of the caspase protein. Caspase-9 gene mutation may not contribute to the pathogenesis of this cancer
Manually annotated by BRENDA team
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gingivial cancer cells (Ca9-22 cells) containing a mutated p53 (mp53) protein by point mutation at codon 248
Manually annotated by BRENDA team
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cells treated with 10 mg/ml recombinant Vibrio vulnificus cytolysin (rVVC) at 37C for 4 h, cell viability assay
Manually annotated by BRENDA team
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isolated from 5-week-old female C57BL/6 mice, intraperitoneal injection of isorhamnetin (0.1 or 0.5 mg/kg) four days after tumor inoculation
Manually annotated by BRENDA team
-
caspase-9 mutations in the tumors are detected, the frequency of the mutations is very low and all the mutations are silent mutations that may not alter the function of the caspase protein. Caspase-9 gene mutation may not contribute to the pathogenesis of this cancer
Manually annotated by BRENDA team
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increased caspase 9 activity in lymphoblasts with heterozygous and homozygous Huntington's disease mutation; increased caspase-9 activity in lymphoblasts with heterozygous and homozygous Huntington's disease mutation
Manually annotated by BRENDA team
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intact protein p53
Manually annotated by BRENDA team
-
human H460 NSCLC cells with and without cytochrome c/(d)ATP-induced activation of apoptosis
Manually annotated by BRENDA team
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wild-type and SOD-antisense
Manually annotated by BRENDA team
-
incubated with 0.5-30 mg/l of sodium fluoride (NaF)
Manually annotated by BRENDA team
caspase-9 genotyping
Manually annotated by BRENDA team
-
FL5.12
Manually annotated by BRENDA team
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caspase-9, which is activated by infection with virulent Mycobacterium tuberculosis, contributes to the inhibition of necrosis of the infected host cells, through suppression of generation of intracellular reactive oxygen species
Manually annotated by BRENDA team
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treated with doxycycline (2 microg/ml in PBS)
Manually annotated by BRENDA team
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cells treated with 10 mg/ml recombinant Vibrio vulnificus cytolysin (rVVC) at 37C for 4 h, cell viability assay
Manually annotated by BRENDA team
-
cells treated with 10 mg/ml recombinant Vibrio vulnificus cytolysin (rVVC) at 37C for 4 h, cell viability assay
Manually annotated by BRENDA team
B6 mice, modified by retroviral transduction
Manually annotated by BRENDA team
retroviral transduction of
Manually annotated by BRENDA team
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ischemia-reperfusion of the testis results in germ-cell-specific apoptosis and a reduction in daily sperm production. Oxidative stress products accumulate in the testis following ischemia-reperfusion and demonstrate that the observed germ-cell-specific apoptosis is stimulated through a mitochondrial caspase-9-dependent pathway
Manually annotated by BRENDA team
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treated with different concentrations of marine sponge extracts of Polymastia janeirensis
Manually annotated by BRENDA team
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treated with doxorubicin (2, 2.5, and 0.25 microg/ml in PBS), doxorubicin-induced cell death
Manually annotated by BRENDA team
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no difference in caspase-9 activity in oocytes compared with zygotes
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
immunohistochemic expression analysis, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35000
-
processed caspase-9 protein, SDS-PAGE
37000
-
processed caspase-9 protein, SDS-PAGE
47000
-
un-processed caspase-9 protein, SDS-PAGE
52000
-
pro-caspase-9, Western blot, increased in hypoxic animals
55000
-
full-length caspase-9, Western blot analysis
68000
-
observed molecular weight of caspase-9 by tandem mass spectrometry in cell lysates with and without cytochrome c/dATP treatment
69200
-
calculated molecular weight of caspase-9 by tandem mass spectrometry in cell lysates with and without cytochrome c/dATP treatment
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
-
gel filtration and SDS-PAGE, caspases are functional as homodimers of monomeric units that comprise an N-terminal prodomain and a catalytic large and small subunit connected by an intersubunit linker. The zymogen (uncleaved) caspase-9 as a monomer has very low activity, which is increased upon dimerization
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
nitrosylation
-
nitrosylation of caspase-9 at C163 is dependent, at least in part, on subcellular localization. 68% of the procaspase-9 in mitochondria is nitrosylated and 11% of the procaspase-9 in the cytoplasm in unstimulated 10C9 human B cells
phosphoprotein
proteolytic modification
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
gel filtration
-
gel filtration, SDS-PAGE
-
gel filtration, SDS-PAGE, recombinant protein
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recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain B21(DE3) inclusion bodies by solubilization with guanidine hydrochloride and dialysis, followed by nickel affinity and anion exchange chromatography
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recombinant His6-tagged enzyme
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recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
adenovirus expression, AdshRNA-C9 and AdshRNA-eGFP vectors, AdBcl-xL and AdNull adenoviral vectors
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B6 splenocytes modified by retroviral transduction, truncated caspase-9 molecule genetically coupled to a modified human FK506-binding protein (FKBPF36V) by generating the iCasp9M-construct, iCasp9M construct (safety switch) and enhanced GFP used for transformation
caspase-9 inactivated by mutation at the catalytic domain, generation of dominant negative caspase-9 overexpressing cell lines, expression in Escherichia coli, follicular lymphoma cells transformed with the lentiviral vector pWPI-IRES-GFP
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caspase-9 splice variant Casp9-gamma contains only a caspase recruitment domain and lacks the catalytic domain, expression in 293T cells.Casp9-gamma does not promote apoptosis when overexpressed in 293T cells
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caspase-9S is cloned from human liver cDNA
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expressed in Escherichia coli
expressed in Escherichia coli, pcmyc vector, pFLAG-CTC vector to generate FLAG-tagged caspase-9 construct
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expressed in Escherichia coli, recombinant protein, pcDNA3, pET28a, pEGFP vectors
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expression in Escherichia coli
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expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain B21(DE3) in incusion bodies
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gene CSP9, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression in Escherichia coli strain BL21(DE3)
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gene Lyccasp9, DNA and maino acid sequence determination and analysis, full-length cDNA of Lyccasp9 is 2595 bp with an open reading frame of 1314 bp encoding a polypeptide of 437 amino acids, which includes a 90-amino acids caspase recruitment domain (CARD, residues 1-90), a 133-amino acids p20 domain (residues 171-303) with two putative caspase family histidine and cysteine active sites, as well as an 87-amino acids p10 domain (residues 348-435)
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human caspase-9 (wild type or mutant R10A) are subcloned into the pIND expression plasmid before cotransfection of recombinant pIND and pVgRXR into U2OS cells
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naturally occuring variant caspase-9S, that is missing most of the large subunit of caspase-9
-
recombinant expression of His6-tagged holoenzyme in Escherichia coli strain BL21(DE3), recombinantindividual expression of large and small subunits in inclusion bodies
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
cadmium induces the enzyme
-
siRNA Si Casp-9-1 efficiently inhibits caspase-9 expression
-
trichothecin induces apoptosis of HepG2 cells via caspase-9 mediated activation of the mitochondrial death pathway, molecular mechanism, overview
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
optical sensor for the detection of caspase-9 in a single cell. LEHD-7-amido-4-methylcoumarin covalently attached on the nanoprobe tip of the optical sensor is cleaved during apoptosis by caspase-9 generating free 7-amino-4-methylcoumarin
C172A
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the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C239S
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the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C272A
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the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C272A/C287A
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the mutant enzyme shows highly reduced zinc binding compared to the wild-type enzyme
C287A/C239S
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the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C403S
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point mutation at C403 of caspase-9 impairs its activation mediated by H2O2, interaction with APAF-1 diminished through the abolition of disulfide formation, weaker association between cytochrome c and the C403S mutant than that between cytochrome c and wild-type caspase-9
DELTA1-111
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a truncated form of procaspase-9 missing the first 111 amino acids, and a variety of mutants derived therefrom are expressed in Echerichia coli inclusion bodies. Upon refolding to active enzyme, DELTA1-111 procaspase-9 and mutants are recovered at purity greater than 95% with a final yield of 20-35 mg/L cell culture. the active procaspaseretains its prosegment, while undergoing major auto processing at ASp315 and a minor cleavage at Glu306
DELTA1-111/DELTAA316-D330
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activity with acetyl-LEHD-7-amido-4-trifluoromethyl coumarin is 6fold higher than the activity of mutant DELTA1-111; activity with acetyl-LEHD-7-amido-4-trifluoromethylcoumarin is 6fold higher than the activity of mutant DELTA1-111
DELTA1-111/E306A/D315A
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E306A/D315A mutation blocks autoprocessing and shifts pH optimum from pH 6.2 for DELTA1-111 to pH 7.2. Activity with acetyl-LEHD-7-amido-4-trifluoromethyl coumarin is identical to the activity of mutant DELTA1-111
DELTA1-111/E306D/D315A
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activity with acetyl-LEHD-7-amido-4-trifluoromethyl coumarin is 90% of the activity of mutant DELTA1-111; activity with acetyl-LEHD-7-amido-4-trifluoromethylcoumarin is 90% of the activity of mutant DELTA1-111
DELTA1-111/E306D/DELTAA316-D330
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activity with acetyl-LEHD-7-amido-4-trifluoromethyl coumarin is 7.6fold higher than the activity of mutant DELTA1-111; activity with acetyl-LEHD-7-amido-4-trifluoromethylcoumarin is 7.6fold higher than the activity of mutant DELTA1-111
H237A
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the active site mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
T125A/C287A
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site-directed mutagenesis, immunofluorescence staining of cells transiently transfected with vectors encoding caspase-9 double mutant
C299G
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site-directed mutagenesis, the mutant displays significantly decreased proteolytic activity compared to the wild-type enzyme
H249D
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site-directed mutagenesis, the mutant displays significantly decreased proteolytic activity compared to the wild-type enzyme
L228V
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site-directed mutagenesis
S348A
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introduction of point mutants into full-length murine caspase-9 (mC-9) cDNA, generated by a two-step PCR method, efficiently cleaved by the active initiator caspase
S348G
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introduction of point mutants into full-length murine caspase-9 (mC-9) cDNA, generated by a two-step PCR method, efficiently cleaved by the active initiator caspase
S348V
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introduction of point mutants into full-length murine caspase-9 (mC-9) cDNA, generated by a two-step PCR method, efficiently cleaved by the active initiator caspase
S350A
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introduction of point mutants into full-length murine caspase-9 (mC-9) cDNA, generated by a two-step PCR method, efficiently cleaved by the active initiator caspase
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain B21(DE3) incusion bodies by solubilization with guanidine hydrochloride and dialysis
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
pharmacology