Information on EC 3.4.22.54 - calpain-3

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The expected taxonomic range for this enzyme is: Coelomata

EC NUMBER
COMMENTARY hide
3.4.22.54
-
RECOMMENDED NAME
GeneOntology No.
calpain-3
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
broad endopeptidase activity
show the reaction diagram
-
-
-
-
broad endopeptidase specificity
show the reaction diagram
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
endopeptidase; peptides, endopeptidase
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CAS REGISTRY NUMBER
COMMENTARY hide
657407-83-5
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78990-62-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
Norway lobster
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
calpain 3 has a central role in the regulation of the important cell fate-governing nuclear factor-kappaB pathway. Calpain 3-mediated cardiac ankyrin repeat protein cleavage strengthens its interaction with titin N2A
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
26S proteasome regulatory subunit 6A + H2O
?
show the reaction diagram
-
-
-
?
AHNAK nucleoprotein + H2O
?
show the reaction diagram
AHNAK-N peptide + H2O
?
show the reaction diagram
-
a putative cleavage site is AHNAK-C2.2
-
-
?
aldolase A + H2O
?
show the reaction diagram
-
not an in vivo substrate or not detectable in total cell extracts
-
-
?
alpha-actinin-3 + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-fodrin + H2O
?
show the reaction diagram
-
-
-
-
?
annexin A1 + H2O
?
show the reaction diagram
-
-
-
?
annexin A2 + H2O
?
show the reaction diagram
-
-
-
?
annexin A7 + H2O
?
show the reaction diagram
-
-
-
?
beta-catenin + H2O
?
show the reaction diagram
calpastatin + H2O
?
show the reaction diagram
-
-
-
-
?
cardiac ankyrin repeat protein + H2O
?
show the reaction diagram
-
-
-
-
?
connectin + H2O
?
show the reaction diagram
cyclin A + H2O
?
show the reaction diagram
eukaryotic elongation factor 1-alpha 1 + H2O
?
show the reaction diagram
-
-
-
?
eukaryotic elongation factor 1-alpha 2 + H2O
?
show the reaction diagram
-
-
-
?
eukaryotic elongation factor 2 + H2O
?
show the reaction diagram
-
-
-
?
eukaryotic translation initiation factor 3 subunit 7 + H2O
?
show the reaction diagram
-
-
-
?
ezrin + H2O
?
show the reaction diagram
-
-
-
-
?
filamin C + H2O
?
show the reaction diagram
filamin-A + H2O
?
show the reaction diagram
-
-
-
?
fodrin + H2O
?
show the reaction diagram
-
-
-
-
?
fructose bisphosphatealdolase A + H2O
?
show the reaction diagram
-
-
-
?
glyceraldehyde-3-phosphate dehydrogenase + H2O
?
show the reaction diagram
-
-
-
?
HSP60 + H2O
?
show the reaction diagram
-
-
-
-
?
importin-7 + H2O
?
show the reaction diagram
-
-
-
?
M-cadherin + H2O
?
show the reaction diagram
MARP2/Ankrd2 + H2O
?
show the reaction diagram
MyoD + H2O
?
show the reaction diagram
-
calpain 3 down-regulates MyoD protein levels
-
-
?
myosin light chain 1 + H2O
?
show the reaction diagram
-
-
-
-
?
p94 + H2O
?
show the reaction diagram
best substrate for p94 is p94 itself
-
-
?
PIAS3 + H2O
?
show the reaction diagram
-
-
-
-
?
ryanodine receptor + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-leucine-tyrosine-aminomethylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
talin + H2O
?
show the reaction diagram
-
-
-
-
?
thioredoxin + H2O
?
show the reaction diagram
-
-
-
?
titin + H2O
?
show the reaction diagram
triosephosphate isomerase + H2O
?
show the reaction diagram
-
-
-
?
tropomyosin + H2O
?
show the reaction diagram
-
-
-
-
?
troponin I + H2O
?
show the reaction diagram
-
-
-
-
?
troponins T + H2O
?
show the reaction diagram
-
-
-
-
?
very long chain acyl-coenzyme A dehydrogenase + H2O
?
show the reaction diagram
-
an in vivo substrate for calpain-3
-
-
?
vimentin + H2O
?
show the reaction diagram
-
-
-
?
vinexin + H2O
?
show the reaction diagram
-
-
-
-
?
cyclin A + H2O
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
AHNAK nucleoprotein + H2O
?
show the reaction diagram
-
AHNAK is lost in cells expressing active CAPN3. Conversely, AHNAK accumulates when calpain 3 is defective in skeletal muscle of calpainopathy patients
-
-
?
alpha-actinin-3 + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-fodrin + H2O
?
show the reaction diagram
-
-
-
-
?
beta-catenin + H2O
?
show the reaction diagram
-
calpain 3 specifically controls the level of membrane-associated beta-catenin and M-cadherin during myogenesis
-
-
?
connectin + H2O
?
show the reaction diagram
filamin C + H2O
?
show the reaction diagram
M-cadherin + H2O
?
show the reaction diagram
-
calpain 3 specifically controls the level of membrane-associated beta-catenin and M-cadherin during myogenesis
-
-
?
MARP2/Ankrd2 + H2O
?
show the reaction diagram
PIAS3 + H2O
?
show the reaction diagram
-
-
-
-
?
ryanodine receptor + H2O
?
show the reaction diagram
-
-
-
-
?
titin + H2O
?
show the reaction diagram
tropomyosin + H2O
?
show the reaction diagram
-
-
-
-
?
troponin I + H2O
?
show the reaction diagram
-
-
-
-
?
troponins T + H2O
?
show the reaction diagram
-
-
-
-
?
cyclin A + H2O
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K+
-
1 mM, moderate increase of hydrolysis rate
Mg2+
-
1 mM, moderate increase of hydrolysis rate
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
calpain inhibitor I
-
IC50: 0.00025 mM
calpain inhibitor II
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IC50: 0.00025 mM
calpastatin
Leupeptin
-
IC50: 0.002 mM
recombinant rat brain calpastatin
-
IC50: 0.0036 mM
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Calmodulin
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calmodulin binds the calpain 3 non-catalytic domain C2L and promotes enzyme activation
additional information
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00025
calpain inhibitor I
0.002
Leupeptin
Homo sapiens
-
IC50: 0.002 mM
0.0036
recombinant rat brain calpastatin
Homo sapiens
-
IC50: 0.0036 mM
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.2
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calculated from amino acid sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
numerous splice variants of Capn3 are expressed, they contain deletions or insertions in or around the IS1, IS2, and NS regions
Manually annotated by BRENDA team
-
calpain 3 or its isoforms is necessary for formation of the nuclear cataract that is observed in the alpha3Cx46-/- lens. In the absence of the CAPN3 gene, the formation of a cataract is delayed, and its appearance is changed to a more diffuse, pulverulent type
Manually annotated by BRENDA team
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poor expression
Manually annotated by BRENDA team
-
papillomavirus-associated urothelial tumors of the urinary bladder
Manually annotated by BRENDA team
additional information
-
activity is almost undetectable in polymorphonuclear cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
bound to titin
Manually annotated by BRENDA team
additional information
-
triad
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
43580
-
recombinantly expressed domain IV of calpain 3 (p94), equilibrium sedimentation
44000
-
recombinantly expressed domain IV of calpain 3 (p94), sedimentation velocity analysis
55000
-
full-length CAPN3 undergoes almost complete autolysis and runs as a 55 kDa band, SDS-PAGE
65900
-
calculated from amino acid sequence
84000
-
full-length splice variant Mp84, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
recombinantly expressed domain IV of calpain 3 (p94) is a stable dimer in solution
homodimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
model of calpain 3 by crystal structures of human calpain2 and calpastatin-inhibited rat calpain2
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
15% autolysis after 1 min exposure to 0.0025 mM Ca2+
-
autodigestion with 50% loss of total activity after exposure to 0.1 mM Ca2+
-
enzyme is not autolyzed with exhaustive exercise in humans
isolation of the intact 94000 Da enzyme is difficult to achieve due to its rapid autolysis. The C-terminally truncated form of the enzyme that comprises the protease core, domains I and II, alone with its insertion sequence, IS1, and N-terminal leader sequence, NS. This 47000 Da p94I-II minicalpain is stable during purification. In the presence of Ca2+, p94I-II cleaves itself within the NS and IS1 sequences. Autolysis is an intramolecular event
-
no autolysis after 1 min exposure to 0.0025 mM Ca2+
-
rapid autodigestion
-
up to 60 min, in presence of 200 nM Ca2+, no spontaneous autolysation
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DEAE-Toyopearl column chromatography
-
Ni-NTA column chromatography
-
recombinant
-
recombinantly expressed domain IV
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of human full-length CDSs in BD Creator(TM) system donor vector
COS-7 cells are transfected with C3 construct ssubcloned into pcDNA 3.1 and/or a C-terminal human FLNC construct subcloned into pCMV Tag2B
-
expressed in NIH-3T3 fibroblasts
-
expression in COS-7 cells
expression in Eschericia coli
-
expression of domain IV in Escherichia coli BL21 (DE3)
-
skeletal muscle enzyme
-
the C-terminally truncated form of the enzyme that comprises the protease cor, domains I and II, alone with its insertion sequence, IS1, and N-terminal leader sequence, NS is expressed in Escherichia coli BL21(DE3)
-
the His6-tagged PEF domain of calpain 3 coexpressed with the PEF domain of the small subunit that has been tagged with an antifreeze protein is expressed in Escherichia coli BL21(DE3) cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
alternative splicing isoform of calpain 3 is increased in facioscapulohumeral muscular dystrophy patients
-
alternative splicing isoform of calpain 3 is increased in FSHD region gene1 mice
-
among melanocytic lesions, the expression of the splicing variants of calpain 3 (Mp78 and Mp84) are significantly downregulated
-
reserve cells express higher levels of endogenous Capn3 mRNA than proliferating myoblasts
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
M18R
influence on meat tenderness estimated
A101K
-
limb-girdle muscular dystrophy 2A
A489W
-
limb-girdle muscular dystrophy 2A
A490W
-
limb-girdle muscular dystrophy 2A
A748Q
-
limb-girdle muscular dystrophy 2A
A788S
-
limb-girdle muscular dystrophy 2A
C129S
-
inactive
D268A
-
limb-girdle muscular dystrophy 2A
D665LfsX18
-
limb-girdle muscular dystrophy 2A
E206K
-
limb-girdle muscular dystrophy 2A
F167AfsX29
-
limb-girdle muscular dystrophy 2A
G222A
-
limb-girdle muscular dystrophy 2A
G691WfsX7
-
limb-girdle muscular dystrophy 2A
H690RfsX9
-
limb-girdle muscular dystrophy 2A
K254del
-
limb-girdle muscular dystrophy 2A
K254E
-
limb-girdle muscular dystrophy 2A
K595VfsX70
-
limb-girdle muscular dystrophy 2A
K729VfsX21
-
limb-girdle muscular dystrophy 2A
L212SfsX8
-
limb-girdle muscular dystrophy 2A
P637HfsX25
-
limb-girdle muscular dystrophy 2A
Q142X
-
limb-girdle muscular dystrophy 2A
Q565P
-
limb-girdle muscular dystrophy 2A
R437C
-
limb-girdle muscular dystrophy 2A
R490Q
-
limb-girdle muscular dystrophy 2A
R572T
-
limb-girdle muscular dystrophy 2A
R748Q
-
limb-girdle muscular dystrophy 2A
R788SfsX14
-
limb-girdle muscular dystrophy 2A
S260F
-
limb-girdle muscular dystrophy 2A
S479G
-
limb-girdle muscular dystrophy 2A
T139I
-
limb-girdle muscular dystrophy 2A
N358D
-
activity-attenuated mutant, in contrast to wild type, which autolyses quickly in the absence of Ca2+, the mutant N358D expressed in Sf-9 cells can be partially purified, N358D is very unstable in solutions with high salt concentrations, autolysis of N358D is NaCl-dependent
W99R/I135T/K347E/F779L
-
mutant enzyme form does not autolyze and does not cleave filamin C
additional information