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Information on EC 3.4.22.1 - cathepsin B and Organism(s) Mus musculus and UniProt Accession P10605
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3.4.22.1 cathepsin BSpecify your search results
Word Map
- 3.4.22.1
- cathepsins
- lysosomal
- proteinases
- papain
- collagen
- metastasis
- pancreatic
- cystatins
-
procathepsin
- upa
-
exopeptidase
- food industry
- myofibrillar
- mansoni
- schistosoma
-
lc3-ii
- calpains
-
permeabilization
- zymogen
-
intralysosomal
- leupeptin
- peptidase
-
hyperamylasemia
- pharmacology
-
papain-like
- diagnostics
- biotechnology
- collagenase
-
antibody-drug
-
autophagy-lysosome
- pepstatin
-
acinar
- ficin
- plasminogen
- caspase-1
- proenzyme
- legumain
-
autophagosomes
- elastase
- caerulein
-
caerulein-induced
- molecular biology
-
dipeptidyl
-
fluorogenic
- inflammasome
- endosomes
-
pro-il-1
-
supramaximal
-
l-like
-
b-mediated
- fasciola
- mu-calpain
- medicine
- trypsinogen
- hepatica
- drug development
-
collagenolytic
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Archaea
Reaction Schemes
Hydrolysis of proteins with broad specificity for peptide bonds. Preferentially cleaves -Arg-Arg-/- bonds in small molecule substrates (thus differing from cathepsin L). In addition to being an endopeptidase, shows peptidyl-dipeptidase activity, liberating C-terminal dipeptides
Synonyms
cathepsin b, cathepsin-b, cysteine cathepsin, devdase, cat b, cathepsin b1, cathb, smcb1, cath b, cath-b, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
APP secretase
-
-
-
-
cathepsin B
cathepsin B1
-
-
-
-
cathepsin II
-
-
-
-
additional information
-
cathepsin B belongs to the class of lysosomal cysteine cathepsins
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
esterification
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9047-22-7
-
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
mouse T7 trypsinogen mutant D22A/K24G + H2O
?
engineering of a mouse T7 trypsinogen mutant (D22A,K24G), which is robustly activated by cathepsin B but cannot undergo autoactivation
-
-
?
Nalpha-benzoyl-Arg-Arg-7-amido-4-methylcoumarin + H2O
Nalpha-benzoyl-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Nalpha-benzoyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
Nalpha-benzoyl-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Z-Arg-Arg-7-amido-4-methylcoumarin + H2O
Z-Arg-Arg + 7-amino-4-methylcoumarin
pH 5, 1 mM EDTA, 4 mM DTT
-
-
?
amyloid beta precursor protein + H2O
?
-
cathepsin B selectively cleaves the wild-type beta-secretase site but not the rare Swedish mutant beta-secretase site
-
-
?
benzoyl-DL-Arg-beta-naphthylamide + H2O
benzoyl-DL-Arg + beta-naphthylamine
-
-
-
?
benzoyl-Phe-Val-Arg-p-nitroanilide + H2O
benzoyl-Phe-Val-Arg + p-nitroaniline
-
-
-
?
benzoyl-Pro-Phe-Arg-p-nitroanilide + H2O
benzoyl-Pro-Phe-Arg + p-nitroaniline
-
-
-
?
benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-beta-naphthylamide + H2O
benzyloxycarbonyl-Ala-Arg-Arg + 4-methoxy-beta-naphthylamine
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-L-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
benzyloxycarbonyl-Val-Lys-Lys-Arg-4-methoxy-beta-naphthylamide + H2O
? + 4-methoxy-beta-naphthylamine
-
-
-
?
N-benzoyl-Arg-Arg-7-amido-4-methylcoumarin + H2O
N-benzoyl-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
N-benzoyl-Val-Asn-Leu-7-amido-4-methylcoumarin + H2O
N-benzoyl-Val-Lys-Met + 7-amino-4-methylcoumarin
-
the substrate represents the wild-type beta-secretase site
-
-
?
N-benzoyl-Val-Lys-Met-7-amido-4-methylcoumarin + H2O
N-benzoyl-Val-Lys-Met + 7-amino-4-methylcoumarin
-
the substrate represents the wild-type beta-secretase site
-
-
?
N-benzyloxycarbonyl-Arg-Arg-4-methylcoumarin 7-amide + H2O
N-benzyloxycarbonyl-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
N-benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
N-benzyloxycarbonyl-Phe-Arg-4-methylcoumarin 7-amide + H2O
N-benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
N-benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
N-benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
amyloid beta peptide + H2O
?
-
cathepsin B is involved in degradation of amyloid beta peptides, its inhibition can lead to amyloid beta accumulation, an early trigger of Alzheimer's disease, cystatin C regulates the enzyme negatively, CysC ablation ameliorates amyloid beta-associated neuronal and synaptic deficits in hippocampal circuits, neuroprotective effects of CysC ablation depend on CatB, overview
-
-
?
Collagen IV + H2O
?
-
collagen IV of the basement membrane damaged by cathepsin B, that is released after mechanical injury, during initial post-traumatic stages, overview
-
-
?
Laminin + H2O
?
-
laminin of the basement membrane damaged by cathepsin B, that is released after mechanical injury, during initial post-traumatic stages, overview
-
-
?
TNF-alpha + H2O
?
-
cathepsin B is required for optimal posttranslational processing of TNF-alpha in response to the bacterial cell wall component lipopolysacchrides
-
-
?
additional information
?
-
-
absence of Ctsb significantly impairs development of high-grade invasive ductal carcinomas and reduces the metastatic burden in the lungs, and cancer cells lacking Ctsb exhibit significantly higher resistance to apoptosis induction by the lysosomotropic agent Leu-Leu-OMe
-
-
?
additional information
?
-
-
cathepsin B belongs to the lysosomal cysteine cathepsins, a third major class of matrix-degrading enzymes involved in tumor invasion and tissue remodeling. Cathepsin B is involved in matrix degradation at podosomes, cysteine protease inhibitors reduce matrix degradation and invasion in vitro
-
-
?
additional information
?
-
-
cathepsin B is involved in the trafficking of TNF-alpha-containing vesicles to the plasma membrane in macrophages
-
-
?
additional information
?
-
-
cathepsin B plays an essential role in the pathogenesis of fulminant hepatic failure, and the cathepsin B inhibitor CA-074me can attenuate apoptosis and liver injury, overview
-
-
?
additional information
?
-
-
inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein
-
-
?
additional information
?
-
-
the enzyme has a principle function in gross protein degradation of internalized proteins within endo-lysosomes, but cathepsins are also involved in the processing of precursor proteins to biologically active peptides in endosomes of entero-endocrine cells. Cathepsin B, released form intestinal mucosa due to mechanical injury, plays an important role in extracellular matrix damage and the onset of postoperative ileus, an inevitable consequence of abdominal surgery, in that it contributes to disintegration of the basement membrane of the gastrointestinal tract in early post-traumatic phases. Cathepsin B is best known for its critical contribution to enhanced tumor cell invasion and metastasis, including colorectal carcinomas, by degradation of extracellular matrix components
-
-
?
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
amyloid beta peptide + H2O
?
-
cathepsin B is involved in degradation of amyloid beta peptides, its inhibition can lead to amyloid beta accumulation, an early trigger of Alzheimer's disease, cystatin C regulates the enzyme negatively, CysC ablation ameliorates amyloid beta-associated neuronal and synaptic deficits in hippocampal circuits, neuroprotective effects of CysC ablation depend on CatB, overview
-
-
?
amyloid beta precursor protein + H2O
?
-
cathepsin B selectively cleaves the wild-type beta-secretase site but not the rare Swedish mutant beta-secretase site
-
-
?
Collagen IV + H2O
?
-
collagen IV of the basement membrane damaged by cathepsin B, that is released after mechanical injury, during initial post-traumatic stages, overview
-
-
?
Laminin + H2O
?
-
laminin of the basement membrane damaged by cathepsin B, that is released after mechanical injury, during initial post-traumatic stages, overview
-
-
?
TNF-alpha + H2O
?
-
cathepsin B is required for optimal posttranslational processing of TNF-alpha in response to the bacterial cell wall component lipopolysacchrides
-
-
?
additional information
?
-
-
absence of Ctsb significantly impairs development of high-grade invasive ductal carcinomas and reduces the metastatic burden in the lungs, and cancer cells lacking Ctsb exhibit significantly higher resistance to apoptosis induction by the lysosomotropic agent Leu-Leu-OMe
-
-
?
additional information
?
-
-
cathepsin B belongs to the lysosomal cysteine cathepsins, a third major class of matrix-degrading enzymes involved in tumor invasion and tissue remodeling. Cathepsin B is involved in matrix degradation at podosomes, cysteine protease inhibitors reduce matrix degradation and invasion in vitro
-
-
?
additional information
?
-
-
cathepsin B is involved in the trafficking of TNF-alpha-containing vesicles to the plasma membrane in macrophages
-
-
?
additional information
?
-
-
cathepsin B plays an essential role in the pathogenesis of fulminant hepatic failure, and the cathepsin B inhibitor CA-074me can attenuate apoptosis and liver injury, overview
-
-
?
additional information
?
-
-
inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein
-
-
?
additional information
?
-
-
the enzyme has a principle function in gross protein degradation of internalized proteins within endo-lysosomes, but cathepsins are also involved in the processing of precursor proteins to biologically active peptides in endosomes of entero-endocrine cells. Cathepsin B, released form intestinal mucosa due to mechanical injury, plays an important role in extracellular matrix damage and the onset of postoperative ileus, an inevitable consequence of abdominal surgery, in that it contributes to disintegration of the basement membrane of the gastrointestinal tract in early post-traumatic phases. Cathepsin B is best known for its critical contribution to enhanced tumor cell invasion and metastasis, including colorectal carcinomas, by degradation of extracellular matrix components
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(acetatato-kO)[2-(1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl-kN4)phenyl-kC1](pyridine)palladium(1+)
-
-
(acetatato-kO)[2-(1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl-kN4)phenyl-kC1](triphenylphosphane)palladium(1+)
-
-
acetyl-YVAD-chloromethyl ketone
-
caspase inhibitor, inhibition of enzyme contributes to neuroprotective properties of the inhibitor
benzyloxycarbonyl-L-phenylalanyl-alanine-fluoromethylketone
-
inhibits cathepsin B, treatment stimulates proliferation of type-II pneumocytes and improves degenerative alterations in injured lung occurring with liver injury induced by D-GalN/TNF-alpha, overview
cathepsin B inhibitor III
-
i.e. L-trans.epoxysuccinyl(propylamide)-Ile-Pro or 1-[3-methyl-2-[[3-(propylcarbamoyl)oxirane]-2-carbonyl]amino]pentanoylpyrrolidine-2-carboxylic acid
cathepsin B inhibitor IV
-
i.e. CA074me or methyl 1-[3-methyl-2-[[3-(propylcarbamoyl)oxirane]-2-carbonyl]amino]pentanoylpyrrolidine-2-carboxylate, bone marrow-derived macrophages treated with the cathepsin B-specific chemical inhibitor CA074 methyl ester secret significantly less TNF-alpha than wild-type or nontreated macrophages
chloro[2-(1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl-kN4)phenyl-kC1](pyridine)palladium(1+)
-
-
chloro[2-(1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl-kN4)phenyl-kC1](triphenylphosphane)palladium(1+)
-
-
CysC
-
natural inhibitor of CatB. CysC deletion in knockout mice leads to an enhanced CatB activity
cystatin C
-
CysC or CST3, an endogenous inhibitor of cysteine proteases, including cathepsin B
-
HNO
-
from Angeli's salt or induced by LPS and IFN-gamma in RAW macrophages, causes DTT-irreversible inhibition and covalently and permanently inactivation of cathepsin B. Cathepsin B activity is reduced to 53%, 25%, and 57% of maximal activity in nonstimulated, LPS-, and IFN-gamma-treated cells, respectively. Endogenous NO production can provide direct protection for the less reactive protein cysteines by scavenging HNO. Additionally, endogenous cellular production of NO can rescue enzyme function by protective nitrosation of cysteines prior to exposure to HNO
L-3-trans-(propylcarbamoyl)oxirane-2-carbonyl-L-isoleucyl-L-proline
treatment with a cathepsin B inhibitor, leads to transient reduction of local induration, expression of inflammatory cytokines, and subsequent attenuation of the systemic adaptive immune response
wortmannilactone E
-
i.e. (19S)-(4S,7R)-7-[(1E,3E,5E,7E)-8-[(2S,5S,6S)-5,6-dihydro-5-hydroxy-3,5,6-trimethyl-2H-pyran-2-yl]nona-1,3,5,7-tetraen-1-yl]-4,6,7-trimethyl-2-oxabicyclo[2.2.1]heptane-3,5-dione, isolated from the culture medium of the soil filamentous fungus Talaromyces wortmannii, Chuxiong, Yunnan Province, China. Determination of structure and relative configuration by 1D- and 2D-NMR techniques, overview
wortmannilactone F
-
i.e. (19R)-(4S,7R)-7-[(1E,3E,5E,7E)-8-[(2S,5R,6S)-5,6-dihydro-5-hydroxy-3,5,6-trimethyl-2H-pyran-2-yl]nona-1,3,5,7-tetraen-1-yl]-4,6,7-trimethyl-2-oxabicyclo[2.2.1]heptane-3,5-dione, isolated from the culture medium of the soil filamentous fungus Talaromyces wortmannii, Chuxiong, Yunnan Province, China. Determination of structure and relative configuration by 1D- and 2D-NMR techniques, overview
wortmannilactone G
-
i.e. methyl (2R)-2-[(3R,4R)-3-[(1E,3E,5E,7E)-8-[(2S,3R,6S)-3,6-dihydro-3-hydroxy-3,5,6-trimethyl-2H-pyran-2-yl]nona-1,3,5,7-tetraen-1-yl]-3,4-dimethyl-5-oxotetrahydrofuran-2-yl]propanoate, isolated from the culture medium of the soil filamentous fungus Talaromyces wortmannii, Chuxiong, Yunnan Province, China. Determination of structure and relative configuration by 1D- and 2D-NMR techniques, overview
wortmannilactone H
-
i.e. (4S,7R)-7-[(1E,3E,5E,7E)-8-[(2S,3R,6S)-3,6-dihydro-3-hydroxy-3,6-dimethyl-2H-pyran-2-yl]nona-1,3,5,7-tetraen-1-yl]-4,6,7-trimethyl-2-oxabicyclo[2.2.1]heptane-3,5-dione, isolated from the culture medium of the soil filamentous fungus Talaromyces wortmannii, Chuxiong, in Chinas Yunnan Province. Determination of structure and relative configuration by 1D- and 2D-NMR techniques, overview
[2-(1-benzyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl-kN4)phenyl-kC1](chloro)(pyridine)palladium(1+)
-
-
[2-(1-benzyl-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-5-yl-kN4)phenyl-kC1](chloro)(triphenylphosphane)palladium(1+)
-
-
[Pd2(1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one)2(m-1,2-ethanebis(diphenylphosphine))Cl2]
CA-074-Me
-
a potent and specific CtsB inhibitor, CtsB inhibition blunts AKT phosphorylation in activated hepatic stellate cells in response to platelet-derived growth factor
CA-074-Me
-
a specific inhibitor, inhibits pro-interleukin-1beta processing in microglia
CA-074-Me
-
CA-074Me clearly inhibits cath-B expression in the subcutaneous heteroplastic pancreatic carcinoma model, and demonstrates an anti-neoplastic and anti-angiogenesis effect, overview
CA-074-Me
-
cathepsin B inhibitor IV. Inhibition of cathepsin B blocks MEK1 cleavage induced by anthrax lethal toxin through delaying LeTx release into the cytoplasm. The cathepsin B inhibitor prevents cell death induced by anthrax lethal toxin in RAW 264.7 macrophages
CA-074-Me
-
i.e. [L-3-trans-(propylcarbamoyl)oxirane-2-carbonyl]-L-isoleucyl-L-proline methyl ester
N-(L-3-trans-propylcarbonyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline
-
i.e. CA074
N-(L-3-trans-propylcarbonyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline
-
i.e. CA074, a cathepsin B-selective inhibitor
N-(L-3-trans-propylcarbonyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline methyl ester
-
i.e. CA074Me
N-(L-3-trans-propylcarbonyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline methyl ester
-
i.e. CA074Me, a cathepsin B-selective inhibitor
[Pd2(1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one)2(m-1,2-ethanebis(diphenylphosphine))Cl2]
-
structure analysis by NMR spectroscopy and in the solid state by X-ray crystallography
[Pd2(1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one)2(m-1,2-ethanebis(diphenylphosphine))Cl2]
-
structure analysis by NMR spectroscopy and in the solid state by X-ray crystallography. It inhibits cathepsin B, and also K562 leukemia cells with an IC50 value of 0.0043 mM after 1 h exposure
additional information
-
the inhibition of cathepsin B causes accumulation of 26-kDa pro-TNF-containing vesicles
-
additional information
-
cathepsin B inhibitory activity of tetraene lactones from the fungus Talaromyces wortmannii, overview
-
additional information
-
growth inhibition of B-16 cells by the palladacycle compounds, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
bafilomycin A1 induces lysosome-associated podosome-like structures and promotes degradation of extracellular gelatin
-
additional information
-
during in vivo liver fibrogenesis, caused by CCl4 administration, CtsB expression increases in hepatic stellate cells but not in hepatocytes
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.226
Nalpha-benzoyl-Arg-Arg-7-amido-4-methylcoumarin
pH 6.0, 37°C, recombinant enzyme
0.043
Nalpha-benzoyl-Phe-Arg-7-amido-4-methylcoumarin
pH 6.0, 37°C, recombinant enzyme
0.07
benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-beta-naphthylamide
-
liver enzyme and tumor enzyme
0.0561
benzyloxycarbonyl-Val-Lys-Lys-Arg-4-methoxy-beta-naphthylamide
-
tumor enzyme
0.091
benzyloxycarbonyl-Val-Lys-Lys-Arg-4-methoxy-beta-naphthylamide
-
liver enzyme
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
34
Nalpha-benzoyl-Arg-Arg-7-amido-4-methylcoumarin
pH 6.0, 37°C, recombinant enzyme
86
Nalpha-benzoyl-Phe-Arg-7-amido-4-methylcoumarin
pH 6.0, 37°C, recombinant enzyme
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000002
N-(L-3-trans-propylcarbonyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline
Mus musculus
-
-
0.003
[Pd2(1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one)2(m-1,2-ethanebis(diphenylphosphine))Cl2]
Mus musculus
-
pH not specified in the publication, temperature not specified in the publication
additional information
additional information
Mus musculus
-
IC50 values for growth inhibition of K-562 cells by palladacycles, overview
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
mercury-inflammation in mice is associated with a selective increase in activity of cysteine cathepsin B
additional information
-
mercury-inflammation in mice is associated with a selective increase in activity of cysteine cathepsin B
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
negligible expression of cathepsin B in hepatic stellate cells
-
isolated from the mixed primary cell cultures from the cerebral cortex of 3-day-old wild-type or CB-/- mice, activated by chromogranin A
-
from subcutaneous heteroplastic pancreatic carcinoma, quantitative cathepsin B expression analysis and modelling
additional information
-
mucosa and muscle, cathepsin B is abundantly expressed in endocytic compartments of all cells of the intestine
additional information
-
two mouse models of Alzheimer's Disease, consisting of one expressing human amyloid precursor protein containing the wild-type beta-secretase site and mutation at the beta-secretase site, London amyloid precursor protein mice, and the other expressing the Swe mutant beta-secretase site and the London mutation, Swedish/London amyloid precursor protein
additional information
-
cathepsin B is expressed ubiquitously and represents the major portion of lysosomal enzymes
additional information
-
during in vivo liver fibrogenesis, caused by CCl4 administration, CtsB expression increases in hepatic stellate cells but not in hepatocytes
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
release from intestine mucosa after mechanical injury and during initial post-traumatic stages
-
-
-
-
cathepsin B is expressed ubiquitously and represents the major portion of lysosomal enzymes
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
increase and leakage of CatB in microglia during aging are responsible for the increased generation of mitochondria-derived reactive oxygen species and proinflammatory mediators, culminating in memory impairment
physiological function
the enzyme has critical role as activators of proinflammatory caspases-11 and the regulatory effect in LPS-induced caspases-11-dependent necrosis
malfunction
metabolism
-
cathepsin B is involved in TNF-alpha-induced signal transduction pathways in lung cells
physiological function
malfunction
-
cathepsin B-mediated autophagy flux facilitates the anthrax toxin receptor 2-mediated delivery of anthrax lethal factor, LeTx, into the cytoplasm, requiring lysosomal fusion with LeTx-containing endosomes. Anthrax lethal toxin is a virulence factor secreted by Bacillus anthracis and has direct cytotoxic effects on most cells once released into the cytoplasm. Inhibition of cathepsin B blocks MEK1 cleavage induced by anthrax lethal toxin through delaying LeTx release into the cytoplasm
malfunction
-
cathespin-B is an important proteolytic enzyme involved in the disease course of invasion in many types of cancer. It correlates with the growth and angiogenesis of tumors, but not with the adhesion induced by CD44v6, in the subcutaneous heteroplastic pancreatic carcinoma model, overview
malfunction
-
CtsB inhibition blunts AKT phosphorylation in activated hepatic stellate cells in response to platelet-derived growth factor. CtsB inactivation mitigates CCl4-induced inflammation, hepatic stellate cell activation, and collagen deposition
malfunction
-
exposure of GSH-depleted B cells to NO-releasing compounds lowers their capacity to present a reduced and alkylated lysozyme due to inhibition of cathepsin B by NO, overview. Cells with a normal GSH content are protected from this inhibition
malfunction
-
genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein
malfunction
-
the cathepsin family of endosomal proteases is required for proteolytic processing of several viruses during entry into host cells, cathepsins contribute to reovirus tropism, spread, and disease outcome. Mammalian reoviruses utilize cathepsins B, L, and S for disassembly of the virus outer capsid and activation of the membrane penetration machinery. The survival rate of Ctsb-/- mice infected with reovirus is enhanced in comparison to that of wild-type mice, viremia in wild-type and cathepsin-deficient mice following peroral inoculation, overview
malfunction
-
enhancing CatB activity by CysC deletion significantly lowers total amyloid-betaand amyloid-beta42 levels in human amyloid precursor protein wild-type mice, whereas CatB deletion increases amyloidbeta levels
malfunction
-
female Ctsb knockout mice, but not males, display a decrease of 31% in cholesterol absorption
malfunction
-
fine-mapping studies along with gene expression efforts and studies in knockout animals identified Ctsb as a gender-dependent modifier of cholesterol absorption from the intestine
malfunction
-
transgenic mice are generated overexpressing CatB under the control of a neuron-specific enolase promoter: Enhancing neuronal CatB activity in human amyloid precursor protein wild-type mice significantly lowers amyloidbeta42 levels
physiological function
-
apoptotic stimuli, e.g. exposure to etoposide, ultraviolet light, FasL or deprivation of interleukin-3, trigger lysosomal membrane permeability, leading to the release of cathepsins, dependent on Bax/Bak and components of the apoptosome, which activate death signaling pathways in the cytosol, overview. Cathepsin B does not contribute to the commitment step of apoptosis, as Bax and Bak do, but enhances the efficiency of apoptosis through an amplification loop
physiological function
-
cathepsin B activity is necessary for TAP-HEL, a reduced and alkylated lysozyme, processing, it is essential for generation of the HEL-derived antigenic peptide recognized by B9.1 cells
physiological function
-
cathepsin B acts as the main executor of caspase dependent or independent cell death in major organs including the liver, kidney, and lungs
physiological function
-
cathepsin B is required for interleukin-1beta maturation, the maturation of pro-IL-1beta in chromogranin A-stimulated microglia is dependent on the enzymatic activities of both cathepsin B and caspase-1
physiological function
-
cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential, the enzyme is required for transdifferentiation of the cells into myofibroblasts, overview. CtsB modulates the phosphoinositide 3-kinase/AKT pathway in activated mouse hepatic stellate cells, overview
physiological function
-
CTSB is a lysosomal cysteine protease primarily involved in the degradation or processing of lysosomal proteins
physiological function
-
infection with Neisseria gonorrhoeae induces cathepsin B in apical controlling of the downstream activities of NLRP3 including interleukin-1beta production, pyronecrosis, and HMGB1 release. NLRP3 mediates cell death in B-lymphocytes and macrophages, overview
physiological function
-
the TLR9 ligand CpG DNA inhibits the proliferation of pro-B, but not pre-B, cells by inducing caspase-independent cell death through a pathway that requires the expression of cathepsin B, mechanism, overview
physiological function
sensitivity to mHgIA is linked to an early cathepsin B regulated inflammatory response which is necessary for the subsequent adaptive autoimmune response leading to disease
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). CATB_MOUSE
339
0
37280
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
26000
-
x * 29000, mature cathepsin B, single-chain form, SDS-PAGE, x * 26000, mature cathepsin B, heavy-chain, SDS-PAGE
29000
-
x * 29000, mature cathepsin B, single-chain form, SDS-PAGE, x * 26000, mature cathepsin B, heavy-chain, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 29000, mature cathepsin B, single-chain form, SDS-PAGE, x * 26000, mature cathepsin B, heavy-chain, SDS-PAGE
additional information
additional information
three-dimensional enzyme structure, modeling, structure comparison to the human enzyme, overview
additional information
-
three-dimensional enzyme structure, modeling, structure comparison to the human enzyme, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
construction of cathepsin B transgenic mouse models for investigation of human pathologies
additional information
-
construction of cathepsin B transgenic mouse models for investigation of human pathologies
additional information
-
bone marrow-derived macrophages from cathepsin B-deficient C57BL/6 mice and macrophages treated with the small interfering RNA against cathepsin B secret significantly less TNF-alpha than wild-type or nontreated macrophages
additional information
-
expression of collagen IV is up-regulated in the intestine of cathepsin B-deficient mice
additional information
-
genetic ablation of CST3 in hAPP-J20 mice significantly lowers soluble amyloid beta levels, the relative abundance of amyloid beta 1-42, and plaque load. CysC removal also attenuates amyloid beta-associated cognitive deficits and behavioral abnormalities and restores synaptic plasticity in the hippocampus
additional information
-
high-grade mammary carcinomas in cathepsin B-deficient mice show reduced tumour cell proliferation and delayed development, tumour necrosis factor-alpha can reverse the effect, phenotype, overview
additional information
-
inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein
additional information
-
cathepsin B deficiency inhibits pro-interleukin-1beta processing and maturation in microglia, no observable expression of the cleaved IL-1beta in the hippocampus of the aged CB-/- mice
additional information
-
cathepsin B silencing or inhibition decreases hepatic stellate cell proliferation and the expression of phenotypic markers of hepatic stellate cell activation, overview
additional information
-
CTB knockout MEF cells are partially resistant to apoptosis induced by etoposide and IL-3 deprivation, but cannot be rescued from cell death in contrast to wild-type cells
additional information
-
generation of cathepsin B deficient mice. Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein. No phenotypes, overview
additional information
-
survival rate of Ctsb-/- mice infected with reovirus is enhanced in comparison to that of wild-type mice
additional information
-
the TLR9 ligand CpG DNA inhibits the proliferation of pro-B, but not pre-B, cells by inducing caspase-independent cell death through a pathway that requires the expression of cathepsin B in Rag-deficient mice carrying an SP6 transgene, in which B lymphopoiesis is compromised, to reduce the size of the B lymphocyte precursor compartments in the bone marrow, phenotype, overview
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant renatured enzyme expressed in inclusion bodies in Escherichia coli
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in inclusion bodies in Escherichia coli, cathepsin B gene is located on chromosome 14 of the mouse genome
expression analysis by semi-quantitative RT-PCR in healthy and fulminant hepatic failure livers
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
chromogranin A markedly induces cathepsin B at both protein and mRNA levels, determined by real-time quantitative RT-PCR
-
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
engineering of a mouse T7 trypsinogen mutant (D22A,K24G), which is robustly activated by cathepsin B but cannot undergo autoactivation. These studies set the stage for the generation of a preclinical mouse model of CTSB-dependent pancreatitis
drug development
medicine
pharmacology
-
use of benzyloxycarbonyl-L-phenylalanyl-alanine-fluoromethylketone for inhibition of cathepsin-B seems a viable therapeutic strategy in TNF-alpha-mediated acute lung damage
drug development
-
cathepsin B is a possible therapeutic target for the control of tumor progression
drug development
-
cathepsin B is a target for development of inhibitors to lower amyloid-beta protein in Alzheimer's disease
medicine
-
enzyme is involved in neuronal cell death, particularly following ischemia
medicine
-
cathepsin B inhibitors are effective therapeutic agents in treatment of Alzheimer's disease reducing the amyloid beta plaque load in brain regions by up to 55%, reducing the formation of amyloid beta 40 and amyloid beta 42 by 45% and 40%, and improving the memory function, overview
medicine
-
pharmacologic modulation of cathepsin activity diminishes reovirus disease severity
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Olstein, A.D.; Liener, I.E.
Comparative studies of mouse liver cathepsin B and an analogous tumor thiol proteinase
J. Biol. Chem.
258
11049-11056
1983
Mus musculus
Chan, S.J; San Segundo, B.; McCormick, M.B.; Steiner, D.
Nucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs
Proc. Natl. Acad. Sci. USA
83
7721-7725
1986
Homo sapiens, Mus musculus
Gray, J.; Haran, M.M.; Schneider, K.; Vesce, S.; Ray, A.M.; Owen, D.; White, I.R.; Cutler, P.; Davis, J.B.
Evidence that inhibition of cathepsin-B contributes to the neuroprotective properties of caspase inhibitor Tyr-Val-Ala-Asp-chloromethyl ketone
J. Biol. Chem.
276
32750-32755
2001
Mus musculus, Rattus norvegicus
Ebert, D.H.; Kopecky-Bromberg, S.A.; Dermody, T.S.
Cathepsin B is inhibited in mutant cells selected during persistent reovirus infection
J. Biol. Chem.
279
3837-3851
2004
Mus musculus (P10605), Mus musculus
Vasiljeva, O.; Papazoglou, A.; Krueger, A.; Brodoefel, H.; Korovin, M.; Deussing, J.; Augustin, N.; Nielsen, B.S.; Almholt, K.; Bogyo, M.; Peters, C.; Reinheckel, T.
Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer
Cancer Res.
66
5242-5250
2006
Mus musculus
Caglic, D.; Kosec, G.; Bojic, L.; Reinheckel, T.; Turk, V.; Turk, B.
Murine and human cathepsin B exhibit similar properties: possible implications for drug discovery
Biol. Chem.
390
175-179
2009
Homo sapiens (P07858), Homo sapiens, Mus musculus (P10605), Mus musculus
Vreemann, A.; Qu, H.; Mayer, K.; Andersen, L.B.; Stefana, M.I.; Wehner, S.; Lysson, M.; Farcas, A.M.; Peters, C.; Reinheckel, T.; Kalff, J.; Brix, K.
Cathepsin B release from rodent intestine mucosa due to mechanical injury results in extracellular matrix damage in early post-traumatic phases
Biol. Chem.
390
481-492
2009
Mus musculus
Tu, C.; Ortega-Cava, C.F.; Chen, G.; Fernandes, N.D.; Cavallo-Medved, D.; Sloane, B.F.; Band, V.; Band, H.
Lysosomal cathepsin B participates in the podosome-mediated extracellular matrix degradation and invasion via secreted lysosomes in v-Src fibroblasts
Cancer Res.
68
9147-9156
2008
Mus musculus
Vaeaenaenen, A.J.; Salmenperae, P.; Hukkanen, M.; Miranda, K.M.; Harjula, A.; Rauhala, P.; Kankuri, E.
Persistent susceptibility of cathepsin B to irreversible inhibition by nitroxyl (HNO) in the presence of endogenous nitric oxide
Free Radic. Biol. Med.
45
749-755
2008
Mus musculus
Hook, V.Y.; Kindy, M.; Hook, G.
Inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein
J. Biol. Chem.
283
7745-7753
2008
Mus musculus
Ha, S.D.; Martins, A.; Khazaie, K.; Han, J.; Chan, B.M.; Kim, S.O.
Cathepsin B is involved in the trafficking of TNF-alpha-containing vesicles to the plasma membrane in macrophages
J. Immunol.
181
690-697
2008
Homo sapiens, Mus musculus, Mus musculus C57BL/6
Sun, B.; Zhou, Y.; Halabisky, B.; Lo, I.; Cho, S.H.; Mueller-Steiner, S.; Devidze, N.; Wang, X.; Grubb, A.; Gan, L.
Cystatin C-cathepsin B axis regulates amyloid beta levels and associated neuronal deficits in an animal model of Alzheimers disease
Neuron
60
247-257
2008
Mus musculus
Vasiljeva, O.; Korovin, M.; Gajda, M.; Brodoefel, H.; Bojic, L.; Krueger, A.; Schurigt, U.; Sevenich, L.; Turk, B.; Peters, C.; Reinheckel, T.
Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice
Oncogene
27
4191-4199
2008
Mus musculus
Yan, B.Z.; Wang, W.; Chen, L.Y.; Bi, M.R.; Lu, Y.J.; Li, B.X.; Yang, B.S.
Role of cathepsin B-mediated apoptosis in fulminant hepatic failure in mice
World J. Gastroenterol.
15
1231-1236
2009
Mus musculus
Hook, V.Y.; Kindy, M.; Reinheckel, T.; Peters, C.; Hook, G.
Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein
Biochem. Biophys. Res. Commun.
386
284-288
2009
Mus musculus, Mus musculus C57BL/6
Oberle, C.; Huai, J.; Reinheckel, T.; Tacke, M.; Rassner, M.; Ekert, P.G.; Buellesbach, J.; Borner, C.
Lysosomal membrane permeabilization and cathepsin release is a Bax/Bak-dependent, amplifying event of apoptosis in fibroblasts and monocytes
Cell Death Differ.
17
1167-1178
2010
Mus musculus
Zhang, C.; Sun, J.B.; Liu, D.C.; Cui, Y.Q.; Liu, S.; Sun, H.C.
Preliminary research on the pathological role of cathepsin-B in subcutaneous heteroplastic pancreatic carcinoma in nude mice
Chin. Med. Sci.
122
2489-2496
2009
Mus musculus
Spencer, J.; Rathnam, R.P.; Motukuri, M.; Kotha, A.K.; Richardson, S.C.; Hazrati, A.; Hartley, J.A.; Male, L.; Hursthouse, M.B.
Synthesis of a 1,4-benzodiazepine containing palladacycle with in vitro anticancer and cathepsin B activity
Dalton Trans.
2009
4299-4303
2009
Mus musculus
Terada, K.; Yamada, J.; Hayashi, Y.; Wu, Z.; Uchiyama, Y.; Peters, C.; Nakanishi, H.
Involvement of cathepsin B in the processing and secretion of interleukin-1beta in chromogranin A-stimulated microglia
Glia
58
114-124
2010
Mus musculus, Mus musculus C57/Bl
Dong, Y.; Lin, J.; Lu, X.; Zheng, Z.; Ren, X.; Zhang, H.; He, J.; Yang, J.
Cathepsin B inhibitory tetraene lactones from the fungus Talaromyces wortmannii
Helv. Chim. Acta
92
567-574
2009
Mus musculus
-
Moles, A.; Tarrats, N.; Fernandez-Checa, J.C.; Mari, M.
Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential
Hepatology
49
1297-1307
2009
Homo sapiens, Mus musculus, Mus musculus C57BL/6
Ha, S.D.; Ham, B.; Mogridge, J.; Saftig, P.; Lin, S.; Kim, S.O.
Cathepsin B-mediated autophagy flux facilitates the anthrax toxin receptor 2-mediated delivery of anthrax lethal factor into the cytoplasm
J. Biol. Chem.
285
2120-2129
2010
Mus musculus, Mus musculus C57BL/6
Duncan, J.A.; Gao, X.; Huang, M.T.; OConnor, B.P.; Thomas, C.E.; Willingham, S.B.; Bergstralh, D.T.; Jarvis, G.A.; Sparling, P.F.; Ting, J.P.
Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome
J. Immunol.
182
6460-6469
2009
Homo sapiens, Mus musculus
Lalanne, A.I.; Moraga, I.; Hao, Y.; Pereira, J.P.; Alves, N.L.; Huntington, N.D.; Freitas, A.A.; Cumano, A.; Vieira, P.
CpG inhibits pro-B cell expansion through a cathepsin B-dependent mechanism
J. Immunol.
184
5678-5685
2010
Mus musculus
Johnson, E.M.; Doyle, J.D.; Wetzel, J.D.; McClung, R.P.; Katunuma, N.; Chappell, J.D.; Washington, M.K.; Dermody, T.S.
Genetic and pharmacologic alteration of cathepsin expression influences reovirus pathogenesis
J. Virol.
83
9630-9640
2009
Mus musculus, Mus musculus C57/BL6J
Oztay, F.; Gezginci-Oktayoglu, S.; Bayrak, B.B.; Yanardag, R.; Bolkent, S.
Cathepsin B inhibition improves lung injury associated to D-galactosamine/tumor necrosis factor-alpha-induced liver injury in mice
Mol. Cell. Biochem.
333
65-72
2010
Mus musculus
Lemaire, G.; Guittet, O.; Vesin, M.; Lepoivre, M.; Cottet, M.
Glutathione depletion reveals impairment of antigen processing and inhibition of cathepsin activity by nitric oxide in antigen-presenting cells
Mol. Immunol.
46
1100-1108
2009
Mus musculus, Mus musculus BALB/c
Wang, C.; Sun, B.; Zhou, Y.; Grubb, A.; Gan, L.
Cathepsin B degrades amyloid-beta in mice expressing wild-type human amyloid precursor protein
J. Biol. Chem.
287
39834-39841
2012
Mus musculus
Wong, W.P.; Altemus, J.B.; Hester, J.F.; Chan, E.R.; Cote, J.F.; Serre, D.; Sehayek, E.
Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine
J. Lipid Res.
54
816-822
2013
Mus musculus
Toomey, C.B.; Cauvi, D.M.; Hamel, J.C.; Ramirez, A.E.; Pollard, K.M.
Cathepsin B regulates the appearance and severity of mercury-induced inflammation and autoimmunity
Toxicol. Sci.
142
339-349
2014
Mus musculus (P07858), Mus musculus
Ni, J.; Wu, Z.; Stoka, V.; Meng, J.; Hayashi, Y.; Peters, C.; Qing, H.; Turk, V.; Nakanishi, H.
Increased expression and altered subcellular distribution of cathepsin B in microglia induce cognitive impairment through oxidative stress and inflammatory response in mice
Aging Cell
18
e12856
2019
Mus musculus (P10605)
Xiaofei, C.; Yanqing, L.; Dongkai, Z.; Dong, C.; Feng, Z.; Weilin, W.
Identification of cathepsin B as a novel target of hypoxia-inducible factor-1-alpha in HepG2 cells
Biochem. Biophys. Res. Commun.
503
1057-1062
2018
Mus musculus (P10605)
Chen, N.; Ou, Z.; Zhang, W.; Zhu, X.; Li, P.; Gong, J.
Cathepsin B regulates non-canonical NLRP3 inflammasome pathway by modulating activation of caspase-11 in Kupffer cells
Cell Prolif.
51
e12487
2018
Homo sapiens (P07858), Homo sapiens, Mus musculus (P10605)
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