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Information on EC 3.4.22.27 - cathepsin S and Organism(s) Mus musculus and UniProt Accession O70370
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3.4.22.27 cathepsin SSpecify your search results
Word Map
- 3.4.22.27
- cathepsins
- lysosomal
-
point-of-care
- cystatins
- dendritic
- atherosclerosis
- proteinases
- elastin
- papain
-
antigen-presenting
-
histocompatibility
- autoimmune
- drug development
-
lacrimal
-
papain-like
- diagnostics
-
ii-associated
-
elastolytic
-
resource-limited
-
s-deficient
-
procathepsins
-
l-like
- pharmacology
- endostatin
- microglial
- fractalkine
- medicine
- par2
-
collagenolytic
- syphilis
-
ii-restricted
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
similar to cathepsin L, but with much less activity on Z-Phe-Arg-/-NHMec, and more activity on the Z-Val-Val-Arg-/- compound
Synonyms
cathepsin s, pocts, cat s, cat-s, pfctssa, socats, cath s, rs1136774, rs7534124, rs16827671, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C01.034
-
-
-
-
cathepsin S
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
71965-46-3
-
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
butyloxycarbonyl-Val-Leu-Lys-7-amido-4-methylcoumarin + H2O
butyloxycarbonyl-Val-Leu-Lys + 7-amino-4-methylcoumarin
-
-
-
-
?
Z-Leu-Leu-Arg-7-amido-4-methylcoumarin + H2O
Z-Leu-Leu-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
Z-Val-Val-Arg-7-amido-4-methylcoumarin + H2O
Z-Val-Val-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
Ii protein + H2O
Ii fragments
-
inhibition of Ii degradation in enzyme-deficient cells leads to accumulation of Ii degradation intermediates in endosomal/lysosomal compartments
-
-
?
MHC class II-associated invariant chain Ii + H2O
?
-
degradation, cathepsin S and MHC class II-associated invariant chain Ii are responsible for in vivo control of endosomal size and multivesicular morphology
-
-
?
additional information
?
-
-
cathepsin S is implicated as a key enzyme in the processing of major histocompatability complex class II molecules
-
-
?
additional information
?
-
-
cathepsin S catalyzes a key step in antigen presentation, detailed overview
-
-
?
additional information
?
-
-
cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors, the enzyme is required for neoplastic progression, overview
-
-
?
additional information
?
-
-
cathepsin S in professional antigen-presenting cells, APC, controls MHC class II-mediated antigen presentation by epithelial cells in vivo, and plays a critical role in invariant chain degradation
-
-
?
additional information
?
-
-
cathepsin S is responsible for murine autoimmune myasthenia gravis pathogenesis, overview
-
-
?
additional information
?
-
-
cathepsin S, a cysteine protease, plays an important role in generating peptides for the vacuolar, TAP-independent MHC class I cross-presentation in vivo
-
-
?
additional information
?
-
-
Cat S forms an alpha-beta-CLIP complex, unlike CatB or CatD, from an alpha-beta-Ii molecule in vitro
-
-
?
additional information
?
-
-
cathepsin S is a potent regulator of both cell and matrix turnover in advanced atherosclerosis
-
-
?
additional information
?
-
-
cathepsins are primarily involved in general protein turnover, CATS belongs to the cathepsins with a distinct substrate specificity
-
-
?
additional information
?
-
-
catS is a potent elastolytic protease and accelerates calcification in atherosclerotic mice with chronic renal disease induced by 5/6 nephrectemy
-
-
?
additional information
?
-
-
CatS is implicated in the regulation of intracellular cholesterol metabolism
-
-
?
additional information
?
-
-
CATS participates in inflammatory processes accompanying aging and pathologies of the central nervous system
-
-
?
additional information
?
-
-
it degrades the invariant chain Ii, which is crucial to the immune response since it acts as an essential step in MHC class II antigen presentation
-
-
?
additional information
?
-
-
cathepsin S substrate Leu-Arg and a poly(ethylene glycol) chain in dendritic arms
-
-
?
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
Ii protein + H2O
Ii fragments
-
inhibition of Ii degradation in enzyme-deficient cells leads to accumulation of Ii degradation intermediates in endosomal/lysosomal compartments
-
-
?
MHC class II-associated invariant chain Ii + H2O
?
-
degradation, cathepsin S and MHC class II-associated invariant chain Ii are responsible for in vivo control of endosomal size and multivesicular morphology
-
-
?
additional information
?
-
-
cathepsin S is implicated as a key enzyme in the processing of major histocompatability complex class II molecules
-
-
?
additional information
?
-
-
cathepsin S catalyzes a key step in antigen presentation, detailed overview
-
-
?
additional information
?
-
-
cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors, the enzyme is required for neoplastic progression, overview
-
-
?
additional information
?
-
-
cathepsin S in professional antigen-presenting cells, APC, controls MHC class II-mediated antigen presentation by epithelial cells in vivo, and plays a critical role in invariant chain degradation
-
-
?
additional information
?
-
-
cathepsin S is responsible for murine autoimmune myasthenia gravis pathogenesis, overview
-
-
?
additional information
?
-
-
cathepsin S, a cysteine protease, plays an important role in generating peptides for the vacuolar, TAP-independent MHC class I cross-presentation in vivo
-
-
?
additional information
?
-
-
cathepsin S is a potent regulator of both cell and matrix turnover in advanced atherosclerosis
-
-
?
additional information
?
-
-
cathepsins are primarily involved in general protein turnover, CATS belongs to the cathepsins with a distinct substrate specificity
-
-
?
additional information
?
-
-
catS is a potent elastolytic protease and accelerates calcification in atherosclerotic mice with chronic renal disease induced by 5/6 nephrectemy
-
-
?
additional information
?
-
-
CatS is implicated in the regulation of intracellular cholesterol metabolism
-
-
?
additional information
?
-
-
CATS participates in inflammatory processes accompanying aging and pathologies of the central nervous system
-
-
?
additional information
?
-
-
it degrades the invariant chain Ii, which is crucial to the immune response since it acts as an essential step in MHC class II antigen presentation
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
BMV083
a near-infrared quenched activity-based probe (qABP) that selectively targets cathepsin S in immune cells
BMV117
a near-infrared quenched activity-based probe (qABP) that selectively targets cathepsin S in immune cells
BMV157
a near-infrared quenched activity-based probe (qABP) that targets cathepsin S in immune cells
LO143
a near-infrared quenched activity-based probe (qABP) that targets cathepsin S in immune cells
LO219
a near-infrared quenched activity-based probe (qABP) that targets cathepsin S in immune cells
RO5461111
inhibits Cat-S activity and reduces podocyte loss, proteinuria, glomerulosclerosis, and renal inflammation in T2D db/db mice
1,2-dichloro-4-([[(2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-phenylethyl]amino]propyl]sulfinyl]oxy)benzene
-
-
1-bromo-3-([[(2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-phenylethyl]amino]propyl]sulfinyl]oxy)benzene
-
-
1-bromo-4-([[(2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-phenylethyl]amino]propyl]sulfinyl]oxy)benzene
-
-
1-[(1S)-1-[[(1R)-2-[(1-cyanocyclopropyl)amino]-1-[[(cyclopropylmethoxy)sulfinyl]methyl]-2-oxoethyl]amino]-2,2,2-trifluoroethyl]-4-fluorobenzene
-
-
1-[(3R)-4-(methylsulfonyl)-2-oxo-3-[[(1S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]amino]butyl]cyclopropanecarbonitrile
-
-
1-[([[(2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]amino]propyl]sulfinyl]oxy)methyl]-2,3-difluorobenzene
-
-
3-[4-chloro-3-[(4-chlorophenyl)ethynyl]phenyl]-5-(methylsulfonyl)-1-[3-(morpholin-4-yl)propyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine
-
-
4-morpholinecarboxamide, N-[(1R)-2-[[(1S)-1-(2-benzoxazolylcarbonyl) propyl] amino]-1-[[(cyclopropylmethyl)-sulfonyl]methyl]-2-oxoethyl]
-
previously reported as 05141, ihbitor-dosed mice are protected against ozone-induced airway hyperresponsiveness
6-[[4-(4-acetylpiperazin-1-yl)-2-fluorophenoxy]methyl]-7-(2-cyclohexylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
-
-
6-[[4-(4-acetylpiperazin-1-yl)phenoxy]methyl]-7-(2-cyclohexylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
-
-
6-[[4-(4-acetylpiperazin-1-yl)phenoxy]methyl]-7-[2-(4,4-difluorocyclohexyl)ethyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
-
-
CLIK60
-
selective CatS inhibitor, CatS inhibition increases macrophage cholesterol accumulation and efflux
methyl (2R)-2-[[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino]-3-[(1-cyanocyclopropyl)amino]-3-oxopropane-1-sulfinate
-
-
methyl (2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]amino]propane-1-sulfenate
-
-
methyl (2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]amino]propane-1-sulfinate
-
-
N-morpholinurea-leucine-homophenylalanine-vinylsulfone-phenyl
-
specific inhibitor
N-morpholinurea-leucyl-homophenylalanyl-vinylsulfone-phenyl
-
i.e. LHVS, irreversible inhibition, the inhibitor binds covalently to the active site
cystatin C
-
endogenous specific enzyme inhibitor, absence of cystatin C results in increased angiogenesis and tumor cell proliferation
-
additional information
design and synthesis of a near-infrared quenched activity-based probes (qABP) that selectively target cathepsin S which is highly expressed in immune cells, green-fluorescent pan-reactive cysteine cathepsin qABP in dual color labeling studies in bone marrow-derived immune cells, and identification of vesicles containing exclusively cathepsin S activity, method optimization and evaluation, overview. The high degree of selectivity is retained both in vitro and in vivo
-
additional information
-
diverse arylaminoethyl amides as noncovalent inhibitors of cathepsin S with IC50 in the nanomolar range, optimization of P1 and N-aryl, binding specificities of positions P1 and P2, and of subsite S1, overview
-
additional information
-
effect of cathepsin S inhibition on bronchoalveolar lavage fluid cytokines: inhibition reduces ozone-induced interleukin-6 levels at 3 h and 20-24 h and TNF-alpha levels are inhibited at 20-24 h
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kainate
kainate treatment (15 mg/kg) induces a 3.3fold increased cathepsin S expression
Ozone
-
cathepsin S levels peak 3 h after ozone exposure in bronchoalveolar lavage cells
TNF-alpha
-
cathepsin S can be upregulated by TNF-alpha in endothelial cells and cathepsin S induces endothelial cell motility, invasion and migration
-
additional information
cathepsin expression is not increased by nicotin treatment (10 mg/kg)
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.011
benzyloxycarbonyl-Val-Val-Arg-7-amido-4-methylcoumarin
-
pH 5.0, room temperature
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
20.3
benzyloxycarbonyl-Val-Val-Arg-7-amido-4-methylcoumarin
-
pH 5.0, room temperature
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00000064
4-morpholinecarboxamide, N-[(1R)-2-[[(1S)-1-(2-benzoxazolylcarbonyl) propyl] amino]-1-[[(cyclopropylmethyl)-sulfonyl]methyl]-2-oxoethyl]
-
excellent selectivity and activity for cathepsin S over the other cathepsin family members L, K and B
0.001
CLIK60
-
CatS activity in RAW264.7 cells or peritoneal macrophages from C57Bl/6 or LDLr-/-mice is completely repressed
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000002
1,2-dichloro-4-([[(2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-phenylethyl]amino]propyl]sulfinyl]oxy)benzene
Mus musculus
-
IC50 less than 0.2 mM
0.0000002
1-bromo-3-([[(2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-phenylethyl]amino]propyl]sulfinyl]oxy)benzene
Mus musculus
-
IC50 less than 0.2 mM
0.0000002
1-bromo-4-([[(2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-phenylethyl]amino]propyl]sulfinyl]oxy)benzene
Mus musculus
-
-
0.0000009
1-[(1S)-1-[[(1R)-2-[(1-cyanocyclopropyl)amino]-1-[[(cyclopropylmethoxy)sulfinyl]methyl]-2-oxoethyl]amino]-2,2,2-trifluoroethyl]-4-fluorobenzene
Mus musculus
-
-
0.0000008
1-[([[(2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]amino]propyl]sulfinyl]oxy)methyl]-2,3-difluorobenzene
Mus musculus
-
-
0.00069
3-[4-chloro-3-[(4-chlorophenyl)ethynyl]phenyl]-5-(methylsulfonyl)-1-[3-(morpholin-4-yl)propyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine
Mus musculus
-
-
0.000014
6-[[4-(4-acetylpiperazin-1-yl)-2-fluorophenoxy]methyl]-7-(2-cyclohexylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Mus musculus
-
mus Cat S, Z-Leu-Leu-Arg-7-amido-4-methylcoumarin as substrate
0.00001
6-[[4-(4-acetylpiperazin-1-yl)phenoxy]methyl]-7-(2-cyclohexylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Mus musculus
-
mus Cat S, Z-Leu-Leu-Arg-7-amido-4-methylcoumarin as substrate
0.00002
6-[[4-(4-acetylpiperazin-1-yl)phenoxy]methyl]-7-[2-(4,4-difluorocyclohexyl)ethyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Mus musculus
-
mus Cat S, Z-Leu-Leu-Arg-7-amido-4-methylcoumarin as substrate
0.00000016
methyl (2R)-2-[[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino]-3-[(1-cyanocyclopropyl)amino]-3-oxopropane-1-sulfinate
Mus musculus
-
-
0.000096
methyl (2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]amino]propane-1-sulfenate
Mus musculus
-
-
0.0000006
methyl (2R)-3-[(1-cyanocyclopropyl)amino]-3-oxo-2-[[(1S)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]amino]propane-1-sulfinate
Mus musculus
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
CATS protein expression increases in the cerebral cortex, the cerebellum and the hippocampus, the proform is the predominant enzymatic form in all analyzed age groups
additional information
-
CATS transcript and protein are strongly increased between 3 and 5 months of age in the central nervous system of SOD1-G93A transgenic mice with amyotrophic lateral sclerosis
additional information
-
in a transgenic mouse model of amyotrophic lateral sclerosis expressing mutant superoxide dismutase 1, CATS transcript and protein levels are significantly upregulated in spinal cord and lower brain regions displaying neuronal degeneration
additional information
-
leucocyte CatS deficiency leads to a markedly altered plaque morphology and composition, which can in part be attributed to fewer elastic lamina ruptures and a higher resistance of macrophages to apoptosis and necrosis
additional information
-
osteogenic activity decreases in apolipoprotein-/-/catS-/- mouse aortas with chronic renal disease
additional information
-
the number of CATS immunopositive cells with glial morphology clearlyincreases in 4-week- and 26-30-month old mice
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3.5 - 8.5
-
pH 3.5: about 55% of maximal activity, pH 7.5: about 50% of maximal activity, pH 8.0: about 70% of maximal activity, pH 8.5: about 35% of maximal activity, hydrolysis of benzyloxycarbonyl-Val-Val-Arg-7-amido-4-methylcoumarin
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
bone marrow-derived immune cells, cathepsin S expression is mainly restricted to antigen-presenting cells (APCs)
additional information
specific localization of cathepsin S activity in dendritic cells
additional information
in mouse type 2 diabetic nephropathy, only CD68+ intrarenal monocytes express Cat-S mRNA, whereasCat-S protein is present along endothelial cells and inside proximal tubular epithelial cells also. Transcriptome analysis
additional information
-
in mouse type 2 diabetic nephropathy, only CD68+ intrarenal monocytes express Cat-S mRNA, whereasCat-S protein is present along endothelial cells and inside proximal tubular epithelial cells also. Transcriptome analysis
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
design and synthesis of a near-infrared quenched activity-based probes (qABP) that selectively target cathepsin S which is highly expressed in immune cells, green-fluorescent pan-reactive cysteine cathepsin qABP in dual color labeling studies in bone marrow-derived immune cells, and identification of vesicles containing exclusively cathepsin S activity. The high degree of selectivity is retained both in vitro and in vivo
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
cathepsin S deficiency as shown in knockout mice induces a high bone turnover, leading to less dense bone and trabecular thinning despite normal bone mass
malfunction
CatS knockdown leads to defective endothelial cell invasion, proliferation, and tube formation as shown in CatS knockout mice and CatS silincing in HUVEC cells
malfunction
in vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2
malfunction
the population of CD11c+ dendritic cells is significantly increased in the splenic marginal zone (MZ) locally of wild-type (DBA/2) mice with splenomegaly but not in that of CatS deficient (CatS-/-) mice after systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (PgLPS) for 7 consecutive days
physiological function
CatS activity controls ischemia-induced neovascularization partially via the modulation of PPAR-gamma and VEGF/Akt signaling activation
physiological function
cathepsin S (Cat-S) is a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. Cathepsin S cleavage of protease-activated receptor-2 on endothelial cells promotes microvascular diabetes complications. Cat-S is a monocyte/macrophage-derived circulating PAR2 agonist and mediator of endothelial dysfunction-related microvascular diabetes complications. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuates albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuates albumin leakage into the retina and other structural markers of diabetic retinopathy
physiological function
cathepsin S (CatS) is involved in Th17 differentiation through the upregulation of interleukin-6 by activating PAR-2 after systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (PgLPS). Lysosomal proteinase CatS is known to be involved in dendritic cell functions. CatS is essential for the production of interleukin-6 by splenic CD11cC dendritic cells after systemic exposure to PgLPS
physiological function
cathepsin S expression is mainly restricted to antigen-presenting cells (APCs) where it contributes to antigen presenting capacity by controlling trafficking and maturation of major histocompatibility complex (MHC) class II molecules
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). CATS_MOUSE
340
0
38475
Swiss-Prot
Secretory Pathway (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
the prepeptide of CATS is removed during the passage to the endoplasmic reticulum and the procathepsin undergoes proteolytic processing to the mature enzyme in the lysosomal compartment
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
addition of a carboxy-terminal hexahistidine purification tag has no effect on the kinetic characterization of any of the enzyme forms against butyloxycarbonyl-Val-Leu-Lys-7-amido-4-methylcoumarin substrate
additional information
-
cathepsin S-deficient mutant mice lack the TAP-independent vacuolar pathway of MHC class I crosspresentation, and have reduced crosspriming to particulate and cell-associated antigens as well as to influenza virus, overview
additional information
-
cathepsin S-deficient mutant mice show impaired degradation of the invariant chain in antigen presenting cells alng with resistance to collagen-induced arthritis and autoimmune myasthenia gravis
additional information
-
generation of Cat S null mutant mice showing increased resistance to the development of experimental autoimmune myasthenia gravis with reduced responses of B- and T-cells to acetylcholine receptor antigen compared to wild-type mice
additional information
-
generation of Cat S-deficient knockout mice mutants showing accumulation of MHC class II molecules bound to the 10 kDa fragment of Ii, knockout mice phenotype, overview
additional information
-
generation of Cat S-deficient mutant mice, the mutant mice demonstrate impaired angiogenesis and tumor cell proliferation
additional information
-
generation of enzyme-deficient mutant murine splenocytes, which show enlarged endosome forms lacking the multivesicular morphology due to accumulation of MHC class II-associated invariant chain Ii, cells lacking both CatS and MHC class II-associated invariant chain Ii show normal endosome size but absence of endosomal membranes
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
apolipoprotein-deficient with minus or plus catS are assigned to chronic renal disease
-
chimeric LDLr-/-mice deficient in leucocyte cathepsin S are generated by bone marrow transplantation
-
expression in baculovirally infected Sf9 insect cells along with humanized forms truncated by eight residues at the amino-terminus
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
pharmacology
-
the enzyme might be a good target for development of inhibitors in treatment of collagen-induced arthritis and autoimmune myasthenia gravis
drug development
-
discovery of orally bioavailable cathepsin S inhibitors for the reversal of neuropathic pain, cathepsin S inhibitors are attractive targets as immunological therapeutic agents
drug development
-
importance of CATS in inflammatory processes, which has generated much interest in the development of CATS inhibitors as immunomodulatory therapeutics for immune disorders such as bronchial asthma, rheumatoid arthritis and psoriasis, CATS may also be an attractive target in neurodegenerative disorders associated with inflammation
drug development
-
important role for cathepsin S in the regulation of ozone-induced airway hyperresponsiveness and neutrophil cell recruitment, cathepsin S may be a target in the treatment of oxidative stress-induced airway hyperresponsiveness and inflammation
drug development
-
increased risk of mortality and morbidity associates with cardiovascular calcification drives the development of new therapeutic strategies to prevent and potentially reverse this process, new therapeutic options may also include selective inhibition of catS
medicine
-
cathepsin S is a potential therapeutic target for regulation of major histocompatibility complex class II immune responses, possibly resulting in treatments for autoimmune diseases and allergic asthma
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Baker, S.M.; Karlsson, L.; Thurmond, R.L.
Cloning, expression, purification, and activity of dog (Canis familiaris) and monkey (Saimiri boliviensis) cathepsin S
Protein Expr. Purif.
28
93-101
2003
Bos taurus, Canis lupus familiaris, Homo sapiens, Mus musculus, Saimiri boliviensis
Mason, C.S.; Lamers, M.B.; Henderson, I.M.; Monk, T.; Williams, D.H.
Baculoviral expression and characterization of rodent cathepsin S
Protein Expr. Purif.
23
45-54
2001
Homo sapiens, Mus musculus, Rattus norvegicus
Thurmond, R.L.; Sun, S.; Sehon, C.A.; Baker, S.M.; Cai, H.; Gu, Y.; Jiang, W.; Riley, J.P.; Williams, K.N.; Edwards, J.P.; Karlsson, L.
Identification of a potent and selective noncovalent cathepsin S inhibitor
J. Pharmacol. Exp. Ther.
308
268-276
2004
Bos taurus, Canis lupus familiaris, Homo sapiens, Platyrrhini, Mus musculus
Alper, P.B.; Liu, H.; Chatterjee, A.K.; Nguyen, K.T.; Tully, D.C.; Tumanut, C.; Li, J.; Harris, J.L.; Tuntland, T.; Chang, J.; Gordon, P.; Hollenbeck, T.; Karanewsky, D.S.
Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2: optimization of P1 and N-aryl
Bioorg. Med. Chem. Lett.
16
1486-1490
2006
Mus musculus
Liu, W.; Spero, D.M.
Cysteine protease cathepsin S as a key step in antigen presentation
Drug News Perspect.
17
357-363
2004
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Boes, M.; van der Wel, N.; Peperzak, V.; Kim, Y.M.; Peters, P.J.; Ploegh, H.
In vivo control of endosomal architecture by class II-associated invariant chain and cathepsin S
Eur. J. Immunol.
35
2552-2562
2005
Mus musculus
Shen, L.; Sigal, L.J.; Boes, M.; Rock, K.L.
Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo
Immunity
21
155-165
2004
Mus musculus
Wang, B.; Sun, J.; Kitamoto, S.; Yang, M.; Grubb, A.; Chapman, H.A.; Kalluri, R.; Shi, G.P.
Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors
J. Biol. Chem.
281
6020-6029
2006
Homo sapiens, Mus musculus, Mus musculus C57BL/6
Beers, C.; Burich, A.; Kleijmeer, M.J.; Griffith, J.M.; Wong, P.; Rudensky, A.Y.
Cathepsin S controls MHC class II-mediated antigen presentation by epithelial cells in vivo
J. Immunol.
174
1205-1212
2005
Mus musculus, Mus musculus C57BL/6
Yang, H.; Kala, M.; Scott, B.G.; Goluszko, E.; Chapman, H.A.; Christadoss, P.
Cathepsin S is required for murine autoimmune myasthenia gravis pathogenesis
J. Immunol.
174
1729-1737
2005
Mus musculus, Mus musculus C57BL/6
Rodgers, K.J.; Watkins, D.J.; Miller, A.L.; Chan, P.Y.; Karanam, S.; Brissette, W.H.; Long, C.J.; Jackson, C.L.
Destabilizing role of cathepsin S in murine atherosclerotic plaques
Arterioscler. Thromb. Vasc. Biol.
26
851-856
2006
Homo sapiens, Mus musculus
Gauthier, J.Y.; Black, W.C.; Courchesne, I.; Cromlish, W.; Desmarais, S.; Houle, R.; Lamontagne, S.; Li, C.S.; Masse, F.; McKay, D.J.; Ouellet, M.; Robichaud, J.; Truchon, J.F.; Truong, V.L.; Wang, Q.; Percival, M.D.
The identification of potent, selective, and bioavailable cathepsin S inhibitors
Bioorg. Med. Chem. Lett.
17
4929-4933
2007
Homo sapiens, Mus musculus, Rattus norvegicus
Akahoshi, N.; Murashima, Y.L.; Himi, T.; Ishizaki, Y.; Ishii, I.
Increased expression of the lysosomal protease cathepsin S in hippocampal microglia following kainate-induced seizures
Neurosci. Lett.
429
136-141
2007
Mus musculus (O70370)
de Nooijer, R.; Bot, I.; von der Thuesen, J.H.; Leeuwenburgh, M.A.; Overkleeft, H.S.; Kraaijeveld, A.O.; Dorland, R.; van Santbrink, P.J.; van Heiningen, S.H.; Westra, M.M.; Kovanen, P.T.; Jukema, J.W.; van der Wall, E.E.; van Berkel, T.J.; Shi, G.P.; Biessen, E.A.
Leukocyte cathepsin S is a potent regulator of both cell and matrix turnover in advanced atherosclerosis
Arterioscler. Thromb. Vasc. Biol.
29
188-194
2009
Mus musculus
Wendt, W.; Luebbert, H.; Stichel, C.C.
Upregulation of cathepsin S in the aging and pathological nervous system of mice
Brain Res.
1232
7-20
2008
Mus musculus
Aikawa, E.; Aikawa, M.; Libby, P.; Figueiredo, J.L.; Rusanescu, G.; Iwamoto, Y.; Fukuda, D.; Kohler, R.H.; Shi, G.P.; Jaffer, F.A.; Weissleder, R.
Arterial and aortic valve calcification abolished by elastolytic cathepsin S deficiency in chronic renal disease
Circulation
119
1785-1794
2009
Mus musculus
Irie, O.; Kosaka, T.; Ehara, T.; Yokokawa, F.; Kanazawa, T.; Hirao, H.; Iwasaki, A.; Sakaki, J.; Teno, N.; Hitomi, Y.; Iwasaki, G.; Fukaya, H.; Nonomura, K.; Tanabe, K.; Koizumi, S.; Uchiyama, N.; Bevan, S.J.; Malcangio, M.; Gentry, C.; Fox, A.J.; Yaqoob, M.; Culshaw, A.J.; Allan Hallett, A.J.
Discovery of orally bioavailable cathepsin S inhibitors for the reversal of neuropathic pain
J. Med. Chem.
51
5502-5505
2008
Homo sapiens, Mus musculus, Rattus norvegicus (Q02765)
Williams, A.S.; Eynott, P.R.; Leung, S.Y.; Nath, P.; Jupp, R.; De Sanctis, G.T.; Resnick, R.; Adcock, I.M.; Chung, K.F.
Role of cathepsin S in ozone-induced airway hyperresponsiveness and inflammation
Pulm. Pharmacol. Ther.
22
27-32
2009
Mus musculus
Sasaki, T.; Kuzuya, M.; Nakamura, K.; Cheng, X.W.; Hayashi, T.; Song, H.; Hu, L.; Okumura, K.; Murohara, T.; Iguchi, A.; Sato, K.
AT1 blockade attenuates atherosclerotic plaque destabilization accompanied by the suppression of cathepsin S activity in apoE-deficient mice
Atherosclerosis
210
430-437
2010
Mus musculus
Ameriks, M.K.; Axe, F.U.; Bembenek, S.D.; Edwards, J.P.; Gu, Y.; Karlsson, L.; Randal, M.; Sun, S.; Thurmond, R.L.; Zhu, J.
Pyrazole-based cathepsin S inhibitors with arylalkynes as P1 binding elements
Bioorg. Med. Chem. Lett.
19
6131-6134
2009
Homo sapiens, Mus musculus
Lindahl, C.; Simonsson, M.; Bergh, A.; Thysell, E.; Antti, H.; Sund, M.; Wikstroem, P.
Increased levels of macrophage-secreted cathepsin S during prostate cancer progression in TRAMP mice and patients
Cancer Genomics Proteomics
6
149-159
2009
Mus musculus
Samokhin, A.O.; Lythgo, P.A.; Gauthier, J.Y.; Percival, M.D.; Broemme, D.
Pharmacological inhibition of cathepsin S decreases atherosclerotic lesions in Apoe-/- mice
J. Cardiovasc. Pharmacol.
56
98-105
2010
Mus musculus
Baston-Buest, D.M.; Schanz, A.; Buest, S.; Fischer, J.C.; Kruessel, J.S.; Hess, A.P.
The embryos cystatin C and F expression functions as a protective mechanism against the maternal proteinase cathepsin S in mice
Reproduction
139
741-748
2010
Mus musculus
Rauner, M.; Foeger-Samwald, U.; Kurz, M.F.; Bruenner-Kubath, C.; Schamall, D.; Kapfenberger, A.; Varga, P.; Kudlacek, S.; Wutzl, A.; Hoeger, H.; Zysset, P.K.; Shi, G.P.; Hofbauer, L.C.; Sipos, W.; Pietschmann, P.
Cathepsin S controls adipocytic and osteoblastic differentiation, bone turnover, and bone microarchitecture
Bone
64
281-287
2014
Mus musculus (O70370)
Li, X.; Cheng, X.W.; Hu, L.; Wu, H.; Guo-Ping, H.; Hao, C.N.; Jiang, H.; Zhu, E.; Huang, Z.; Inoue, A.; Sasaki, T.; Du, Q.; Takeshita, K.; Okumura, K.; Murohara, T.; Kuzuya, M.
Cathepsin S activity controls ischemia-induced neovascularization in mice
Int. J. Cardiol.
183
198-208
2015
Mus musculus (O70370), Homo sapiens (P25774), Homo sapiens
Dekita, M.; Wu, Z.; Ni, J.; Zhang, X.; Liu, Y.; Yan, X.; Nakanishi, H.; Takahashi, I.
Cathepsin S is involved in Th17 differentiation through the upregulation of IL-6 by activating PAR-2 after systemic exposure to lipopolysaccharide from Porphyromonas gingivalis
Front. Pharmacol.
8
470
2017
Mus musculus (O70370)
Oresic Bender, K.; Ofori, L.; van der Linden, W.A.; Mock, E.D.; Datta, G.K.; Chowdhury, S.; Li, H.; Segal, E.; Sanchez Lopez, M.; Ellman, J.A.; Figdor, C.G.; Bogyo, M.; Verdoes, M.
Design of a highly selective quenched activity-based probe and its application in dual color imaging studies of cathepsin S activity localization
J. Am. Chem. Soc.
137
4771-4777
2015
Mus musculus (O70370)
Kumar Vr, S.; Darisipudi, M.N.; Steiger, S.; Devarapu, S.K.; Tato, M.; Kukarni, O.P.; Mulay, S.R.; Thomasova, D.; Popper, B.; Demleitner, J.; Zuchtriegel, G.; Reichel, C.; Cohen, C.D.; Lindenmeyer, M.T.; Liapis, H.; Moll, S.; Reid, E.; Stitt, A.W.; Schott, B.; Gruner, S.; Haap, W.; Ebeling, M.; Hartmann, G.
Cathepsin S cleavage of protease-activated receptor-2 on endothelial cells promotes microvascular diabetes complications
J. Am. Soc. Nephrol.
27
1635-1649
2016
Mus musculus (O70370), Mus musculus, Homo sapiens (P25774), Homo sapiens
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