Information on EC 3.4.22.53 - calpain-2

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The expected taxonomic range for this enzyme is: Opisthokonta

EC NUMBER
COMMENTARY
3.4.22.53
-
RECOMMENDED NAME
GeneOntology No.
calpain-2
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
broad endopeptidase specificity
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
endopeptidase; peptides, endopeptidase
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
3.4.22.17
Bos grunniens mutus
-
formerly
Cal II
-
-
calcium-activated neutral protease II
-
-
-
-
calpain 2
-
-
-
-
calpain 2
-
-
calpain 2
P04632
-
calpain 2
P07384
-
calpain 2
P17655
-
calpain 2
Q07009
-
calpain II
-
-
-
-
calpain II
-
-
calpain II
-
-
calpain II
-
-
calpain xCL-2 (Xenopus leavis)
-
-
-
-
calpain-2
D2IKJ8
-
calpain-2
-
-
calpain-2-like
D2IKJ8
-
calpain2
-
-
CAPN II
Bos grunniens mutus
-
-
CAPN2
-
-
CAPN2
O08529
catalytic subunit of m-calpain
CAPN2 g.p. (Homo sapiens)
-
-
-
-
CPN2
-
-
cysteine protease
-
-
EC 3.4.22.17
-
formerly
human calpain 2
P04632
-
m-calpain
-
-
-
-
m-calpain
Bos grunniens mutus
-
-
m-calpain
D2IKJ8
-
m-calpain
-
-
milli-calpain
-
-
-
-
mitochondrial m-calpain
-
m-calpain large subunit
nCL-2
-
-
rat calpain 2
Q07009
-
CAS REGISTRY NUMBER
COMMENTARY
702693-80-9
-
78990-62-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
Bos grunniens mutus
-
-
-
Manually annotated by BRENDA team
Atlantic halibut
UniProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
calpain-1 catalytic subunit
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
homozygous disruption of the Capn2 gene (encoding the catalytic subunit of m-calpain) results in preimplantation embryonic lethality between the morula and blastocyst stage
SwissProt
Manually annotated by BRENDA team
male Wistar
-
-
Manually annotated by BRENDA team
Shumixy cataract animals
-
-
Manually annotated by BRENDA team
Tilapia nilotica * Tilapia aurea
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
calpain inhibition blocks the increased colonic epithelial cell invasion caused by NM IIA knockdown
malfunction
-
in vivo knockdown of calpain2 disrupts metastasis among apoptosis-resistant tumors
malfunction
-
short interfering RNA-induced silencing of m-calpain results in increased RhoA activity and hyperpermeability in the aortic arch, which is accompanied by ROCK inhibitor-sensitive phosphorylation of downstream effecter LIM kinase 2, stress fibre accumulation in endothelium and enhanced interendothelial gaps
malfunction
-
calpain 2 depletion impairs mitosis and induces apoptosis, low Capn2 levels induce chromosome alignment defects, the loss of histone H3 threonine 3 phosphorylation at centromeres, and premature sister chromatid separation
malfunction
-
inhibition of m-calpain induces expression of the adult alpha- and beta-globin genes
malfunction
-
the blockage of calpain 2 suppresses p38 MAPK phosphorylation
malfunction
-
inhibition of calpain activity limits cell migration and in vitro wound healing of IEC-6 cells
malfunction
-
knockdown of calpain 2 expression or chemical inhibition of calpain activity reduces glioblastoma cell invasion by 90%. Decreased expression of calpain 2 does not influence morphology or migration
malfunction
-
knockdown of calpain 2 inhibits T cell migration at both the level of single cell tracking and general cell speed
physiological function
-
mitochondrial m-calpain is associated with ERp75 and plays an important role in releasing of truncated apoptosis-inducing factor from mitochondria
physiological function
-
calpain-2 is involved in cell motility
physiological function
-
mitochondrial m-calpain plays a role in the release of truncated apoptosis-inducing factor from the mitochondria by cleaving voltage-dependent anion channel
physiological function
-
calpain-2 is crucial for promotion of migration and metastasis by caspase-8
physiological function
-
m-calpain antagonizes RhoA overactivation and endothelial barrier dysfunction under disturbed shear conditions
physiological function
-
an endoplasmic reticulum stress-related calpain-down-regulated PPAR-gamma/HO-1 pathway is involved in the interleukin-13-enhanced activated death of microglia
physiological function
-
calpain 2 is required for sister chromatid cohesion
physiological function
-
Ca2+ overload induces apoptosis, which was correlated with calpain-2 activation
physiological function
-
m-calpain up-regulates alpha- and beta-actin in alveolar rhabdomyosarcoma cells
physiological function
-
calpain 2-mediated proteolysis of focal adhesion kinase regulates adhesion dynamics in motile cells
physiological function
-
calpain 2 plays a role in the generation of the low molecular weight-androgen receptor in CWR22-R1 cells
physiological function
-
calpain 2 activation is an early event in heat stress-induced male germ cell apoptosis
physiological function
-
m-calpain translocates during ischemia and activates at reperfusion in isolated rat hearts
physiological function
-
calpain 2 proteolysis of mAbp1 negatively regulates dorsal ruffle formation
physiological function
-
the Ca2+-dependent release of m-calpain from the mitochondrial outer membrane has important implications in facilitating apoptotic cell death
physiological function
-
calpain-2 is a mediator of beta cell dysfunction and apoptosis in type 2 diabetes
physiological function
-
calpain 2 is required for matrix metalloproteinase-2 activity in glioblastoma cells. Calpain 2 is required for glioblastoma cell invasion, but not migration
physiological function
-
calpain 2 controls turnover of lymphocyte function-associated antigen-1 adhesions on migrating T lymphocytes
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
AIF + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-2 spectrin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-actin + H2O
?
show the reaction diagram
-
slow degradation
-
-
?
alpha-adaptin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-fodrin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-neoendorphin + H2O
?
show the reaction diagram
-
cleavage of the 6Arg-7Lys bond
-
-
?
alpha-spectrin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-spectrin + H2O
145000 Da fragment + ?
show the reaction diagram
-
-
-
-
?
alpha-Tubulin + H2O
?
show the reaction diagram
-
complete digestion of alpha-tubulin with little effect on beta-tubulin
-
-
?
aminopeptidase B + H2O
?
show the reaction diagram
-
-
-
-
?
androgen receptor + H2O
?
show the reaction diagram
-
-
-
-
?
androgen receptor + H2O
low molecular weight androgen receptor + ?
show the reaction diagram
-
-
-
-
?
Angiotensin + H2O
?
show the reaction diagram
-
clevage of the 4tyr-5Ile bond
-
-
?
Bcl-xL + H2O
?
show the reaction diagram
-
-
-
-
?
benzoyl-Arg p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
beta-lipotropin(61-91) + H2O
?
show the reaction diagram
-
cleavage of the bonds: Thr76-Leu77, Lys84-Asn85 and Lys88-Lys89
-
-
?
beta-neoendorphin + H2O
?
show the reaction diagram
-
cleavage of the 6Arg-7Lys bond
-
-
?
beta-subunit of coatomer complex beta-COP + H2O
?
show the reaction diagram
-
-
-
-
?
beta-transducin repeat containing protein + H2O
?
show the reaction diagram
-
-
-
-
?
beta2-adaptin + H2O
?
show the reaction diagram
-
-
-
-
?
Boc-Leu-Met-7-amido-4-chloromethylcoumarin + H2O
Boc-Leu-Met + 7-amino-4-chloromethylcoumarin
show the reaction diagram
-
10 microM, 20 min, 37 C, with or without magnetic bead stimulation
-
-
?
Boc-Leu-Met-7-amino-4-chloromethylcoumarin
?
show the reaction diagram
-
-
-
-
?
Boc-Val-Leu-Lys-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
-
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
caspase-3 + H2O
?
show the reaction diagram
-
-
-
-
?
collapsin response mediator protein 1 + H2O
?
show the reaction diagram
-
-
-
-
?
collapsin response mediator protein 2 + H2O
?
show the reaction diagram
-
-
-
-
?
collapsin response mediator protein 3 + H2O
?
show the reaction diagram
-
-
-
-
?
collapsin response mediator protein 4 + H2O
?
show the reaction diagram
-
-
-
-
?
collapsin response mediator protein-1 + H2O
?
show the reaction diagram
-
collapsin response mediator protein-1 is cleaved by calpain-2 at the C-terminus
-
-
?
collapsin response mediator protein-2 + H2O
?
show the reaction diagram
-
collapsin response mediator protein-2 is cleaved by calpain-2 at the C-terminus
-
-
?
collapsin response mediator protein-4 + H2O
?
show the reaction diagram
-
collapsin response mediator protein-4 is cleaved by calpain-2 at the C-terminus
-
-
?
collapsin response mediator protein-5 + H2O
?
show the reaction diagram
-
-
-
-
?
cortactin + H2O
?
show the reaction diagram
-
-
-
-
?
crystallin + H2O
?
show the reaction diagram
-
-, alphaA crystallin in lenses from wild-type mice is proteolyzed by both calpain 2 and Lp82. Crystallins proleolyzed by calpain Lp82 are more susceptible to insolubilization than crystallins proteolyzed by calpain 2
-
-
?
dihydropteridine reductase + H2O
?
show the reaction diagram
-
the dihydropteridine reductase 29000 Da subunit is cleaved just before the 35th Ser and the 48th Val residue from the N-terminus, generating two new fragments of 21000 Da and 19000 Da which are more active than the native enzyme
-
-
?
dynorphin (1-13) + H2O
?
show the reaction diagram
-
cleavage of the 6Arg-7Arg bond
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
-
-
-
?
filamin A + H2O
?
show the reaction diagram
-
-
-
-
?
focal adhesion kinase + H2O
?
show the reaction diagram
-
the preferred calpain cleavage site is between the two C-terminal proline-rich regions after Ser-745
-
-
?
frequenin homolog + H2O
?
show the reaction diagram
-
-
-
-
?
FRET-based substrate PLFAER + H2O
?
show the reaction diagram
-
10 microM, pH 7.4, 1 mM of CaCl2 added to initiate the reaction
-
-
?
GAP-43 + H2O
GAP-43-3 + ?
show the reaction diagram
-
GAP-43 cleavage at Ser41 residue in synaptosomes is mediated by m-calpain, a GAP-43 fragment, lacking about 40 N-terminal residues (named GAP-43-3), is produced by m-calpain. The fragment prevents complete cleavage of intact GAP-43 by m-calpain as a negative feedback
-
-
?
GAP-43 + H2O
GAP-43-3 + ?
show the reaction diagram
-
a GAP-43 fragment, lacking about 40 N-terminal residues (named GAP-43-3), is produced by m-calpain. The fragment prevents complete cleavage of intact GAP-43 by m-calpain as a negative feedback
-
-
?
heterogeneous nuclear ribonucleoprotein F + H2O
?
show the reaction diagram
-
-
-
-
?
heterogeneous nuclear ribonucleoprotein K + H2O
?
show the reaction diagram
-
-
-
-
?
IkappaBalpha + H2O
?
show the reaction diagram
-
-, a parallel pathway that degrades IkappaBalpha and activates NF-kappaB activation independently of the ubiquitin-proteasome pathway
-
-
?
internexin + H2O
?
show the reaction diagram
-
-
-
-
?
IP3R1 + H2O
?
show the reaction diagram
-
in presence of Ca2, m-calpain cleaves IP3R1 in the endoplasmic lumen
-
-
?
laminin receptor 1 + H2O
?
show the reaction diagram
-
-
-
-
?
Leu-enkephalin + H2O
?
show the reaction diagram
-
cleaved only slightly at the 1Tyr-2Gly bond
-
-
?
mammalian actin-binding protein-1 + H2O
?
show the reaction diagram
-
the preferred cleavage site occurs between the actin-binding domain and the proline-rich region, generating a C-terminal mAbp1 fragment
-
-
?
Met-enkephalin + H2O
?
show the reaction diagram
-
cleaved only slightly at the 1Tyr-2Gly bond
-
-
?
microtubule-associated protein 1
?
show the reaction diagram
-
-
-
-
?
microtubule-associated protein 1B + H2O
?
show the reaction diagram
-
-
-
-
?
myocillin + H2O
?
show the reaction diagram
-
-, calpain II is responsible for the intracellular processing of myocilin in the lumen of the endoplasmic reticulum. It is proposed that this cleavage might regulate extracellular interactions of myocilin, contributing to the control of intraocular pressure
-
-
?
myosin II heavy chain + H2O
?
show the reaction diagram
-
rapid proteolysis
-
-
?
N-acetyl-LLY-7-amido-4-trifluoromethylcoumarin + H2O
N-acetyl-LLY + 7-amino-4-trifluoromethylcoumarin
show the reaction diagram
-
-
-
-
?
Na+/Ca2+ exchanger + H2O
82000 Da fragment + ?
show the reaction diagram
-
-
-
-
?
Na+/Ca2+ exchanger-1 + H2O
82 kDa fragment + ?
show the reaction diagram
-
calcium-dependent proteolytic cleavage of Na+/Ca2+ exchanger-1 occurs in the caveolae vesicles
-
-
?
NCX1 + H2O
?
show the reaction diagram
-
-
-
-
?
neurofilament + H2O
?
show the reaction diagram
-
-
-
-
?
neurotensin + H2O
?
show the reaction diagram
-
cleavage of the 3Tyr-4Glu bond and the 5Asn-6Lys bond
-
-
?
nucleolin + H2O
?
show the reaction diagram
-
-
-
-
?
p35 + H2O
25000 Da fragment of p35 + ?
show the reaction diagram
-
calpain-specific substrate
-
-
?
proteolysis-resistant fragment 130 + H2O
proteolysis-resistant fragment 45 + ?
show the reaction diagram
-
-
-
-
?
proteolysis-resistant fragment 72 + H2O
proteolysis-resistant fragment 45 + ?
show the reaction diagram
-
-
-
-
?
RRRRRRRR-(EDANS)-GQQEVYGMMPRDG-(DABCYL) + H2O
?
show the reaction diagram
-
-
-
-
?
selenoprotein K + H2O
?
show the reaction diagram
-
cleavage occurs only in unactivated macrophages, m-calpain cleavage at Arg81-Gly82 generates the two selenoprotein K isoforms
-
-
?
SLLVY-7-amido-4-methylcoumarin + H2O
SLLVY + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
succinyl-bovine-serum-albumin + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-casein + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-insulin B + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methyl coumarin + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
succinyl-Leu-Leu-Val-Tyr + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Leu-Val-Tyr-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Met-7-amido-4-methylcoumarin + H2O
succinyl-Leu-Met + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Tyr-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Tyr-7-amido-4-methylcoumarin + H2O
succinyl-Leu-Tyr + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Tyr-7-amido-4-methylcoumarin + H2O
succinyl-Leu-Tyr + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Tyr-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-protamine + H2O
?
show the reaction diagram
-
-
-
-
?
synaptotagmin-1 + H2O
?
show the reaction diagram
-
-
-
-
?
t-Boc-Leu-Met-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
t-butyloxycarbonyl-Val-Leu-Lys-7-amido-4-methylcoumarin + H2O
t-butyloxycarbonyl-Val-Leu-Lys + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
talin + H2O
?
show the reaction diagram
-
-
-
-
?
talin + H2O
?
show the reaction diagram
-
-
-
-
?
tert-butoxycarbonyl-Leu-Met-7-amido-4-chloromethylcoumarin + H2O
tert-butoxycarbonyl-Leu-Met + 7-amino-4-chloromethylcoumarin
show the reaction diagram
-
-
-
-
?
tert-butyloxycarbonyl-L-leucyl-L-methionine-7-amido-4-chloromethylcoumarin + H2O
tert-butyloxycarbonyl-L-leucyl-L-methionine + 7-amino-4-chloromethylcoumarin
show the reaction diagram
-
-
-
-
?
transgelin-3 + H2O
?
show the reaction diagram
-
-
-
-
?
ubiquitin-activating enzyme E1 + H2O
?
show the reaction diagram
-
-
-
-
?
vimentin + H2O
?
show the reaction diagram
-
-
-
-
?
voltage dependent anion channel + H2O
?
show the reaction diagram
-
-
-
-
?
voltage-dependent anion channel + H2O
?
show the reaction diagram
-
mitochondrial m-calpain truncates voltage-dependent anion channel in Ca2+-dependent manner
-
-
?
cyclin dependent kinase-5 + H2O
p25-CDK5
show the reaction diagram
-
-
-
-
?
desmin + H2O
additional information
-
-
-
two proteolytic fragments of 35000 Da and of 16000 Da
?
microtubule-associated protein 2
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
no proteolysis of actin
-
-
-
additional information
?
-
P43367
enzyme is involved in myofibrillar protein degradation
-
-
-
additional information
?
-
-
mu-calpain, m-calpain, 20S proteasome, dipeptidyl peptidase II and III and soluble alanyl aminopeptidase are thought to induce lens opacification kinetically during cataract formation in Shumiya cataract rats through the intracellular turnover of lens proteins
-
-
-
additional information
?
-
P17655
enzyme is involved in cytoskeleton remodelling and signal transduction
-
-
-
additional information
?
-
-
enzyme is involved in essential cellular functions mediated by calcium. Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit
-
-
-
additional information
?
-
-
hypoxia upregulates calpain activity and mRNA expression in pulmonary artery endothelial cells
-
-
-
additional information
?
-
-
the enzyme might be involved in light-dependent regulation of disk membrane morphogenesis by proteolysis of myosin II
-
-
-
additional information
?
-
-
the enzyme is involved in myoblast fusion by cleaving certain proteins. This cleavage could modify membrane and cytoskeleton organization for the myoblast to fuse
-
-
-
additional information
?
-
-
epidermal growth factor receptor activation of calpain is required for fibroblast motility and occurs via an ERK/MAP kinase signaling pathway
-
-
-
additional information
?
-
-
enzyme plays a pivotal role during the earlier stages of myogenesis, particularly during fusion. MyoD and myogenin can transactivate capn2, but MyoD shows a higher transactivation level for the regulatory sequences
-
-
-
additional information
?
-
-
calpain 2 is likely to be involved with signal transduction events in the lens
-
-
-
additional information
?
-
-
calpain 2 plays a role in limiting membrane protrusion and in regulating lamellipodial dynamics at the leading edge of migrating cells
-
-
-
additional information
?
-
-
calpain mediates calcium-induced activation of the Erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons
-
-
-
additional information
?
-
-
calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion contributes to cell death after myocardial ischemia
-
-
-
additional information
?
-
-
functions for nCL-2 involve the membrane trafficking of mucus cells by interacting with coat proteins
-
-
-
additional information
?
-
P07384
pathological conditions associated with the gene of calpain 2: muscular dystrophy, stroke, traumatic brain injury, spinal cord injury, Alzheimer's diseases, Parkinson's disease, neurodegenerative disorders, cataracts, cancer
-
-
-
additional information
?
-
-
calpain 2activity is critical for the life cycle of echovirus 1 and important in the multiplication of the viral RNA genome
-
-
-
additional information
?
-
-
calpain mediates angiogenic effects induced by vascular endothelial growth factor by modulating actin cytoskeletal organization
-
-
-
additional information
?
-
-
calpain-2 plays an important role in lung endothelial cell migration and proliferation
-
-
-
additional information
?
-
-
CAPN2 may represent a key factor in development from the first cell division
-
-
-
additional information
?
-
-
catalytic activity of calpain is required to limit pseudopod formation in the direction of chemoattractant and for efficient chemotaxis. Calpain 2 is a novel component of the frontness signal that promotes polarization during chemotaxis
-
-
-
additional information
?
-
-
fetuin A is a potential extracellular regulator of m-calpain at nascent sites of plasma membrane wounding
-
-
-
additional information
?
-
-
m-calpain activity is triggered by Ca2+-influx and promoted mainly through the phosphatidylinositol 3-kinase pathway
-
-
-
additional information
?
-
-
M-calpain is the major candidate of the proteinase to generate the aggrecan product with the COOH terminal neoepitope VPGVA709 (consisting of two NH2 terminal globular domain G1 and G2 and KS side chains) during the intracellular aggrecan processing
-
-
-
additional information
?
-
O08529
m-calpain is vital for development of the preimplantation murine embryo
-
-
-
additional information
?
-
-
ERp75 plays important role in the refolding of mitochondrial m-calpain large subunit, cytosolic m-calpain does not associate with ERp57
-
-
-
additional information
?
-
-
caspase-8 associates with calpain-2
-
-
-
additional information
?
-
-
representatives of the protein phosphatase 2A subunit classes C, PR65/A, PR55/B and PR61/B' are resistant to m-calpain-mediated degradation
-
-
-
upstream stimulatory factor + H2O
?
show the reaction diagram
-
-
-
-
?
vimentin + H2O
additional information
-
-
-
four proteolytic fragments: 3 major compounds of 54000 Da, 46000 Da and 20000 Da, and a minor fragment of 28000 Da
?
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
alpha-2 spectrin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-spectrin + H2O
145000 Da fragment + ?
show the reaction diagram
-
-
-
-
?
aminopeptidase B + H2O
?
show the reaction diagram
-
-
-
-
?
androgen receptor + H2O
?
show the reaction diagram
-
-
-
-
?
beta-transducin repeat containing protein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
caspase-3 + H2O
?
show the reaction diagram
-
-
-
-
?
collapsin response mediator protein-1 + H2O
?
show the reaction diagram
-
collapsin response mediator protein-1 is cleaved by calpain-2 at the C-terminus
-
-
?
collapsin response mediator protein-2 + H2O
?
show the reaction diagram
-
collapsin response mediator protein-2 is cleaved by calpain-2 at the C-terminus
-
-
?
collapsin response mediator protein-4 + H2O
?
show the reaction diagram
-
collapsin response mediator protein-4 is cleaved by calpain-2 at the C-terminus
-
-
?
collapsin response mediator protein-5 + H2O
?
show the reaction diagram
-
-
-
-
?
cortactin + H2O
?
show the reaction diagram
-
-
-
-
?
crystallin + H2O
?
show the reaction diagram
-
alphaA crystallin in lenses from wild-type mice is proteolyzed by both calpain 2 and Lp82. Crystallins proleolyzed by calpain Lp82 are more susceptible to insolubilization than crystallins proteolyzed by calpain 2
-
-
?
dihydropteridine reductase + H2O
?
show the reaction diagram
-
the dihydropteridine reductase 29000 Da subunit is cleaved just before the 35th Ser and the 48th Val residue from the N-terminus, generating two new fragments of 21000 Da and 19000 Da which are more active than the native enzyme
-
-
?
filamin A + H2O
?
show the reaction diagram
-
-
-
-
?
frequenin homolog + H2O
?
show the reaction diagram
-
-
-
-
?
GAP-43 + H2O
GAP-43-3 + ?
show the reaction diagram
-
GAP-43 cleavage at Ser41 residue in synaptosomes is mediated by m-calpain
-
-
?
heterogeneous nuclear ribonucleoprotein F + H2O
?
show the reaction diagram
-
-
-
-
?
heterogeneous nuclear ribonucleoprotein K + H2O
?
show the reaction diagram
-
-
-
-
?
IkappaBalpha + H2O
?
show the reaction diagram
-
a parallel pathway that degrades IkappaBalpha and activates NF-kappaB activation independently of the ubiquitin-proteasome pathway
-
-
?
internexin + H2O
?
show the reaction diagram
-
-
-
-
?
IP3R1 + H2O
?
show the reaction diagram
-
in presence of Ca2, m-calpain cleaves IP3R1 in the endoplasmic lumen
-
-
?
laminin receptor 1 + H2O
?
show the reaction diagram
-
-
-
-
?
mammalian actin-binding protein-1 + H2O
?
show the reaction diagram
-
the preferred cleavage site occurs between the actin-binding domain and the proline-rich region, generating a C-terminal mAbp1 fragment
-
-
?
myocillin + H2O
?
show the reaction diagram
-
calpain II is responsible for the intracellular processing of myocilin in the lumen of the endoplasmic reticulum. It is proposed that this cleavage might regulate extracellular interactions of myocilin, contributing to the control of intraocular pressure
-
-
?
NCX1 + H2O
?
show the reaction diagram
-
-
-
-
?
neurofilament + H2O
?
show the reaction diagram
-
-
-
-
?
nucleolin + H2O
?
show the reaction diagram
-
-
-
-
?
p35 + H2O
25000 Da fragment of p35 + ?
show the reaction diagram
-
calpain-specific substrate
-
-
?
selenoprotein K + H2O
?
show the reaction diagram
-
cleavage occurs only in unactivated macrophages, m-calpain cleavage at Arg81-Gly82 generates the two selenoprotein K isoforms
-
-
?
synaptotagmin-1 + H2O
?
show the reaction diagram
-
-
-
-
?
transgelin-3 + H2O
?
show the reaction diagram
-
-
-
-
?
ubiquitin-activating enzyme E1 + H2O
?
show the reaction diagram
-
-
-
-
?
vimentin + H2O
?
show the reaction diagram
-
-
-
-
?
microtubule-associated protein 1B + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
P43367
enzyme is involved in myofibrillar protein degradation
-
-
-
additional information
?
-
-
mu-calpain, m-calpain, 20S proteasome, dipeptidyl peptidase II and III and soluble alanyl aminopeptidase are thought to induce lens opacification kinetically during cataract formation in Shumiya cataract rats through the intracellular turnover of lens proteins
-
-
-
additional information
?
-
P17655
enzyme is involved in cytoskeleton remodelling and signal transduction
-
-
-
additional information
?
-
-
enzyme is involved in essential cellular functions mediated by calcium. Tandemly reiterated negative enhancer-like elements regulate transcription of a human gene for the large subunit
-
-
-
additional information
?
-
-
hypoxia upregulates calpain activity and mRNA expression in pulmonary artery endothelial cells
-
-
-
additional information
?
-
-
the enzyme might be involved in light-dependent regulation of disk membrane morphogenesis by proteolysis of myosin II
-
-
-
additional information
?
-
-
the enzyme is involved in myoblast fusion by cleaving certain proteins. This cleavage could modify membrane and cytoskeleton organization for the myoblast to fuse
-
-
-
additional information
?
-
-
epidermal growth factor receptor activation of calpain is required for fibroblast motility and occurs via an ERK/MAP kinase signaling pathway
-
-
-
additional information
?
-
-
enzyme plays a pivotal role during the earlier stages of myogenesis, particularly during fusion. MyoD and myogenin can transactivate capn2, but MyoD shows a higher transactivation level for the regulatory sequences
-
-
-
additional information
?
-
-
calpain 2 is likely to be involved with signal transduction events in the lens
-
-
-
additional information
?
-
-
calpain 2 plays a role in limiting membrane protrusion and in regulating lamellipodial dynamics at the leading edge of migrating cells
-
-
-
additional information
?
-
-
calpain mediates calcium-induced activation of the Erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons
-
-
-
additional information
?
-
-
calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion contributes to cell death after myocardial ischemia
-
-
-
additional information
?
-
-
functions for nCL-2 involve the membrane trafficking of mucus cells by interacting with coat proteins
-
-
-
additional information
?
-
P07384
pathological conditions associated with the gene of calpain 2: muscular dystrophy, stroke, traumatic brain injury, spinal cord injury, Alzheimer's diseases, Parkinson's disease, neurodegenerative disorders, cataracts, cancer
-
-
-
additional information
?
-
-
calpain 2activity is critical for the life cycle of echovirus 1 and important in the multiplication of the viral RNA genome
-
-
-
additional information
?
-
-
calpain mediates angiogenic effects induced by vascular endothelial growth factor by modulating actin cytoskeletal organization
-
-
-
additional information
?
-
-
calpain-2 plays an important role in lung endothelial cell migration and proliferation
-
-
-
additional information
?
-
-
CAPN2 may represent a key factor in development from the first cell division
-
-
-
additional information
?
-
-
catalytic activity of calpain is required to limit pseudopod formation in the direction of chemoattractant and for efficient chemotaxis. Calpain 2 is a novel component of the frontness signal that promotes polarization during chemotaxis
-
-
-
additional information
?
-
-
fetuin A is a potential extracellular regulator of m-calpain at nascent sites of plasma membrane wounding
-
-
-
additional information
?
-
-
m-calpain activity is triggered by Ca2+-influx and promoted mainly through the phosphatidylinositol 3-kinase pathway
-
-
-
additional information
?
-
-
M-calpain is the major candidate of the proteinase to generate the aggrecan product with the COOH terminal neoepitope VPGVA709 (consisting of two NH2 terminal globular domain G1 and G2 and KS side chains) during the intracellular aggrecan processing
-
-
-
additional information
?
-
O08529
m-calpain is vital for development of the preimplantation murine embryo
-
-
-
additional information
?
-
-
ERp75 plays important role in the refolding of mitochondrial m-calpain large subunit, cytosolic m-calpain does not associate with ERp57
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Al3+
-
millimolar concentrations of Al3+ activate at at submillimolar concentrations of Ca2+
Ba2+
-
slight activation
Ba2+
-
5 mM 85.4% of the activation with 5 mM Ca2+
Ba2+
-
1 mM, decreases the Ca2+-requirement for maximal activity from 0.4 mM to 0.3 mM. Synergistic activating effect with Ca2+
Ba2+
-
5 mM, activates
Ba2+
-
activates
Ca2+
-
Kd-value: 0.325 mM. 25% of the difference in Kd values between mu-calpain and m-calpain can be ascribed to the N-terminal peptide of the large subunit, whereas the C-terminal EF-hand-containing domain IV accounts for 65% of the difference
Ca2+
-
half-maximal activation at 0.5 mM
Ca2+
-
half-maximal activation at 0.8 mM, maximal activation at 1.5 mM
Ca2+
-
half-maximal activation at 0.2 mM, maximal activation at 1 mM
Ca2+
-
-
Ca2+
-
half-maximal activation at 0.15 mM, maximal activation at 1 mM
Ca2+
-
half-maximal activity at 0.18 mM
Ca2+
-
half-maximal activation at 0.2 mM, full activity at 1 mM
Ca2+
-
Ka-value: 0.7 mM
Ca2+
-
activates. The results support the hypothesis that Ca2+ induces movement of domains I and II closer together to form the functional active site of calpain
Ca2+
-
half-maximal activity is 0.242 mM for wilde-type enzyme, 0.129 mM for the E504S mutant, 0.226 mM for the K226S mutant, 0.261 mM for the K230S mutant, 0.183 mM for the K234 mutant, 0.256 mM for the K230E mutant and 0.159 mM for the K234E mutant; half-maximal activity of wild-type enzyme at 0.242 mM
Ca2+
-
Ca2+-binding must induce conformational changes that reorient the protease domains to form a functional active site
Ca2+
-
absolute requirement
Ca2+
-
activates
Ca2+
-
half-maximal activity at 0.4 mM, maximal activity at 1.5 mM
Ca2+
-
0.4 mM Ca2+ is required for 50% caseinolysis of recombinant enzyme
Ca2+
-
half maximal activity for retina and brain enzyme is 0.262 mM and 0.311 mM, maximal activity near 1 mM, no activity in presence of 0.03 mM
Ca2+
-
half-maximal activity at 2.4 mM, maximal activity at 5 mM
Ca2+
-
half-maximal activity at 0.23 mM, maximal activity at 1-2.5 mM
Ca2+
-
requires millimolar order calcium ions for activation
Ca2+
-
5 mM required for optimal activity
Ca2+
-
wild-type enzyme has a Kd-value of 0.325 mM
Ca2+
-
best activator at 2.5 mM, maximal caseinolytic activity at 2.2 mM, half-maximal caseinolytic activity at 0.312 mM
Ca2+
Bos grunniens mutus
-
requires approximately 0.3 mM Ca2+ for half-maximal activity in vivo
Ca2+
-
dependent on
Ca2+
-
the Ca2+ dependency of mitochondrial m-calpain is similar to that of cytosolic m-calpain, 1 mM Ca2+ activates.
Ca2+
-
calcium-dependent cysteine protease
Ca2+
-
treatment of the endoplasmic reticulum with Ca2+ (5 mM) dissociates m-calpain-calpastatin association leading to the activation of m-calpain
Ca2+
-
optimum activity at 5 mM Ca2+
Ca2+
-
required for activity
Ca2+
-
dependent on
Ca2+
-
calpain 2 is activated with addition of CaCl+ to 1 mM
Ca2+
-
dependent on
Ca2+
-
Ca2+-induced calpain translocation to the membrane during ischemia is independent of its activation; Ca2+ induces calpain translocation to the membrane during ischemia
Ca2+
-
requires millimolar calcium concentrations for activation
Ca2+
-
dependent on
Ca2+
-
maximum calcium requirement of 0.6 mM
Ca2+
-
required for activity
Ca2+
-
activates
Ca2+
-
required for activity
Co2+
-
5 mM, activates
Cu2+
-
activates
K+
-
5 mM, activates in presence of 5 mM Ca2+
Mg2+
-
slight activation
Mg2+
-
1 mM decreases the Ca2+-requirement for maximal activity from 0.4 mM to 0.3 mM. Synergistic activating effect with Ca2+
Mg2+
-
5 mM, activates in presence of 5 mM Ca2+
Mn2+
-
5 mM 73.6% of the activation with 5 mM Ca2+. Synergistic activating effect with Ca2+
Mn2+
-
1 mM, decreases the half-maximal Ca2+-requirement from 0.4 mM to 0.1 mM, decreases the Ca2+-requirement for maximal activity from 1.5 mM to 1 mM
Mn2+
-
5 mM, activates
Mn2+
-
activates
Na+
-
5 mM, activates in presence of 5 mM Ca2+
Sr2+
-
activates
Sr2+
-
activates, Ka: 5.1 mM
Sr2+
-
5 mM 91% of the activation with 5 mM Ca2+
Sr2+
-
1 mM, decreases the half-maximal Ca2+-requirement from 0.4 mM to 0.1 mM, decreases the Ca2+-requirement for maximal activity from 1.5 mM to 1 mM. Synergistic activating effect with Ca2+
Sr2+
-
5 mM, activates
Sr2+
-
2.5 mM, 66% of the activation obtained with Ca2+, maximal caseinolytic activity at 5.9 mM, half-maximal caseinolytic activity at 1.886 mM. Autolysis in presence of 5 mM Ca2+. The 80000 Da subunit is rapidly autolyzed in two smaller bands of 73000 Da and 69000 Da. The small subunit of 24000 da is degraded into three bands of 22000 Da, 19300 Da and 17800 Da. It is not clear whether autolysis is necessary for calpain to become proteolytically active
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(2S)-3-phenyl-2-([[(2S)-1-(phenylsulfonyl)pyrrolidin-2-yl]carbonyl]amino)propanoic acid
-
-
(2S)-4-methyl-2-[(phenylsulfonyl)amino]pentanoic acid
-
-
(2S,3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester
-
0.01 mM, 50% inhibition
1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester
-
-
110 kDa calpastatin
-
-
-
3,4-Dichloroisocoumarin
-
0.05 mM, 11% inhibition
70 kDa calpastatin
-
-
-
acetyl-Leu-Leu-Met-CHO
-
selectively inhibits the activity of calpain-2
acetyl-Leu-Leu-Nle-CHO
-
complete inhibition at 0.001 mM
acetyl-Leu-Leu-Nle-CHO
-
broad spectrum calpain inhibitor
acetyl-Leu-Leu-Nle-CHO
-
-
Al3+
-
inactivation at millimolar concentration of Ca2+
alpha2-Macroglobulin
-
0.05 mg/ml, 11% inhibition
-
antipain
-
0.01 mM, 80-90% inhibition
antipain
-
0.01 mM 56% inhibition
antipain
-
0.02 mM, 82% loss of activity
antipain
-
0.02 mM, 87% loss of activity
antipain
-
0.05 mM, complete inhibition
benzyloxycarbonyl-L-leucyl-L-leucinal
-
-
benzyloxycarbonyl-Leu-Leu-leucinal
-
-
benzyloxycarbonyl-Leu-Leu-phenylalaninal
-
-
benzyloxycarbonyl-Leu-Leu-Tyr diazomethyl ketone
-
-
benzyloxycarbonyl-Leu-norleucinal
-
-
benzyloxycarbonyl-LLY-fluoromethylketone
-
-
Ca2+
-
initiation of autolysis of calpain 2 by adding of 1 mM CaCl2
Calmidazolium
-
calpain-specific inhibitor
calpain inhibitor I
-
0.002 mM, 95% loss of activity
calpain inhibitor I
-
0.002 mM, 90% loss of activity
calpain inhibitor I
-
0.05 mM, 99% inhibition
calpain inhibitor II
-
0.002 mM, 67% loss of activity
calpain inhibitor II
-
0.002 mM, 93% loss of activity
calpain inhibitor II
-
0.05 mM, complete inhibition
Calpastatin
-
-
-
Calpastatin
-
inhibition of m-calpain is greater at pH 7.5 than at pH 6.5 at both 165 mM and 295 mM NaCl. Percentage inhibition is greater at 295 mM than at 165 mM NaCl
-
Calpastatin
-
oxidation lowers calpastatin inhibition of m-calpain at al pH and ionic strength combinations
-
Calpastatin
Bos grunniens mutus
-
specific competitive inhibitor
-
Calpastatin
-
endogenous inhibitor
-
Calpastatin
-
-
-
Calpastatin
-
endogenous inhibitor
-
Calpastatin
-
-
-
Calpastatin
-
; endogenous inhibitor
-
Calpastatin
-
endogenous inhibitor of calpain
-
Calpastatin
-
specific inhibitor
-
Calpastatin
-
-
-
Calpastatin
-
-
-
calpastatin II
-
-
-
Calpeptin
-
50% inhibition of maximal caseinolytic activity at 10 nM and 21 nM for retinal and brain calpain
Calpeptin
-
complete inhibition at 0.001 mM
Calpeptin
-
Z-Leu-Nle-CHO
Calpeptin
-
-
Calpeptin
-
-
caplastatin 2
-
-
-
Cbz-Leu-DL-Abu-CONH-(CH2)3-(4-methylpiperazin-1-yl)
-
-
-
Cbz-Leu-DL-Abu-CONH-(CH2)3-2-methoxyadenin-9-yl
-
-
-
Cbz-Leu-DL-Abu-CONH-(CH2)3-adenin-9-yl
-
-
-
Cbz-Leu-DL-Abu-CONH-(CH2)3-cytosin-3-yl
-
-
-
Cbz-Leu-DL-Abu-CONH-(CH2)3-morpholine
-
-
-
Cbz-Leu-DL-Phe-CONH-(CH2)2-N-(CH3)2
-
-
-
Cbz-Leu-DL-Phe-CONH-(CH2)3-(4-methylpiperazin-1-yl)
-
-
-
Cbz-Leu-DL-Phe-CONH-(CH2)3-2-methoxyadenin-9-yl
-
-
-
Cbz-Leu-DL-Phe-CONH-(CH2)3-adenin-9-yl
-
best inhibitor
-
Cbz-Leu-DL-Phe-CONH-(CH2)3-cytosin-3-yl
-
-
-
Cbz-Leu-DL-Phe-CONH-(CH2)3-N-(CH3)2
-
-
-
Cd2+
-
5 mM, inhibits in presence of 5 mM Ca2+
Cd2+
-
5 mM, completely blocks activation of the enzyme by Ca2+
Co2+
-
5 mM, inhibits in presence of 5 mM Ca2+
Co2+
-
5 mM, completely blocks activation of the enzyme by Ca2+
Co2+
-
2.5 mM, strong
Cu2+
-
5 mM, inhibits in presence of 5 mM Ca2+
Cu2+
-
5 mM, completely blocks activation of the enzyme by Ca2+
E-64
-
0.05 mg/ml, complete inhibition
E-64
-
0.01 mM 89% inhibition
E-64
-
i.e. trans-epoxysuccinyl-L-leucylamido-(4-guanido)butane
E-64
-
0.01 mM, 98% inhibition
E-64c
-
0.01 mM, 80-90% inhibition
EDTA
-
5 mM, complete inhibition
EDTA
-
completely inactivated by 4 mM EDTA plus 4 mM EGTA
EGTA
-
completely inactivated by 4 mM EDTA plus 4 mM EGTA
Ep-475
-
0.001 mM, 49% inhibition of the enzyme from retina, 46% inhibition of the enzyme from brain
ethyl N-(phenylsulfonyl)-L-leucyl-L-phenylalaninate
-
-
Fe2+
-
5 mM, inhibits in presence of 5 mM Ca2+
-
Fe2+
-
2.5 mM, strong
-
Fe3+
-
2.5 mM, complete
-
GAP-43-3
-
a GAP-43 fragment, lacking about 40 N-terminal residues (named GAP-43-3), is produced by m-calpain-mediated cleavage of GAP-43. The fragment prevents complete cleavage of intact GAP-43 by m-calpain as a negative feedback. GAP-43-3 also blocks m-calpain activity against casein
-
Hg2+
-
5 mM, inhibits in presence of 5 mM Ca2+
Hg2+
-
2.5 mM, complete
Indomethacin
-
-
iodoacetamide
-
1 mM, 64% inhibition
iodoacetic acid
-
1 mM, 76% inhibition
iodoacetic acid
-
1 mM, complete loss of activity
iodoacetic acid
-
1 mM, 99% loss of activity
iodoacetic acid
-
0.1 mM, 99% inhibition
K+
-
inhibits at high concentrations
K+
-
5 mM, inhibits in presence of 5 mM Ca2+
Leupeptin
-
0.05 mg/ml, complete inhibition
Leupeptin
-
0.01 mM, 80-90% inhibition
Leupeptin
-
0.01 mM 85% inhibition
Leupeptin
-
0.001 mM, 67% inhibition of enzyme from retina and brain
Leupeptin
-
0.002 mM, complete loss of activity
Leupeptin
-
0.002 mM, 93% loss of activity
Leupeptin
-
0.05 mM, 99% inhibition
Leupeptin
-
-
MDL28170
-
selective calpain inhibitor
Mg2+
-
5 mM, inhibits in presence of 5 mM Ca2+
N-acetyl-L-leucyl-L-leucyl-L-methioninal
-
-
N-acetyl-Leu-Leu-Met
-
-
N-tosyl-Lys-chloromethyl ketone
-
0.5 mM, 69% inhibition
N-tosyl-Phe-chloromethyl ketone
-
0.5 mM, 91% inhibition
Na+
-
inhibits at high concentrations
Na+
-
5 mM, inhibits in presence of 5 mM Ca2+
NaCl
-
m-calpain is more active at 165 mM NaCl than at 295 mM NaCl
NEM
-
3.0 mM, high inhibition of activity in presence or absence of Ca2+
NEM
-
1 mM, 93% inhibition
NEM
-
5 mM, complete inhibition
Ni2+
-
5 mM, inhibits in presence of 5 mM Ca2+
Ni2+
-
5 mM, completely blocks activation of the enzyme by Ca2+
Ni2+
-
2.5 mM, complete
PCMB
-
1 mM, 56% inhibition
PCMB
-
1 mM, 42% inhibition
PCMB
-
5 mM, 24% inhibition
Pepstatin
-
0.01 mM, 99% inhibition
pepstatin A
-
1 mM, 60-80% inhibition
PMSF
-
1 mM, 6% inhibition
Polyethylene glycol
-
PEG-4000, PEG-100000 or PEG-20000, inhibition at concentrations higher than 0.5%
protease inhibitor
-
0.002 mg/ml, 6% inhibition
-
TLCK
-
0.1 mM, 60-80% inhibition
Z-Val-Phe-CHO
-
i.e. MDL-28710m, 1.0 microM
Zn2+
-
5 mM, inhibits in presence of 5 mM Ca2+
Zn2+
-
5 mM, completely blocks activation of the enzyme by Ca2+
Zn2+
-
2.5 mM, complete
Mn2+
-
2.5 mM, strong
additional information
-
suppression of calpain-2 expression with adenovirus vector-mediated RNAi
-
additional information
-
specific capn2 shRNA reduces expression of the targeted isoform
-
additional information
-
not inhibited by benzyloxycarbonyl-VAD-fluoromethylketone
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
1 mM, activates
calcium lactate
-
-
-
dithiothreitol
-
1 mM, activates
TNF-alpha
-
activates cytosolic enzyme
-
glutathione
-
1 mM, activates
additional information
-
increase of m-calpain expression by mechanical stimulation via laminin receptors
-
additional information
-
upregulation of calpain 2 post eccentric exercise
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
7.5
-
Boc-Val-Leu-Lys-methylcoumarin
-
pH 7.5, room temperature
2.2
-
succinyl-bovine-serum albumin
-
pH 7.5, 25C
-
10
-
succinyl-casein
-
pH 7.5, 25C
-
453.7
-
succinyl-insulin B
-
pH 7.5, 25C
-
0.459
-
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
0.461
-
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
19.32
-
succinyl-Leu-Leu-Val-Tyr-methylcoumarin
-
pH 7.5, room temperature
4.66
-
succinyl-Leu-Met-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
4.68
-
succinyl-Leu-Met-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
0.431
-
succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
-
2.1
-
succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
2.13
-
succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
3.18
-
succinyl-Leu-Tyr-methylcoumarin
-
pH 7.5, room temperature
101.3
-
succinyl-protamine
-
pH 7.5, 25C
-
5.33
-
t-Boc-Leu-Met-methylcoumarin
-
pH 7.5, room temperature
8.11
-
t-butyloxycarbonyl-Val-Leu-Lys-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
8.12
-
t-butyloxycarbonyl-Val-Leu-Lys-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.341
-
Boc-Val-Leu-Lys-methylcoumarin
-
pH 7.5, room temperature
0.062
-
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
0.063
-
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
0.0394
-
succinyl-Leu-Leu-Val-Tyr-methylcoumarin
-
pH 7.5, room temperature
0.186
-
succinyl-Leu-Met-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
0.189
-
succinyl-Leu-Met-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
0.083
-
succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
0.084
-
succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
0.04
-
succinyl-Leu-Tyr-methylcoumarin
-
pH 7.5, room temperature
0.546
-
t-Boc-Leu-Met-methylcoumarin
-
-
1.06
-
t-butyloxycarbonyl-Val-Leu-Lys-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
1.08
-
t-butyloxycarbonyl-Val-Leu-Lys-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.135
-
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
34549
0.137
-
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
34549
0.0399
-
succinyl-Leu-Met-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
34550
0.0404
-
succinyl-Leu-Met-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
34550
0.0394
-
succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
146806
0.0395
-
succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
146806
0.131
-
t-butyloxycarbonyl-Val-Leu-Lys-7-amido-4-methylcoumarin
-
endoplasmic reticulum membrane m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
199823
0.133
-
t-butyloxycarbonyl-Val-Leu-Lys-7-amido-4-methylcoumarin
-
endoplasmic reticulum lumen m-calpain, in 100 mM imidazole-HCl buffer (pH 7.5), 5 mM L-cysteine, 2.5 mM 2-mercaptoethanol, 5 mM CaCl2, and 4% (v/v) dimethyl sulfoxide, at 30C
199823
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00206
-
antipain
-
room temperature, pH 7.5, with succinyl-Met-Leu-methylcoumarin as substrate
0.000286
-
Cbz-Leu-DL-Abu-CONH-(CH2)3-(4-methylpiperazin-1-yl)
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.000077
-
Cbz-Leu-DL-Abu-CONH-(CH2)3-2-methoxyadenin-9-yl
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.00007
-
Cbz-Leu-DL-Abu-CONH-(CH2)3-adenin-9-yl
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.00114
-
Cbz-Leu-DL-Abu-CONH-(CH2)3-cytosin-3-yl
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.000041
-
Cbz-Leu-DL-Abu-CONH-(CH2)3-morpholine
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.00352
-
Cbz-Leu-DL-Phe-CONH-(CH2)2-N-(CH3)2
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.00636
-
Cbz-Leu-DL-Phe-CONH-(CH2)3-(4-methylpiperazin-1-yl)
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.000209
-
Cbz-Leu-DL-Phe-CONH-(CH2)3-2-methoxyadenin-9-yl
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.000068
-
Cbz-Leu-DL-Phe-CONH-(CH2)3-adenin-9-yl
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.000438
-
Cbz-Leu-DL-Phe-CONH-(CH2)3-cytosin-3-yl
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.000844
-
Cbz-Leu-DL-Phe-CONH-(CH2)3-N-(CH3)2
-
in 50 mM Tris-HCl, 50 mM NaCl, 1 mM EDTA, 1 mM EGTA, 0.1% CHAPS, pH 7.5, 10 mM dithiothreitol, 5 mM CaCl2, and less than 5% (v/v) DMSO, temperature not specified in the publication
-
0.00092
-
Leupeptin
-
room temperature, pH 7.5, with succinyl-Met-Leu-methylcoumarin as substrate
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00014
-
(2S)-3-phenyl-2-([[(2S)-1-(phenylsulfonyl)pyrrolidin-2-yl]carbonyl]amino)propanoic acid
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00041
-
(2S)-4-methyl-2-[(phenylsulfonyl)amino]pentanoic acid
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00000052
-
110 kDa calpastatin
-
in 100 mM imidazole-HCl buffer (pH 7.5),5 mM cysteine and 5 mM CaCl2, at 30C
-
0.0000008
-
70 kDa calpastatin
-
in 100 mM imidazole-HCl buffer (pH 7.5),5 mM cysteine and 5 mM CaCl2, at 30C
-
0.00024
-
ethyl N-(phenylsulfonyl)-L-leucyl-L-phenylalaninate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00015
-
MDL28170
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
initial activity as relative fluorescence units per s: 1.3 for wild type calpain 2, 0.84 for mutant G423R, 0.19 for mutant R628Q, 0.36 for mutant T344M, 0.7 for mutant D346E, 1.0 for mutant D362K
additional information
-
-
endoplasmic reticulum membrane m-calpain shows 170 units/mg specific activity after 323fold purification, endoplasmic reticulum lumen m-calpain shows 324 units/mg specific activity after 463fold purification one unit is defined as the amount of the enzyme that causes a change of 1.0 in A750 for the trichloroacetic acid-soluble products after incubation of the enzyme in the assay mixture
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.9
-
-
enzyme from retina and brain
7.4
-
-
1 mM CaCL2 added to start reaction
7.5
-
-
m-calpain
7.5
-
-
-
7.7
-
-
-
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
8.5
-
pH 5.0: about 50% of maximal activity, pH 8.5: about 30% of maximal activity
6
8
-
pH 6.0: about 40% of maximal activity, pH 8.0: about 50% of maximal activity, enzyme from retina and brain
6
8.5
-
pH 6.0: about 50% of maximal activity, pH 8.5: about 60% of maximal activity
6.5
7.5
-
activity of m-calpain is greater at pH 7.5 than at pH 6.5
6.5
8.5
-
pH 6.5: about 50% of maximal activity, pH 8.5: about 40% of maximal activity
additional information
-
-
the enzyme is not proteolytically active at pH 5.8
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
-
30
-
-
-
37
-
-
20 min, with or without magnetic bead stimulation
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
10
40
-
10C: about 60% of maximal activity, 40C: about 45% of maximal activity
10
45
-
10C: about 60% of maximal activity, 45C: about 35% of maximal activity
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4.5
-
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
relatively high m-calpain expression levels in the inferior arch
Manually annotated by BRENDA team
-
calpain 2 is important for both the formation of invadopodia and invasive capacity of breast cancer cells
Manually annotated by BRENDA team
-
nCL-2 is localized strictly to the surface cells in the gastric epithelium and the mucus-secreting goblet cells in the duodenum
Manually annotated by BRENDA team
-
analysis from E8.5 to 14.5 stages indicates high levels of capn2 expression in the nervous system, heart and mesodermal tissues. Up-regulation is maintained during later developmental stages in proliferating cells and in precursor cells involved in muscle (myoblasts) or bone formation (chondrocytes). At later developmental stages, elevated mRNA levels coincide with CAPN2 nuclear localization in these cell types, while differentiated cells maintain cytoplasmic expression
Manually annotated by BRENDA team
-
pulmonary microvascular endothelial cell. Incubation of the cells with vascular endothelial growth factor results in dose- and time-dependent increases in calpain activity and protein content of calpain-2. Vascular endothelial growth factor does not change the protein contents of calpain-1 and the small subunit or of calpastatin. Inhibition of calpain activity by siRNA directed against calpain-2 and by overexpression of calpastatin prevents vascular endothelial growth factor-induced increases in actin stress fibers in endothelial cells and angiogenesis
Manually annotated by BRENDA team
-
calpain 2 is first expressed late in embryonic development and localizes to the lens epithelium and transition zone
Manually annotated by BRENDA team
-
nCL-2 is localized strictly to the surface cells in the gastric epithelium and the mucus-secreting goblet cells in the duodenum
Manually annotated by BRENDA team
-
calpain 2 localizes to GM-3-rich lipid rafts at the leading edge
Manually annotated by BRENDA team
-
prefominantly localized in the growing hyphal and rhizoidal apices
Manually annotated by BRENDA team
-
derived from Shumiya cataract animals
Manually annotated by BRENDA team
-
membrane abnormalities and altered signaling pathways observed in Duchenne muscular dystrophy lymphocytes may be due to the increased association of calpain II onto membrane and cytosol
Manually annotated by BRENDA team
-
fibro-cartilagenous disks from meniscal tissue explants
Manually annotated by BRENDA team
-
post-mortem
Manually annotated by BRENDA team
-
longissimus dorsi lumbar, longissimus dorsi thoracic, psoas major, semimembraneous triceps brachii. Activity of m-calpain decreases more slowly in the triceps brachii muscle than in the other 4 muscvles during postmortem storage
Manually annotated by BRENDA team
-
primary neutrophil
Manually annotated by BRENDA team
-
m-calpain localizes to phosphoinositide lipids in membranes in contact with the extracellular matrix. m-Calpain accumulates towards the rear membrane of a moving cell in an epidermal growth factor-dependent manner. Its activation is absent from forming lamellipodia
Manually annotated by BRENDA team
-
outer segment
Manually annotated by BRENDA team
-
originated from kidney
Manually annotated by BRENDA team
-
highest activity in plexiform layers and in the photoreceptor outer segments. In dark-adapted retinas the label is distributed throughout the outer segments. In light-adapted retinas, outer segment labelling is concentrated in the connecting cilium and the inner segments are labeled
Manually annotated by BRENDA team
-
calpain 2 activity is critical for the life cycle of echovirus 1 and important in the multiplication of the viral RNA genome
Manually annotated by BRENDA team
-
calpains 2 is involved in atrophy development in slow type muscle. Calpains 2 is autolyzed in the early stage of skeletal muscle atrophy. This autolysis is specific to the soluble fraction for calpain 2. Calpain 2 autolysis is associated with an increased amount of calpain 2 content. Calpain autolysis is only seen in the slow soleus muscle, while the fast plantaris muscle is not affected
Manually annotated by BRENDA team
-
active calpain 2 is concentrated in the trailing edge of the migrating T cell
Manually annotated by BRENDA team
-
physiological shear stress elicits Ca2+ influx-sensitive activation of m-calain in umbilical vein endothelial cells
Manually annotated by BRENDA team
-
present in very low amounts, only 0.0033%
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
from ES cells and the 8-cell stage to late neurulation stages, CAPN2 is expressed in the cytoplasm and nuclear compartments
Manually annotated by BRENDA team
-
membrane abnormalities and altered signaling pathways observed in Duchenne muscular dystrophy lymphocytes may be due to the increased association of calpain II onto membrane and cytosol
Manually annotated by BRENDA team
-
the 80000 Da catalytic subunit and the 28000 Da regulatory subunit of m-calpain are localized at the cytolsolic side of the ER membrane
Manually annotated by BRENDA team
-
membrane abnormalities and altered signaling pathways observed in Duchenne muscular dystrophy lymphocytes may be due to the increased association of calpain II onto membrane and cytosol
Manually annotated by BRENDA team
-
; in isolated rat hearts, ischemia induces a time-dependent translocation of m-calpain to the membrane that is not associated with calpain activation
Manually annotated by BRENDA team
-
3.9% of the activity
-
Manually annotated by BRENDA team
-
m-calpain is present in the intermembrane space of the mitochondria
Manually annotated by BRENDA team
-
0.2% of the activity
Manually annotated by BRENDA team
-
from ES cells and the 8-cell stage to late neurulation stages, CAPN2 is expressed in the cytoplasm and nuclear compartments, with a clear co-localisation with chromatin. Nuclear localization was associated either with active cell mitosis in embryonic stem cells and early developmental stages or with precursor cells later during organogenesis
Manually annotated by BRENDA team
-
m-calpain localizes to phosphoinositide lipids in membranes in contact with the extracellular matrix. m-Calpain accumulates towards the rear membrane of a moving cell in an epidermal growth factor-dependent manner. Its activation is absent from forming lamellipodia
Manually annotated by BRENDA team
-
in caveolae vesicles isolated from bovine pulmonary artery smooth muscle plasma membrane
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
58000
-
-
active form, SDS-PAGE
70000
-
-
SDS-PAGE
79920
-
-
m-calpain large subunit, calculated from amino acid sequence
80000
-
-
catalytic subunit, SDS-PAGE
80000
-
-
subunit, SDS-PAGE
90000
-
-
gel filtration
100000
-
Bos grunniens mutus
-
-
105000
-
-
gel filtration
110000
-
-
gel filtration
110000
-
-
gel filtration
115000
-
-
gel filtration
124000
-
-
gel filtration
160000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 84000, SDS-PAGE
?
-
x * 80000, large subunit of m-calpain, SDS-PAGE
?
-
x * 80000, SDS-PAGE
?
-
x * 58000, active form, SDS-PAGE; x * 80000, inactive form, SDS-PAGE
dimer
-
1 * 80000 + 1 * 21000
dimer
-
1 * 80000 + 1 * 28000, SDS-PAGE
dimer
-
1 * 80000 + 1 * 29000, SDS-PAGE
dimer
-
1 * 80000 + 1 * 32000, only the 80000 Da subunit shows catalytic ativity, SDS-PAGE
dimer
-
1 * 80000 + 1 * 28000, SDS-PAGE
dimer
-
1 * 80000 + 1 * 25000, SDS-PAGE
dimer
-
1 * 78000 + 1 * 28000, SDS-PAGE
dimer
-
2 * 80000, SDS-PAGE
dimer
-
1 * 80000 + 1 * 28000, SDS-PAGE
dimer
-
1 * 74000 + 1 * 20000, SDS-PAGE
dimer
-
1 * 80000 + 1 * 24000, SDS-PAGE
dimer
-
1 * 80000 + 1 * 21000, SDS-PAGE
heterodimer
-
-
heterodimer
Bos grunniens mutus
-
-
heterodimer
-
1 * 80000 + 1 * 30000
heterodimer
-
1 * 80000 + 1 * ?, SDS-PAGE
heterodimer
-
1 * 8000 + 1 * 28000, gel filtration, the endoplasmic reticulum membrane m-calpain containing 80000 Da large and 28000 Da small subunit is non-phosphorylated
heterodimer
-
1 * 80000 + 1 * 28000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
phosphoprotein
-
brain-derived neurotrophic factor stimulates m-calpain serine phosphorylation
side-chain modification
-
calpain-2 is small ubiquitin-like modifier-modified at lysine residue 390, sumoylation is important for calpain-2 activity
phosphoprotein
-
the endoplasmic reticulum lumen m-calpain containing only 80000 Da large subunit is phosphorylated
additional information
-
the enzyme is neither glycosylated nor phosphorylated
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-
P04632
full-length human m-calpain containing an N-terminal Gly-Arg-Arg-Asp-Arg-Ser L-chain elongation overexpressed in a baculovirus expression system. Crystals grown by vapor diffusion. The 2.3 A crystal structure of full length heterodimeric m-calpain crystallized in the absence of calcium reveals an oval disc-like shape, with the papain-like catalytic domain dII and the two calmodulin, like domains dIV+dVI occupying opposite poles, and the tumor necrosis factor alpha-like beta-sandwich domain dIII and the N-terminal segments dI+dV located between
-
2.6 A crystal structure of m-calpain that has a C-terminal histidine-tag and a mutation of the active site C105S in the large subunit in the Ca2+-free form
-
calpastatin inhibitory domain 1 crystallized with calpain 2, calpastatin inhibitory domain 4 crystallized with calpain 2
-
crystallization of recombinant C105S mutant enzyme by hanging drop method
-
the refined crystal structure of the mutant enzymes K226S, K230E, K234S and E504S in absence of Ca2+ are indistinguishable from wilde-type calpain; wild-type and mutant calpains
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
9
-
25C, 30 min, stable in presence of 20 mM 2-mercaptoethanol
5.5
-
-
25C, 30 min, about 30% loss of activity
6.5
7.5
-
25C, 30 min, stable in presence of 6 mM 2-mercaptoethanol
8.5
-
-
25C, 30 min, about 50% loss of activity
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
48.5
-
-
10 min, 50% loss of activity
54
-
-
pH 7.5, 10 min, 50% loss of activity
55
-
-
10 min, in absence of Ca2+, about 10% loss of activity
58
-
-
10 min, complete inactivation
60
-
-
10 min, complete loss of activity
60
-
-
10 min, in absence of Ca2+, about 90% loss of activity
61
-
-
10 min, 50% loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
bovine fetuin A stabilizes proteolytic activity of purified m-calpain incubated in the presence of mM calcium chloride and prevents calcium-dependent m-calpain aggregation
-
m-calpain loses 50-55% of its proteolytic activity within 5 min during incubation at pH 7.5 in 300 mM or high salt and at a slower rat in 100 mM salt. This loss of activity is not reversed by dialysis for 18 h against a low-ionic-strength buffer at pH 7.5. Proteolytic activity of the unautolyzed calpains is not affected by incubation for 45 min at ionic strength up to 1000 mM. Ionic strengths of 100 mM or above cause dissociation of the two subunits of autolyzed calpains. The dissociated large subunits aggregate to form dimers and trimers, which are proteolytically inactive
-
50% inactivation by autolysis after 1 min at 30C, pH 7.5, 10 mM Ca2+
-
50% inhibition by trypsin after 3 min at 30C, pH 7.5
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the pre-incubation of m-calpain with H2O2 results in a significant decrease of m-calpain activity under non-reducing condition. The addition of calcium lactate (5 mM) to the pre-incubation mixture of m-calpain with H2O2 (0.05 mM) results in a more extensive loss of m-calpain activity compared to the equal amount of CaCl2 addition to the pre-incubation mixture
-
717628
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, stable for 8 days, 70% inactivation after 2 months
-
-20C, stable for 8 days, complete inactivation after 2 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ammonium sulfate precipitation, DEAE-cellulose column chromatography, phenyl-Sepharose column chromatography, DEAE-TSK column chromatography, and Reactive Red gel filtration
-
ammonium sulfate precipitation, DEAE-cellulose column chromatography, phenyl-Sepharose column chromatography, Reactive Red column chromatography, and DEAE-TSK anion exchange column chromatography
-
recombinant enzyme
-
E-F hand structure-domains
-
DEAE-Sepharose CL-6B column chromatography
-
DEAE-Sepharose column chromatography
-
recombinant enzyme
-
recombinant wild-type and mutant enzymes; wild-type and mutant calpains
-
DEAE Sephacel gel filtration
-
large-scale
-
m-calpain
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
cloning of the cDNA for the large subunit
-
development of an adenoviral vector harboring calpain-2 siRNA expression unit in which sense and anti-sense strands composing the siRNA duplex are connected by a loop and transcribed into a siRNA in porcine pulmonary artery endothelial cells. The adenoviral vector harboring calpain-2 siRNA expression unit is a valuable tool to study the biology of calpains
-
functional analysis of the upstream region of the gene for the large subunit by means of transient expression assay on HeLa cells using chloramphenicol transferase constructs identifies four negative regulatory regions tandemly reiterated just upstream of the promoter region, P1 and P2
-
m-calpain is produced in a soluble form using a baculovirus expression system
-
-
O08529
expression of mutated calpain 2 C105A is driven in lens by coupling the mutated gene to the betaB1-crystallin promoter
-
cDNA fragments corresponding to the domains with E-F hand structures in the large and small subunits are inserted into an expression vector pIC18 or pUC8. The resulting plasmids are used to transform Escherichia coli and isopropyl-1-thio-beta-D-galactoside-inducible expression is induced
-
isolation of cDNA clone for the 80000 Da subunit
-
coexpression from large-subunit and small-subunit plasmids in Escherichia coli strain BL21(DE3)
-
molecular cloning of the cDNA for the 80000 Da subunit and expression in Escherichia coli
-
the bacterial production of recombinant rat calpain II is improved greatly by the use of two compatible plasmids for the two subunits. The calpain small subunit C-terminal fragment is expressed from a new A15-based vector created by cloning T7 contol elements into pACYC177. This vector is compatible with the ColE1-based pET-24d(+) vector containing the calpain large subunit and the yield of calpain activity is increased at least 16fold by coexpression from theses two vectors. A high level of activity is also obtained from a bicistronic construct containing the subunit cDNAs under the control of one T7 promoter
-
a 629 bp fragment is cloned into the EcoRV site of pBluescript II KS+ vector
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
inhibition of MEK1/2 using PD98059 reduces the expression of calpain-2
-
a 6-day treatment with siRNA results in an about 60% reduction of calpain 2 protein levels in R1 cells
-
0.1 mM indomethacin and 0.1 mM NS-398 decrease expression of calpain 2 in total membrane fractions and in plasma membranes by 70%, while 0.001 mM SC-560 decreases expression of calpain 2 in total membrane fractions and in plasma membranes by 30%
-
p38 MAPK and JNK are required to stimulate m-calpain activity when TRPM7 is overexpressed, TRPM7-mediated activation of m-calpain is not dependent on the nature of the divalent conducted by the channel
-
brain-derived neurotrophic factor and epidermal growth factor activate neuronal m-calpain via mitogen-activated protein kinase-dependent phosphorylation
-
incubation of human retinal microvascular endothelial cells with vascular endothelial growth factor results in 1.6fold increased activity of calpain 2 at 24 h
-
m-calpain expression levels in aorta in siRNAtreated mice are significantly diminished by 63.5% in comparison to those in control RNA-transfected mice with no alteration of m-calpain or beta-actin expression
-
calpain 2 is upregulated in mouse pancreas exposed to caerulein for 12 h
-
endoplasmic reticulum stress stimulates calpain II activation, interleukin-13 enhances endoplasmic reticulum stress-regulated calpain activation and calpain-II expression in lipopolysaccaride-activated microglia
-
a heat stress stimulus induces massive germ cells apoptosis, which is associated with an increase in the levels of mRNA encoding calpain 2
-
calpain activation occurs during reperfusion, but only after intracellular pH normalization, and is not prevented by inhibiting its translocation during ischemia with methyl-beta-cyclodextrin; m-calpain activation occurs during reperfusion, but only after intracellular pH normalization, and is not prevented by inhibiting its translocation during ischemia with methyl-beta-cyclodextrin
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
C105S
-
mutant enzyme of mutant large subunit m-C105S-80K, coexpressed with 30000 Da subunit in Sf-9 cells does not degrade casein nor the artificial substrate succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide. The mutant enzyme does not show autolytic activity with Ca2+
C105S
-
inactive mutant enzyme
C105S
-
inactive mutant enzyme. The mutant enzyme provides a purified calpain, that is stable to autolysis and oxidation, which is likely to facilitate crystallization in both the presence and absence of calcium
D346E
-
mutant with decreased enzymatic activity, increased rate of autoproteolytic degradation
D362K
-
mutant with decreased enzymatic activity, increased rate of autoproteolytic degradation
E504S
-
Ca2+ concentration required for half-maximal activity is 0.129 mM compared to 0.242 mM for the wild-type enzyme. Refined structure of the mutant enzyme in absence of Ca2+ is indistinguishable from wild-type enzyme; mutation decreases specific activity to 90% compared to wild-type enzyme
G423R
-
mutant with decreased enzymatic activity, increased rate of autoproteolytic degradation
H262A
-
inactive mutant enzyme
K225S
-
mutation decreases specific activity to 88% compared to wild-type enzyme
K226S
-
Ca2+ concentration required for half-maximal activity is 0.226 mM compared to 0.242 mM for the wild-type enzyme. Refined structure of the mutant enzyme in absence of Ca2+ is indistinguishable from wild-type enzyme
K230E
-
Ca2+ concentration required for half-maximal activity is 0.256 mM compared to 0.242 mM for the wild-type enzyme. Refined structure of the mutant enzyme in absence of Ca2+ is indistinguishable from wild-type enzyme; mutation decreases the specific activity of the enzyme to 16% compared with the wild-type enzyme
K230S
-
Ca2+ concentration required for half-maximal activity is 0.261 mM compared to 0.242 mM for the wild-type enzyme; mutation has no significant effect on specific activity
K234E
-
mutation decreases the specific activity of the enzyme to 16% compared with the wild-type enzyme
K234S
-
Ca2+ concentration required for half-maximal activity is 0.183 mM compared to 0.242 mM for the wild-type enzyme. Refined structure of the mutant enzyme in absence of Ca2+ is indistinguishable from wild-type enzyme; mutation decreases specific activity to 81% compared to wild-type enzyme
N286A
-
inactive mutant enzyme
N286D
-
mutant enzyme with low activity
R417W
-
mutant with decreased enzymatic activity, increased rate of autoproteolytic degradation
R628Q
-
mutant with decreased enzymatic activity
S369D
-
inactive mutant enzyme
S50D
-
mutant enzyme has the same specific activity and Ca2+ requirement as the wild-type enzyme
S50E
-
mutant enzyme has the same specific activity and Ca2+ requirement as the wild-type enzyme
S67E
-
mutant enzyme has the same specific activity and Ca2+ requirement as the wild-type enzyme
T344M
-
mutant with decreased enzymatic activity, increased rate of autoproteolytic degradation
T370E
-
inactive mutant enzyme
T70E
-
mutant enzyme has the same specific activity and Ca2+ requirement as the wild-type enzyme
W288Y
-
mutant enzyme with low activity
K390R
-
overexpression of K390R mutant fails to increase the calpain activity since sumoylation at K390 is important for calpain-2 activity
additional information
P04632
used as a model for calpain 3 in combination with calpastatin-inhibited rat calpain 2
K234W
-
Ca2+ concentration required for half-maximal activity is 0.159 mM compared to 0.242 mM for the wild-type enzyme
additional information
-
replacement of the five m-calpain residues 517-521, Glu-Ala-Asn-Ile-Glu by the corresponding six mu-calpain residues 528-533, Gln-Ala-Asn-Leu-Pro-Asp, replacement of three m-calpain residues 639-641, Pro-Cys-Gln, by the corresponding three mu-calpain residues 651-653, Asn-Lys-Lys, or replacement of two m-calpain residues 578-579, Lys-Ile by the corresponding mu-calpain residues 590-591, Arg-Ser. Mutations do not affect the expression and Kd values of the resultant calpains. In a series of hybrid mu/m large-subunit calpains, the Kd values decrease progressively towards that of mu-calpain as the portion of mu-type sequence increases from 0 to 90%
additional information
-
used as a model for calpain 3 in combination with calpastatin-inhibited rat calpain 2
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
m-calpain is a marker of tumor aggressiveness and is apotential target for limiting development of rhabdomyosarcoma tumor as well as their metastatic behavior
medicine
-
m-calpain inhibition at the time of reperfusion is a potentially useful strategy to limit infarct size