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Information on EC 3.4.22.62 - caspase-9 and Organism(s) Homo sapiens and UniProt Accession P55211

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.22 Cysteine endopeptidases
                3.4.22.62 caspase-9
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Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
UNIPROT: P55211 not found.
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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
Synonyms
caspase-9, caspase 9, casp9, casp-9, ice-lap6, casp9-gamma, apaf-3, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
casp9-gamma
APAF
-
-
-
-
Apaf-3
-
-
-
-
apoptotic protease activating factor 3
-
-
-
-
apoptotic protease Mch-6
-
-
-
-
C14.010
-
-
-
-
CASP-9
-
-
-
-
casp9
-
-
caspase 9
ICE-LAP6
-
-
-
-
ICE-like apoptotic protease 6
-
-
-
-
Mch6
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
180189-96-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-Asp-Glu-Val-Asp-p-nitroanilide + H2O
acetyl-Asp-Glu-Val-Asp + p-nitroaniline
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-trifluoromethylcoumarin + H2O
acetyl-DEVD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
apoptosome inhibitors analyzed, caspase-9 activity indirectly measured by caspase-3 assay
-
-
?
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
poly(ADP-ribose) polymerase + H2O
?
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
acetyl-DEVD-7-amido-4-methylcoumarin + H2O
acetyl-DEVD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
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-VEHD-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
Bcl-2 + H2O
?
show the reaction diagram
-
-
-
-
?
BclxL + H2O
?
show the reaction diagram
-
-
-
-
?
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
inactive procaspase-7 variant C186A + H2O
active caspase-7 variant C186A + ?
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
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
-
activated caspase-9 cleaves and activates caspase-3
-
-
?
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
-
-
-
-
?
procaspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
Bcl-2 + H2O
?
show the reaction diagram
-
-
-
-
?
BclxL + H2O
?
show the reaction diagram
-
-
-
-
?
inactive procaspase-7 variant C186A + H2O
active caspase-7 variant C186A + ?
show the reaction diagram
-
-
-
-
?
poly (ADP-ribose) polymerase + H2O
?
show the reaction diagram
-
i.e. PARP
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
-
activated caspase-9 cleaves and activates caspase-3
-
-
?
pro-caspase-3 + H2O
caspase-3 + caspase-3 propeptide
show the reaction diagram
-
-
-
-
?
procaspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Cd2+
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, cadmium chloride pre-treatment of cells significantly inhibits caspase-9 activation in a dose dependent manner, 40% and 52% inhibition at 10 and 20 microM cadmium chloride, respectively
Cd2+
-
slight activation
Co2+
-
slight activation
Pb2+
-
slight activation
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
benzyloxycarbonyl-LEHD-fluoromethylketone
benzyloxycarbonyl-Leu-Glu-His-Asp-fluoromethylketone
i.e. z-LEHD-FMK, inhibitor concentration 100 microM
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
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-[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
PGA-1
PGA-peptoid conjugate, inhibitor of apoptotic protease activating factor 1 (Apaf-1) coupled to poly-L-glutamic acid (PGA), at concentrations of 50 and 100 microM inhibition of caspase-3 activity, reaches values up to 100% at 50 microM drug after 48 h in HeLa-cells and and after 72 h in SAOS-2 cells
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
(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
-
-
benzyloxycarbonyl-VAD-fluoromethylketone
benzyloxycarbonyl-VAE-fluoromethylketone
-
-
cowpox serpin CrmA
-
the Ki-value is below 2.3 nM
-
L-alanyl-L-valyl-L-prolyl-L-isoleucinamide
-
-
Mn2+
-
slight inhibition
N-Fmoc-S-2-(2'-octyl)alanine
-
-
N-Fmoc-S-2-(2'-pentyl)alanine
-
-
NO3-
-
slight inhibition
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
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
interaction with APAF-1 promotes auto-cleavage and activation of caspase-9
-
(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)
-
-
APAF-1
-
apoptosome
-
activates caspase-9 by dimerization
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.466 - 0.686
acetyl-LEHD-7-amido-4-trifluoromethyl coumarin
0.466 - 0.686
acetyl-LEHD-7-amido-4-trifluoromethylcoumarin
0.139
procaspase-3
caspase-9 holoenzyme
-
0.408 - 0.78
acetyl-VEHD-7-amido-4-methylcoumarin
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, 25°C
0.00006
acetyl-DEVD-CHO
-
pH 7.5, 25°C
0.000108
acetyl-IETD-CHO
-
pH 7.5, 25°C
0.000508
acetyl-WEHD-CHO
-
pH 7.5, 25°C
0.00097
acetyl-YVAD-CHO
-
pH 7.5, 25°C
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
7.5
caspase activity assay at
6.2
-
mutant DELTA1-111
6.5
-
assay at
6.5 - 7
-
reaction with acetyl-VEHD-7-amido-4-methylcoumarin
7.2
-
mutant DELTA1-111/E306A/D315A
7.4
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
human fibroblast GM03349
Manually annotated by BRENDA team
cell line HF1A3, wild-type, dominant negative caspase-9 overexpressing
Manually annotated by BRENDA team
cell line HF1A3, wild-type, dominant negative caspase-9 overexpressing
Manually annotated by BRENDA team
gingivial cancer cells (Ca9-22 cells) containing a mutated p53 (mp53) protein by point mutation at codon 248
Manually annotated by BRENDA team
cells treated with 10 mg/ml recombinant Vibrio vulnificus cytolysin (rVVC) at 37°C for 4 h, cell viability assay
Manually annotated by BRENDA team
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
wild-type and SOD-antisense
Manually annotated by BRENDA team
caspase-9 genotyping
Manually annotated by BRENDA team
treated with doxycycline (2 microg/ml in PBS)
Manually annotated by BRENDA team
cells treated with 10 mg/ml recombinant Vibrio vulnificus cytolysin (rVVC) at 37°C for 4 h, cell viability assay
Manually annotated by BRENDA team
cells treated with 10 mg/ml recombinant Vibrio vulnificus cytolysin (rVVC) at 37°C for 4 h, cell viability assay
Manually annotated by BRENDA team
treated with different concentrations of marine sponge extracts of Polymastia janeirensis
Manually annotated by BRENDA team
treated with doxorubicin (2, 2.5, and 0.25 microg/ml in PBS), doxorubicin-induced cell death
Manually annotated by BRENDA team
-
10C9
Manually annotated by BRENDA team
-
caspase-9 is released into the cerebrospinal fluid after severe traumatic brain injury
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
-
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
-
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
-
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
phosphorylation of caspase-9 by DYRK1A involves co-localization to the nucleus
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
key structural and catalytic features are conserved across the entire family of cysteine-dependent aspartate-specific proteases (caspases)
malfunction
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CASP9_HUMAN
416
0
46281
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30000
x * 30000, caspase 9S, SDS-PAGE
35000
processed caspase-9 protein, SDS-PAGE
37000
processed caspase-9 protein, SDS-PAGE
46200
x * 46200, calculation from nucleotide sequence
47000
un-processed caspase-9 protein, SDS-PAGE
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
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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
phosphoprotein
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C287A
immunofluorescence staining of cells transiently transfected with vectors encoding caspase-9 point mutation
C403S
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
T125A/C287A
site-directed mutagenesis, immunofluorescence staining of cells transiently transfected with vectors encoding caspase-9 double mutant
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
-
the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C239S
-
the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C272A
-
the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C272A/C287A
-
the mutant enzyme shows highly reduced zinc binding compared to the wild-type enzyme
C287A
-
the active site mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
C287A/C239S
-
the mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
DELTA1-111
-
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
DELTA1-111/E306A/D315A
-
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
DELTA1-111/E306D/DELTAA316-D330
H237A
-
the active site mutant enzyme shows reduced zinc binding compared to the wild-type enzyme
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
gel filtration
gel filtration, SDS-PAGE
recombinant His6-tagged enzyme
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 from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
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
expressed in Escherichia coli, recombinant protein, pcDNA3, pET28a, pEGFP vectors
naturally occuring variant caspase-9S, that is missing most of the large subunit of caspase-9
caspase-9S is cloned from human liver cDNA
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain B21(DE3) in incusion bodies
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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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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
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
-
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
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
pharmacology
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Duan H.; Orth K.; Chinnaiyan A.M.; Poirier G.G.; Froelich C.J.; He W.W.; Dixit V.M.
ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated by the cytotoxic T cell protease granzyme B
J. Biol. Chem.
271
16720-16724
1996
Homo sapiens (P55211)
Manually annotated by BRENDA team
Srinivasula, S.M.; Fernandes-Alnemri, T.; Zangrilli, J.; Robertson, N.; Armstrong, R.C.; Wang, L.; Trapani, J.A.; Tomaselli, K.J.; Litwack, G.; Alnemri E.S.
The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32
J. Biol. Chem.
271
27099-27106
1996
Homo sapiens (P55211)
Manually annotated by BRENDA team
Seol, D.W.; Billiar, T.R.
A caspase-9 variant missing the catalytic site is an endogenous inhibitor of apoptosis
J. Biol. Chem.
274
2072-2076
1999
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Allan, L.A.; Morrice, N.; Brady, S.; Magee, G.; Pathak, S.; Clarke, P.R.
Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK
Nat. Cell Biol.
5
647-654
2003
Homo sapiens
Manually annotated by BRENDA team
Chou, K.C.; Tomasselli, A.G.; Heinrikson, R.L.
Prediction of the tertiary structure of a caspase-9/inhibitor complex
FEBS Lett.
470
249-256
2000
Homo sapiens
Manually annotated by BRENDA team
Kuida, K.
Caspase-9
Int. J. Biochem. Cell Biol.
32
121-124
2000
Homo sapiens
Manually annotated by BRENDA team
Rodriguez, J.; Lazebnik, Y.
Caspase-9 and APAF-1 form an active holoenzyme
Genes Dev.
13
3179-3184
1999
Homo sapiens
Manually annotated by BRENDA team
Zhivotovsky, B.; Samali, A.; Gahm, A.; Orrenius, S.
Caspases: their intracellular localization and translocation during apoptosis
Cell Death Differ.
6
644-651
1999
Homo sapiens
Manually annotated by BRENDA team
Pan, G.; O'Rourke, K.; Dixit, V.M.
Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex
J. Biol. Chem.
273
5841-5845
1998
Homo sapiens
Manually annotated by BRENDA team
Garcia-Calvo, M.; Peterson, E.P.; Leiting, B.; Ruel, R.; Nicholson, D.W.; Thornberry, N.A.
Inhibition of human caspases by peptide-based and macromolecular inhibitors
J. Biol. Chem.
273
32608-32613
1998
Homo sapiens
Manually annotated by BRENDA team
Garcia-Calvo, M.; Peterson, E.P.; Rasper, D.M.; Vaillancourt, J.P.; Zamboni, R.; Nicholson, D.W.; Thornberry, N.A.
Purification and catalytic properties of human caspase family members
Cell Death Differ.
6
362-369
1999
Homo sapiens
Manually annotated by BRENDA team
Li, P.; Nijhawan, D.; Budihardjo, I.; Srinivasula, S.M.; Ahman, M.; Alnemric, E.S.; Wang, X.
Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade
Cell
91
479-489
1997
Homo sapiens
Manually annotated by BRENDA team
Srinivasula, S.M.; Ahmad, M.; Fernandes-Alnemric, T.; Alnemri, E.S.
Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization
Mol. Cell
1
949-957
1998
Homo sapiens
Manually annotated by BRENDA team
Cardone, M.H.; Roy, N.; Stennicke, H.R.; Salvesen, G.S.; Franke, T.F.; Stanbridge, E.; Frisch, S.; Reed, J.C.
Regulation of cell death protease caspase-9 by phosphorylation
Science
282
1318-1321
1998
Homo sapiens
Manually annotated by BRENDA team
Chang, H.Y.; Yang, X.
Proteases from cell suicide: functions and regulation of caspases
Microbiol. Mol. Biol. Rev.
64
821-846
2000
Homo sapiens
Manually annotated by BRENDA team
Thornberry, N.A.; Rano, T.A.; Peterson, E.P.; et al.
A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis
J. Biol. Chem.
272
17907-17911
1997
Homo sapiens
Manually annotated by BRENDA team
Soung, Y.H.; Lee, J.W.; Kim, S.Y.; Park, W.S.; Nam, S.W.; Lee, J.Y.; Yoo, N.J.; Lee, S.H.
Mutational analysis of proapoptotic caspase-9 gene in common human carcinomas
APMIS
114
292-297
2006
Homo sapiens
Manually annotated by BRENDA team
Johnson, C.R.; Jarvis, W.D.
Caspase-9 regulation: an update
Apoptosis
9
423-427
2004
Homo sapiens
Manually annotated by BRENDA team
Cheung, H.H.; Lynn Kelly, N.; Liston, P.; Korneluk, R.G.
Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: a role for the IAPs
Exp. Cell Res.
312
2347-2357
2006
Homo sapiens
Manually annotated by BRENDA team
Martelli, A.M.; Cappellini, A.; Tazzari, P.L.; Billi, A.M.; Tassi, C.; Ricci, F.; Fala, F.; Conte, R.
Caspase-9 is the upstream caspase activated by 8-methoxypsoralen and ultraviolet-A radiation treatment of Jurkat T leukemia cells and normal T lymphocytes
Haematologica
89
471-479
2004
Homo sapiens
Manually annotated by BRENDA team
Kasili, P.M.; Song, J.M.; Vo-Dinh, T.
Optical sensor for the detection of caspase-9 activity in a single cell
J. Am. Chem. Soc.
126
2799-2806
2004
Homo sapiens
Manually annotated by BRENDA team
Akasaki, Y.; Liu, G.; Matunda, H.H.; Ng, H.; Yuan, X.; Zeng, Z.; Black, K.L.; Yu, J.S.
A peroxisome proliferator-activated receptor-gamma agonist, troglitazone, facilitates caspase-8 and -9 activities by increasing the enzymatic activity of protein-tyrosine phosphatase-1B on human glioma cells
J. Biol. Chem.
281
6165-6174
2006
Homo sapiens
Manually annotated by BRENDA team
Wang, P.; Shi, T.; Ma, D.
Cloning of a novel human caspase-9 splice variant containing only the CARD domain
Life Sci.
79
934-940
2006
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Maglione, V.; Cannella, M.; Gradini, R.; Cislaghi, G.; Squitieri, F.
Huntingtin fragmentation and increased caspase 3, 8, and 9 activities in lymphoblasts with heterozygous and homozygous Huntington's disease mutation
Mech. Ageing Dev.
127
213-216
2006
Homo sapiens
Manually annotated by BRENDA team
Yin, Q.; Park, H.H.; Chung, J.Y.; Lin, S.C.; Lo, Y.C.; da Graca, L.S.; Jiang, X.; Wu, H.
Caspase-9 holoenzyme is a specific and optimal procaspase-3 processing machine
Mol. Cell
22
259-268
2006
Homo sapiens (P55211)
Manually annotated by BRENDA team
Pop, C.; Timmer, J.; Sperandio, S.; Salvesen, G.S.
The apoptosome activates caspase-9 by dimerization
Mol. Cell
22
269-275
2006
Homo sapiens
Manually annotated by BRENDA team
Sadhukhan, R.; Leone, J.W.; Lull, J.; Wang, Z.; Kletzien, R.F.; Heinrikson, R.L.; Tomasselli, A.G.
An efficient method to express and refold a truncated human procaspase-9: a caspase with activity toward Glu-X bonds
Protein Expr. Purif.
46
299-308
2006
Homo sapiens
Manually annotated by BRENDA team
Samraj, A.K.; Keil, E.; Ueffing, N.; Schulze-Osthoff, K.; Schmitz, I.
Loss of caspase-9 provides genetic evidence for the type I/II concept of CD95-mediated apoptosis
J. Biol. Chem.
281
29652-29659
2006
Homo sapiens
Manually annotated by BRENDA team
Chen, M.; Guerrero, A.D.; Huang, L.; Shabier, Z.; Pan, M.; Tan, T.H.; Wang, J.
Caspase-9-induced mitochondrial disruption through cleavage of anti-apoptotic BCL-2 family members
J. Biol. Chem.
282
33888-33895
2007
Homo sapiens
Manually annotated by BRENDA team
Martin, M.C.; Allan, L.A.; Mancini, E.J.; Clarke, P.R.
The docking interaction of caspase-9 with ERK2 provides a mechanism for the selective inhibitory phosphorylation of caspase-9 at threonine 125
J. Biol. Chem.
283
3854-3865
2008
Homo sapiens
Manually annotated by BRENDA team
Samraj, A.K.; Sohn, D.; Schulze-Osthoff, K.; Schmitz, I.
Loss of caspase-9 reveals its essential role for caspase-2 activation and mitochondrial membrane depolarization
Mol. Biol. Cell
18
84-93
2007
Homo sapiens
Manually annotated by BRENDA team
Allan, L.A.; Clarke, P.R.
Phosphorylation of caspase-9 by CDK1/cyclin B1 protects mitotic cells against apoptosis
Mol. Cell
26
301-310
2007
Homo sapiens
Manually annotated by BRENDA team
Eeva, J.; Nuutinen, U.; Ropponen, A.; Maettoe, M.; Eray, M.; Pellinen, R.; Wahlfors, J.; Pelkonen, J.
The involvement of mitochondria and the caspase-9 activation pathway in rituximab-induced apoptosis in FL cells
Apoptosis
14
687-698
2009
Homo sapiens (P55211)
Manually annotated by BRENDA team
Day, T.W.; Huang, S.; Safa, A.R.
c-FLIP knockdown induces ligand-independent DR5-, FADD-, caspase-8-, and caspase-9-dependent apoptosis in breast cancer cells
Biochem. Pharmacol.
76
1694-1704
2008
Homo sapiens (P55211)
Manually annotated by BRENDA team
Yamakawa, N.; Takahashi, A.; Mori, E.; Imai, Y.; Furusawa, Y.; Ohnishi, K.; Kirita, T.; Ohnishi, T.
High LET radiation enhances apoptosis in mutated p53 cancer cells through Caspase-9 activation
Cancer Sci.
99
1455-1460
2008
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Zuo, Y.; Xiang, B.; Yang, J.; Sun, X.; Wang, Y.; Cang, H.; Yi, J.
Oxidative modification of caspase-9 facilitates its activation via disulfide-mediated interaction with APAF-1
Cell Res.
19
449-457
2009
Homo sapiens (P55211)
Manually annotated by BRENDA team
Seifert, A.; Allan, L.A.; Clarke, P.R.
DYRK1A phosphorylates caspase 9 at an inhibitory site and is potently inhibited in human cells by harmine
FEBS J.
275
6268-6280
2008
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Yiang, G.T.; Yu, Y.L.; Hu, S.C.; Chen, M.H.; Wang, J.J.; Wei, C.W.
PKC and MEK pathways inhibit caspase-9/-3-mediated cytotoxicity in differentiated cells
FEBS Lett.
582
881-885
2008
Homo sapiens (P55211)
Manually annotated by BRENDA team
Tichy, A.; Zaskodova, D.; Pejchal, J.; Rezacova, M.; Osterreicher, J.; Vavrova, J.; Cerman, J.
Gamma irradiation of human leukaemic cells HL-60 and MOLT-4 induces decrease in Mcl-1 and Bid, release of cytochrome c, and activation of caspase-8 and caspase-9
Int. J. Radiat. Biol.
84
523-530
2008
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Conte da Frota, M.L.; Braganhol, E.; Delgado Canedo, A.; Klamt, F.; Apel, M.A.; Mothes, B.; Lerner, C.; Oliveira Battastini, A.M.; Henriques, A.T.; Fonseca Moreira, J.C.
Extracts of marine sponge Polymastia janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway in human U138MG glioma cell line
Invest. New Drugs
27
440-446
2008
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Yasuda, Y.; Saito, M.; Yamamura, T.; Yaguchi, T.; Nishizaki, T.
Extracellular adenosine induces apoptosis in Caco-2 human colonic cancer cells by activating caspase-9/-3 via A(2a) adenosine receptors
J. Gastroenterol.
44
56-65
2009
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Mondragon, L.; Orzaez, M.; Sanclimens, G.; Moure, A.; Arminan, A.; Sepulveda, P.; Messeguer, A.; Vicent, M.J.; Perez-Paya, E.
Modulation of cellular apoptosis with apoptotic protease-activating factor 1 (Apaf-1) inhibitors
J. Med. Chem.
51
521-529
2008
Rattus norvegicus, Homo sapiens (P55211)
Manually annotated by BRENDA team
Andreoli, V.; Trecroci, F.; La Russa, A.; Valentino, P.; Condino, F.; Latorre, V.; Nistico, R.; Pirritano, D.; Del Giudice, F.; Canino, M.; Cittadella, R.; Quattrone, A.
CASP-9: A susceptibility locus for multiple sclerosis in Italy
J. Neuroimmunol.
210
100-103
2009
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Checinska, A.; Giaccone, G.; Rodriguez, J.A.; Kruyt, F.A.; Jimenez, C.R.
Comparative proteomics analysis of caspase-9-protein complexes in untreated and cytochrome c/dATP stimulated lysates of NSCLC cells
J. Proteomics
72
575-585
2009
Homo sapiens (P55211)
Manually annotated by BRENDA team
Zhao, J.F.; Sun, A.H.; Ruan, P.; Zhao, X.H.; Lu, M.Q.; Yan, J.
Vibrio vulnificus cytolysin induces apoptosis in HUVEC, SGC-7901 and SMMC-7721 cells via caspase-9/3-dependent pathway
Microb. Pathog.
46
194-200
2009
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Mukherjee, J.J.; Gupta, S.K.; Kumar, S.
Inhibition of benzopyrene-diol-epoxide (BPDE)-induced bax and caspase-9 by cadmium: role of mitogen activated protein kinase
Mutat. Res.
661
41-46
2009
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Darwish, R.S.; Amiridze, N.S.
Detectable levels of cytochrome C and activated caspase-9 in cerebrospinal fluid after human traumatic brain injury
Neurocrit. Care
12
337-341
2010
Homo sapiens
Manually annotated by BRENDA team
Jeong, H.S.; Choi, H.Y.; Lee, E.R.; Kim, J.H.; Jeon, K.; Lee, H.J.; Cho, S.G.
Involvement of caspase-9 in autophagy-mediated cell survival pathway
Biochim. Biophys. Acta
1813
80-90
2011
Homo sapiens
Manually annotated by BRENDA team
Abou-Kandil, A.; Chamias, R.; Huleihel, M.; Godbey, W.T.; Aboud, M.
Role of caspase 9 in activation of HTLV-1 LTR expression by DNA damaging agents
Cell Cycle
10
3337-3345
2011
Homo sapiens
Manually annotated by BRENDA team
Wu, Y.; Wang, D.; Wang, X.; Wang, Y.; Ren, F.; Chang, D.; Chang, Z.; Jia, B.
Caspase 3 is activated through caspase 8 instead of caspase 9 during H2O2-induced apoptosis in HeLa cells
Cell. Physiol. Biochem.
27
539-546
2011
Homo sapiens
Manually annotated by BRENDA team
Li, T.; Cui, Z.B.; Ke, X.X.; Tan, J.; Li, F.F.; Li, T.; Wang, X.W.; Cui, H.J.
Essential role for p53 and caspase-9 in DNA damaging drug-induced apoptosis in neuroblastoma IMR32 cells
DNA Cell Biol.
30
1045-1050
2011
Homo sapiens
Manually annotated by BRENDA team
Du, R.H.; Cui, J.T.; Wang, T.; Zhang, A.H.; Tan, R.X.
Trichothecin induces apoptosis of HepG2 cells via caspase-9 mediated activation of the mitochondrial death pathway
Toxicon
59
143-150
2012
Homo sapiens
Manually annotated by BRENDA team
Bourguet, C.B.; Boulay, P.L.; Claing, A.; Lubell, W.D.
Design and synthesis of novel azapeptide activators of apoptosis mediated by caspase-9 in cancer cells
Bioorg. Med. Chem. Lett.
24
3361-3365
2014
Homo sapiens
Manually annotated by BRENDA team
Huber, K.L.; Ghosh, S.; Hardy, J.A.
Inhibition of caspase-9 by stabilized peptides targeting the dimerization interface
Biopolymers
98
451-465
2012
Homo sapiens
Manually annotated by BRENDA team
Nie, C.; Luo, Y.; Zhao, X.; Luo, N.; Tong, A.; Liu, X.; Yuan, Z.; Wang, C.; Wei, Y.
Caspase-9 mediates Puma activation in UCN-01-induced apoptosis
Cell Death Dis.
5
e1495
2014
Homo sapiens
Manually annotated by BRENDA team
Wuerstle, M.L.; Laussmann, M.A.; Rehm, M.
The central role of initiator caspase-9 in apoptosis signal transduction and the regulation of its activation and activity on the apoptosome
Exp. Cell Res.
318
1213-1220
2012
Homo sapiens
Manually annotated by BRENDA team
Huber, K.L.; Hardy, J.A.
Mechanism of zinc-mediated inhibition of caspase-9
Protein Sci.
21
1056-1065
2012
Homo sapiens
Manually annotated by BRENDA team
Wei, X.; Li, Q.; Han, Z.; Lin, D.; Yu, P.
Differences in caspase-8 and -9 activity and sperm motility in infertile males of Li nationality in China
Int. J. Clin. Exp. Med.
8
4721-4726
2015
Homo sapiens (P55211), Homo sapiens
Manually annotated by BRENDA team
Diaconu, I.; Ballard, B.; Zhang, M.; Chen, Y.; West, J.; Dotti, G.; Savoldo, B.
Inducible caspase-9 selectively modulates the toxicities of CD19-specific chimeric antigen receptor-modified T cells
Mol. Ther.
25
580-592
2017
Homo sapiens (P55211)
Manually annotated by BRENDA team