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Information on EC 3.4.23.5 - cathepsin D and Organism(s) Rattus norvegicus and UniProt Accession P24268
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3.4.23.5 cathepsin DSpecify your search results
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- 3.4.23.5
- lysosomal
- pepstatin
- estrogen
- metastasis
- alzheimer
- proteinases
-
aspartyl
- node
- vacuole
- lymph
- renin
- pepsin
- endosomes
- progesterone
- hydrolases
-
endocytic
-
phagosomes
-
amyloid
- beta-glucuronidase
- plasminogen
- mannose
- 6-phosphate
-
axillary
-
autophagosomes
-
saposins
-
lysosomal-associated
- leupeptin
-
plasmepsins
- beta-hexosaminidase
-
missorting
- mannose-6-phosphate
- chymosin
-
lysotracker
- lipofuscinosis
-
lc3-ii
-
autophagy-lysosomal
- rab7
-
ceroid
-
estrogen-regulated
-
immunoradiometric
- medicine
- lc3
- lamp-1
-
node-negative
-
trans-golgi
- upa
-
endocytosed
-
node-positive
-
c-erbb-2
-
autolysosomes
-
cation-independent
- molecular biology
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
Specificity similar to, but narrower than, that of pepsin A. Does not cleave the Gln4-His bond in B chain of insulin
Synonyms
cathepsin d, cath-d, cath d, cat d, cathd, pro-cathepsin d, cat-d, pro-cathepsin, cad 1, cad 2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CAS REGISTRY NUMBER
COMMENTARY
9025-26-7
-
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
(7-methoxycoumarin-4-yl)acetyl-Gly-Lys-Pro-Ile-Ile-Phe-Phe-Arg-Leu-Lys(Dnp)-D-Arg-NH2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Pro-Ala-Phe-Leu-Ala-Lys(Dnp)-D-Arg-NH2 + H2O
?
-
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Ser-Ala-Phe-Leu-Ala-Phe-Lys(Dnp)-D-Arg-NH2 + H2O
?
-
-
-
-
?
2-aminobenzoyl-ANKFFSRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-ANKF + FSRQ-N-(2,4-dinitrophenyl)ethylenediamine
-
-
-
-
?
AMCA-Glu-Glu-L-Lys-L-Pro-L-Ile-L-Ser-L-Phe-L-Phe-L-Arg-L-Leu-Gly-L-Lys(biotinyl)-NH2 + H2O
AMCA-Glu-Glu-L-Lys-L-Pro-L-Ile-L-Ser-L-Phe + L-Phe-L-Arg-L-Leu-Gly-L-Lys(biotinyl)-NH2
-
-
-
-
?
benzoyl-L-Arg-Gly-L-Phe-L-Phe-L-Leu-4-methoxy-2-naphthylamide + H2O
?
-
-
-
-
?
benzoyl-L-Arg-L-Pro-L-Phe-L-Phe-L-Leu-4-methoxy-2-naphthylamide + H2O
?
-
-
-
-
?
benzyloxycarbonyl-L-Pro-L-Phe-L-His-L-Leu-L-Leu-L-Val-L-Tyr-L-Ser-2-naphthylamide + H2O
?
-
-
-
-
?
D-Phe-L-Ser-L-Phe-L-Phe-L-Ala-L-Ala-4-aminobenzoate + H2O
D-Phe-L-Ser-L-Phe + L-Phe-L-Ala-L-Ala-4-aminobenzoate
-
-
-
-
?
Gly-L-Phe-L-Leu-Gly-D-Phe-L-Leu + H2O
Gly-L-Phe-L-Leu-Gly + D-Phe-L-Leu
-
3.0% cleavage
-
-
?
Gly-L-Phe-L-Leu-Gly-L-Phe-D-Leu + H2O
Gly-L-Phe-L-Leu-Gly + L-Phe-D-Leu
-
6.0% cleavage
-
-
?
Gly-L-Phe-L-Leu-Gly-L-Phe-L-Leu + H2O
Gly-L-Phe-L-Leu-Gly + L-Phe-L-Leu
-
100% cleavage
-
-
?
L-Asp-L-Arg-L-Val-L-Tyr-L-Ile-L-His-L-Pro-L-Phe-L-His-L-Leu-L-Leu-L-Val-L-Tyr-L-Ser-OH + H2O
?
-
-
-
-
?
L-Asp-L-Arg-L-Val-L-Tyr-L-Ile-L-His-L-Pro-L-Phe-L-His-L-Leu-L-Val-L-Ile-L-His-OH + H2O
?
-
-
-
-
?
L-Asp-L-Val-L-Arg-L-Tyr-L-Ile-L-His-L-Pro-L-Phe-L-His-L-Leu-L-Leu-L-Val-L-Tyr-L-Ser-OH + H2O
?
-
-
-
-
?
L-Phe-L-Ala-L-Ala-L-Phe(NO2)-L-Phe-L-Val-L-Leu-4-hydroxymethyl(pyridine) + H2O
L-Phe-L-Ala-L-Ala-L-Phe(NO2) + L-Phe-L-Val-L-Leu-4-hydroxymethyl(pyridine)
-
-
-
-
?
Lys-Pro-Ile-Glu-Phe-(4-nitro)Phe-Arg-Leu + H2O
Lys-Pro-Ile-Glu-Phe + (4-nitro)Phe-Arg-Leu
-
-
-
-
?
additional information
?
-
-
at the P1 site the enzyme prefers hydrophobic residues except Ile and Val, that are branched at the beta-carbon. Strong and weak hydrophobicities are required at P1' and P2 sites, respectively. A lower potency for beta-turn formation is essential for the sequence around the P1 site
-
-
?
additional information
?
-
-
enzyme catalyzes angiotensin I generation
-
-
?
additional information
?
-
-
the enzyme can be mainly responsible for the rapid degradation of macrophage proteins observed in protein deficient rats
-
-
?
additional information
?
-
-
does not cleave gamma-globulin and fibrinogen
-
-
?
additional information
?
-
-
does not cleave Gly-D-Phe-L-Leu-Gly-L-Phe-L-Leu, Gly-D-Phe-L-Leu-Gly-D-Phe-L-Leu, and cyclic Gly-L-Phe-L-Leu-Gly-L-Phe-L-Leu
-
-
?
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 can be mainly responsible for the rapid degradation of macrophage proteins observed in protein deficient rats
-
-
?
additional information
?
-
-
does not cleave gamma-globulin and fibrinogen
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
H-261
-
i.e. L-His-L-His-L-Pro-L-Phe-L-His-(2S,4S,5S)-5-amino-4-hydroxy-7-methyl-2-(1-methylethyl)octanoyl-L-Ile
pepstatin A
-
pretreatment inhibits apoptosis in cells exposed to naphthazarin (5,8-dihydroxy-1,4-naphthoquinone)
additional information
-
cathepsin D has neither endogenous lysosomal nor cytosolic inhibitors
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0037
(7-methoxycoumarin-4-yl)acetyl-Gly-Lys-Pro-Ile-Ile-Phe-Phe-Arg-Leu-Lys(Dnp)-D-Arg-NH2
-
40°C, pH 4.0, gastric cathepsin D
0.0022 - 0.00265
(7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Pro-Ala-Phe-Leu-Ala-Lys(Dnp)-D-Arg-NH2
0.00212
(7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Ser-Ala-Phe-Leu-Ala-Phe-Lys(Dnp)-D-Arg-NH2
-
40°C, pH 4.0, gastric cathepsin D
0.0022
(7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Pro-Ala-Phe-Leu-Ala-Lys(Dnp)-D-Arg-NH2
-
40°C, pH 4.0, spleen cathepsin D
0.00265
(7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Pro-Ala-Phe-Leu-Ala-Lys(Dnp)-D-Arg-NH2
-
40°C, pH 4.0, gastric cathepsin D
0.05
Lys-Pro-Ile-Glu-Phe-(4-nitro)Phe-Arg-Leu
-
enzyme from AH-130 hepatoma cells
0.07
Lys-Pro-Ile-Glu-Phe-(4-nitro)Phe-Arg-Leu
-
enzyme from liver of AH-130 hepatoma-bearing rats
0.015
Pro-Pro-Thr-Ile-Phe-(4-nitro)Phe-Arg-Leu
-
enzyme from liver of AH-130 hepatoma-bearing rats
0.04
Pro-Pro-Thr-Ile-Phe-(4-nitro)Phe-Arg-Leu
-
enzyme from cells from AH-130 hepatoma
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
59.6
(7-methoxycoumarin-4-yl)acetyl-Gly-Lys-Pro-Ile-Ile-Phe-Phe-Arg-Leu-Lys(Dnp)-D-Arg-NH2
-
40°C, pH 4.0, gastric cathepsin D
0.75
(7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Ser-Ala-Phe-Leu-Ala-Phe-Lys(Dnp)-D-Arg-NH2
-
40°C, pH 4.0, gastric cathepsin D
2.2
(7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Pro-Ala-Phe-Leu-Ala-Lys(Dnp)-D-Arg-NH2
-
40°C, pH 4.0, spleen cathepsin D
2.5
(7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Pro-Ala-Phe-Leu-Ala-Lys(Dnp)-D-Arg-NH2
-
40°C, pH 4.0, gastric cathepsin D
50
Lys-Pro-Ile-Glu-Phe-(4-nitro)Phe-Arg-Leu
-
enzyme from liver of AH-130 hepatoma-bearing rats
65
Lys-Pro-Ile-Glu-Phe-(4-nitro)Phe-Arg-Leu
-
enzyme from AH-130 hepatoma cells
25
Pro-Pro-Thr-Ile-Phe-(4-nitro)Phe-Arg-Leu
-
enzyme from liver of AH-130 hepatoma-bearing rats
95
Pro-Pro-Thr-Ile-Phe-(4-nitro)Phe-Arg-Leu
-
enzyme from AH-130 hepatoma cells
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0000027
pepstatin A
-
40°C, pH 4.0, gastric cathepsin D, hydrolysis of (7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Pro-Ala-Phe-Leu-Ala-Lys(Dnp)-D-Arg-NH2
0.0000031
pepstatin A
-
40°C, pH 4.0, spleen cathepsin D, hydrolysis of (7-methoxycoumarin-4-yl)acetyl-Gly-Ser-Pro-Ala-Phe-Leu-Ala-Lys(Dnp)-D-Arg-NH2
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00001
pepstatin A
Rattus norvegicus
-
IC50 less than 0.00001 mM, pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3
-
complexification of hemoglobin with haptoglobin reduces the optimum pH from 3.0 to 2.8 for degradation and simultaneously causes a 50% decrease in degradation rate 50%
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3 - 5
-
at pH 3.0: about 25% of maximum activity, at pH 5.0: about 45% of maximum activity, beta-endorphin hydrolysis
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 50
-
at 20°C: about 70% of maximum activity, at 50°C: about 30% of maximum activity
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
procathepsin D is transported from cisterns of the rough endoplasmic reticulum to the Golgi apparatus
-
cathepsin D is synthesized in the rough endoplasmic reticulum as preprocathepsin D
-
cathepsin D is translocated from lysosomes to cytosol under apoptosis-inducing conditions like oxidative stress caused by 0.15 mM tert-butyl hydroperoxide and proteasome inhibition by 0.1 mM lactacystin
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
cathepsin D is the primary protease for the generation of adenohypophyseal vasoinhibins
physiological function
-
the presence of cathepsin D in the cytosol affects the inhibitory potency of stefin B, thus preventing the regulation of cysteine cathepsin activities in various biological processes
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). CATD_RAT
407
0
44681
Swiss-Prot
Secretory Pathway (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40000 - 50000
-
by cathepsin D-immunoblotting, major bands of 40000 to 50000 Da molecular weight are observed
44000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
side-chain modification
-
cathepsin D-I: neutral sugar content 6%, contains mannose, glucose, galactose, fucose and glucosamine in a ratio of 8:2:1:1:5
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
2.5 - 8
-
completely stable at pH 4.5-5.5, 90% loss of activity at pH 2.5, about 40% loss of activity at pH 3.0, about 5% loss of activity at pH 3.5-4.0, about 10% loss of activity at pH 6.0, about 30% loss of activity at pH 7.0, about 50% loss of activity at pH 7.5, about 80% loss of activity at pH 8.0
712050
3.8
-
10 min, 60°C, loss of a large portion of activity of enzyme form cathepsin D-I and cathepsin D-II
36948
7
-
10 min, 60°C, loss of a large portion of activity of enzyme form cathepsin D-I and cathepsin D-II
36948
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 65
-
completely stable between 20 and 40°C, thereafter activity decreases continuously, 20% loss of activity at 50°C, 80% loss of activity at 60°C, complete inactivation at 65°C
60
-
10 min, pH 3.8 or pH 7.0, loss of a large portion of activity of enzyme form cathepsin D-I and cathepsin D-II
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
affinity purification, 2 enzyme forms, the major form is termed cathepsin D-1, the minor form is termed cathepsin D-II
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme expression is not influenced by the lysosomotropic agent Leu-Leu-OMe
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
inhibitors CEL5-A, CEL5-G, EA-1, block production of known precursors to neurofibrillary tangles in hippocampal slices, link of enzyme lysosomal disfunction to the etiology of Alzheimers disease
medicine
-
pretreatment with pepstatin A inhibits apoptosis in cells exposed to naphthazarin (5,8-dihydroxy-1,4-naphthoquinone), naphthazarin releases enzyme from lysosomes to cytosol, later, enzyme reappears in granules of increased size, and activity is restored
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bonelli, G.; Kay, J.; Tessitore, L.; Jupp, R.A.; Isidoro, C.; Norey, C.G.; Autelli, R.; Richards, A.D.; Baccino, F.M.
Purification and properties of cathepsin D from rat Yoshida ascites hepatoma AH-130
Biol. Chem. Hoppe-Seyler
369
323-327
1988
Rattus norvegicus
Sakamoto, W.; Satoh, F.; Nagasawa, S.; Handa, H.
Identification of T-kinin-Leu (T-kinin-containing peptide) released from T-kininogen by cathepsin D of granulomatous tissues in rats
Biochem. Biophys. Res. Commun.
150
1199-1206
1988
Rattus norvegicus
Imoto, T.; Okazaki, K.; Koga, H.; Yamada, H.
Specificity of rat liver cathepsin D
J. Biochem.
101
575-580
1987
Rattus norvegicus
Machaiah, S.S.J.P.; Nair, P.M.
Activation of protease activity in rat peritoneal macrophages in protein deficiency: characterization of cathepsin D
Indian J. Exp. Biol.
34
641-646
1996
Rattus norvegicus
Barrett, A.J.
Cathepsin D and other carboxyl proteinases
Proteinases in Mammalian Cells and Tissues (Barrett, A. J. , ed. )
2
209-248
1977
Bos taurus, Gallus gallus, Oryctolagus cuniculus, Homo sapiens, Rattus norvegicus, Sus scrofa
-
Figueiredo, A.F.S.; Takii, Y.; Tsuji, H.; Kato, K.; Inagami, T.
Rat kidney renin and cathepsin D: purification and comparison of properties
Biochemistry
22
5476-5481
1983
Rattus norvegicus
Yamamoto, K.; Katsuda, N.; Himeno, M.; Kato, K.
Cathepsin D of rat spleen. Affinity purification and properties of two types of cathepsin D
Eur. J. Biochem.
95
459-467
1979
Rattus norvegicus
Ollinger, K.
Inhibition of cathepsin D prevents free-radical-induced apoptosis in rat cardiomyocytes
Arch. Biochem. Biophys.
373
346-351
2000
Rattus norvegicus
Bi, X.; Haque, T.S.; Zhou, J.; Skillman, A.G.; Lin, B.; Lee, C.E.; Kuntz, I.D.; Ellman, J.A.; Lynch, G.
Novel cathepsin D inhibitors block the formation of hyperphosphorylated tau fragments in hippocampus
J. Neurochem.
74
1469-1477
2000
Rattus norvegicus
Yasuda, Y.; Kohmura, K.; Kadowaki, T.; Tsukuba, T.; Yamamoto, K.
A new selective substrate for cathepsin E based on the cleavage site sequence of alpha2-macroglobulin
Biol. Chem.
386
299-305
2005
Rattus norvegicus
Zaragoza, R.; Torres, L.; Garcia, C.; Eroles, P.; Corrales, F.; Bosch, A.; Lluch, A.; Garcia-Trevijano, E.R.; Vina, J.R.
Nitration of cathepsin D enhances its proteolytic activity during mammary gland remodelling after lactation
Biochem. J.
419
279-288
2009
Mus musculus, Rattus norvegicus (P24268)
Castino, R.; Delpal, S.; Bouguyon, E.; Demoz, M.; Isidoro, C.; Ollivier-Bousquet, M.
Prolactin promotes the secretion of active cathepsin D at the basal side of rat mammary acini
Endocrinology
149
4095-4105
2008
Rattus norvegicus (P24268)
Moon, C.; Lee, T.K.; Kim, H.; Ahn, M.; Lee, Y.; Kim, M.D.; Sim, K.B.; Shin, T.
Immunohistochemical study of cathepsin D in the spinal cords of rats with clip compression injury
J. Vet. Med. Sci.
70
937-941
2008
Rattus norvegicus
Miura, Y.; Sakurai, Y.; Hayakawa, M.; Shimada, Y.; Zempel, H.; Sato, Y.; Hisanaga, S.; Endo, T.
Translocation of lysosomal cathepsin D caused by oxidative stress or proteasome inhibition in primary cultured neurons and astrocytes
Biol. Pharm. Bull.
33
22-28
2010
Rattus norvegicus
Cruz-Soto, M.E.; Cosio, G.; Jeziorski, M.C.; Vargas-Barroso, V.; Aguilar, M.B.; Carabez, A.; Berger, P.; Saftig, P.; Arnold, E.; Thebault, S.; Martinez de la Escalera, G.; Clapp, C.
Cathepsin D is the primary protease for the generation of adenohypophyseal vasoinhibins: cleavage occurs within the prolactin secretory granules
Endocrinology
150
5446-5454
2009
Rattus norvegicus
Minarowska, A.; Karwowska, A.; Gacko, M.
Quantitative determination and localization of cathepsin D and its inhibitors
Folia Histochem. Cytobiol.
47
153-177
2009
Rattus norvegicus
Chida, K.; Taguchi, M.
Localization of alkaline phosphatase and cathepsin D during cell restoration after colchicine treatment in primary cultures of fetal rat hepatocytes
Acta Histochem. Cytochem.
44
155-158
2011
Rattus norvegicus
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