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Information on EC 3.4.22.59 - caspase-6 and Organism(s) Homo sapiens
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3.4.22.59 caspase-6Specify your search results
Word Map
- 3.4.22.59
-
caspases
- bcl-2
- alzheimer
- neurodegenerative
-
pro-apoptotic
- huntington
- lamins
-
apoptosis-related
- parp
-
executioner
-
caspase-dependent
-
anti-apoptotic
-
polyadp-ribose
-
tunel
-
caspase-mediated
-
casps
-
jurkat
- bid
-
pan-caspase
- zvad-fmk
- apaf-1
- medicine
- procaspase-3
- fadd
- diagnostics
-
fas-associated
- drug development
- molecular biology
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp-/-
Synonyms
caspase-6, casp6, caspase 6, veidase, casp-6, csp-6, hlcaspase-6, caspase-6a, caspase-6b, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
apoptotic protease Mch-2
-
-
-
-
C14.005
-
-
-
-
Casp6
caspase 6
caspase-6
MCH2
-
-
-
-
caspase 6
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
182372-15-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin + H2O
Ac-Val-Glu-Ile-Asp + 7-amino-4-trifluoromethylcoumarin
Ac-VEID-4-trifluoromethylcoumarin 7-amide + H2O
Ac-VEID + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
acetyl-VEHD-7-amido-4-methylcoumarin + H2O
acetyl-VEHD + 7-amino-4-methylcoumarin
-
VEHD is the optimal tetrapeptide recognition motif
-
-
?
DEVD-7-amido-4-methylcoumarin + H2O
DEVD + 7-amino-4-methylcoumarin
-
-
-
?
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Asp-Glu-Val-Asp + 7-amino-4-methylcoumarin
-
-
-
?
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin + H2O
N-acetyl-Asp-Glu-Val-Asp + 7-amino-4-trifluoromethylcoumarin
-
-
-
?
N-acetyl-Asp-Leu-Asn-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Asp-Leu-Asn-Asp + 7-amino-4-methylcoumarin
-
-
-
?
N-acetyl-Asp-Val-Val-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Asp-Val-Val-Asp + 7-amino-4-methylcoumarin
-
-
-
?
N-acetyl-Ile-Val-Leu-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Ile-Val-Leu-Asp + 7-amino-4-methylcoumarin
-
-
-
?
N-acetyl-Thr-Glu-Val-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Thr-Glu-Val-Asp + 7-amino-4-methylcoumarin
-
-
-
?
N-acetyl-Val-Glu-His-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Val-Glu-His-Asp + 7-amino-4-methylcoumarin
-
-
-
?
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Val-Glu-Ile-Asp + 7-amino-4-methylcoumarin
-
-
-
?
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin + H2O
N-acetyl-Val-Glu-Ile-Asp + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
N-acetyl-VEID-4-nitroanilide + H2O
N-acetyl-VEID + 4-nitroaniline
-
-
-
?
nuclear mitotic apparatus protein + H2O
?
-
cleavage at sites distict from caspase-3
-
-
?
pro-caspase-6 + H2O
?
-
caspase-8 activates caspase-3, and caspase-3 in turn activates caspase-6. Caspase 3 has a major role in nuclear apoptosis
-
-
?
pro-caspase-6 + H2O
caspase-6 + ?
the enzyme can self-process and self-activate
-
-
?
procaspase-6 mutant C163S + H2O
?
cleavage at the intersubunit linker position Asp-193
-
-
?
Z-VEID-R110 + H2O
2 Z-VEID + R110
caspase-6 recognition peptide covalently linked to two amine groups of the fluorescent dye rhodamine 110, fluorogenic assay
-
-
?
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin + H2O
Ac-Val-Glu-Ile-Asp + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin + H2O
Ac-Val-Glu-Ile-Asp + 7-amino-4-trifluoromethylcoumarin
-
-
-
?
cyclin B1 + H2O
truncated cyclin B1 + ?
-
overriding the G2 DNA damage checkpoint permits precocious entry into mitosis that ultimately leads to mitotic catastrophe, caused by caffeine. Mitotic catastrophe is manifested by an unscheduled activation of CDK1, caspase activation and apoptotic cell death. Cyclin B1 is required for mitotic catastrophe, but is also cleaved into a 35 kDa protein by a caspase-dependent mechanism during the process, overview
expression of the truncated product enhanced cell death
-
?
cyclin B1 + H2O
truncated cyclin B1 + ?
-
cleavage occurs after Asp123 in the motif ILVD123k, mutation of this motif to D123N attenuates the cleavage, cleavage still occurred in the control D160N mutant
lacking part of the NH2-terminal regulatory domain including the destruction box sequence
-
?
human telomerase + H2O
?
-
caspase-6 cleaves human telomerase, hTERT, during apoptosis in cultured cells
-
-
?
human telomerase + H2O
?
-
caspase-6 cleaves human telomerase, hTERT, at residues D129 and D637, generation of three major proteolytic fragments, cleavage site determination using caspase-6 resistant substrate mutants D129A, D637A, and D129A/D637A, overview
-
-
?
huntingtin + H2O
huntingtin peptide fragments
-
a key step in the onset of Huntingtons disease is the caspase-6 mediated cleavage of the protein huntingtin into toxic fragments
-
-
?
N-acetyl-VEID-7-amido-4-methylcoumarin + H2O
N-acetyl-VEID + 7-amino-4-methylcoumarin
-
-
-
-
?
N-acetyl-VEID-7-amido-4-methylcoumarin + H2O
N-acetyl-VEID + 7-amino-4-methylcoumarin
-
-
-
?
periplakin + H2O
?
-
caspase 6 cleaves periplakin at an unconventional recognition site, amino acid sequence TVAD
-
-
?
periplakin + H2O
?
-
caspase 6 has a specific epidermal target which is periplakin
-
-
?
poly(ADP-ribose)polymerase + H2O
?
the enzyme may participate in poly(ADP-ribose)polymerase cleavage observed during apoptosis
-
-
?
pro-caspase-8 + H2O
?
-
caspase-8 precursor is initially cleaved between the p18 and p10 domains resulting in fragments of 42000 Da and 10000 Da. The 42000 Da fragment is further cleaved resulting in fragments of 25000 Da and 18000 Da
-
-
?
pro-caspase-8 + H2O
?
-
caspase-6 is the major activator of caspase-8 in the cytochrome c-induced apoptosis pathway. Caspase-8 precursor is initially cleaved between the p18 and p10 domains resulting in fragments of 42000 Da and 10000 Da. The 42000 Da fragment is further cleaved resulting in fragments of 25000 Da and 18000 Da
-
-
?
receptor-interacting protein kinase-1 + H2O
?
-
cleavage site between 324-Asp and 325-Cys
-
-
?
SATB1 + H2O
?
-
specifically cleaves at amino acid position 254 to produce a 65000 Da major fragment containing both a base-unpairing region (BUR)-binding domain and a homeodomain. This cleavage separates the DNA-binding domains from amino acids 90 to 204, a region which is a dimerization domain. The resulting SATB1 monomer loses its BUR-binding activity
-
-
?
SATB1 + H2O
?
-
cleavage disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis
-
-
?
Tau + H2O
?
-
microtubule-associated protein, caspase-6 cleaves the N-terminus at D13 of tau in vitro
-
-
?
transcription factor AP-2alpha + H2O
?
-
cleaves at Asp19 of the sequence DRHD19
-
-
?
transcription factor AP-2alpha + H2O
?
-
AP-2alpha is cleaved is at Asp19 of the sequence DRHD19 by caspase-6 before DNA framentation during TNF-alpha-induced apoptosis
-
-
?
transcription factor AP-2alpha + H2O
?
-
activates caspase-6 which in turn cleaves transcription factor AP2alpha
-
-
?
Ufd2p + H2O
?
-
cleavage of polyubiquitination factor Ufd2p at Asp123 within the putative regulatory N-terminal domain might have important functional consequences within the apoptotic cascade
-
-
?
VEID-7-amido-4-trifluoromethylcoumarin + H2O
VEID + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
VEID-7-amido-4-trifluoromethylcoumarin + H2O
VEID + 7-amino-4-trifluoromethylcoumarin
-
preferred substrate for caspase-6
-
-
?
viral nucleocapsid protein of transmissible gastroenteritis coronovirus + H2O
?
-
cleavage site VVPD359-/-
-
-
?
viral nucleocapsid protein of transmissible gastroenteritis coronovirus + H2O
?
-
cleavage site VVPD359-/-. Destruction of viral protein by the host cell death machinery
-
-
?
additional information
?
-
Mch2alpha but not Mch2beta possesses protease activity
-
-
?
additional information
?
-
-
the enzyme has a major role in nuclear apoptosis
-
-
?
additional information
?
-
-
bile acid-induced apoptosis, e.g. by glycochenodeoxycholic acid, in hepatocytes is caspase-6-dependent. Caspase-6 appears to play an important regulatory role in the promotion of bile acid-induced apoptosis as part of a feedback loop. Inhibition of caspase-9 reduces glycochenodeoxycholic acid-induced activation of caspase-6, whereas inhibition of caspase-6 reduces activation of caspase-8 placing caspase-6 between caspase-9 and caspase-8
-
-
?
additional information
?
-
-
caspase 6, an apoptosis-related cysteine peptidase, is upregulated in the skin of keloid prone patients. Caspase-6 plays a crucial role during apoptosis
-
-
?
additional information
?
-
-
caspase-6 activation occurs early in Alzheimer's disease and sometimes precedes the clinical manifestation of the disease in aged individuals. Early and neuritic activation of caspase-6 in Alzheimer disease can disrupt the cytoskeleton network of neurons, resulting in impaired neuronal structure and function in the absence of cell death. Proteomics analysis of caspase-6-mediated cleavage of human neuronal proteins, cleavage site determinations and cleavage specificity, overview
-
-
?
additional information
?
-
-
caspase-6 is a short pro-domain caspase that is activated early in Alzheimer disease, its activation does not induce apoptosis in HEK-293T cells, overview
-
-
?
additional information
?
-
-
possible involvement of caspase-6 and -7 but not caspase-3 in the regulation of hypoxia-induced apoptosis in tube-forming endothelial cells, caspase-6 is responsible for DNA ladder formation durirng hypoxia, overview
-
-
?
additional information
?
-
-
resveratrol-mediated activation of caspase-6 leads to apoptosis in HCT-116 colon cancer cells involving also p53, overview
-
-
?
additional information
?
-
-
ZBP-89, a Kruppel-type, zinc finger transcription factor, induces caspase-6 activation leading to inhibition of cell death in hepatoccellular carcinoma cells, inhibition of caspase-6 abolishes the effect of ZBP-89
-
-
?
additional information
?
-
-
development of an assay method for specifically detecting caspase-6 activity in an intact cell environment, evaluation of a 384-well whole-cell chemiluminescent ELISA assay that monitors the proteolytic degradation of endogenously expressed lamin A/C during the early stages of caspase-dependent apoptosis, overview
-
-
?
additional information
?
-
CLK3, alcohol dehydrogenase 4 and malate dehydrogenase 1B are not cleaved by caspase-6
-
-
?
additional information
?
-
-
the enzyme does not cleave receptor-interacting protein kinase-3
-
-
?
additional information
?
-
stabilization of the N- and C-terminal loops by the tri-arginine patch is critical for the dynamics of caspase-6. This change in dynamics plays a key role in the mechanism by which the enzyme recognizes protein substrates
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin + H2O
Ac-Val-Glu-Ile-Asp + 7-amino-4-trifluoromethylcoumarin
-
-
-
?
cyclin B1 + H2O
truncated cyclin B1 + ?
-
overriding the G2 DNA damage checkpoint permits precocious entry into mitosis that ultimately leads to mitotic catastrophe, caused by caffeine. Mitotic catastrophe is manifested by an unscheduled activation of CDK1, caspase activation and apoptotic cell death. Cyclin B1 is required for mitotic catastrophe, but is also cleaved into a 35 kDa protein by a caspase-dependent mechanism during the process, overview
expression of the truncated product enhanced cell death
-
?
human telomerase + H2O
?
-
caspase-6 cleaves human telomerase, hTERT, during apoptosis in cultured cells
-
-
?
huntingtin + H2O
huntingtin peptide fragments
-
a key step in the onset of Huntingtons disease is the caspase-6 mediated cleavage of the protein huntingtin into toxic fragments
-
-
?
periplakin + H2O
?
-
caspase 6 has a specific epidermal target which is periplakin
-
-
?
poly(ADP-ribose)polymerase + H2O
?
the enzyme may participate in poly(ADP-ribose)polymerase cleavage observed during apoptosis
-
-
?
pro-caspase-6 + H2O
?
-
caspase-8 activates caspase-3, and caspase-3 in turn activates caspase-6. Caspase 3 has a major role in nuclear apoptosis
-
-
?
pro-caspase-6 + H2O
caspase-6 + ?
the enzyme can self-process and self-activate
-
-
?
pro-caspase-8 + H2O
?
-
caspase-6 is the major activator of caspase-8 in the cytochrome c-induced apoptosis pathway. Caspase-8 precursor is initially cleaved between the p18 and p10 domains resulting in fragments of 42000 Da and 10000 Da. The 42000 Da fragment is further cleaved resulting in fragments of 25000 Da and 18000 Da
-
-
?
SATB1 + H2O
?
-
cleavage disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis
-
-
?
Ufd2p + H2O
?
-
cleavage of polyubiquitination factor Ufd2p at Asp123 within the putative regulatory N-terminal domain might have important functional consequences within the apoptotic cascade
-
-
?
viral nucleocapsid protein of transmissible gastroenteritis coronovirus + H2O
?
-
cleavage site VVPD359-/-. Destruction of viral protein by the host cell death machinery
-
-
?
transcription factor AP-2alpha + H2O
?
-
AP-2alpha is cleaved is at Asp19 of the sequence DRHD19 by caspase-6 before DNA framentation during TNF-alpha-induced apoptosis
-
-
?
transcription factor AP-2alpha + H2O
?
-
activates caspase-6 which in turn cleaves transcription factor AP2alpha
-
-
?
additional information
?
-
-
the enzyme has a major role in nuclear apoptosis
-
-
?
additional information
?
-
-
bile acid-induced apoptosis, e.g. by glycochenodeoxycholic acid, in hepatocytes is caspase-6-dependent. Caspase-6 appears to play an important regulatory role in the promotion of bile acid-induced apoptosis as part of a feedback loop. Inhibition of caspase-9 reduces glycochenodeoxycholic acid-induced activation of caspase-6, whereas inhibition of caspase-6 reduces activation of caspase-8 placing caspase-6 between caspase-9 and caspase-8
-
-
?
additional information
?
-
-
caspase 6, an apoptosis-related cysteine peptidase, is upregulated in the skin of keloid prone patients. Caspase-6 plays a crucial role during apoptosis
-
-
?
additional information
?
-
-
caspase-6 activation occurs early in Alzheimer's disease and sometimes precedes the clinical manifestation of the disease in aged individuals. Early and neuritic activation of caspase-6 in Alzheimer disease can disrupt the cytoskeleton network of neurons, resulting in impaired neuronal structure and function in the absence of cell death. Proteomics analysis of caspase-6-mediated cleavage of human neuronal proteins, cleavage site determinations and cleavage specificity, overview
-
-
?
additional information
?
-
-
caspase-6 is a short pro-domain caspase that is activated early in Alzheimer disease, its activation does not induce apoptosis in HEK-293T cells, overview
-
-
?
additional information
?
-
-
possible involvement of caspase-6 and -7 but not caspase-3 in the regulation of hypoxia-induced apoptosis in tube-forming endothelial cells, caspase-6 is responsible for DNA ladder formation durirng hypoxia, overview
-
-
?
additional information
?
-
-
resveratrol-mediated activation of caspase-6 leads to apoptosis in HCT-116 colon cancer cells involving also p53, overview
-
-
?
additional information
?
-
-
ZBP-89, a Kruppel-type, zinc finger transcription factor, induces caspase-6 activation leading to inhibition of cell death in hepatoccellular carcinoma cells, inhibition of caspase-6 abolishes the effect of ZBP-89
-
-
?
additional information
?
-
-
development of an assay method for specifically detecting caspase-6 activity in an intact cell environment, evaluation of a 384-well whole-cell chemiluminescent ELISA assay that monitors the proteolytic degradation of endogenously expressed lamin A/C during the early stages of caspase-dependent apoptosis, overview
-
-
?
additional information
?
-
CLK3, alcohol dehydrogenase 4 and malate dehydrogenase 1B are not cleaved by caspase-6
-
-
?
additional information
?
-
-
the enzyme does not cleave receptor-interacting protein kinase-3
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5Z)-1-(furan-2-ylmethyl)-5-([1-[2-(2-methylpiperidin-1-yl)-2-oxoethyl]-1H-indol-3-yl]methylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
-
(5Z)-1-(furan-2-ylmethyl)-5-([1-[2-(morpholin-4-yl)-2-oxoethyl]-1H-indol-3-yl]methylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
(5Z)-1-(furan-2-ylmethyl)-5-([1-[2-(morpholin-4-yl)-2-oxoethyl]-1H-indol-3-yl]methylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
-
(5Z)-1-(furan-2-ylmethyl)-5-([1-[2-oxo-2-(piperidin-1-yl)ethyl]-1H-indol-3-yl]methylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
-
(5Z)-1-(furan-2-ylmethyl)-5-([1-[2-oxo-2-(pyrrolidin-1-yl)ethyl]-1H-indol-3-yl]methylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
-
1-(3,4-dichlorobenzyl)-5-(morpholin-4-ylsulfonyl)-1H-indole-2,3-dione
-
slight inhibition
2-(3-[(E)-[1-(furan-2-ylmethyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)-N-(2-methoxyethyl)acetamide
-
2-(3-[(E)-[1-(furan-2-ylmethyl)-4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)-N-(2-methoxyethyl)acetamide
-
2-(3-[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)-N-(3-methoxypropyl)acetamide
-
2-(3-[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)-N-(tetrahydrofuran-2-ylmethyl)acetamide
-
2-(3-[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)acetamide
-
2-(3-[(Z)-[1-(furan-2-ylmethyl)-4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)-N-(tetrahydrofuran-2-ylmethyl)acetamide
-
2-([[(6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl)sulfanyl]acetyl]amino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide
-
2-([[1-(4-chlorophenyl)-1H-tetrazol-5-yl]sulfanyl]methyl)quinazolin-4(1H)-one
-
2-amino-7-[4-[(3-fluorobenzyl)oxy]phenyl]-6,7-dihydro[1,3]thiazolo[4,5-b]pyridin-5(4H)-one
-
2-[(4-methylquinazolin-2-yl)amino]-6-[(pyridin-2-ylsulfanyl)methyl]pyrimidin-4(3H)-one
-
2-[1-(2-chloro-4-fluorobenzyl)-3-oxopiperazin-2-yl]-N-cyclooctylacetamide
-
2-[1-(3-methoxybenzyl)-3-oxopiperazin-2-yl]-N-[[1-(2-methylphenyl)-1H-pyrazol-4-yl]methyl]acetamide
-
3-[(5E)-5-(2-chlorobenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-N-(adamantan-1-yl)propanamide
-
6-amino-4-[3-(benzyloxy)phenyl]-3-methyl-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
-
benzyloxycarbonyl-Val-Glu(OMe)-Ile-Asp(OMe)-fluoromethyl ketone
-
caspase-6-selective inhibitor
carbobenzyloxy-VAD-fluoromethyl ketone
-
i.e. zVAD-fmk, a broad-spectrum caspase inhibitor, which inhibits activation of caspase-6 and caspase-3, but not of caspase-7
methyl 3-([[(2,3-dimethyl-1H-indol-7-yl)carbonyl]amino]methyl)-5-[(furan-2-ylcarbonyl)amino]benzoate
-
methyl 3-[(furan-2-ylcarbonyl)amino]-5-([[(5-methyl-3-phenyl-1,2-oxazol-4-yl)carbonyl]amino]methyl)benzoate
-
methyl 3-[([[1-(4-chlorophenyl)cyclobutyl]carbonyl]amino)methyl]-5-[(furan-2-ylcarbonyl)amino]benzoate
-
methyl 3-[[(2,2-dimethylpropanoyl)amino]methyl]-5-[(furan-2-ylcarbonyl)amino]benzoate
-
methyl 3-[[(2,3-dihydro-1-benzofuran-2-ylcarbonyl)amino]methyl]-5-[(furan-2-ylcarbonyl)amino]benzoate
-
methyl 3-[[(2,3-dihydro-1-benzofuran-2-ylcarbonyl)amino]methyl]-5-[(phenylacetyl)amino]benzoate
-
methyl 3-[[(3,5-dimethylbenzoyl)amino]methyl]-5-[(furan-2-ylcarbonyl)amino]benzoate
-
N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carboxamide
-
N-(furan-2-ylmethyl)-2-(3-[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)acetamide
-
N-acetyl-L-alpha-aspartyl-L-alpha-glutamyl-N-[(2S)-1-carboxy-3-oxopropan-2-yl]-L-valinamide
N-[(2R)-1-(3-cyanophenyl)-3-hydroxypropan-2-yl]-5-(3,4-dimethoxyphenyl)furan-3-carboxamide
selective inhibitor
SB203580
-
a p38 inhibitor, also inhibits activation of caspase-6, caspase-3, and caspase-7
Sox11
reduces caspase-6 activity and prevents caspase-6 self-cleavage. Several regions, including amino acids 117-214 and 362-395 within sox11 as well as a nuclear localization signal (NLS) all contribute to the reduction in caspase-6 activity
-
Zn2+
caspase-6 is allosterically inhibited by zinc and binds one zinc/monomer at an exosite distal from the active site. Complete inhibition at 0.0015 mM
ZVEID-fmk
-
caspase 6-specific inhibitor, reduces apoptosis and prevents periplakin cleavage in adherent cells, although it does not completely prevent cells from detaching
[1-(3,4-dichlorobenzyl)-2-oxo-5-(piperidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-(3,4-dichlorobenzyl)-2-oxo-5-(pyrrolidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-(3,4-dichlorobenzyl)-2-oxo-5-(thiomorpholin-4-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-(3,4-dichlorobenzyl)-5-(morpholin-4-ylsulfonyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-(4-methoxybenzyl)-2-oxo-5-(piperidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-(4-methoxybenzyl)-2-oxo-5-(pyrrolidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-(4-methoxybenzyl)-2-oxo-5-(thiomorpholin-4-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-(4-methoxybenzyl)-5-(morpholin-4-ylsulfonyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-benzyl-2-oxo-5-(piperidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-benzyl-2-oxo-5-(pyrrolidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-benzyl-2-oxo-5-(thiomorpholin-4-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[1-benzyl-5-(morpholin-4-ylsulfonyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[5-(azetidin-1-ylsulfonyl)-1-(3,4-dichlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[5-(azetidin-1-ylsulfonyl)-1-(4-methoxybenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
[5-(azetidin-1-ylsulfonyl)-1-benzyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
-
-
Ac-VEID-CHO
a reversible caspase-6 inhibitor, enzyme-inhibitor complex structure, overview
N-acetyl-L-alpha-aspartyl-L-alpha-glutamyl-N-[(2S)-1-carboxy-3-oxopropan-2-yl]-L-valinamide
-
pan-caspase inhibitor
N-acetyl-L-alpha-aspartyl-L-alpha-glutamyl-N-[(2S)-1-carboxy-3-oxopropan-2-yl]-L-valinamide
-
-
additional information
-
because the mutant pro-Casp6C163A is not cleaved in serum-deprived conditions and is a dominant negative inhibitor of Casp6 activation
-
additional information
-
carbobenzyloxy-LEHD-fluoromethyl ketone specifically inhibits initiator caspase-9 upstream of caspase-3 and caspase-3 activation, but fails to inhibit caspase-6 and caspase-7 activation
-
additional information
-
development and synthesis of nonpeptidic caspase-6 inhibitors, overview. No inhibition of caspase-6 by Ac-IETD-CHO, Ac-YVAD-CHO, and Ac-DEVD-CHO
-
additional information
-
alternatively spliced caspase-6B isoform inhibits the proteolytic self-activation of caspase-6A in vitro and in cells. But purified bacterially expressed recombinant pro-Casp6b does not possess catalytic activity and does not inhibit the active form of Casp6a
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
adriamycin
-
increases caspase-6 mRNA levels in HCT116 p53+ and neo cells but not in E6 cells
RCasp1
-
mediates increased self-processing of pro-Casp6a into its active subunits
-
Tumor necrosis factor alpha
-
activates caspase-6 which in turn cleaves transcription factor AP2alpha
-
resveratrol
-
activates caspase-6, and interacts in a synergistic manner with 5-fluorouracil. In p53-deficient cells it activates 5-fluorouracil-induced apoptosis and caspase-6 activity at low and high doses, while in P53 containing cells, it inhibits the activations at low concentrations, overview
additional information
-
caspase-6 can be entirely self-activated through self-processing, the prodomain of Casp6 entirely prevents self-processing and activation in vivo but not in vitro, removal of the pro-domain promotes Casp6 activation
-
additional information
-
glycochenodeoxycholic acid induces activation of caspase-6, which is inhibited by inhibition of caspase-9
-
additional information
-
ZBP-89, a Kruppel-type, zinc finger transcription factor, induces caspase-6 activation leading to inhibition of cell death in hepatoccellular carcinoma cells, inhibition of caspase-6 abolishes the effect of ZBP-89
-
additional information
-
activation of CASP6 in response to ischemia-induced injury. Activation by proteolytic self-cleavage, during activation, the N-terminal prodomain is removed by cleavage at a TETD site. Double cleavage in an unstructured linker region at a DVVD and a TEVD site gives rise to a large 20-kDa and a small 10-kDa subunit. The two large p20 and two small p10 subunits then assemble to form the active CASP6 complex
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.08
(N-acetyl-VEID)2-rhodamine110
in 50 mM HEPES (pH 7.0), 25 mM MgSO4, 0.5 mM EGTA, 5 mM glutathione, 0.01% (v/v) Triton X-100 containing 0.1% (w/v) bovine gamma-globulin, at 22°C
0.0227
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme A34E
0.0312
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7., wild-type enzyme
0.0326
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme K284A
0.0333
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme T182S
0.0345
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme A109T
0.0371
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme E35K
0.315
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme L200A
0.02371
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
pH 7.5, 37°C, mutant enzyme R44K
0.0277
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
pH 7.5, 37°, wild-type enzyme
0.03063
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
pH 7.5, 37°C, mutant enzyme R42A/R43A/R44A
0.082
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme E244A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.093
N-acetyl-VEID-7-amido-4-methylcoumarin
wild type enzyme, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.109
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme K36A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.14
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme H287A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.176
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme E244A/H287A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme L200A
1.71
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme E35K
2
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme K284A
2.04
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme A34E
2.27
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, wild-type enzyme
2.42
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme T182S
2.51
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme A109T
1.39
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
pH 7.5, 37°C, mutant enzyme R44K
1.59
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
pH 7.5, 37°, wild-type enzyme
1.66
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
pH 7.5, 37°C, mutant enzyme R42A/R43A/R44A
0.015
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme E244A/H287A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.051
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme E244A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.309
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme H287A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.371
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme K36A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.7
N-acetyl-VEID-7-amido-4-methylcoumarin
wild type enzyme, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.39
receptor-interacting protein kinase-1
-
in 0.8 M sodium citrate, 20 mM PIPES, 100 mM NaCl, pH 7.2, 5 mM dithiothreitol, at 37°C
-
0.15
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme L200A
46.833
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme E35K
58.65
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme K284A
72.65
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme T182S
72.68
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme A109T
76
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7., wild-type enzyme
89.8
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
37°C, pH 7.2, mutant enzyme A34E
51.9
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
pH 7.5, 37°C, mutant enzyme R44K
54.7
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
pH 7.5, 37°C, mutant enzyme R42A/R43A/R44A
58.3
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
pH 7.5, 37°, wild-type enzyme
100
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme E244A/H287A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
600
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme E244A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
2200
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme H287A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
3400
N-acetyl-VEID-7-amido-4-methylcoumarin
mutant enzyme K36A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
7500
N-acetyl-VEID-7-amido-4-methylcoumarin
wild type enzyme, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00015
Zn2+
wild type enzyme, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.003
Zn2+
mutant enzyme E244A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.0046
Zn2+
mutant enzyme K36A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.007
Zn2+
mutant enzyme H287A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.0072
Zn2+
mutant enzyme E244A/H287A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0164
(5Z)-1-(furan-2-ylmethyl)-5-([1-[2-(2-methylpiperidin-1-yl)-2-oxoethyl]-1H-indol-3-yl]methylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
Homo sapiens
37°C, pH 6.8
0.0076
(5Z)-1-(furan-2-ylmethyl)-5-([1-[2-(morpholin-4-yl)-2-oxoethyl]-1H-indol-3-yl]methylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
37°C, pH 6.8
0.0128
(5Z)-1-(furan-2-ylmethyl)-5-([1-[2-(morpholin-4-yl)-2-oxoethyl]-1H-indol-3-yl]methylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
Homo sapiens
37°C, pH 6.8
0.011
(5Z)-1-(furan-2-ylmethyl)-5-([1-[2-oxo-2-(piperidin-1-yl)ethyl]-1H-indol-3-yl]methylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
Homo sapiens
37°C, pH 6.8
0.0098
(5Z)-1-(furan-2-ylmethyl)-5-([1-[2-oxo-2-(pyrrolidin-1-yl)ethyl]-1H-indol-3-yl]methylidene)pyrimidine-2,4,6(1H,3H,5H)-trione
Homo sapiens
37°C, pH 6.8
0.0015
1-(3,4-dichlorobenzyl)-5-(morpholin-4-ylsulfonyl)-1H-indole-2,3-dione
Homo sapiens
-
above
0.0165
2-(3-[(E)-[1-(furan-2-ylmethyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)-N-(2-methoxyethyl)acetamide
Homo sapiens
37°C, pH 6.8
0.0168
2-(3-[(E)-[1-(furan-2-ylmethyl)-4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)-N-(2-methoxyethyl)acetamide
Homo sapiens
37°C, pH 6.8
0.0129
2-(3-[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)-N-(3-methoxypropyl)acetamide
Homo sapiens
37°C, pH 6.8
0.0302
2-(3-[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)-N-(tetrahydrofuran-2-ylmethyl)acetamide
Homo sapiens
37°C, pH 6.8
0.0105
2-(3-[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)acetamide
Homo sapiens
37°C, pH 6.8
0.0044
2-(3-[(Z)-[1-(furan-2-ylmethyl)-4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)-N-(tetrahydrofuran-2-ylmethyl)acetamide
Homo sapiens
37°C, pH 6.8
0.1095
2-([[(6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl)sulfanyl]acetyl]amino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide
Homo sapiens
37°C, pH 6.8
0.1418
2-([[1-(4-chlorophenyl)-1H-tetrazol-5-yl]sulfanyl]methyl)quinazolin-4(1H)-one
Homo sapiens
37°C, pH 6.8
0.289
2-amino-7-[4-[(3-fluorobenzyl)oxy]phenyl]-6,7-dihydro[1,3]thiazolo[4,5-b]pyridin-5(4H)-one
Homo sapiens
37°C, pH 6.8
0.2334
2-[(4-methylquinazolin-2-yl)amino]-6-[(pyridin-2-ylsulfanyl)methyl]pyrimidin-4(3H)-one
Homo sapiens
37°C, pH 6.8
0.0464
2-[1-(2-chloro-4-fluorobenzyl)-3-oxopiperazin-2-yl]-N-cyclooctylacetamide
Homo sapiens
37°C, pH 6.8
0.0441
2-[1-(3-methoxybenzyl)-3-oxopiperazin-2-yl]-N-[[1-(2-methylphenyl)-1H-pyrazol-4-yl]methyl]acetamide
Homo sapiens
37°C, pH 6.8
0.123
3-[(5E)-5-(2-chlorobenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-N-(adamantan-1-yl)propanamide
Homo sapiens
37°C, pH 6.8
0.159
6-amino-4-[3-(benzyloxy)phenyl]-3-methyl-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
Homo sapiens
37°C, pH 6.8
1.922
methyl 3-(aminomethyl)-5-[(furan-2-ylcarbonyl)amino]benzoate
Homo sapiens
37°C, pH 6.8
0.719
methyl 3-([[(2,3-dimethyl-1H-indol-7-yl)carbonyl]amino]methyl)-5-[(furan-2-ylcarbonyl)amino]benzoate
Homo sapiens
37°C, pH 6.8
2.047
methyl 3-[(furan-2-ylcarbonyl)amino]-5-([[(5-methyl-3-phenyl-1,2-oxazol-4-yl)carbonyl]amino]methyl)benzoate
Homo sapiens
37°C, pH 6.8
0.027
methyl 3-[([[1-(4-chlorophenyl)cyclobutyl]carbonyl]amino)methyl]-5-[(furan-2-ylcarbonyl)amino]benzoate
Homo sapiens
37°C, pH 6.8
3.37
methyl 3-[[(2,2-dimethylpropanoyl)amino]methyl]-5-[(furan-2-ylcarbonyl)amino]benzoate
Homo sapiens
37°C, pH 6.8
0.0132
methyl 3-[[(2,3-dihydro-1-benzofuran-2-ylcarbonyl)amino]methyl]-5-[(furan-2-ylcarbonyl)amino]benzoate
Homo sapiens
37°C, pH 6.8
1.545
methyl 3-[[(2,3-dihydro-1-benzofuran-2-ylcarbonyl)amino]methyl]-5-[(phenylacetyl)amino]benzoate
Homo sapiens
37°C, pH 6.8
0.0215
methyl 3-[[(3,5-dimethylbenzoyl)amino]methyl]-5-[(furan-2-ylcarbonyl)amino]benzoate
Homo sapiens
37°C, pH 6.8
0.09
N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carboxamide
Homo sapiens
37°C, pH 6.8
0.0042
N-(furan-2-ylmethyl)-2-(3-[(Z)-[1-(furan-2-ylmethyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl]-1H-indol-1-yl)acetamide
Homo sapiens
37°C, pH 6.8
0.0799
N-(furan-2-ylmethyl)-2-[3-(phenoxyacetyl)-1H-indol-1-yl]acetamide
Homo sapiens
37°C, pH 6.8
0.000011
N-[(2R)-1-(3-cyanophenyl)-3-hydroxypropan-2-yl]-5-(3,4-dimethoxyphenyl)furan-3-carboxamide
Homo sapiens
in 50 mM HEPES (pH 7.0), 25 mM MgSO4, 0.5 mM EGTA, 5 mM glutathione, 0.01% (v/v) Triton X-100 containing 0.1% (w/v) bovine gamma-globulin, at 22°C
0.02
N-[[5-(3,4-dimethoxyphenyl)-2-methylfuran-3-yl]carbonyl]phenylalanine
Homo sapiens
in 50 mM HEPES (pH 7.0), 25 mM MgSO4, 0.5 mM EGTA, 5 mM glutathione, 0.01% (v/v) Triton X-100 containing 0.1% (w/v) bovine gamma-globulin, at 22°C
0.000568
[1-(3,4-dichlorobenzyl)-2-oxo-5-(piperidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000468
[1-(3,4-dichlorobenzyl)-2-oxo-5-(pyrrolidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.00023
[1-(3,4-dichlorobenzyl)-2-oxo-5-(thiomorpholin-4-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000592
[1-(3,4-dichlorobenzyl)-5-(morpholin-4-ylsulfonyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000545
[1-(4-methoxybenzyl)-2-oxo-5-(piperidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000358
[1-(4-methoxybenzyl)-2-oxo-5-(pyrrolidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000188
[1-(4-methoxybenzyl)-2-oxo-5-(thiomorpholin-4-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000453
[1-(4-methoxybenzyl)-5-(morpholin-4-ylsulfonyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000325
[1-benzyl-2-oxo-5-(piperidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000241
[1-benzyl-2-oxo-5-(pyrrolidin-1-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000151
[1-benzyl-2-oxo-5-(thiomorpholin-4-ylsulfonyl)-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000425
[1-benzyl-5-(morpholin-4-ylsulfonyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.00028
[5-(azetidin-1-ylsulfonyl)-1-(3,4-dichlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000197
[5-(azetidin-1-ylsulfonyl)-1-(4-methoxybenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.000156
[5-(azetidin-1-ylsulfonyl)-1-benzyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]propanedinitrile
Homo sapiens
-
-
0.0034
Zn2+
Homo sapiens
wild type enzyme, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.0107
Zn2+
Homo sapiens
mutant enzyme E244A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.0158
Zn2+
Homo sapiens
mutant enzyme K36A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
0.0249
Zn2+
Homo sapiens
mutant enzyme H287A, in 100 mM HEPES, pH 7.5, 10% (w/v) sucrose, 0.1% (w/v) CHAPS, 20 mM TCEP, and 120 mM NaCl, at 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
additional information
caspase-6 activity is optimal around neutral pH and is almost entirely lost at pH 5.0 and below
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
647462, 647463, 647464, 647465, 647466, 647467, 647468, 647471, 647472, 647473, 667134, 667462, 668193, 668194, 668908, 669243, 669749, 669944, 670437, 670722, 670854, 677621, 679034, 680072, 696453, 697069, 697089, 697790, 698943, 699459, 700196, 700524, 703561
-
-
-
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
A549 cell line infected by unencapsulated Streptococcus pneumoniae type 2 strain R6x and capsulated Streptococcus pneumoniae strain D39 and the pneumolysin-deficient R6xply mutant
-
BEAS-2B cell line infected by unencapsulated Streptococcus pneumoniae type 2 strain R6x
-
keloid fioblasts show a decreased expression of apoptosis-related genes compared to scars
additional information
-
caspase-6 is elevated in Huntington disease brain, active caspase-6 is present in post mortem brains of Huntington and Alzheimer disease subjects that do not yet display apoptotic morphology
-
invasive operable pT1 and pT2 ductal breast carcinoma are analysed of 210 patients: caspase-6 is overexpressed in 52.9%
-
a human hepatoma cell line expressing the sodium taurocholate cotransporting polypeptide, Ntcp
-
transfected with Ntcp, sodium taurocholate cotransporting polypeptide
-
a human hepatoma cell line expressing the sodium taurocholate cotransporting polypeptide, Ntcp
-
primary neurons, active caspase-6 is localized in neuritic plaques, in neuropil threads, and in neurofibrillary tangles containing neurons that are not morphologically apoptotic in nature
additional information
-
p53 up-regulates caspase -6mRNA in H460, H460-neo, H460-E6, HCT16-neo, HCT16-E6, HCT16-P53-, SKBR3, U2OS, M3, HCC1937 and SW13 cell lines, MCF7 cells fail to show induction of caspase 6-mRNA
additional information
-
present in neurophil threads and neuritic plaques, not in the cerebellum
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
active Csp-6 is not present in the nuclei of Alzheimer´s disease neurons
-
-
caspase shows predominant cytoplasmic with some nuclear staining
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
the caspase-cleavage motifs in teleomerases from old world monkeys and apes, and the caspase-6 sites appear conserved in all primates
malfunction
physiological function
additional information
-
the pro-Casp6b protein resulting from CASP6beta translation lacks part of the pro-domain and part of the large p20 subunit of pro-Casp6a
malfunction
-
gene deletion of caspase-6 did not affect the outcome of brain injury following mild (50 min) or severe (60 min) hypoxia-ischaemia
malfunction
caspase-6 down-regulation suppresses 7A6 localization to mitochondria
malfunction
the excess neuronal activity of Caspase-6 is associated with Alzheimer disease neuropathology and age-dependent cognitive impairment
physiological function
-
alternatively spliced caspase-6B isoform inhibits the activation of caspase-6A. Pro-Casp6b can negatively regulate pro-Casp6a activation in neurons and prevent Casp6a-mediated axonal degeneration. Pro-Casp6b inhibits RCasp1-mediated processing of Pro-Casp6a in vitro
physiological function
-
caspase-6 is a cysteinyl protease implicated in neurodegenerative conditions including Alzheimer's and Huntington's diseases
physiological function
caspase-6 is a key component in the pathway of neurodegenerative diseases such as Alzheimer's disease and Huntington's diseases
physiological function
-
caspase-6 is an end-stage executioner caspase with an important role in nuclear apoptosis by cleaving the nuclear structural protein NuMA and the lamin proteins, which induces nuclear shrinkage and fragmentation. Roles for CASP6 in neurodegenerative diseases, including Huntington disease and Alzheimer disease, signaling pathway leading to activation of caspases and neurodegeneration in Huntington disease, overview. Caspase cleavage of proteins involved in autophagic pathways also occurs and may contribute to the reduction in protein clearance observed in some neurodegenerative diseases. Caspase-6 cleaves also caspases-2, 3 and 8. Role of caspase-6 in neurodegeneration, overview. Activation of CASP6 as a crucial step in the pathogenesis of stroke, activation of CASP6 in response to ischemia-induced injury
physiological function
-
telomerase can inhibit or activate apoptosis depending upon cell type and experimental conditions, mechanism for telomerase downregulation through caspase-mediated cleavage
physiological function
-
caspase-6 activity in the CA1 region of the hippocampus induces age-dependent memory impairment
physiological function
caspase-6 activity is intimately associated with the pathologies of Alzheimer's disease. The enzyme is already highly abundant at the beginning of the symptomatic phase of the disease. Caspase-6 activation is necessary for increased amyloid beta levels in serum-deprived primary human neurons. Caspase cleavage of tau protein impairs microtubule polymerization and stability, and may lead to tangle formation. The enzyme also plays a role in axonal degeneration of both peripheral and central nervous system
physiological function
-
caspase-6 has a supporting role in apoptosis by cleaving receptor-interacting-kinase-1, thus preventing production of inflammatory cytokines as well as inhibiting the necroptotic pathway
physiological function
-
the impact of caspase-6 on the developing brain is subtle and the enzyme is not essential for the cell death processes in the immature brain
physiological function
an exosite tri-arginine patch, 42RRR44, located within the disordered N-terminal domain on caspase-6 is critical for protein substrate recognition and turnover and therefore highly relevant for diseases such as cancer in which caspase-6-mediated apoptosis is often disrupted, and in neurodegeneration in which caspase-6 plays a central role
physiological function
caspase-6 is highly involved in axon degeneration and neurodegenerative diseases, such as Huntington's disease and Alzheimer's disease
physiological function
caspase-6 regulates 7A6 localization to mitochondria during anti-FAS-induced apoptosis of Jurkat cells
physiological function
the enzyme plays essential roles in programmed cell death, axonal degeneration, and development
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CASP6_HUMAN
293
0
33310
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
34000
35000
-
x * 35000, Western blot analysis, small subunit (15000) resulting from cleavage at Asp194
additional information
Mch2alpha transcript encodes the full-length Mch2, whereas the Mch2beta transcript encodes a shorter Mch2 isoform, probably as a result of alternative slicing
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
2 * 32183.5, mass spectrometry, dimer: 63070, multi-angle light scattering, 58000, ultracentrifugation, after proteolytic maturation each subunit of the active enzyme is a two-chain molecule consisting of the p18 (19668.1 Da, residues 24-179) and p11 (12563.5 Da, residues 194-293), mass spectrometry
additional information
?
-
x * 35000, Western blot analysis, small subunit (15000) resulting from cleavage at Asp194
?
x * about 30000, caspase-6 with a 23-amino-acid deletion in the pro-domain, SDS-PAGE
dimer
-
procaspase 6, SDS-PAGE, chemical cross-linking and gel filtration, nearly identical CD spectra of rCaspase 6 and D316A caspase 6, indicating that overal structures of both precursor and mature forms of caspase 6 should be almost indistinguishable
additional information
-
cyclin B1 migrates anomalously on SDS-PAGE with 48 kDa predicted size versus 67 kDa experimental size
additional information
-
activation by proteolytic self-cleavage, during activation, the N-terminal prodomain is removed by cleavage at a TETD site. Double cleavage in an unstructured linker region at a DVVD and a TEVD site gives rise to a large 20-kDa and a small 10-kDa subunit. The two large p20 and two small p10 subunits then assemble to form the active CASP6 complex
additional information
active canonical conformation of the apoenzyme apo-caspase-6, comparison to the apostructure of pH-inactivated caspase-6,crystal structure analysis, overview. Caspase-6 subunits p20 and p10 comprise residues 24179 and 194293, respectively
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
-
viral nucleocapsid protein of transmissible gastroenteritis coronavirus triggers the processing of procaspase 6 in human rectal tumor cell line HRT18jap1
proteolytic modification
-
caspase-6 is inactive until the short 23 amino acid prodomain is removed
proteolytic modification
-
activation through cleavage mainly by caspase-8, partly by caspase-2 and caspase-9
proteolytic modification
-
caspase-6 activates itself through self-processing, processing at either intersubunit linker sites D23, D179 and D193, the prodomain of Casp6 entirely prevents self-processing and activation in vivo but not in vitro, removal of the pro-domain promotes Casp6 activation. Processing of caspase-6 mutants by recombinant caspase-3, overview
proteolytic modification
-
activation by proteolytic self-cleavage, during activation, the N-terminal prodomain is removed by cleavage at a TETD site. Double cleavage in an unstructured linker region at a DVVD and a TEVD site gives rise to a large 20-kDa and a small 10-kDa subunit. The two large p20 and two small p10 subunits then assemble to form the active CASP6 complex
proteolytic modification
-
pro-forms of caspase-6 isozymes need to be proteolytically self-activated. RCasp1-mediated increased processing of pro-Casp6a, while pro-Casp6b inhibits pro-Casp6a activationinto its active subunits
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, using 0.1 M sodium acetate, pH 4.6, 2 M NaCl, and 3% (v/v) ethanol
in complex with benzyloxycarbonyl-VEID, using 12% (w/v) PEG 3350, 0.2 M sodium malonate pH 4.0
recombinant caspase-6 comprising residues 24179 and 194293 after self-cleavage of the zymogen, overall structure of the four caspase-6 p202/p102 tetramers in the asymmetric unit, and caspase-6 in complex with inhibitor Ac-VEID-CHO, hanging-drop vapor diffusion method, mixing of 0.001 ml protein solution containing 20 mM sodium acetate, pH 5.5, 50 mM NaCl, and 0.5 mM Tris(hydroxypropyl)phosphine with 0.001 ml of reservoir solution consisting of 3.3 M sodium nitrate, 0.1 M Tris, pH 7.4, 0.5% ethyl acetate, and 5 mM Tris(hydroxypropyl)phosphine, and microseeding, 1 week, 20°C, X-ray diffraction structure determination and analysis at 2.53 A resolution, molecular replacement, structure comparisons, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A109T
missense rare variants with amino acid substitution located remotely from Casp6 active site. Activity with the substrate Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin is comparable to that of wild-type enzyme. No significant changes in kinetic parameters, KM, and kcat, for Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
A34E
missense rare variants with amino acid substitution located remotely from Casp6 active site. Lower activity than wild-type enzyme with the substrate Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin. No significant changes in kinetic parameters, KM, and kcat, for Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
C163A
C163S
D163A
-
site-directed mutagenesis, uncleavable and catalytically inactive mutant of pro-caspase-6
D179A
-
site-directed mutagenesis, the mutant of pro-caspase-6 is altered in one cleavage site residue, and is about half as catalytically active as the wild-type enzyme
D179A/D193A
-
site-directed mutagenesis, the mutant of pro-caspase-6 is altered in two cleavage site residues, and is catalytically inactive
D193A
-
site-directed mutagenesis, uncleavable and catalytically inactive mutant of pro-caspase-6
D23A
-
site-directed mutagenesis, the mutant of pro-caspase-6 is altered in one cleavage site residue, but is still catalytically active similar to the wild-type enzyme
D23A/D179A
-
site-directed mutagenesis, the mutant of pro-caspase-6 is altered in two cleavage site residues, and is only slightly to not catalytically active
D23A/D179A/D193A
-
site-directed mutagenesis, the triple mutant of pro-caspase-6 is altered in three cleavage site residues becoming uncleavable for activation and thus is catalytically inactive or very poorly active
D23A/D193A
-
site-directed mutagenesis, the mutant of pro-caspase-6 is altered in two cleavage site residues, and is catalytically inactive
D316A
-
to prevent autocatalytic processing of the specific site of procaspase 6, Asp316 of rCaspase 6 is replaced with Ala
E244A
the function of the mutant is crippled by 2fold compared to the wild type enzyme
E244A/H287A
the function of the mutant is crippled by 47fold compared to the wild type enzyme
E35K
missense rare variants with amino acid substitution located remotely from Casp6 active site. Lower activity than wild-type enzyme with the substrate Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin. Slightly reduced kcat and about 2fold reduced catalytic efficiency kcat/KM
H287A
the function of the mutant is crippled by 14fold compared to the wild type enzyme
K36A
the function of the mutant is crippled by 2fold compared to the wild type enzyme
R42A/R43A/R44A
substitutions of the tri-arginine patch Arg-42-Arg-44 markedly alters rates of protein substrate hydrolysis. Turnover of protein substrates but not of short peptide substrates is affected. The mutant is unable to fully hydrolyze itself to the mature form
R44K
cancer-associated mutation markedly alters rates of protein substrate hydrolysis. Turnover of protein substrates but not of short peptide substrates is affected
S257A
-
mutant caspase-6, not phosphorylated in the presence of active AMPK-related kinase 5
T182S
missense rare variants with amino acid substitution located remotely from Casp6 active site. Lower activity than wild-type enzyme with the substrate Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin. No significant changes in kinetic parameters, KM, and kcat, for Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin
additional information
C163S
the mutant is catalytically inactive and not capable of self-cleavage
additional information
-
a flag-tagged dominant-negative caspase-6 point mutant is expressed in Saos-2 cells
additional information
-
downregulation of caspase-6 by siRNA reduces bile acid-induced apoptosis and caspase-8 activation in Hep-G2-Ntcp cells
additional information
-
generation of stable caspase-6 knockdown cell lines using K562 cells. Mutations at residues D442, D444, D516, D768, and D936 do not prevent cleavage in vitro
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
immobilized metal ion affinity chromatography (Ni2+), hydrophobic interaction chromatography, gel filtration
recombinant His-tagged apo-caspase-6 and caspase-6 from Escherichia coli by nickel affinity chromatography and gel filtration
recombinant His-tagged pro-Casp6b from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, recombinant catalytic mutant pro-Casp6aC163A from Escherichia coli strain BL21(DE3)
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
a caspase-6 with a 23-amino-acid deletion in the pro-domain is expressed in Escherichia coli BL21 Codon Plus (DE3) RIL cells
Casp6 genetic organization, expression of His-tagged wild-type and mutant pro-caspase-6 in Escherichia coli and in HEK-293T cells
-
recombinant DELTA23 caspase-6 and DELTA23 caspase-6 mutant C163S with C-terminal His-tag are expressed in Escherichia coli BL21 codon plus (DE3) RIL cells
the CASP6 gene generates an alternatively spliced transcript known as CASP6beta in addition to the CASP6alpha transcript that encodes pro-Casp6a. Individual expression of His-tagged pro-Casp6b and of catalytic mutant pro-Casp6aC163A in Escherichia coli strain BL21(DE3), Expression of pro-Casp6b from the pCep4beta construct in SK-N-SH cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
molecular biology
drug development
-
selective inhibitors of caspase-6 may have therapeutic potential for various neurodegenerative disorders
drug development
-
the enzyme is a target for therapeutic intervention in Alzheimer's and Huntington's diseases
medicine
-
caspase-6 is active early in the pathogenesis of Alzheimer´s disease, the enzyme is strongly implicated in human neuronal degeneration and apoptosis, its inhibition may be an efficient treatment
medicine
-
caspase-6 is phosphorylated by AMP-activated protein kinase related kinase 5 at Ser257 in colorectal cancer cells, leading to inactivation of caspase-6 and resulting in resistance to cell death via cFLIPs protection and leading to resistance to the FAS ligand/Fas system
medicine
-
caspase-6 is upregulated in response to p53 overexpression, induction of caspase-6 expression lowers the cell death threshold in response to apoptotic signals that activate caspase-6, potential mechanism of lowering the death threshold, which could be important for chemosensitization
medicine
-
critical role of caspase-6 and its cleavage of lamin A in apoptotic signaling triggered by resveratrol in the colon carcinoma cells
medicine
-
role for caspase-6 and N-terminal truncation of tau during neurovibrillary tangle evolution and the progression of Alzheimer´s disease
medicine
-
Streptococcus pneumoniae induces apoptosis of human alveolar and bronchial epithelial cells, programmed cell death is excecuted by caspase 6, and can be blocked by overexpression of Bcl2
medicine
-
compared to caspase-3 there is a siginificant correlation between caspase-6 protein and necrosis and proliferation index of the analysed tumors
medicine
-
lamin A/C cleavage by caspase-6 is crucial for apoptotic induction by photodynamic therapy with hexaminolevulinate in human B-cell lymphoma cells
medicine
caspase-6 inhibition is a promising strategy to stop early stage neurodegenerative events
molecular biology
-
it is shown that caspase-6 is the major caspase responsible for the death of cells infected with Adeno-associated virus (AAV) infection
molecular biology
-
it is shown that trifolin acetate-induced cell death in human leukemia cells is dependent on caspase-6
molecular biology
-
the results show that caspase-1 is an upstream positive regulator of caspase-6-mediated cell death in primary human neurons
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Strausberg R.L.; Feingold E.A.; Grouse L.H.; Derge J.G.; et al.
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences
Proc. Natl. Acad. Sci. USA
99
16899-16903
2002
Homo sapiens (P55212)
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 (P55212)
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
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
Chang, H.Y.; Yang, X.
Proteases from cell suicide: functions and regulation of caspases
Microbiol. Mol. Biol. Rev.
64
821-846
2000
Homo sapiens
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
Fernandes-Alnemri, T.; Litwack, G.; Alnemri, E.S.
Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family
Cancer Res.
55
2737-2742
1995
Homo sapiens (P55212)
Cowling, V.; Downward, J.
Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain
Cell Death Differ.
9
1046-1056
2002
Homo sapiens
Eleouet, J.F.; Slee, E.A.; Saurini, F.; Castagne, N.; Poncet, D.; Garrido, C.; Solary, E.; Martin, S.J.
The viral nucleocapsid protein of transmissible gastroenteritis coronavirus (TGEV) is cleaved by caspase-6 and -7 during TGEV-induced apoptosis
J. Virol.
74
3975-3983
2000
Homo sapiens
Galande, S.; Dickinson, L.A.; Mian, I.S.; Sikorska, M.; Kohwi-Shigematsu, T.
SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis
Mol. Cell. Biol.
21
5591-5604
2001
Homo sapiens
Mahoney, J.A.; Odin, J.A.; White, S.M.; Shaffer, D.; Koff, A.; Casciola-Rosen, L.; Rosen, A.
The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during apoptosis
Biochem. J.
361
587-595
2002
Homo sapiens
Nyormoi, O.; Wang, Z.; Doan, D.; Ruiz, M.; McConkey, D.; Bar-Eli, M.
Transcription factor AP-2alpha is preferentially cleaved by caspase 6 and degraded by proteasome during tumor necrosis factor alpha-induced apoptosis in breast cancer cells
Mol. Cell. Biol.
21
4856-4867
2001
Homo sapiens
Nyormoi, O.; Wang, Z.; Bar-Eli, M.
Sequence-based discovery of a synthetic peptide inhibitor of caspase 6
Apoptosis
8
371-376
2003
Homo sapiens
Hill, J.; Duckworth, M.; Murdock, P.; Rennie, G.; Sabido-David, C.; Ames, R.S.; Szekeres, P.; Wilson, S.; Bergsma, D.J.; Gloger, I.S.; Levy, D.S.; Chambers, J.K.; Muir, A.I.
Molecular cloning and functional characterization of MCH2, a novel human MCH receptor
J. Biol. Chem.
276
20125-20129
2001
Homo sapiens
Talanian, R.V.; Quinlan, C.; Trautz, S.; Hackett, M.C.; Mankovich, J.A.; Banach, D.; Ghayur, T.; Brady, K.D.; Wong, W.W.
Substrate specificities of caspase family proteases
J. Biol. Chem.
272
9677-9682
1997
Homo sapiens
Samejima, K.; Svigen, P.A.; Basi, G.S.; Kottke, T.; Mesner, P.W.; Stewart, L.; Durrieu, F.; Poirier, G.G.; Alnemri, E.S.; Champoux, J.J.; Kaufmann, S.H.; Earnshaw, W.C.
caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis
J. Biol. Chem.
274
4335-4340
1999
Homo sapiens
Hirata, H.; Takahashi, A.; Kobayashi, S.; Yonehara, S.; Sawai, H.; Okazaki, T.; Yamamoto, K.; Sasada, M.
Caspases are activated in a branched protease cascade and control didtinct downstream processes in fas-induced apoptosis
J. Exp. Med.
187
587-600
1998
Homo sapiens
Guo, H.; Albrecht, S.; Bourdeau, M.; Petzke, T.; Bergeron, C.; LeBlanc, A.C.
Active caspase-6 and caspase-6-cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer's disease
Am. J. Pathol.
165
523-531
2004
Homo sapiens
Kang, B.H.; Ko, E.; Kwon, O.K.; Choi, K.Y.
The structure of procaspase 6 is similar to that of active mature caspase 6
Biochem. J.
364
629-634
2002
Homo sapiens
Guo, H.; Petrin, D.; Zhang, Y.; Bergeron, C.; Goodyer, C.G.; LeBlanc, A.C.
Caspase-1 activation of caspase-6 in human apoptotic neurons
Cell Death Differ.
13
285-292
2006
Homo sapiens
Loegering, D.A.; Ruchaud, S.; Earnshaw, W.C.; Kaufmann, S.H.
Evaluation of the role of caspase-6 in anticancer drug-induced apoptosis
Cell Death Differ.
13
346-347
2006
Gallus gallus, Homo sapiens
Schmeck, B.; Gross, R.; N'Guessan, P.D.; Hocke, A.C.; Hammerschmidt, S.; Mitchell, T.J.; Rosseau, S.; Suttorp, N.; Hippenstiel, S.
Streptococcus pneumoniae-induced caspase 6-dependent apoptosis in lung epithelium
Infect. Immun.
72
4940-4947
2004
Homo sapiens
Foley, J.D.; Rosenbaum, H.; Griep, A.E.
Temporal regulation of VEID-7-amino-4-trifluoromethylcoumarin cleavage activity and caspase-6 correlates with organelle loss during lens development
J. Biol. Chem.
279
32142-32150
2004
Homo sapiens, Mus musculus, Rattus norvegicus
Kalinin, A.E.; Kalinin, A.E.; Aho, M.; Uitto, J.; Aho, S.
Breaking the connection: caspase 6 disconnects intermediate filament-binding domain of periplakin from its actin-binding N-terminal region
J. Invest. Dermatol.
124
46-55
2005
Homo sapiens
Horowitz, P.M.; Patterson, K.R.; Guillozet-Bongaarts, A.L.; Reynolds, M.R.; Carroll, C.A.; Weintraub, S.T.; Bennett, D.A.; Cryns, V.L.; Berry, R.W.; Binder, L.I.
Early N-terminal changes and caspase-6 cleavage of tau in Alzheimer's disease
J. Neurosci.
24
7895-7902
2004
Homo sapiens
Suzuki, A.; Kusakai, G.; Kishimoto, A.; Shimojo, Y.; Miyamoto, S.; Ogura, T.; Ochiai, A.; Esumi, H.
Regulation of caspase-6 and FLIP by the AMPK family member ARK5
Oncogene
23
7067-7075
2004
Homo sapiens
MacLachlan, T.K.; El-Deiry, W.S.
Apoptotic threshold is lowered by p53 transactivation of caspase-6
Proc. Natl. Acad. Sci. USA
99
9492-9497
2002
Homo sapiens
Lee, S.C.; Chan, J.; Clement, M.V.; Pervaiz, S.
Functional proteomics of resveratrol-induced colon cancer cell apoptosis: caspase-6-mediated cleavage of lamin A is a major signaling loop
Proteomics
6
2386-2394
2006
Homo sapiens
Torres, F.; Quintana, J.; Diaz, J.G.; Carmona, A.J.; Estevez, F.
Trifolin acetate-induced cell death in human leukemia cells is dependent on caspase-6 and activates the MAPK pathway
Apoptosis
13
716-728
2008
Homo sapiens
Garner, E.; Martinon, F.; Tschopp, J.; Beard, P.; Raj, K.
Cells with defective p53-p21-pRb pathway are susceptible to apoptosis induced by p84N5 via caspase-6
Cancer Res.
67
7631-7637
2007
Homo sapiens
Blazquez, S.; Sirvent, J.J.; Olona, M.; Aguilar, C.; Pelegri, A.; Garcia, J.F.; Palacios, J.
Caspase-3 and caspase-6 in ductal breast carcinoma: a descriptive study
Histol. Histopathol.
21
1321-1329
2006
Homo sapiens
Nassiri, M.; Woolery-Lloyd, H.; Ramos, S.; Jacob, S.E.; Gugic, D.; Viciana, A.; Romanelli, P.; Elgart, G.; Berman, B.; Vincek, V.
Gene expression profiling reveals alteration of caspase 6 and 14 transcripts in normal skin of keloid-prone patients
Arch. Dermatol. Res.
301
183-188
2009
Homo sapiens
Klaiman, G.; Champagne, N.; Leblanc, A.C.
Self-activation of Caspase-6 in vitro and in vivo: Caspase-6 activation does not induce cell death in HEK293T cells
Biochim. Biophys. Acta
1793
592-601
2009
Homo sapiens
Chan, J.Y.; Phoo, M.S.; Clement, M.V.; Pervaiz, S.; Lee, S.C.
Resveratrol displays converse dose-related effects on 5-fluorouracil-evoked colon cancer cell apoptosis: the roles of caspase-6 and p53
Cancer Biol. Ther.
7
1305-1312
2008
Homo sapiens
Chen, G.G.; Chan, U.P.; Bai, L.C.; Fung, K.Y.; Tessier, A.; To, A.K.; Merchant, J.L.; Lai, P.B.
ZBP-89 reduces the cell death threshold in hepatocellular carcinoma cells by increasing caspase-6 and S phase cell cycle arrest
Cancer Lett.
283
52-58
2009
Homo sapiens
Eguchi, R.; Tone, S.; Suzuki, A.; Fujimori, Y.; Nakano, T.; Kaji, K.; Ohta, T.
Possible involvement of caspase-6 and -7 but not caspase-3 in the regulation of hypoxia-induced apoptosis in tube-forming endothelial cells
Exp. Cell Res.
315
327-335
2009
Homo sapiens
Rust, C.; Wild, N.; Bernt, C.; Vennegeerts, T.; Wimmer, R.; Beuers, U.
Bile acid-induced apoptosis in hepatocytes is caspase-6-dependent
J. Biol. Chem.
284
2908-2916
2009
Homo sapiens, Rattus norvegicus
Chu, W.; Rothfuss, J.; Chu, Y.; Zhou, D.; Mach, R.H.
Synthesis and in vitro evaluation of sulfonamide isatin Michael acceptors as small molecule inhibitors of caspase-6
J. Med. Chem.
52
2188-2191
2009
Homo sapiens
Klaiman, G.; Petzke, T.L.; Hammond, J.; Leblanc, A.C.
Targets of caspase-6 activity in human neurons and Alzheimer disease
Mol. Cell. Proteomics
7
1541-1555
2008
Homo sapiens
Chan, Y.W.; Chen, Y.; Poon, R.Y.
Generation of an indestructible cyclin B1 by caspase-6-dependent cleavage during mitotic catastrophe
Oncogene
28
170-183
2009
Homo sapiens
Beretta, F.; Bassani, S.; Binda, E.; Verpelli, C.; Bello, L.; Galli, R.; Passafaro, M.
The GluR2 subunit inhibits proliferation by inactivating Src-MAPK signalling and induces apoptosis by means of caspase 3/6-dependent activation in glioma cells
Eur. J. Neurosci.
30
25-34
2009
Homo sapiens
Baumgartner, R.; Meder, G.; Briand, C.; Decock, A.; Darcy, A.; Hassiepen, U.; Morse, R.; Renatus, M.
The crystal structure of caspase-6, a selective effector of axonal degeneration
Biochem. J.
423
429-439
2009
Homo sapiens (P55212)
Soares, J.; Lowe, M.M.; Jarstfer, M.B.
The catalytic subunit of human telomerase is a unique caspase-6 and caspase-7 substrate
Biochemistry
50
9046-9055
2011
Homo sapiens
Lee, A.W.; Champagne, N.; Wang, X.; Su, X.D.; Goodyer, C.; Leblanc, A.C.
Alternatively spliced caspase-6B isoform inhibits the activation of caspase-6A
J. Biol. Chem.
285
31974-31984
2010
Homo sapiens
Mueller, I.; Lamers, M.B.; Ritchie, A.J.; Park, H.; Dominguez, C.; Munoz-Sanjuan, I.; Maillard, M.; Kiselyov, A.
A new apo-caspase-6 crystal form reveals the active conformation of the apoenzyme
J. Mol. Biol.
410
307-315
2011
Homo sapiens (P55212)
Mintzer, R.; Ramaswamy, S.; Shah, K.; Hannoush, R.N.; Pozniak, C.D.; Cohen, F.; Zhao, X.; Plise, E.; Lewcock, J.W.; Heise, C.E.
A whole cell assay to measure caspase-6 activity by detecting cleavage of lamin a/c
PLoS ONE
7
e30376
2012
Homo sapiens, Mus musculus, Mus musculus C57BL/6
Graham, R.K.; Ehrnhoefer, D.E.; Hayden, M.R.
Caspase-6 and neurodegeneration
Trends Neurosci.
34
646-656
2011
Homo sapiens
Cho, J.H.; Lee, P.Y.; Son, W.C.; Chi, S.W.; Park, B.C.; Kim, J.H.; Park, S.G.
Identification of the novel substrates for caspase-6 in apoptosis using proteomic approaches
BMB Rep.
46
588-593
2013
Homo sapiens (P55212)
Shahzidi, S.; Brech, A.; Sioud, M.; Li, X.; Suo, Z.; Nesland, J.M.; Peng, Q.
Lamin A/C cleavage by caspase-6 activation is crucial for apoptotic induction by photodynamic therapy with hexaminolevulinate in human B-cell lymphoma cells
Cancer Lett.
339
25-32
2013
Homo sapiens
van Raam, B.J.; Ehrnhoefer, D.E.; Hayden, M.R.; Salvesen, G.S.
Intrinsic cleavage of receptor-interacting protein kinase-1 by caspase-6
Cell Death Differ.
20
86-96
2013
Homo sapiens
LeBlanc, A.C.; Ramcharitar, J.; Afonso, V.; Hamel, E.; Bennett, D.A.; Pakavathkumar, P.; Albrecht, S.
Caspase-6 activity in the CA1 region of the hippocampus induces age-dependent memory impairment
Cell Death Differ.
21
696-706
2014
Homo sapiens
Baburamani, A.A.; Miyakuni, Y.; Vontell, R.; Supramaniam, V.G.; Svedin, P.; Rutherford, M.; Gressens, P.; Mallard, C.; Takeda, S.; Thornton, C.; Hagberg, H.
Does caspase-6 have a role in perinatal brain injury?
Dev. Neurosci.
37
321-337
2015
Homo sapiens, Rattus norvegicus, Mus musculus (Q3TPJ9)
LeBlanc, A.C.
Caspase-6 as a novel early target in the treatment of Alzheimers disease
Eur. J. Neurosci.
37
2005-2018
2013
Mus musculus, Homo sapiens (P55212), Homo sapiens
Velazquez-Delgado, E.M.; Hardy, J.A.
Zinc-mediated allosteric inhibition of caspase-6
J. Biol. Chem.
287
36000-36011
2012
Homo sapiens (P55212)
Lee, P.Y.; Cho, J.H.; Chi, S.W.; Bae, K.H.; Cho, S.; Park, B.C.; Kim, J.H.; Park, S.G.
Expression of the pro-domain-deleted active form of caspase-6 in Escherichia coli
J. Microbiol. Biotechnol.
24
719-723
2014
Homo sapiens (P55212)
Heise, C.E.; Murray, J.; Augustyn, K.E.; Bravo, B.; Chugha, P.; Cohen, F.; Giannetti, A.M.; Gibbons, P.; Hannoush, R.N.; Hearn, B.R.; Jaishankar, P.; Ly, C.Q.; Shah, K.; Stanger, K.; Steffek, M.; Tang, Y.; Zhao, X.; Lewcock, J.W.; Renslo, A.R.; Flygare, J.; Arkin, M.R.
Mechanistic and structural understanding of uncompetitive inhibitors of caspase-6
PLoS ONE
7
e50864
2012
Homo sapiens (P55212)
Wang, X.; Cao, Q.; Zhang, Y.; Su, X.
Activation and regulation of caspase-6 and its role in neurodegenerative diseases
Annu. Rev. Pharmacol. Toxicol.
55
553-572
2015
Homo sapiens (P55212)
Suita, H.; Shinomiya, T.; Nagahara, Y.
Caspase-6 induces 7A6 antigen localization to mitochondria during FAS-induced apoptosis of Jurkat cells
Anticancer Res.
37
1697-1704
2017
Homo sapiens (P55212), Homo sapiens
MacPherson, D.J.; Mills, C.L.; Ondrechen, M.J.; Hardy, J.A.
Tri-arginine exosite patch of caspase-6 recruits substrates for hydrolysis
J. Biol. Chem.
294
71-88
2019
Homo sapiens (P55212)
Waldron-Roby, E.; Hoerauf, J.; Arbez, N.; Zhu, S.; Kulcsar, K.; Ross, C.A.
Sox11 reduces caspase-6 cleavage and activity
PLoS ONE
10
e0141439
2015
Homo sapiens (P55212)
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