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Information on EC 3.4.22.38 - cathepsin K and Organism(s) Rattus norvegicus and UniProt Accession O35186
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3.4.22.38 cathepsin KSpecify your search results
Word Map
- 3.4.22.38
- resorption
- osteoporosis
-
osteoclastogenesis
- rankl
-
tartrate-resistant
- osteoblast
- collagen
- nfatc1
-
rankl-induced
-
multinucleated
- mmp-9
- c-fos
-
fracture
-
trabecular
- pi
- calcitonin
- osteocalcin
- osteoprotegerin
-
osteolytic
-
resorb
- m-csf
-
collagenolytic
- bisphosphonates
-
osteoclast-mediated
-
trap-positive
-
osteoclast-specific
- odanacatib
- oscar
-
antiresorptive
- tracp
- lacuna
-
ovariectomy-induced
-
rankl-mediated
-
dc-stamp
-
bone-resorbing
-
sclerostin
-
osteoclast-related
-
telopeptide
-
osteoclast-like
-
osteoclastogenic
-
denosumab
-
preosteoclasts
-
teriparatide
- pharmacology
-
anti-osteoclastogenic
- osteosclerosis
-
anti-osteoporotic
- atp6v0d2
- medicine
-
ranelate
- drug development
-
deoxypyridinoline
-
rankl-stimulated
- diagnostics
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
cathepsin k, cathepsin-k, cat k, cath k, cat-k, cathepsin o2, oc-2 protein, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Cathepsin O2
-
-
-
-
OC-2 protein
-
-
-
-
rhCK
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
94716-09-3
-
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
carbobenzyloxy-Leu-Arg-4-methylcoumaryl-7-amide + H2O
carbobenzyloxy-Leu-Arg + 7-amino-4-methylcoumarin
-
-
-
?
collagen I + H2O
?
-
cathepsin K is the only cathepsin that can degrade native type-I collagen in a triple-helix structure
-
-
?
Z-Phe-Arg-4-methylcoumarin 7-amide + H2O
Z-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
Z-Phe-Arg-7-amido-4-methylcoumarin + H2O
Z-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
additional information
?
-
rat cathepsin K preferentially hydrolyses the substrates at the P2 Hyp position, substrate specificity compared to the human enzyme, overview
-
-
?
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
collagen I + H2O
?
-
cathepsin K is the only cathepsin that can degrade native type-I collagen in a triple-helix structure
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S,3S)-3-([(1S)-3-methyl-1-[(2-methylpropoxy)methyl]butyl]carbamoyl)oxirane-2-carboxylate
-
through screening, a potent orally active cathepsin K inhibitor named NC-2300 is obtained, which suppresses autoimmune inflammation of the joints as well as osteoclastic bone resorption in an adjuvant-induced arthritis animal model in rats. Computer-assisted simulation of the cathepsin K/NC-2300 complex indicates that NC-2300 blocks the active-site cleft where Cys25 and His162 of cathepsin K form the catalytic site. Pharmacological inhibition of cathepsin K results in defective Toll-like receptor 9 signaling in dendritic cells in response to unmethylated CpG DNA, which in turn leads to an attenuated induction of T helper 17 cells, without affecting the antigen-presenting ability of dendritic cells
1-Isopropyl-2-methylpropyl (1S)-1-[oxo(1H-pyrazol-5-ylamino)acetyl]pentylcarbamate
-
IC50: 13 nM
1-Isopropyl-2-methylpropyl (1S)-1-[oxo[(1-phenyl-1H-pyrazol-5-yl)amino]acetyl]pentylcarbamate
-
IC50: 790 nM
1-Isopropyl-2-methylpropyl (1S)-1-[oxo[(1-pyridin-2-yl-1H-pyrazol-5-yl)amino]acetyl]pentylcarbamate
-
IC50: 0.0012 mM
1-Isopropyl-2-methylpropyl (1S)-1-[oxo[(1-pyridin-4-yl-1H-pyrazol-5-yl)amino]acetyl]pentylcarbamate
-
IC50: 470 nM
1-Isopropyl-2-methylpropyl (1S)-1-[oxo[(3-phenyl-1H-pyrazol-5-yl)amino]acetyl]pentylcarbamate
-
IC50: 12 nM
1-Isopropyl-2-methylpropyl (1S)-1-[oxo[(4-phenyl-1H-pyrazol-5-yl)amino]acetyl]pentylcarbamate
-
IC50: 1.8 nM
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-cyclobutyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
-
IC50: 0.0011 mM
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-cyclohexyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
-
IC50: 0.0012 mM
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-cyclopentyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
-
IC50: 0.0011 mM
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-ethyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
-
IC50: 0.0015 mM
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-isobutyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
-
IC50: 0.0027 mM
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-isopropyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
-
IC50: 0.001 mM
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-methyl-1H-pyrazol-3-yl)amino](oxo)acetyl]pentylcarbamate
-
IC50: 11 nM
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-methyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
-
IC50: 0.0017 mM
1-Isopropyl-2-methylpropyl (1S)-1-[[(4-methyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
-
IC50: 5.5 nM
1-Isopropyl-2-methylpropyl (1S)-1-[[[1-(3,3-dimethyl)-1H-pyrazol-5-yl]amino](oxo)acetyl]pentylcarbamate
-
IC50: 0.0016 mM
1-Isopropyl-2-methylpropyl (1S)-1-[[[1-(cyclopropylmethyl)-1H-pyrazol-5-yl]amino](oxo)acetyl]pentylcarbamate
-
IC50: 0.0017 mM
2-cyano-4-(cyclohexylamino)-N-(4-methoxyphenethyl)-pyrimidine-5-carboxamide
-
-
2-cyano-N-(4-methoxyphenethyl)-4-(neopentylamino)pyrimidine-5-carboxamide
-
-
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
-
-
7-(2,2-dimethyl-propyl)-6-(1,3-dioxo-2,8-diaza-spiro[4.5]dec-2-ylmethyl)-7H-pyrrolo[2,3-d] pyrimidine-2-carbonitrile
-
-
7-(2,2-dimethylpropyl)-6-[(2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
-
-
7-(2,2-dimethylpropyl)-6-[(2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
-
-
7-(2,2-dimethylpropyl)-6-[(2,4-dioxo-3-propyl-1,3,8-triazaspiro[4.5]dec-8-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
-
-
7-(2,2-dimethylpropyl)-6-[(2,4-dioxo-8-propyl-1,3,8-triazaspiro[4.5]dec-3-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
-
-
7-(2,2-dimethylpropyl)-6-[(3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
-
-
7-(2,2-dimethylpropyl)-6-[(5-fluoro-2-oxospiro[indole-3,4'-piperidin]-1(2H)-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
-
-
7-(2,2-dimethylpropyl)-6-[(5-methoxy-2-oxospiro[indole-3,4'-piperidin]-1(2H)-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
-
-
benzyl [(2S)-1-{2-[(2-{(2S)-2-[(2-amino-3-phenylpropanoyl)amino]-4-methylpentanoyl}hydrazinyl)carbonyl]hydrazinyl}-4-methyl-1-oxopentan-2-yl]carbamate
-
-
dibenzyl [(2-oxopropane-1,3-diyl)bis{imino[(2S)-4-methyl-1-oxopentane-1,2-diyl]}]biscarbamate
-
-
L-006235
-
shows no selectivity in cell-based assays over cathepsins B, L, and S
N-(4-methyl-1-oxo-1-[[3-oxo-1-(pyridin-2-ylsulfonyl)azepan-4-yl]amino]pentan-2-yl)-1-benzofuran-2-carboxamide
-
-
N-[(1S)-3-methyl-1-([(4S)-3-oxo-1-[(3-pyridin-2-ylphenyl)acetyl]azepan-4-yl]carbamoyl)butyl]-5-(2-morpholin-4-ylethoxy)-1-benzofuran-2-carboxamide
-
-
N-[(2S)-1-[[(2R,4S)-2,4-dimethyl-3-oxo-1-(pyridin-2-ylsulfonyl)azepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide
-
-
N-[(2S)-1-[[(4S,5S)-4,5-dimethyl-3-oxo-1-(pyridin-2-ylsulfonyl)azepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide
-
-
N-[4-methyl-1-oxo-1-([2-oxo-3-[(pyridin-2-ylsulfonyl)amino]propyl]amino)pentan-2-yl]-1-benzofuran-2-carboxamide
-
-
L-873724
-
highly selective for cathespin K over other cathepsins, metabolization, overview
odanacatib
-
i.e. MK-0822, a selective cathepsin K inhibitor, pharmacokinetics of odanacatib
additional information
-
P2/S2 and P3/S3 interaction of cathepsin K inhibitors with pyrrolopyrimidine scaffold and structure of the common intermediate, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
procathepsin K is activated by incubation at 37°C in the presence of DTT and dextran sulfate at final concentrations of 1 mM and 100 mg/ml, respectively
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.005
carbobenzyloxy-Leu-Arg-4-methylcoumaryl-7-amide
pH 7.0, 37°C, recombinant mutant S134A/V160L
0.016
carbobenzyloxy-Leu-Arg-4-methylcoumaryl-7-amide
pH 7.0, 37°C, recombinant mutant S134A
0.026
carbobenzyloxy-Leu-Arg-4-methylcoumaryl-7-amide
pH 7.0, 37°C, recombinant mutant V160L
0.293
carbobenzyloxy-Leu-Arg-4-methylcoumaryl-7-amide
pH 7.0, 37°C, recombinant wild-type enzyme
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
21.1
carbobenzyloxy-Leu-Arg-4-methylcoumaryl-7-amide
pH 7.0, 37°C, recombinant mutant S134A/V160L
46.3
carbobenzyloxy-Leu-Arg-4-methylcoumaryl-7-amide
pH 7.0, 37°C, recombinant mutant V160L
95.7
carbobenzyloxy-Leu-Arg-4-methylcoumaryl-7-amide
pH 7.0, 37°C, recombinant wild-type enzyme
97.5
carbobenzyloxy-Leu-Arg-4-methylcoumaryl-7-amide
pH 7.0, 37°C, recombinant mutant S134A
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00000016
N-(4-methyl-1-oxo-1-[[3-oxo-1-(pyridin-2-ylsulfonyl)azepan-4-yl]amino]pentan-2-yl)-1-benzofuran-2-carboxamide
-
pH and temperature not specified in the publication
0.0000048
N-[(1S)-3-methyl-1-([(4S)-3-oxo-1-[(3-pyridin-2-ylphenyl)acetyl]azepan-4-yl]carbamoyl)butyl]-5-(2-morpholin-4-ylethoxy)-1-benzofuran-2-carboxamide
-
-
0.00000014
N-[(2S)-1-[[(2R,4S)-2,4-dimethyl-3-oxo-1-(pyridin-2-ylsulfonyl)azepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide
-
pH and temperature not specified in the publication
0.0000000099
N-[(2S)-1-[[(4S,5S)-4,5-dimethyl-3-oxo-1-(pyridin-2-ylsulfonyl)azepan-4-yl]amino]-4-methyl-1-oxopentan-2-yl]-1-benzofuran-2-carboxamide
-
pH and temperature not specified in the publication
0.0000016
N-[4-methyl-1-oxo-1-([2-oxo-3-[(pyridin-2-ylsulfonyl)amino]propyl]amino)pentan-2-yl]-1-benzofuran-2-carboxamide
-
pH and temperature not specified in the publication
0.000000041
relacatib
-
pH and temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000013
1-Isopropyl-2-methylpropyl (1S)-1-[oxo(1H-pyrazol-5-ylamino)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 13 nM
0.00079
1-Isopropyl-2-methylpropyl (1S)-1-[oxo[(1-phenyl-1H-pyrazol-5-yl)amino]acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 790 nM
0.0012
1-Isopropyl-2-methylpropyl (1S)-1-[oxo[(1-pyridin-2-yl-1H-pyrazol-5-yl)amino]acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 0.0012 mM
0.00047
1-Isopropyl-2-methylpropyl (1S)-1-[oxo[(1-pyridin-4-yl-1H-pyrazol-5-yl)amino]acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 470 nM
0.000012
1-Isopropyl-2-methylpropyl (1S)-1-[oxo[(3-phenyl-1H-pyrazol-5-yl)amino]acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 12 nM
0.0000018
1-Isopropyl-2-methylpropyl (1S)-1-[oxo[(4-phenyl-1H-pyrazol-5-yl)amino]acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 1.8 nM
0.0011
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-cyclobutyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 0.0011 mM
0.0012
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-cyclohexyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 0.0012 mM
0.0011
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-cyclopentyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 0.0011 mM
0.0015
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-ethyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 0.0015 mM
0.0027
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-isobutyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 0.0027 mM
0.001
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-isopropyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 0.001 mM
0.000011
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-methyl-1H-pyrazol-3-yl)amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 11 nM
0.0017
1-Isopropyl-2-methylpropyl (1S)-1-[[(1-methyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 0.0017 mM
0.0000055
1-Isopropyl-2-methylpropyl (1S)-1-[[(4-methyl-1H-pyrazol-5-yl)amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 5.5 nM
0.0016
1-Isopropyl-2-methylpropyl (1S)-1-[[[1-(3,3-dimethyl)-1H-pyrazol-5-yl]amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 0.0016 mM
0.0017
1-Isopropyl-2-methylpropyl (1S)-1-[[[1-(cyclopropylmethyl)-1H-pyrazol-5-yl]amino](oxo)acetyl]pentylcarbamate
Rattus norvegicus
-
IC50: 0.0017 mM
0.00003
7-(2,2-dimethyl-propyl)-6-(1,3-dioxo-2,8-diaza-spiro[4.5]dec-2-ylmethyl)-7H-pyrrolo[2,3-d] pyrimidine-2-carbonitrile
Rattus norvegicus
-
-
0.000076
7-(2,2-dimethylpropyl)-6-[(2,4-dioxo-1,3,8-triazaspiro[4.5]dec-3-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Rattus norvegicus
-
-
0.000027
7-(2,2-dimethylpropyl)-6-[(2,4-dioxo-8-propyl-1,3,8-triazaspiro[4.5]dec-3-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Rattus norvegicus
-
-
0.000012
7-(2,2-dimethylpropyl)-6-[(3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Rattus norvegicus
-
-
0.0000078
7-(2,2-dimethylpropyl)-6-[(5-fluoro-2-oxospiro[indole-3,4'-piperidin]-1(2H)-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Rattus norvegicus
-
-
0.000044
7-(2,2-dimethylpropyl)-6-[(5-methoxy-2-oxospiro[indole-3,4'-piperidin]-1(2H)-yl)methyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Rattus norvegicus
-
-
0.000035
benzyl [(2S)-1-{2-[(2-{(2S)-2-[(2-amino-3-phenylpropanoyl)amino]-4-methylpentanoyl}hydrazinyl)carbonyl]hydrazinyl}-4-methyl-1-oxopentan-2-yl]carbamate
Rattus norvegicus
-
pH and temperature not specified in the publication
0.000269
Boc-Phe-Leu-NHNH-CO-NHNH-Leu-Z
Rattus norvegicus
-
pH and temperature not specified in the publication
0.002588
dibenzyl [(2-oxopropane-1,3-diyl)bis{imino[(2S)-4-methyl-1-oxopentane-1,2-diyl]}]biscarbamate
Rattus norvegicus
-
pH and temperature not specified in the publication
0.0000076
Mu-Leu-Hph-fluoromethylketone
Rattus norvegicus
-
pH and temperature not specified in the publication
additional information
6-[[4-(4-acetylpiperazin-1-yl)-2-fluorophenoxy]methyl]-7-(2-cyclohexylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
additional information
6-[[4-(4-acetylpiperazin-1-yl)-2-fluorophenoxy]methyl]-7-(2-cyclohexylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Rattus norvegicus
-
IC50 is above 0.01 mM, Z-Phe-Arg-7-amido-4-methylcoumarin as substrate
additional information
6-[[4-(4-acetylpiperazin-1-yl)phenoxy]methyl]-7-(2-cyclohexylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Rattus norvegicus
-
IC50 is above 0.01 mM, Z-Phe-Arg-7-amido-4-methylcoumarin as substrate
additional information
6-[[4-(4-acetylpiperazin-1-yl)phenoxy]methyl]-7-[2-(4,4-difluorocyclohexyl)ethyl]-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile
Rattus norvegicus
-
IC50 is above 0.01 mM, Z-Phe-Arg-7-amido-4-methylcoumarin as substrate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
cathepsin K activity is confirmed in dendritic cells
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
on the dental root side, expression pattern of cathepsin K, high expression level in the age of 4-5 weeks, when physiological root resorption occurs actively, co-expression with matrix metalloproteinase-9
localized on the surface of alveolar bone, expression pattern of cathepsin K, no co-expression with matrix metalloproteinase-9
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
cathepsin K expression is essential for normal bone resorption
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). CATK_RAT
329
0
36791
Swiss-Prot
Secretory Pathway (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the human sequence contains Tyr at S3 positions 61 and 67, and residues Met, Ser, Val, Ala, and Leu at S2 positions 68, 134, 160, 163, and 209, respectively, comparison with the human enzyme
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S134A
site-directed mutagenesis of the rat residue Ser to the correspondent Ala of the human sequence, the mutant looses the P2 Hyp specificity
S134A/V160L
site-directed mutagenesis of the rat residues Ser and Val to the correspondent Ala and Leu, respectively, of the human sequence, the mutant looses the P2 Hyp specificity
V160L
site-directed mutagenesis of the rat residue Val to the correspondent Leu of the human sequence, the mutant looses the P2 Hyp specificity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
CTSK expression is stimulated by nuclear factor kappaB ligand. Both, nuclear factor kappaB ligand treatment and overexpression of nuclear factor of activated T-cells c1 dramatically enhances CTSK promoter activity. Proximal nuclear factor of activated T-cells binding sites play a significant role in the nuclear factor of activated T-cells c1-mediated stimulation of CTSK gene expression by nuclear factor kappaB ligand
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expression of cathepsin K is significantly increased (2.7-1.6fold) in the low-energy laser irradiated group on days 2-7 compared with those in the non-irradiated group
-
inhibiting calcineurin or chelation of intracellular Ca2+, prevents the stimulation of CTSK expression by nuclear factor kappaB ligand
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
it is shown that cathepsin K acts as a potent kinin-degrading enzyme in bloodstream. Contrary to cathepsin L, cathepsin K attenuates kallikrein-induced decrease of rat blood pressure, and reduces the hypotensive effect of bradykinin in a dose-dependant manner
medicine
-
the results suggest that cathepsin K plays an important role in the immune system and serves as a valid therapeutic target in autoimmune diseases
medicine
-
cathepsin K is a target for the pharmacological treatment of osteoporosis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Marquis, R.W.; Ru, Y.; LoCastro, S.M.; Zeng, J.; et al.
Azepanone-based Inhibitors of human and rat cathepsin K
J. Med. Chem.
44
1380-1395
2001
Homo sapiens, Rattus norvegicus
Katunuma, N.; Matsui, A.; Inubushi, T.; Murata, E.; Kakegawa, H.; Ohba, Y.; Turk, D.; Turk, V.; Tada, Y.; Asao, T.
Structure-based development of pyridoxal propionate derivatives as specific inhibitors of cathepsin K in vitro and in vivo
Biochem. Biophys. Res. Commun.
267
850-854
2000
Rattus norvegicus
Tavares, F.X.; Boncek, V.; Deaton, D.N.; Hassell, A.M.; Long, S.T.; Miller, A.B.; Payne, A.A.; Miller, L.R.; Shewchuk, L.M.; Wells-Knecht, K.; Willard, D.H., Jr.; Wright, L.L.; Zhou, H.Q.
Design of potent, selective, and orally bioavailable inhibitors of cysteine protease cathepsin k
J. Med. Chem.
47
588-599
2004
Homo sapiens, Rattus norvegicus
Lecaille, F.; Vandier, C.; Godat, E.; Herve-Grepinet, V.; Broemme, D.; Lalmanach, G.
Modulation of hypotensive effects of kinins by cathepsin K
Arch. Biochem. Biophys.
459
129-136
2007
Homo sapiens, Rattus norvegicus
Asagiri, M.; Hirai, T.; Kunigami, T.; Kamano, S.; Gober, H.J.; Okamoto, K.; Nishikawa, K.; Latz, E.; Golenbock, D.T.; Aoki, K.; Ohya, K.; Imai, Y.; Morishita, Y.; Miyazono, K.; Kato, S.; Saftig, P.; Takayanagi, H.
Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis
Science
319
624-627
2008
Mus musculus, Rattus norvegicus
Tsuchiya, M.; Akiba, Y.; Takahashi, I.; Sasano, Y.; Kashiwazaki, J.; Tsuchiya, S.; Watanabe, M.
Comparison of expression patterns of cathepsin K and MMP-9 in odontoclasts and osteoclasts in physiological root resorption in the rat molar
Arch. Histol. Cytol.
71
89-100
2008
Rattus norvegicus (O35186)
Gauthier, J.Y.; Chauret, N.; Cromlish, W.; Desmarais, S.; Duong, l.e..T.; Falgueyret, J.P.; Kimmel, D.B.; Lamontagne, S.; Leger, S.; LeRiche, T.; Li, C.S.; Masse, F.; McKay, D.J.; Nicoll-Griffith, D.A.; Oballa, R.M.; Palmer, J.T.; Percival, M.D.; Riendeau, D.; Robichaud, J.; Rodan, G.A.; Rodan, S.B.; Seto, C.
The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K
Bioorg. Med. Chem. Lett.
18
923-928
2008
Canis lupus familiaris, Oryctolagus cuniculus, Macaca fascicularis, Homo sapiens, Macaca mulatta, Rattus norvegicus
Boyd, M.J.; Crane, S.N.; Robichaud, J.; Scheigetz, J.; Black, W.C.; Chauret, N.; Wang, Q.; Masse, F.; Oballa, R.M.
Investigation of ketone warheads as alternatives to the nitrile for preparation of potent and selective cathepsin K inhibitors
Bioorg. Med. Chem. Lett.
19
675-679
2009
Oryctolagus cuniculus, Homo sapiens, Rattus norvegicus
Tada, S.; Tsutsumi, K.; Ishihara, H.; Suzuki, K.; Gohda, K.; Teno, N.
Species differences between human and rat in the substrate specificity of cathepsin K
J. Biochem.
144
499-506
2008
Rattus norvegicus (O35186), Homo sapiens (P43235), Homo sapiens
Teno, N.; Masuya, K.; Ehara, T.; Kosaka, T.; Miyake, T.; Irie, O.; Hitomi, Y.; Matsuura, N.; Umemura, I.; Iwasaki, G.; Fukaya, H.; Toriyama, K.; Uchiyama, N.; Nonomura, K.; Sugiyama, I.; Kometani, M.
Effect of cathepsin K inhibitors on bone resorption
J. Med. Chem.
51
5459-5462
2008
Homo sapiens, Rattus norvegicus
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, Rattus norvegicus
Veber, D.
Factors that influence oral bioavailability: a cathepsin K inhibitor for human studies
Adv. Exp. Med. Biol.
611
607-610
2009
Rattus norvegicus
Desmarais, S.; Masse, F.; Percival, M.D.
Pharmacological inhibitors to identify roles of cathepsin K in cell-based studies: a comparison of available tools
Biol. Chem.
390
941-948
2009
Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus
Yamaguchi, M.; Hayashi, M.; Fujita, S.; Yoshida, T.; Utsunomiya, T.; Yamamoto, H.; Kasai, K.
Low-energy laser irradiation facilitates the velocity of tooth movement and the expressions of matrix metalloproteinase-9, cathepsin K, and alpha(v) beta(3) integrin in rats
Eur. J. Orthod.
32
131-139
2010
Rattus norvegicus
Balkan, W.; Martinez, A.F.; Fernandez, I.; Rodriguez, M.A.; Pang, M.; Troen, B.R.
Identification of NFAT binding sites that mediate stimulation of cathepsin K promoter activity by RANK ligand
Gene
446
90-98
2009
Rattus norvegicus
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