Information on EC 3.4.22.59 - caspase-6

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.22.59
-
RECOMMENDED NAME
GeneOntology No.
caspase-6
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp-/-
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
182372-15-2
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
YAC128 mice
-
-
Manually annotated by BRENDA team
the salmon genome contains two genetically distinct variants of both salmon caspase-3 and caspase-6 that are likely the result of two independent chromosome or genome duplications
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
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
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(Ac-VEID)2-Rh110 + H2O
?
show the reaction diagram
-
-
-
-
?
(N-acetyl-VEID)2-rhodamine110 + H2O
?
show the reaction diagram
-
-
-
-
?
Ac-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin + H2O
Ac-Val-Glu-Ile-Asp + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
Ac-VEID-4-trifluoromethylcoumarin 7-amide + H2O
Ac-VEID + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
Ac-VEID-7-amido-4-methylcoumarin + H2O
Ac-VEID + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
acetyl-DEVD-4-nitroanilide + H2O
acetyl-DEVD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-DQMD-4-nitroanilide + H2O
acetyl-DQMD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-VDQQD-4-nitroanilide + H2O
acetyl-VDQQD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-VEHD-7-amido-4-methylcoumarin + H2O
acetyl-VEHD + 7-amino-4-methylcoumarin
show the reaction diagram
-
VEHD is the optimal tetrapeptide recognition motif
-
-
?
acetyl-VEID-4-nitroanilide + H2O
acetyl-VEID + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-VQVD-4-nitroanilide + H2O
acetyl-VQVD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-YEVD-4-nitroanilide + H2O
acetyl-YEVD + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
actin + H2O
?
show the reaction diagram
-
-
-
-
?
actinin-4 + H2O
?
show the reaction diagram
alpha-actinin-4 + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-drebrin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-spinophilin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-Tubulin + H2O
?
show the reaction diagram
amyloid precursor protein + H2O
?
show the reaction diagram
annexin V + H2O
?
show the reaction diagram
-
-
-
-
?
beta-actin + H2O
?
show the reaction diagram
-
-
-
-
?
beta-catenin + H2O
?
show the reaction diagram
capping protein alpha + H2O
?
show the reaction diagram
-
-
-
-
?
caspase-8 + H2O
?
show the reaction diagram
-
caspase-6 cleaves, but does not activate caspase-8
-
-
?
CBP + H2O
?
show the reaction diagram
cFLIP + H2O
?
show the reaction diagram
-
-
-
-
?
cofilin I + H2O
?
show the reaction diagram
-
-
-
-
?
cyclin B1 + H2O
truncated cyclin B1 + ?
show the reaction diagram
DEVD-7-amido-4-methylcoumarin + H2O
DEVD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
drebrin + H2O
?
show the reaction diagram
eukaryotic elongation factor 1 + H2O
?
show the reaction diagram
-
-
-
-
?
ezrin + H2O
?
show the reaction diagram
-
-
-
-
?
GEP100 + H2O
?
show the reaction diagram
-
-
-
-
?
glial fibrillary acidic protein + H2O
?
show the reaction diagram
-
-
-
-
?
glyceraldehyde-3-phosphate dehydrogenase + H2O
?
show the reaction diagram
-
-
-
-
?
heat shock protein gp96 precursor + H2O
?
show the reaction diagram
-
-
-
-
?
herpesvirus associated ubiquitin-specific protease + H2O
?
show the reaction diagram
-
-
-
-
?
Hsp90alpha + H2O
?
show the reaction diagram
-
-
-
-
?
human telomerase + H2O
?
show the reaction diagram
huntingtin + H2O
?
show the reaction diagram
huntingtin + H2O
huntingtin peptide fragments
show the reaction diagram
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
inhibitor-2 of protein phosphatase 2A + H2O
?
show the reaction diagram
-
-
-
-
?
inorganic pyrophosphatase + H2O
?
show the reaction diagram
-
-
-
-
?
kinesin5B + H2O
?
show the reaction diagram
-
-
-
-
?
lamin A + H2O
?
show the reaction diagram
lamin A/C + H2O
?
show the reaction diagram
-
-
-
-
?
lamin c + H2O
?
show the reaction diagram
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Asp-Glu-Val-Asp + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin + H2O
N-acetyl-Asp-Glu-Val-Asp + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
N-acetyl-Asp-Leu-Asn-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Asp-Leu-Asn-Asp + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
N-acetyl-Asp-Val-Val-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Asp-Val-Val-Asp + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
N-acetyl-Ile-Val-Leu-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Ile-Val-Leu-Asp + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
N-acetyl-Thr-Glu-Val-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Thr-Glu-Val-Asp + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
N-acetyl-Val-Glu-His-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Val-Glu-His-Asp + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin + H2O
N-acetyl-Val-Glu-Ile-Asp + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin + H2O
N-acetyl-Val-Glu-Ile-Asp + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
N-acetyl-VEID-4-nitroanilide + H2O
N-acetyl-VEID + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
N-acetyl-VEID-7-amido-4-methylcoumarin + H2O
N-acetyl-VEID + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
neurolysin + H2O
?
show the reaction diagram
-
-
-
-
?
NF-kappaB + H2O
?
show the reaction diagram
-
-
-
-
?
nuclear mitotic apparatus protein + H2O
?
show the reaction diagram
-
cleavage at sites distict from caspase-3
-
-
?
p97 + H2O
?
show the reaction diagram
PARP + H2O
?
show the reaction diagram
-
-
-
-
?
partitioning-defective 3-like protein splice variant c + H2O
?
show the reaction diagram
-
-
-
-
?
periplakin + H2O
?
show the reaction diagram
poly(ADP-ribose) polymerase + H2O
?
show the reaction diagram
-
-
-
-
?
poly(ADP-ribose)polymerase + H2O
?
show the reaction diagram
pro-caspase-2 + H2O
caspase-2 + ?
show the reaction diagram
-
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
-
?
pro-caspase-6 + H2O
?
show the reaction diagram
-
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 + ?
show the reaction diagram
pro-caspase-8 + H2O
?
show the reaction diagram
pro-caspase-8 + H2O
caspase-8 + ?
show the reaction diagram
-
-
-
-
?
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
procaspase-6 mutant C163S + H2O
?
show the reaction diagram
-
cleavage at the intersubunit linker position Asp-193
-
-
?
procaspase-8 + H2O
caspase-8 + ?
show the reaction diagram
prolyl endopeptidase + H2O
?
show the reaction diagram
-
-
-
-
?
protein 14-3-3epsilon + H2O
?
show the reaction diagram
-
-
-
-
?
protein 14-3-3zeta + H2O
?
show the reaction diagram
-
-
-
-
?
Rab GDP dissociation factor inhibitor alpha + H2O
?
show the reaction diagram
-
-
-
-
?
receptor-interacting protein kinase-1 + H2O
?
show the reaction diagram
SATB1 + H2O
?
show the reaction diagram
serologically defined colon cancer antigen 3 + H2O
?
show the reaction diagram
-
-
-
-
?
spinophilin + H2O
?
show the reaction diagram
Tau + H2O
?
show the reaction diagram
tau protein + H2O
?
show the reaction diagram
topoisomerase I + H2O
?
show the reaction diagram
-
cleavage at PEDD123-/-G and EEED170-/-G
-
-
?
transcription factor AP-2alpha + H2O
?
show the reaction diagram
tubulin + H2O
?
show the reaction diagram
-
-
-
-
?
Ufd2p + H2O
?
show the reaction diagram
Val-Glu-Ile-Asp 4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
valosin-containing protein + H2O
?
show the reaction diagram
-
-
-
-
?
VEID-7-amido-4-trifluoromethylcoumarin + H2O
VEID + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
vimentin + H2O
?
show the reaction diagram
-
-
-
-
?
viral nucleocapsid protein of transmissible gastroenteritis coronovirus + H2O
?
show the reaction diagram
Z-VEID-R110 + H2O
Z-VEID + R110
show the reaction diagram
-
caspase-6 recognition peptide covalently linked to two amine groups of the fluorescent dye rhodamine 110, fluorogenic assay
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
actin + H2O
?
show the reaction diagram
-
-
-
-
?
actinin-4 + H2O
?
show the reaction diagram
alpha-actinin-4 + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-drebrin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-spinophilin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-Tubulin + H2O
?
show the reaction diagram
amyloid precursor protein + H2O
?
show the reaction diagram
annexin V + H2O
?
show the reaction diagram
-
-
-
-
?
beta-actin + H2O
?
show the reaction diagram
-
-
-
-
?
beta-catenin + H2O
?
show the reaction diagram
-
processing of beta-catenin, production of a 70000 Da fragment
-
-
?
capping protein alpha + H2O
?
show the reaction diagram
-
-
-
-
?
caspase-8 + H2O
?
show the reaction diagram
-
caspase-6 cleaves, but does not activate caspase-8
-
-
?
CBP + H2O
?
show the reaction diagram
-
-
-
-
?
cofilin I + H2O
?
show the reaction diagram
-
-
-
-
?
cyclin B1 + H2O
truncated cyclin B1 + ?
show the reaction diagram
-
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
-
?
drebrin + H2O
?
show the reaction diagram
eukaryotic elongation factor 1 + H2O
?
show the reaction diagram
-
-
-
-
?
ezrin + H2O
?
show the reaction diagram
-
-
-
-
?
GEP100 + H2O
?
show the reaction diagram
-
-
-
-
?
glial fibrillary acidic protein + H2O
?
show the reaction diagram
-
-
-
-
?
glyceraldehyde-3-phosphate dehydrogenase + H2O
?
show the reaction diagram
-
-
-
-
?
heat shock protein gp96 precursor + H2O
?
show the reaction diagram
-
-
-
-
?
herpesvirus associated ubiquitin-specific protease + H2O
?
show the reaction diagram
-
-
-
-
?
Hsp90alpha + H2O
?
show the reaction diagram
-
-
-
-
?
human telomerase + H2O
?
show the reaction diagram
-
caspase-6 cleaves human telomerase, hTERT, during apoptosis in cultured cells
-
-
?
huntingtin + H2O
?
show the reaction diagram
huntingtin + H2O
huntingtin peptide fragments
show the reaction diagram
-
a key step in the onset of Huntington’s disease is the caspase-6 mediated cleavage of the protein huntingtin into toxic fragments
-
-
?
inhibitor-2 of protein phosphatase 2A + H2O
?
show the reaction diagram
-
-
-
-
?
inorganic pyrophosphatase + H2O
?
show the reaction diagram
-
-
-
-
?
kinesin5B + H2O
?
show the reaction diagram
-
-
-
-
?
lamin A + H2O
?
show the reaction diagram
lamin A/C + H2O
?
show the reaction diagram
-
-
-
-
?
lamin c + H2O
?
show the reaction diagram
neurolysin + H2O
?
show the reaction diagram
-
-
-
-
?
NF-kappaB + H2O
?
show the reaction diagram
-
-
-
-
?
p97 + H2O
?
show the reaction diagram
PARP + H2O
?
show the reaction diagram
-
-
-
-
?
partitioning-defective 3-like protein splice variant c + H2O
?
show the reaction diagram
-
-
-
-
?
periplakin + H2O
?
show the reaction diagram
-
caspase 6 has a specific epidermal target which is periplakin
-
-
?
poly(ADP-ribose)polymerase + H2O
?
show the reaction diagram
-
the enzyme may participate in poly(ADP-ribose)polymerase cleavage observed during apoptosis
-
-
?
pro-caspase-2 + H2O
caspase-2 + ?
show the reaction diagram
-
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
-
?
pro-caspase-6 + H2O
?
show the reaction diagram
-
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 + ?
show the reaction diagram
pro-caspase-8 + H2O
?
show the reaction diagram
-
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
-
-
?
pro-caspase-8 + H2O
caspase-8 + ?
show the reaction diagram
-
-
-
-
?
procaspase-3 + H2O
caspase-3 + ?
show the reaction diagram
procaspase-8 + H2O
caspase-8 + ?
show the reaction diagram
prolyl endopeptidase + H2O
?
show the reaction diagram
-
-
-
-
?
protein 14-3-3epsilon + H2O
?
show the reaction diagram
-
-
-
-
?
protein 14-3-3zeta + H2O
?
show the reaction diagram
-
-
-
-
?
Rab GDP dissociation factor inhibitor alpha + H2O
?
show the reaction diagram
-
-
-
-
?
receptor-interacting protein kinase-1 + H2O
?
show the reaction diagram
-
-
-
-
?
SATB1 + H2O
?
show the reaction diagram
-
cleavage disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis
-
-
?
serologically defined colon cancer antigen 3 + H2O
?
show the reaction diagram
-
-
-
-
?
spinophilin + H2O
?
show the reaction diagram
tau protein + H2O
?
show the reaction diagram
transcription factor AP-2alpha + H2O
?
show the reaction diagram
tubulin + H2O
?
show the reaction diagram
-
-
-
-
?
Ufd2p + H2O
?
show the reaction diagram
-
cleavage of polyubiquitination factor Ufd2p at Asp123 within the putative regulatory N-terminal domain might have important functional consequences within the apoptotic cascade
-
-
?
valosin-containing protein + H2O
?
show the reaction diagram
-
-
-
-
?
vimentin + H2O
?
show the reaction diagram
-
-
-
-
?
viral nucleocapsid protein of transmissible gastroenteritis coronovirus + H2O
?
show the reaction diagram
-
cleavage site VVPD359-/-. Destruction of viral protein by the host cell death machinery
-
-
?
additional information
?
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-(3,4-dichlorobenzyl)-5-(morpholin-4-ylsulfonyl)-1H-indole-2,3-dione
-
slight inhibition
1-benzyl-5-(thiomorpholin-4-ylsulfonyl)-1H-indole-2,3-dione
-
-
4-hydroxy-5-iodo-3-nitrophenylacetyl-Leu-Leu-Leu-vinylsulfone
-
-
5-(azetidin-1-ylsulfonyl)-1-benzyl-1H-indole-2,3-dione
-
-
5-(morpholin-4-ylsulfonyl)-1H-indole-2,3-dione
-
slight inhibition
Ac-DEVD-CHO
-
-
Ac-IETD-CHO
-
-
Ac-Val-Glu-Ile-Asp-CHO
-
-
Ac-VEID-CHO
acetyl-AEVD-aldehyde
-
-
acetyl-DEVD-aldehyde
-
-
acetyl-IETD-aldehyde
-
-
acetyl-Val-Ile-Asp-aldehyde
-
-
acetyl-WEHD-aldehyde
-
-
benzyloxycarbonyl-DRHD-fluoromethylketone
-
-
benzyloxycarbonyl-VAD-fluoromethylketone
benzyloxycarbonyl-Val-Glu(OMe)-Ile-Asp(OMe)-fluoromethyl ketone
-
caspase-6-selective inhibitor
benzyloxycarbonyl-VEID-fluoromethylketone
-
-
-
beta-lactone
-
-
-
BOC-Asp(OMe)-fluoromethyl ketone
-
for general caspase inhibition
carbobenzoxy-Val-Ala-Asp-fluoromethylketone
-
-
-
carbobenzyloxy-LEHD-fluoromethyl ketone
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
carbobenzyloxy-VEID-fluoromethyl ketone
DMSO
-
-
epoxomicin
-
-
IETD-CHO
-
caspase-6 in lens extracts from neonatal mice partially inhibited by 0.0005 mM
lactacystin
-
-
N-carbobenzyloxy-IETD-fluoromethyl ketone
N-[(2R)-1-(3-cyanophenyl)-3-hydroxypropan-2-yl]-5-(3,4-dimethoxyphenyl)furan-3-carboxamide
-
selective inhibitor
N-[[5-(3,4-dimethoxyphenyl)-2-methylfuran-3-yl]carbonyl]phenylalanine
-
-
Q-VD-OH
-
Q-VD-OPH
SB203580
-
a p38 inhibitor, also inhibits activation of caspase-6, caspase-3, and caspase-7
siRNA
-
silencing of caspase-6 expression
-
sulfonamide isatin Michael acceptors
-
small molecule inhibitors of caspase-6
-
VEID-CHO
VEID-fluoromnethylketone
-
-
-
VEID-FMK
-
-
Z -VEID-fluoromethylketone
-
-
Z-DEVD-fluoromethylketone
-
-
Z-IETD-fluoromethylketone
-
for Csp-6- and caspase-8-like inhibition
Z-VAD-fluoromethylketone
Z-Val-Ala-Asp-fluoromethylketone
Z-VE(OMe)ID(OMe)-fluoromethylketone
-
specific inhibitor
-
Z-VEID-fluoromethylketone
Z-VEID-fmk
-
-
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
-
specific caspase 6 inhibitor
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
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
adriamycin
-
increases caspase-6 mRNA levels in HCT116 p53+ and neo cells but not in E6 cells
caspase-1
-
caspase-1 activates caspase-6 in vitro
-
etoposide
-
mild induction of the enzyme in HCT116 p53+ cells
RCasp1
-
mediates increased self-processing of pro-Casp6a into its active subunits
-
resveratrol
Tumor necrosis factor alpha
-
activates caspase-6 which in turn cleaves transcription factor AP2alpha
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
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
0.18
acetyl-DEVD-4-nitroanilide
-
pH 7.5, 30°C
1.3
acetyl-DQMD-4-nitroanilide
-
pH 7.5, 30°C
0.16
acetyl-LEVD-4-nitroanilide
-
pH 7.5, 30°C
7
acetyl-VDQQD-4-nitroanilide
-
pH 7.5, 30°C
0.17
acetyl-VEHD-7-amido-4-methylcoumarin
-
pH 7.0 or pH 7.5
0.03
acetyl-VEID-4-nitroanilide
-
pH 7.5, 30°C
0.58
acetyl-VQVD-4-nitroanilide
-
pH 7.5, 30°C
1.2
acetyl-YEVD-4-nitroanilide
-
pH 7.5, 30°C
0.126
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin
-
-
0.087
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin
-
-
0.246
N-acetyl-Val-Glu-His-Asp-7-amido-4-methylcoumarin
-
-
0.0134
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
-
-
0.082 - 0.176
N-acetyl-VEID-7-amido-4-methylcoumarin
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.5
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin
Homo sapiens
-
-
3.2
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin
Homo sapiens
-
-
1
N-acetyl-Ile-Val-Leu-Asp-7-amido-4-methylcoumarin
Homo sapiens
-
-
6
N-acetyl-Thr-Glu-Val-Asp-7-amido-4-methylcoumarin
Homo sapiens
-
-
43
N-acetyl-Val-Glu-His-Asp-7-amido-4-methylcoumarin
Homo sapiens
-
-
3.6
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
Homo sapiens
-
-
0.015 - 0.7
N-acetyl-VEID-7-amido-4-methylcoumarin
additional information
additional information
Homo sapiens
-
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
44
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin
Homo sapiens
-
-
27613
37
N-acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin
Homo sapiens
-
-
40626
2.53
N-acetyl-Ile-Val-Leu-Asp-7-amido-4-methylcoumarin
Homo sapiens
-
-
81570
295
N-acetyl-Thr-Glu-Val-Asp-7-amido-4-methylcoumarin
Homo sapiens
-
-
81569
175
N-acetyl-Val-Glu-His-Asp-7-amido-4-methylcoumarin
Homo sapiens
-
-
40628
270
N-acetyl-Val-Glu-Ile-Asp-7-amido-4-methylcoumarin
Homo sapiens
-
-
40627
100 - 7500
N-acetyl-VEID-7-amido-4-methylcoumarin
202474
1.39
receptor-interacting protein kinase-1
Homo sapiens
-
in 0.8 M sodium citrate, 20 mM PIPES, 100 mM NaCl, pH 7.2, 5 mM dithiothreitol, at 37°C
202545
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000052
acetyl-AEVD-aldehyde
-
pH 7.5, 25°C
0.000031
acetyl-DEVD-aldehyde
-
pH 7.5, 25°C
0.0000056
acetyl-IETD-aldehyde
-
pH 7.5, 25°C
0.003
acetyl-WEHD-aldehyde
-
pH 7.5, 25°C
0.0013
cowpox serpin CrmA
-
pH 7.5, 25°C
-
0.00015 - 0.0072
Zn2+
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0015
1-(3,4-dichlorobenzyl)-5-(morpholin-4-ylsulfonyl)-1H-indole-2,3-dione
Homo sapiens
-
above
0.00128
1-benzyl-5-(thiomorpholin-4-ylsulfonyl)-1H-indole-2,3-dione
Homo sapiens
-
-
0.00983
5-(azetidin-1-ylsulfonyl)-1-benzyl-1H-indole-2,3-dione
Homo sapiens
-
-
0.002
5-(morpholin-4-ylsulfonyl)-1H-indole-2,3-dione
Homo sapiens
-
above
0.0000305
Ac-DEVD-CHO
Homo sapiens
-
pH 7.2, 37°C, recombinant enzyme
0.0000532
Ac-IETD-CHO
Homo sapiens
-
pH 7.2, 37°C, recombinant enzyme
0.0000162
Ac-VEID-CHO
Homo sapiens
-
pH 7.2, 37°C, recombinant enzyme
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
0.0004023
Z-DEVD-fluoromethylketone
Homo sapiens
-
pH 7.2, 37°C, recombinant enzyme
0.002112
Z-VAD-fluoromethylketone
Homo sapiens
-
pH 7.2, 37°C, recombinant enzyme
0.0001286
Z-VEID-fluoromethylketone
Homo sapiens
-
pH 7.2, 37°C, recombinant enzyme
0.0034 - 0.0256
Zn2+
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
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.5
-
reaction with acetyl-VEHD-7-amido-4-methylcoumarin
7.2
-
assay at
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 hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
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
Manually annotated by BRENDA team
-
BEAS-2B cell line infected by unencapsulated Streptococcus pneumoniae type 2 strain R6x
Manually annotated by BRENDA team
-
active recombinant caspase-6
Manually annotated by BRENDA team
-
B-cell lymphoma cell line
Manually annotated by BRENDA team
-
in the inner molecular layer
Manually annotated by BRENDA team
-
HUVECs are isolated from human umbilical cord
Manually annotated by BRENDA team
-
primary fiber cells
Manually annotated by BRENDA team
-
keloid fioblasts show a decreased expression of apoptosis-related genes compared to scars
Manually annotated by BRENDA team
-
leukemic T cell line
Manually annotated by BRENDA team
-
THP-1 human monocytic cell culture
Manually annotated by BRENDA team
-
HL-60 and U937 cells are used
Manually annotated by BRENDA team
-
parental and caspase-6-DT40 chicken lymphoma cells
Manually annotated by BRENDA team
-
human primary neuronal culture
Manually annotated by BRENDA team
-
Saos-2 and U2OS
Manually annotated by BRENDA team
-
B-cell lymphoma cell line
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
-
-
Manually annotated by BRENDA team
additional information
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15000
-
x * 15000, cleaved enzyme, SDS-PAGE
23000
-
x * 34000, pro-Casp6a, SDS-PAGE, x * 23000, pro-Casp6b, SDS-PAGE
24000
-
Western blot analysis, processed large subunit and the attached prodomain of caspase 6
32000
-
x * 32000, pro-enzyme, SDS-PAGE
35000
-
x * 35000, Western blot analysis, small subunit (15000) resulting from cleavage at Asp194
58000
-
ultracentrifugation
63070
-
multi-angle light scattering
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
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
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 24–179 and 194–293 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
-
sitting drop vapour diffusion method
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Hi-Trap nickel-affinity column chromatography
-
immobilized metal ion affinity chromatography (Ni2+), hydrophobic interaction chromatography, gel filtration
-
Ni-NTA agarose column chromatography
-
Ni-NTA agarose column chromatography, and gel filtration
-
purified to homogeneity
-
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
-
a His-tagged version (residues 24-293) expressed in Escherichia coli
-
Casp6 genetic organization, expression of His-tagged wild-type and mutant pro-caspase-6 in Escherichia coli and in HEK-293T cells
-
caspase-6 expression analysis
-
cloned into pET-23 bacterial expression vector; expression in MDCK cells
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Mus musculus
-
expressed in Mus musculus hippocampus
-
expression in Escherichia coli
-
expression of His-tagged apo-caspase-6 and caspase-6 in Escherichia coli
-
inserted into the pIVEX vector
-
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
caspase-6 mRNA levels decrease 3fold in the brains of adult mice exposed to an enriched environment
-
caspase-6 mRNA levels increase 2-3fold in the aging mouse cortex and hypothalamus
-
staurosporine induces caspase-6
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D129A
-
site-directed mutagenesis, inactive mutant
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
E637A
-
site-directed mutagenesis, inactive mutant
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
S257A
-
mutant caspase-6, not phosphorylated in the presence of active AMPK-related kinase 5
W175F
-
reduced autocatalytic processing activity
C163A
-
the catalytic mutant is unabble to self-activate
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
drug development
medicine
molecular biology