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Information on EC 3.4.22.15 - cathepsin L and Organism(s) Rattus norvegicus and UniProt Accession P07154
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3.4.22.15 cathepsin LSpecify your search results
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- 3.4.22.15
- cathepsins
- lysosomal
- proteinases
- cystatins
- papain
- metastasis
- peptidase
- fasciola
- hepatica
-
fluorogenic
-
collagenolytic
- pepstatin
-
trematode
- tmprss2
-
metacercariae
-
stefins
- medicine
- endosomal
-
procathepsin
- kininogens
- endolysins
- pharmacology
-
papain-like
- fluke
-
b-like
- covid-19
- trypanosoma
- mers-cov
- leupeptin
- calpains
-
proregions
-
excysted
- azocasein
- prodomains
- osteoclast
- coronavirus
-
fasciolosis
- collagen
- cruzain
- drug development
-
excretory-secretory
- ace2
- heparanase
- legumain
- endopeptidases
- sars-cov-2
-
elastinolytic
- propeptide
- gigantica
- diagnostics
- proenzyme
-
helminth
- microplus
-
surimi
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
Reaction Schemes
similar to that of papain. As compared to cathepsin B, cathepsin L exhibits higher activity towards protein substrates, but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-dipeptidase activity
Synonyms
cathepsin l, cathepsin l-like, cathepsin-l, human cathepsin l, cpl-1, cat l, cwp84, cathl, major excreted protein, smcl1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Aldrichina grahami cysteine proteinase
-
-
-
-
major excreted protein
-
-
-
-
MEP
-
-
-
-
PDP
-
-
-
-
progesterone-dependent protein
-
-
-
-
SMCL1
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
60616-82-2
-
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
benzyloxycarbonyl-Arg-Arg-4-methylcoumarin 7-amide + H2O
?
-
weak activity
-
-
?
benzyloxycarbonyl-Lys-p-nitrophenyl ester + H2O
benzyloxycarbonyl-Lys + 4-nitrophenol
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-4-methylcoumarin 7-amide + H2O
?
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
N-acetyl-Phe-Arg-7-amido-4-trifluoromethylcoumarin + H2O
N-acetyl-Phe-Arg + 7-amino-4-trifluoromethylcoumarin
-
-
-
-
?
Nalpha-benzoyl-L-Arg 2-naphthylamide + H2O
Nalpha-benzoyl-L-Arg + 2-naphthylamine
-
-
-
-
?
Tyr-Gly-Gly-Phe-Leu-Arg-Arg + H2O
Tyr-Gly + Gly-Phe-Leu-Arg-Arg
-
-
-
?
Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile + H2O
Tyr-Gly + Gly-Phe-Leu-Arg-Arg-Ile
-
-
-
?
Tyr-Gly-Gly-Phe-Met-Arg-Gly-Leu + H2O
?
-
cleavage sites Gly-Gly and Met-Arg
-
-
?
Tyr-Gly-Gly-Phe-Met-Arg-Phe + H2O
?
-
cleavage sites: Gly-Gly and Met-Arg
-
-
?
Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2 + H2O
?
-
cleavage sites Gly-Gly and Met-Arg
-
-
?
Z-Phe-Arg-7-amido-4-methylcoumarin + H2O
Z-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
-
substrate for both cathepsin L and cathepsin B
-
-
?
Collagen + H2O
?
-
selective cleavage of terminal peptides leads to conversion of beta- and higher components mainly to alpha-chains
-
-
?
Collagen + H2O
?
-
conversion of cross-linked beta-chain dimers into uncross-linked alpha-chain monomers
-
-
?
Tyr-Gly-Gly-Phe-Met-Arg-Arg + H2O
Tyr-Gly + Gly-Phe-Met-Arg-Arg
-
-
-
?
additional information
?
-
-
the enzyme plays a most important role in intralysosomal proteolysis in hepatocytes
-
-
?
additional information
?
-
-
plays a crucial role in the pathogenesis of adjuvant arthritis
-
-
?
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
additional information
?
-
-
the enzyme plays a most important role in intralysosomal proteolysis in hepatocytes
-
-
?
additional information
?
-
-
plays a crucial role in the pathogenesis of adjuvant arthritis
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S,3S)-oxirane-2,3-dicarboxylic acid 2-[((S)-1-benzylcarbamoyl-2-phenyl-ethyl)-amide] 3-[[2-(4-hydroxy-phenyl)-ethyl]-amide]
-
i.e. CAA0225. IC50 value for rat liver cathepsin B above 1 microM
(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucine(3-methylbutyl)-amide
-
0.01 mg/ml
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
-
-
diazomethanes
-
irreversible inhibition of hydrolysis of leucine enkephalin
-
additional information
-
in vivo inhibitor from bovine skeletal muscle, purification, MW 30000 Da
-
trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane
-
i.e. E-64, in vivo, the inhibitor is transported to the liver cytosol in the free form in the blood and permeated into the lysosomes, where it binds to, and inactivates the enzyme
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
strong activation of hydrolysis of insulin or albumin, at pH 4.0 and at pH 5.5
cysteamine
-
strong activation of hydrolysis of insulin or albumin, at pH 4.0 and at pH 5.5
dithiothreitol
-
strong activation of hydrolysis of insulin or albumin, at pH 4.0 and at pH 5.5
glutathione
-
strong activation of hydrolysis of insulin or albumin, at pH 4.0 and at pH 5.5
Cys
-
strong activation of hydrolysis of insulin or albumin, at pH 4.0 and at pH 5.5
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000019
(2S,3S)-oxirane-2,3-dicarboxylic acid 2-[((S)-1-benzylcarbamoyl-2-phenyl-ethyl)-amide] 3-[[2-(4-hydroxy-phenyl)-ethyl]-amide]
Rattus norvegicus
-
-
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-amino-4-methylcumarin 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-amino-4-methylcumarin 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-amino-4-methylcumarin as substrate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3 - 7
-
pH 3.0: 40-50% of maximal activity, pH 7.0: 20-30% of maximal activity
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
cells originating from 15-day-old rats treated in utero with the anti-androgen flutamide do no longer protect adult germ cells against apoptosis. Untreated spermatocytes or spermatids exhibit increased active caspase-3 levels when co-cultured with Sertoli cells isolated from rat testes exposed in utero to the anti-androgen
additional information
-
the concentration of cathepsin L is highest in the kidney, where it is more than 3 times higher than in the liver, spleen, lungs and brain. Nervous tissues, especially the cerebellar cortex, also contains fairly high concentrations of cathepsin L, but the heart, skeletal muscle, and gastrointestinal tract contain low concentrations, as do peripheral blood cells. The enzyme content of the macrophages is 20% of that of cathepsin B. The concentration of cathepsin L in lymphocytes, neutrophils, and erythrocytes is 10%, 20% and less than 0.2% respectively, of those in resident macrophages
-
-
-
adult testes exposed in utero to anti-androgens display decreased levels of several genes mainly expressed in adult Sertoli cells such as anti-Mullerian hormone receptor type II, Cox-1, cyclin D2, cathepsin L, and GSTalpha
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
cathepsin L pharmacological inhibition significantly attenuates lysosomal membrane permeabilization, mitochondrial membrane permeabilization, and apoptosis
physiological function
-
cathepsin L plays a role in glutamate receptor-induced nuclear factor-kappa B activation and excitotoxicity in rat striatal neurons
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). CATL1_RAT
334
0
37660
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25000
30000
-
1 * 30000, the enzyme consists of a single chain form of 30000 Da and of a two-chain form, SDS-PAGE in presence of 2-mercaptoethanol
25000
-
1 * 25000 + 1 * 5000, the enzyme consists of a single chain form of 30000 Da and of a two-chain form, SDS-PAGE in presence of 2-mercaptoethanol
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
-
1 * 30000, the enzyme consists of a single chain form of 30000 Da and of a two-chain form, SDS-PAGE in presence of 2-mercaptoethanol
dimer
-
1 * 25000 + 1 * 5000, the enzyme consists of a single chain form of 30000 Da and of a two-chain form, SDS-PAGE in presence of 2-mercaptoethanol
dimer
-
1 * 22000-25000 + 1 * 5000-7000, SDS-PAGE under reducing conditions
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
side-chain modification
proteolytic modification
-
the enzyme is initially synthesized on membrane-bound polysomes as a 37500 Da prepropeptide. The cotranslational cleavage of the 1500 Da signal peptide and the core glycosylation convert the precursor to the 39000 Da proform, which is subsequently processed to the mature form during biosynthesis
proteolytic modification
-
the protein deduced from full-length DNA comprises 334 amino acid residues, containing a typical signal sequence, N-terminal 17 residues, propeptide 96 residues and the sequence of the mature cathepsin L 221 residues
side-chain modification
-
two potential N-glycosylation sites, Asn108 and Asn155, in the heavy chain
side-chain modification
-
precursor and mature enzyme are N-glycosylated with high-mannose-type oligosaccharides
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
increased immunoreactivities of cathepsin L is seen in the impaired substantia nigra after 12 h 0.008 mg 6-hydroxydopamine treatment
-
pretreatment of rats or primary DA neurons with 200 nM olomoucine results in a partial blockade of nuclear translocation of cathepsin L after 12 h 0.008 mg 6-hydroxydopamine exposure
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Towatari, T.; Katunuma, N.
Amino acid sequence of rat liver cathepsin L
FEBS Lett.
236
57-61
1988
Rattus norvegicus
Nishimura, Y.; Furuno, K.; Kato, K.
Biosynthesis and processing of lysosomal cathepsin L in primary cultures of rat hepatocytes
Arch. Biochem. Biophys.
263
107-116
1988
Rattus norvegicus
Kirschke, H.; Wikstrom, P.; Shaw, E.
Active center differences between cathepsins L and B: the S1 binding region
FEBS Lett.
228
128-130
1988
Rattus norvegicus
Hiwasa, T.; Sakiyama, S.; Yokoyama, S.; Ha, J.M.; Fujita, J.; Noguchi, S.; Bando, Y.; Kominami, E.; Katunuma, N.
Inhibition of cathepsin L-induced degradation of epidermal growth factor receptors by c-Ha-ras gene products
Biochem. Biophys. Res. Commun.
151
78-85
1988
Rattus norvegicus
Ishidoh, K.; Towatari, T.; Imajoh, S.; Kawasaki, H.; Kominami, E.; Katunuma, N.; Suzuki, K.
Molecular cloning and sequencing of cDNA for rat cathepsin L
FEBS Lett.
223
69-73
1987
Rattus norvegicus
Marks, N.; Berg, M.J.
Rat brain cathepsin L: characterization and differentiation from cathepsin B utilizing opioid peptides
Arch. Biochem. Biophys.
259
131-143
1987
Rattus norvegicus
Mason, R.W.
Species variants of cathepsin L and their immunological identification
Biochem. J.
240
285-288
1986
Bos taurus, Oryctolagus cuniculus, Ovis aries, Homo sapiens, Rattus norvegicus
Bando, Y.; Kominami, E.; Katunuma, N.
Purification and tissue distribution of rat cathepsin L
J. Biochem.
100
35-42
1986
Rattus norvegicus
Recklies, A.D.; Mort, J.S.
Rat mammary gland in culture secretes a stable high molecular weight form of cathepsin L
Biochem. Biophys. Res. Commun.
131
402-407
1985
Rattus norvegicus
Berri, M.; Rouchon, P.; Zabari, M.; Quali, A.
Purification and characterization of a new potential in vivo inhibitor of cathepsin L from bovine skeletal muscle
Comp. Biochem. Physiol. B
119
283-288
1998
Rattus norvegicus
Kooistra, T.; Millard, P.C.; Lloyd, J.B.
Role of thiols in degradation of proteins by cathepsins
Biochem. J.
204
471-477
1982
Rattus norvegicus
Kirschke, H.; Kembhavi, A.A.; Bohley, P.; Barrett, A.J.
Action of rat liver cathepsin L on collagen and other substrates
Biochem. J.
201
376-372
1982
Rattus norvegicus
-
Aranishi, F.; Ogata, H.; Hara, K.; Osatomi, K.; Ishihara, T.M.
Purification and characterization of cathepsin L from hepatopancreas of carp Cyprinus carpio
Comp. Biochem. Physiol. B
118
531-537
1997
Cyprinus carpio, Rattus norvegicus
Hashida, S.; Kominami, E.; Katunuma, N.
Inhibitions of cathepsin B and cathepsin L by E-64 in vivo. II. Incorporation of [3H]E-64 into rat liver lysosomes in vivo
J. Biochem.
91
1373-1380
1982
Rattus norvegicus
Kirschke, H.; Langner, J.; Wiederanders, B.; Ansorge, S.; Bohley, P.
Cathepsin L. A new proteinase from rat-liver lysosomes
Eur. J. Biochem.
74
293-301
1977
Rattus norvegicus
Katunuma, N.; Kominami, E.
Lysosomal sequestration of cytosolic enzymes and lysosomal thiol cathepsins
Adv. Enzyme Regul.
23
159-168
1985
Rattus norvegicus
Reddy, C.K.; Dhar, S.C.
Purification and characterization of collagenolytic property of renal cathepsin L from arthritic rat
Int. J. Biochem.
24
1465-1473
1992
Rattus norvegicus
Hiwasa, T.; Yokoyama, S.; Ha, J.M.; Noguchi, S.; Sakiyama, S.
c-Ha-ras gene products are potent inhibitors of cathepsin B and L
FEBS Lett.
211
23-26
1987
Rattus norvegicus
Anagli, J.; Abounit, K.; Stemmer, P.; Han, Y.; Allred, L.; Weinsheimer, S.; Movsisyan, A.; Seyfried, D.
Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain
Biochem. Biophys. Res. Commun.
366
86-91
2008
Rattus norvegicus (P07154)
Ohshita, T.; Hiroi, Y.
Cathepsin L plays an important role in the lysosomal degradation of L-lactate dehydrogenase
Biosci. Biotechnol. Biochem.
70
2254-2261
2006
Rattus norvegicus
Takahashi, K.; Ueno, T.; Tanida, I.; Minematsu-Ikeguchi, N.; Murata, M.; Kominami, E.
Characterization of CAA0225, a novel inhibitor specific for cathepsin L, as a probe for autophagic proteolysis
Biol. Pharm. Bull.
32
475-479
2009
Homo sapiens, Rattus norvegicus
Benbrahim-Tallaa, L.; Siddeek, B.; Bozec, A.; Tronchon, V.; Florin, A.; Friry, C.; Tabone, E.; Mauduit, C.; Benahmed, M.
Alterations of Sertoli cell activity in the long-term testicular germ cell death process induced by fetal androgen disruption
J. Endocrinol.
196
21-31
2008
Rattus norvegicus
Ito, H.; Watanabe, M.; Kim, Y.T.; Takahashi, K.
Inhibition of rat liver cathepsins B and L by the peptide aldehyde benzyloxycarbonyl-leucyl-leucyl-leucinal and its analogues
J. Enzyme Inhib. Med. Chem.
24
279-286
2009
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
Visone, T.; Charron, M.; Wright, W.W.
Activation and repression domains within the promoter of the rat cathepsin L gene orchestrate sertoli cell-specific and stage-specific gene transcription in transgenic mice
Biol. Reprod.
81
571-579
2009
Rattus norvegicus
Fei, X.F.; Qin, Z.H.; Xiang, B.; Li, L.Y.; Han, F.; Fukunaga, K.; Liang, Z.Q.
Olomoucine inhibits cathepsin L nuclear translocation, activates autophagy and attenuates toxicity of 6-hydroxydopamine
Brain Res.
1264
85-97
2009
Rattus norvegicus
Almaguel, F.G.; Liu, J.W.; Pacheco, F.J.; De Leon, D.; Casiano, C.A.; De Leon, M.
Lipotoxicity-mediated cell dysfunction and death involve lysosomal membrane permeabilization and cathepsin L activity
Brain Res.
1318
133-143
2010
Rattus norvegicus
Yoshii, H.; Kamiyama, H.; Minematsu, K.; Goto, K.; Mizota, T.; Oishi, K.; Katunuma, N.; Yamamoto, N.; Kubo, Y.
Cathepsin L is required for ecotropic murine leukemia virus infection in NIH3T3 cells
Virology
394
227-234
2009
Homo sapiens, Mus musculus, Rattus norvegicus
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