Information on EC 3.4.22.53 - calpain-2 and Organism(s) Homo sapiens

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Homo sapiens


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.22.53
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RECOMMENDED NAME
GeneOntology No.
calpain-2
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CAS REGISTRY NUMBER
COMMENTARY hide
702693-80-9
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78990-62-2
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
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calpain 2 regulates endothelial nitric oxide synthase phosphorylation during cord formation by lymphatic endothelial cells on Matrigel
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
alpha-2 spectrin + H2O
?
show the reaction diagram
-
-
-
-
?
alpha-spectrin + H2O
?
show the reaction diagram
-
-
-
-
?
androgen receptor + H2O
?
show the reaction diagram
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-
-
-
?
androgen receptor + H2O
low molecular weight androgen receptor + ?
show the reaction diagram
-
-
-
-
?
Bcl-xL + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
filamin A + H2O
?
show the reaction diagram
-
-
-
-
?
myocillin + H2O
?
show the reaction diagram
RRRRRRRR-(EDANS)-GQQEVYGMMPRDG-(DABCYL) + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
talin + H2O
?
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
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-
-
-
?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
alpha-2 spectrin + H2O
?
show the reaction diagram
-
-
-
-
?
androgen receptor + H2O
?
show the reaction diagram
-
-
-
-
?
filamin A + H2O
?
show the reaction diagram
-
-
-
-
?
myocillin + H2O
?
show the reaction diagram
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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
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?
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-Leu-Leu-Nle-CHO
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complete inhibition at 0.001 mM
ALLM
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ALLN
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benzyloxycarbonyl-L-leucyl-L-leucinal
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calpastatin
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Calpeptin
PD150606
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SNJ-1945
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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upregulation of calpain 2 post eccentric exercise
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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calpain 2 is important for both the formation of invadopodia and invasive capacity of breast cancer cells
Manually annotated by BRENDA team
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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
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calpain 2 localizes to GM-3-rich lipid rafts at the leading edge
Manually annotated by BRENDA team
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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
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primary neutrophil
Manually annotated by BRENDA team
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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
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active calpain 2 is concentrated in the trailing edge of the migrating T cell
Manually annotated by BRENDA team
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physiological shear stress elicits Ca2+ influx-sensitive activation of m-calain in umbilical vein endothelial cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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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
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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
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
32000
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1 * 80000 + 1 * 32000, only the 80000 Da subunit shows catalytic ativity, SDS-PAGE
80000
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1 * 80000 + 1 * 32000, only the 80000 Da subunit shows catalytic ativity, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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1 * 80000 + 1 * 32000, only the 80000 Da subunit shows catalytic ativity, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
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brain-derived neurotrophic factor stimulates m-calpain serine phosphorylation
side-chain modification
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calpain-2 is small ubiquitin-like modifier-modified at lysine residue 390, sumoylation is important for calpain-2 activity
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of the cDNA for the large subunit
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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
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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
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m-calpain is produced in a soluble form using a baculovirus expression system
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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%
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a 6-day treatment with siRNA results in an about 60% reduction of calpain 2 protein levels in R1 cells
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brain-derived neurotrophic factor and epidermal growth factor activate neuronal m-calpain via mitogen-activated protein kinase-dependent phosphorylation
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incubation of human retinal microvascular endothelial cells with vascular endothelial growth factor results in 1.6fold increased activity of calpain 2 at 24 h
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inhibition of MEK1/2 using PD98059 reduces the expression of calpain-2
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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
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C105S
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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+
K390R
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overexpression of K390R mutant fails to increase the calpain activity since sumoylation at K390 is important for calpain-2 activity
additional information
used as a model for calpain 3 in combination with calpastatin-inhibited rat calpain 2
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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m-calpain is a marker of tumor aggressiveness and is apotential target for limiting development of rhabdomyosarcoma tumor as well as their metastatic behavior