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Information on EC 3.4.22.54 - calpain-3 and Organism(s) Mus musculus and UniProt Accession Q64691
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3.4.22.54 calpain-3Specify your search results
Word Map
- 3.4.22.54
- calpains
- dystrophy
- muscular
-
limb-girdle
-
girdle
-
lgmd2a
- limb
-
calpainopathy
- titin
- calpastatin
- myopathy
-
dysferlin
-
tender
-
autolytic
- sarcomere
- mu-calpains
-
sarcoglycans
- myofibrillar
-
telethonin
-
scapular
-
alpha-sarcoglycan
-
merosin
-
autolyzed
-
caveolin-3
-
nebulin
- lumborum
-
m-lines
-
dysferlinopathy
- sarcoglycanopathy
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
Synonyms
capn3, calpain 3, calpain-3, ncl-1, calpain3, muscle calpain, skeletal muscle-specific calpain, muscle-specific calpain, calpain 3 (p94), calpain p94, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
calcium-activated neutral proteinase 3
calpain L3
calpain p94
CANP 3
Cn94
-
-
-
-
muscle-specific calcium-activated neutral protease 3
nCL-1
-
-
-
-
p94
p94-calpain
-
-
-
-
calcium-activated neutral proteinase 3
-
-
-
-
calpain L3
-
-
-
-
calpain p94
-
-
-
-
CANP 3
-
-
-
-
muscle-specific calcium-activated neutral protease 3
-
-
-
-
p94
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
657407-83-5
-
78990-62-2
-
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
connectin + H2O
?
p94 binds to connectin at multiple sites including loci in the N2A and PEVK regions of connectin. Functionally, p94-N2A interactions suppress p94 autolysis and protected connectin from proteolysis. Dynamic nature of connectin molecule as a regulatory scaffold of p94 functions
-
-
?
aldolase A + H2O
?
-
not an in vivo substrate or not detectable in total cell extracts
-
-
?
very long chain acyl-coenzyme A dehydrogenase + H2O
?
-
an in vivo substrate for calpain-3
-
-
?
titin + H2O
?
the enzyme binds the C-terminus of titin at recognition motifs [LIMV]X(3,4) [LIMV]X(2)[LIMV][DE] and [LIMV]X(3,4)[LIMVA]X(2)[LIMV][DE]
-
-
?
beta-catenin + H2O
?
-
calpain 3 specifically controls the level of membrane-associated beta-catenin and M-cadherin during myogenesis
-
-
?
filamin C + H2O
?
-
enzyme specifically cleaves the C-terminal portion in living cells. Filamin C may be an in vivo substrate to c3, functioning to regulate protein-protein interactions with the sarcoglycans
-
-
?
M-cadherin + H2O
?
-
calpain 3 specifically controls the level of membrane-associated beta-catenin and M-cadherin during myogenesis
-
-
?
titin + H2O
?
-
calpain 3 expression is required for normal myofibril formation. Calpain 3 may influence the role of titin in sarcomere formation through proteolytic cleavage. The limb girdle muscular dystrophy 2A mutations in calpain C3 influence binding of calpain C3 to titin
-
-
?
additional information
?
-
the enzyme is associated with limb-girdle muscular dystrophy 2A
-
-
?
additional information
?
-
p94 proteolytic activity is involved in responses to muscle conditions, p94 inactivation causes limb-girdle muscular dystrophy
-
-
?
cyclin A + H2O
additional information
-
-
calpain 3-mediated cleavage of cyclin A in dividing myeloid pregenitor cells is important for the onset of differentiation
production of a truncated product that lacks the N-terminal destruction box required for its degradation at the end of mitosis. The cleaved form of cyclin A retains the cyclin-dependent kinase binding domain and forms active complexes with cdk2
?
additional information
?
-
-
important protein for normal muscle function. Mutations in the c3 gene result in limb-girdle muscular dystrophy type 2A
-
-
?
additional information
?
-
-
calpain 3/p94 is not involved in postmortem proteolysis
-
-
?
additional information
?
-
-
neither the reduction of calpain 3 nor its aberrant activity is responsible for the muscular dystrophy with myositis (mdm). Overexpression of calpain 3 exacerbates muscular dystrophy with myositis (mdm)
-
-
?
additional information
?
-
-
skeletal muscle-specific calpain participates in the regulation of the conventional calpain-calpastatin system in skeletal muscle
-
-
?
additional information
?
-
-
calpain-3 does not cleave acetyl-coenzyme A acyltransferase, carnitine O-palmitoyl transferase II, carnitine acetyltransferase, and trifunctional protein alpha subunit
-
-
?
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
connectin + H2O
?
p94 binds to connectin at multiple sites including loci in the N2A and PEVK regions of connectin. Functionally, p94-N2A interactions suppress p94 autolysis and protected connectin from proteolysis. Dynamic nature of connectin molecule as a regulatory scaffold of p94 functions
-
-
?
titin + H2O
?
the enzyme binds the C-terminus of titin at recognition motifs [LIMV]X(3,4) [LIMV]X(2)[LIMV][DE] and [LIMV]X(3,4)[LIMVA]X(2)[LIMV][DE]
-
-
?
beta-catenin + H2O
?
-
calpain 3 specifically controls the level of membrane-associated beta-catenin and M-cadherin during myogenesis
-
-
?
filamin C + H2O
?
-
enzyme specifically cleaves the C-terminal portion in living cells. Filamin C may be an in vivo substrate to c3, functioning to regulate protein-protein interactions with the sarcoglycans
-
-
?
M-cadherin + H2O
?
-
calpain 3 specifically controls the level of membrane-associated beta-catenin and M-cadherin during myogenesis
-
-
?
titin + H2O
?
-
calpain 3 expression is required for normal myofibril formation. Calpain 3 may influence the role of titin in sarcomere formation through proteolytic cleavage. The limb girdle muscular dystrophy 2A mutations in calpain C3 influence binding of calpain C3 to titin
-
-
?
additional information
?
-
the enzyme is associated with limb-girdle muscular dystrophy 2A
-
-
?
additional information
?
-
p94 proteolytic activity is involved in responses to muscle conditions, p94 inactivation causes limb-girdle muscular dystrophy
-
-
?
cyclin A + H2O
additional information
-
-
calpain 3-mediated cleavage of cyclin A in dividing myeloid pregenitor cells is important for the onset of differentiation
production of a truncated product that lacks the N-terminal destruction box required for its degradation at the end of mitosis. The cleaved form of cyclin A retains the cyclin-dependent kinase binding domain and forms active complexes with cdk2
?
additional information
?
-
-
important protein for normal muscle function. Mutations in the c3 gene result in limb-girdle muscular dystrophy type 2A
-
-
?
additional information
?
-
-
calpain 3/p94 is not involved in postmortem proteolysis
-
-
?
additional information
?
-
-
neither the reduction of calpain 3 nor its aberrant activity is responsible for the muscular dystrophy with myositis (mdm). Overexpression of calpain 3 exacerbates muscular dystrophy with myositis (mdm)
-
-
?
additional information
?
-
-
skeletal muscle-specific calpain participates in the regulation of the conventional calpain-calpastatin system in skeletal muscle
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Ca2+
Ca2+
regulated by Ca2+, contains 2 EF-hand calcium-binding domains. Activated by micromolar concentrations of calcium
Ca2+
-
autolysis of skeletal muscle-specific calpain does not require Ca2+, calpastatinolysis occurs in a Ca2+-dependent manner
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Calmodulin
calmodulin binds the calpain 3 non-catalytic domain C2L and promotes enzyme activation
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
from quadriceps femoris and the soleus muscles. A series of p94 splice variants is expressed immediately after muscle differentiation and differentially change localization during myofibrillogenesis. Endogenous N-terminal (but not C-terminal) domain of p94 is not only localized in the Z-bands but also directly bound to sarcomeric alpha-actinin. Incorporation of proteolytic N-terminal fragments of p94 into the Z-bands. In myofibrils localization of exogenously expressed p94 shifts from the M-line to N2A as the sarcomere lengthens beyond about 0.0026 and 0.0028 mm for wild-type and protease inactive p94, respectively
the single large catalytic subunit of calpain 3 is expressed predominantly in the submandibular gland at markedly higher levels in males than in females and in a manner dependent on androgens. In granular convoluted tubule cell calpain 3 immunoreactivity is localized predominantly in the cytosolic region and is absent in the secretory granules. Granular convoluted tubule is the primary site of production of calpain 3 submandibular gland
-
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
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calpain-3 is localized at the skeletal muscle M-line, Z-band, and the N2A region of the large myofibrillar protein, titin
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
in granular convoluted tubule cells calpain 3 immunoreactivity is localized predominantly in the cytosolic region and is absent in the secretory granules
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
proteolytic processing of C-terminal titin by calpain 3 has an important role in normal muscle
malfunction
physiological function
malfunction
mutations in calpain 3 underlie limb-girdle muscular dystrophy 2A
malfunction
-
deficiency in calpain 3 is associated with apoptosis as indicated by increases of caspase 3 activity, the absence of calpain 3 modifies the sarcoplasmic reticulum Ca2+ release, by a decrease of the sarcoplasmic reticulum content, an impairment of ryanodine receptor signalling, and an increase of L-type Ca2+ channel activity
malfunction
-
inactivating mutations of the CAPN3 gene, encoding the muscle-specific calpain-3, result in the limb-girdle muscular dystrophy-2A
malfunction
-
mitochondrial abnormalities, energy deficit and oxidative stress are features of calpain 3 deficiency in skeletal muscle
physiological function
-
calcium-dependent plasma membrane repair does not require calpain-3
physiological function
-
calpain 3 is involved in the myogenic differentiation process, calpain 3 participates in the establishment of the pool of reserve cells by decreasing the transcriptional activity of the key myogenic regulator MyoD via proteolysis independently of the ubiquitin-proteasome degradation pathway
physiological function
-
calpain 3-dependent proteolysis plays a role in activating support proteins of intracellular Ca2+ signalling at a stage of cellular differentiation which is crucial for skeletal muscle regeneration
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). CAN3_MOUSE
821
0
94242
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55000
-
full-length CAPN3 undergoes almost complete autolysis and runs as a 55 kDa band, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C129S
C129S
additional information
-
mutations result in limb girdle muscular dystrophy type 2A
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
alternative splicing isoform of calpain 3 is increased in FSHD region gene1 mice
reserve cells express higher levels of endogenous Capn3 mRNA than proliferating myoblasts
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boeckmann, B.; Bairoch, A.; Apweiler, R.; Blatter, M.C.; Estreicher, A.; Gasteiger, E.; Martin M.J.; Michoud, K.; O'Donovan, C.; Phan, I.; Pilbout, S.; Schneider, M.
The SWISS-PROT protein knowledgebase and its supplement TrEMBL
Nucleic Acids Res.
31
365-370
2003
Bos taurus (P51186), Homo sapiens (P20807), Mus musculus (Q64691), Sus scrofa (P43368)
Guyon, J.R.; Kudryashova, E.; Potts, A.; Dalkilic, I.; Brosius, M.A.; Thompson, T.G.; Beckmann, J.S.; Kunkel, L.M.; Spencer, M.J.
Calpain 3 cleaves filamin C and regulates its ability to interact with gamma- and delta-sarcoglycans
Muscle Nerve
28
472-483
2003
Mus musculus, Rattus norvegicus
Welm, A.L.; Timchenko, N.A.; Ono, Y.; Sorimachi, H.; Radomska, H.S.; Tenen, D.G.; Lekstrom-Himes, J.; Darlington, G.J.
C/EBPalpha is required for proteolytic cleavage of cyclin A by calpain 3 in myeloid precursor cells
J. Biol. Chem.
277
33848-33856
2002
Homo sapiens, Mus musculus
Richard, I.; Beckmann, J.S.
Molecular cloning of mouse canp3, the gene associated with limb-girdle muscular dystrophy 2A in human
Mamm. Genome
7
377-379
1996
Mus musculus (Q64691)
Kramerova, I.; Kudryashova, E.; Tidball, J.G.; Spencer, M.J.
Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro
Hum. Mol. Genet.
13
1373-1388
2004
Mus musculus
Kramerova, I.; Kudryashova, E.; Venkatraman, G.; Spencer, M.J.
Calpain 3 participates in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway
Hum. Mol. Genet.
14
2125-2134
2005
Mus musculus
Huebsch, K.A.; Kudryashova, E.; et.al.
Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain
Hum. Mol. Genet.
14
2801-2811
2005
Mus musculus
Geesink, G.H.; Taylor, R.G.; Koohmaraie, M.
Calpain 3/p94 is not involved in postmortem proteolysis
J. Anim. Sci.
83
1646-1652
2005
Mus musculus
Ono, Y.; Kakinuma, K.; Torii, F.; Irie, A.; Nakagawa, K.; Labeit, S.; Abe, K.; Suzuki, K.; Sorimachi, H.
Possible regulation of the conventional calpain system by skeletal muscle-specific calpain, p94/calpain 3
J. Biol. Chem.
279
2761-2771
2004
Mus musculus
Kramerova, I.; Kudryashova, E.; Wu, B.; Spencer, M.J.
Regulation of the M-cadherin-beta-catenin complex by calpain 3 during terminal stages of myogenic differentiation
Mol. Cell. Biol.
26
8437-8447
2006
Mus musculus
Cohen, N.; Kudryashova, E.; Kramerova, I.; Anderson, L.V.; Beckmann, J.S.; Bushby, K.; Spencer, M.J.
Identification of putative in vivo substrates of calpain 3 by comparative proteomics of overexpressing transgenic and nontransgenic mice
Proteomics
6
6075-6084
2006
Mus musculus
Tang, Y.; Liu, X.; Zoltoski, R.K.; Novak, L.A.; Herrera, R.A.; Richard, I.; Kuszak, J.R.; Kumar, N.M.
Age-related cataracts in alpha3Cx46-knockout mice are dependent on a calpain 3 isoform
Invest. Ophthalmol. Vis. Sci.
48
2685-2694
2007
Mus musculus
Hayashi, C.; Ono, Y.; Doi, N.; Kitamura, F.; Tagami, M.; Mineki, R.; Arai, T.; Taguchi, H.; Yanagida, M.; Hirner, S.; Labeit, D.; Labeit, S.; Sorimachi, H.
Multiple molecular interactions implicate connectin/titin N2A region as a modulating scaffold for p94/calpain 3 activity in skeletal muscle
J. Biol. Chem.
23
14801-14814
2008
Homo sapiens (P20807), Mus musculus (Q64691)
Ojima, K.; Ono, Y.; Doi, N.; Yoshioka, K.; Kawabata, Y.; Labeit, S.; Sorimachi, H.
Myogenic stage, sarcomere length, and protease activity modulate localization of muscle-specific calpain
J. Biol. Chem.
282
14493-14504
2007
Homo sapiens (P20807), Mus musculus (Q64691)
Kramerova, I.; Kudryashova, E.; Wu, B.; Ottenheijm, C.; Granzier, H.; Spencer, M.J.
Novel role of calpain-3 in the triad-associated protein complex regulating calcium release in skeletal muscle
Hum. Mol. Genet.
17
3271-3280
2008
Mus musculus
Beckmann, J.S.; Spencer, M.
Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance
Neuromuscul. Disord.
18
913-921
2008
Mus musculus
Mellgren, R.L.; Miyake, K.; Kramerova, I.; Spencer, M.J.; Bourg, N.; Bartoli, M.; Richard, I.; Greer, P.A.; McNeil, P.L.
Calcium-dependent plasma membrane repair requires m- or mu-calpain, but not calpain-3, the proteasome, or caspases
Biochim. Biophys. Acta
1793
1886-1893
2009
Mus musculus
Kramerova, I.; Kudryashova, E.; Wu, B.; Germain, S.; Vandenborne, K.; Romain, N.; Haller, R.G.; Verity, M.A.; Spencer, M.J.
Mitochondrial abnormalities, energy deficit and oxidative stress are features of calpain 3 deficiency in skeletal muscle
Hum. Mol. Genet.
18
3194-3205
2009
Mus musculus
Dayanithi, G.; Richard, I.; Viero, C.; Mazuc, E.; Mallie, S.; Valmier, J.; Bourg, N.; Herasse, M.; Marty, I.; Lefranc, G.; Mangeat, P.; Baghdiguian, S.
Alteration of sarcoplasmic reticulum ca release in skeletal muscle from calpain 3-deficient mice
Int. J. Cell Biol.
2009
340346
2009
Mus musculus
Stuelsatz, P.; Pouzoulet, F.; Lamarre, Y.; Dargelos, E.; Poussard, S.; Leibovitch, S.; Cottin, P.; Veschambre, P.
Down-regulation of MyoD by calpain 3 promotes generation of reserve cells in C2C12 myoblasts
J. Biol. Chem.
285
12670-12683
2010
Mus musculus
Charton, K.; Sarparanta, J.; Vihola, A.; Milic, A.; Jonson, P.H.; Suel, L.; Luque, H.; Boumela, I.; Richard, I.; Udd, B.
CAPN3-mediated processing of C-terminal titin replaced by pathological cleavage in titinopathy
Hum. Mol. Genet.
24
3718-3731
2015
Homo sapiens (P20807), Mus musculus (Q64691)
Ermolova, N.; Kramerova, I.; Spencer, M.J.
Autolytic activation of calpain 3 proteinase is facilitated by calmodulin protein
J. Biol. Chem.
290
996-1004
2015
Mus musculus (Q64691), Mus musculus
Pistoni, M.; Shiue, L.; Cline, M.S.; Bortolanza, S.; Neguembor, M.V.; Xynos, A.; Ares, M.; Gabellini, D.
Rbfox1 downregulation and altered calpain 3 splicing by FRG1 in a mouse model of facioscapulohumeral muscular dystrophy (FSHD)
PLoS Genet.
9
e1003186
2013
Homo sapiens (P20807), Homo sapiens, Mus musculus (Q64691), Mus musculus
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