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Information on EC 3.4.22.59 - caspase-6 and Organism(s) Mus musculus and UniProt Accession O08738
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3.4.22.59 caspase-6Specify your search results
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- 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: Mus musculus
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
-
-
-
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C14.005
-
-
-
-
Casp6
caspase 6
-
-
-
-
MCH2
-
-
-
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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
Val-Glu-Ile-Asp-7-amido-4-trifluoromethylcoumarin + H2O
Val-Glu-Ile-Asp + 7-amino-4-trifluoromethylcoumarin
-
-
-
?
IETD-7-amido-4-trifluoromethylcoumarin + H2O
IETD + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
pro-caspase-6 + H2O
caspase-6 + ?
-
the enzyme can self-process and self-activate
-
-
?
beta-catenin + H2O
?
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processing of beta-catenin, production of a 70000 Da fragment
-
-
?
huntingtin + H2O
?
-
cleavage at the capase-6 consensus sequence at amino acid 586 in the nucleus, proteolysis of mutant huntingtin is crucial to the development of Huntington disease. Cell stress induced by staurosporine results in the nuclear translocation and activation of caspase-6 and increased cleavage of huntingtin, overview. Differential localization of different endogenous caspase-cleaved huntingtin fragments in perinuclear and nuclear regions, overview
-
-
?
huntingtin + H2O
?
-
cleavage at the capase-6 consensus sequence at amino acid 586, a position 586 mutant of huntingtin is not cleaved by caspase-6, mutational caspase cleavage site analysis of huntingtin, overview
-
-
?
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
-
-
?
additional information
?
-
-
caspase 6 is an effector caspase in apoptosis pathways and regulates B cell activation and differentiation into plasma cells by modifying cell cycle entry, Casp6 is cleaved after B cell activation
-
-
?
additional information
?
-
-
caspase-6 is a key caspase known to play both initiator and effector roles in programmed cell death, excessive activation of the enzyme is an early marker of neuronal dysfunction and implicated in the pathogenesis of Huntington disease, Alzheimer's disease and other forms of cognitive impairment
-
-
?
additional information
?
-
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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
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-
?
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
beta-catenin + H2O
?
-
processing of beta-catenin, production of a 70000 Da fragment
-
-
?
pro-caspase-6 + H2O
caspase-6 + ?
-
the enzyme can self-process and self-activate
-
-
?
huntingtin + H2O
?
-
cleavage at the capase-6 consensus sequence at amino acid 586 in the nucleus, proteolysis of mutant huntingtin is crucial to the development of Huntington disease. Cell stress induced by staurosporine results in the nuclear translocation and activation of caspase-6 and increased cleavage of huntingtin, overview. Differential localization of different endogenous caspase-cleaved huntingtin fragments in perinuclear and nuclear regions, overview
-
-
?
additional information
?
-
-
caspase 6 is an effector caspase in apoptosis pathways and regulates B cell activation and differentiation into plasma cells by modifying cell cycle entry, Casp6 is cleaved after B cell activation
-
-
?
additional information
?
-
-
caspase-6 is a key caspase known to play both initiator and effector roles in programmed cell death, excessive activation of the enzyme is an early marker of neuronal dysfunction and implicated in the pathogenesis of Huntington disease, Alzheimer's disease and other forms of cognitive impairment
-
-
?
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
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IETD-CHO
-
caspase-6 in lens extracts from neonatal mice partially inhibited by 0.0005 mM
N-acetyl-L-alpha-aspartyl-L-alpha-glutamyl-N-[(2S)-1-carboxy-3-oxopropan-2-yl]-L-valinamide
-
VEID-CHO
-
caspase-6 in lens extracts from neonatal mice efficiently inhibited by 0.0005 mM
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
cell stress induced by staurosporine results in the nuclear translocation and activation of caspase-6
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
expression of Casp6 protein and mRNA in distal branches of sensory axons undergoing axonal degeneration. Intra-axonal synthesis of Casp6 emerges at early time points following axotomy
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
expression of Casp6 protein and mRNA in distal branches of sensory axons undergoing axonal degeneration. Intra-axonal synthesis of Casp6 emerges at early time points following axotomy
additional information
-
cell stress induced by staurosporine results in the nuclear translocation and activation of caspase-6
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
caspase-6 inhibition or knockdown slows the progress of axon damage in serially imaged cutaneous nerves. Inhibition of caspase-6 delays neurofilament dissolution following nerve resection. Mice lacking Casp6 exhibit subtle delays in axonal degeneration
physiological function
malfunction
gene deletion of caspase-6 did not affect the outcome of brain injury following mild (50 min) or severe (60 min) hypoxia-ischaemia
physiological function
physiological function
alternatively activated macrophages play essential roles in the promotion of tissue remodeling, vasculogenesis, and tumor progression. Caspase-6 is a regulator of alternatively activated macrophages
physiological function
caspase-6 does not exacerbate pathogenesis of amyotrophic lateral sclerosis, but may have a protective role
physiological function
caspase-6 mediates resistance against Burkholderia pseudomallei infection, influences the expression of detrimental cytokines and seems to be important for achieving a well-balanced immune response
physiological function
caspase-6 regulates B-cell programs both during early development and after antigen stimulation in the periphery
physiological function
increases in capase-6 expression and action contribute to the progression of axonal degeneration
physiological function
-
the enzyme plays a role in clearance pathways for the huntingtin protein whose proteolysis is a critical pathological event in Huntington's diesease
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
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_MOUSE
276
0
31595
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
proliferation and cell death are not enhanced in Casp6 KO B cells, immunoresponses, overview. B cells from Casp6 knockout mice examined ex vivo have more cells in G1 than wild-type B cells, and mitogen-induced G1 entry of Casp6 KO B cells is much faster than that of wild-type B cells. Even so, S phase entry and proliferation are not increased in Casp6 KO B cells. Rather than proliferating, activated Casp6 KO B cells preferentially differentiate into syndecan-1+ plasma cells and produce Abs. In Casp6 KO mice compared with wild-type mice, serum levels of IgG1, IgG2a, and IgG2b are increased and Ag-specific Ab responses are also enhanced along with increased percentages of syndecan-1+ plasma cells
additional information
-
generation of knockout mice by using a construct for targeting the C57BL/6 caspase-6 locus in ES cells. lamin A/C degradation is markedly reduced in fibroblasts extracted from caspase-6 knock-out mice relative to fibroblasts from wild type mice
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
caspase-6 mRNA levels decrease 3fold in the brains of adult mice exposed to an enriched environment
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caspase-6 mRNA levels increase 2-3fold in the aging mouse cortex and hypothalamus
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
caspase-6 might be a key nod molecule to regulate immunological steady-state and be a therapeutic candidate for tumor immunotherapy
diagnostics
-
excessive activation of caspase-6 is an early marker of neuronal dysfunction and implicated in the pathogenesis of Huntington disease, Alzheimer's disease and other forms of cognitive impairment
medicine
-
difference between normal fiber cell differentation and apoptosis and the capacity of the lens to differentially regulate these two processes
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
van de Craen, M.; Berx, G.; van den Brande, I.; Fiers, W.; Declercq, W.; Vandenabeele, P.
Proteolytic cleavage of beta-catenin by caspases: an in vitro analysis
FEBS Lett.
458
167-170
1999
Mus musculus
van de Craen, M.; Vandenabeele, P.; Declercq, W.; van den Brande, I.; van Loo, G.; Molemans, F.; Schotte, P.; van Criekinge, W.; Beyaert, R.; Fiers, W.
Characterization of seven murine caspase family members
FEBS Lett.
403
61-69
1997
Mus musculus (O08738)
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
Warby, S.C.; Doty, C.N.; Graham, R.K.; Carroll, J.B.; Yang, Y.Z.; Singaraja, R.R.; Overall, C.M.; Hayden, M.R.
Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus
Hum. Mol. Genet.
17
2390-2404
2008
Mus musculus, Mus musculus YAC128
Watanabe, C.; Shu, G.L.; Zheng, T.S.; Flavell, R.A.; Clark, E.A.
Caspase 6 regulates B cell activation and differentiation into plasma cells
J. Immunol.
181
6810-6819
2008
Mus musculus, Mus musculus C57BL/6
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
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
Gafni, J.; Papanikolaou, T.; Degiacomo, F.; Holcomb, J.; Chen, S.; Menalled, L.; Kudwa, A.; Fitzpatrick, J.; Miller, S.; Ramboz, S.; Tuunanen, P.I.; Lehtimaeki, K.K.; Yang, X.W.; Park, L.; Kwak, S.; Howland, D.; Park, H.; Ellerby, L.M.
Caspase-6 activity in a BACHD mouse modulates steady-state levels of mutant huntingtin protein but is not necessary for production of a 586 amino acid proteolytic fragment
J. Neurosci.
32
7454-7465
2012
Mus musculus
Hogg, M.C.; Mitchem, M.R.; Koenig, H.G.; Prehn, J.H.
Caspase 6 has a protective role in SOD1(G93A) transgenic mice
Biochim. Biophys. Acta
1862
1063-1073
2016
Mus musculus (O08738), Mus musculus
Watanabe, C.; Shu, G.L.; Giltiay, N.V.; Clark, E.A.
Regulation of B-lineage cells by caspase 6
Immunol. Cell Biol.
96
1072-1082
2018
Mus musculus (O08738)
Yao, Y.; Shi, Q.; Chen, B.; Wang, Q.; Li, X.; Li, L.; Huang, Y.; Ji, J.; Shen, P.
Identification of caspase-6 as a new regulator of alternatively activated macrophages
J. Biol. Chem.
291
17450-17466
2016
Mus musculus (O08738)
Woo, V.; Cheng, C.; Duraikannu, A.; Chandrasekhar, A.; Purdy, K.; Martinez, J.A.; Zochodne, D.W.
Caspase-6 is a dispensable enabler of adult mammalian axonal degeneration
Neuroscience
371
242-253
2018
Mus musculus (O08738)
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