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Information on EC 3.4.23.5 - cathepsin D and Organism(s) Mus musculus and UniProt Accession P10605
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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: Mus musculus
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
cathepsin D
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-GKPILFFRLK(Dnp)-RNH2 + H2O
(7-methoxycoumarin-4-yl)acetyl-GKPILF + FRLK(Dnp)-RNH2
-
-
-
-
?
additional information
?
-
-
the enzyme does not activate trypsinogen in vitro
-
-
?
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
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pepstatin A
-
blocking the activity of CTSD reduces ABCA1 expression and protein abundance in both macrophages and CHO cells and apolipoprotein A-I-mediated lipid efflux by more than 70%. Consistent with its role in the proteolytic processing of prosaposin, inactivation of CTSD function results in the accumulation of glycosphingolipid and free cholesterol in late endosomes/lysosomes. Inhibition of CTSD also causes retention of ABCA1 in lysosomal compartments, reducing its trafficking to the plasma membrane
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
DELTA9-tetrahydrocannabinol
-
at 10 nM, almost doubles enzyme activity in cell culture
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
cathepsin D immunoreactivity is also detected in extracellular compartments surrounded by trophoblast processes containing either cell debris or extracellular matrix components such as collagen fibrils
-
-
in manganese treated astrocyte, cathepsin D is distributed uniformly in the cytosol
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
-
cathepsin D plays a significant role in the removal of advanced glycation end product-modified proteins
physiological function
malfunction
-
murine cathepsin D deficiency is associated with dysmyelination/myelin disruption and accumulation of cholesteryl esters in the brain
malfunction
-
pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocks macrophage apoptosis. Inhibition of cathepsin D has no effect on early bacterial killing but inhibits the late phase of apoptosis-associated killing of pneumococci in vitro. Cathepsin deficient mice demonstrate reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. Cathepsin D enhances Mcl-1 ubiquitination
malfunction
-
enzyme deletion alters the severity of acute experimental pancreatitis
malfunction
-
enzyme inhibition leads to an improvement in kidney function, a reduction in apoptosis and a decrease in tubular cell damage in kidneys with nephrotoxic or ischemia reperfusion-induced acute kidney injury
malfunction
-
enzyme suppression has an inhibitory effect on cell apoptosis and the expression of proapoptotic proteins
malfunction
-
inhibition of enzyme activity dramatically improves lipid metabolism and diminishes hepatic inflammation in non-alcoholic steatohepatitis
physiological function
-
cathepsin D mediates a lysosomal pathway of macrophage apoptosis in pulmonary host defense against pneumococci
physiological function
-
the enzyme is a key player in the development of hepatic inflammation and dyslipidemia
physiological function
-
the enzyme is involved in the oxygen and glucose deprivation/reperfusion-induced apoptosis of astrocytes. Enzyme overexpression enhances cell apoptosis and the levels of apoptogenic proteins, including Bax and caspase-3
physiological function
-
the enzyme plays a role in apoptosis during acute kidney injury
physiological function
-
the enzyme regulates cathepsin B activation and disease severity predominantly in inflammatory cells during experimental pancreatitis
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). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 20000-60000, SDS-PAGE, epididymosomes possess many enzyme forms ranging from 20 to 60 kDa with the highest reactive intensity at the 26000 and 34000 Da bands
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
synthesized as a 53000 Da precursor protein and converted to the active 46000 da protease following transport through golgi compartments
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D293N
-
complete loss of activity, enzyme is unstable and proteolytically modified during early steps of secretory pathway resulting in loss of mass by 1 kDa, enzyme transport to the lysosome is delayed
additional information
additional information
-
mice deficient in enzyme show progressive atrophy of intestinal mucosa, a massive destruction of lymphoid organs, and a profound accumulation of ceroid lipofuscin
additional information
-
blocking the expression of CTSD by small interfering RNA reduces ABCA1 expression and protein abundance in macrophages and apolipoprotein A-I-mediated lipid efflux by more than 70%. Conversely, overexpression increases both ABCA1 mRNA expression and cellular ABCA1 protein
additional information
-
cathepsin deficient mice show a delayed caspase activation and reduced neutrophil apoptosis. Furthermore, cathepsin D deficiency prolongs innate immune responses in experimental bacterial infection and in septic shock
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is upregulated in damaged tubular cells in nephrotoxic and ischemia reperfusion induced acute kidney injury. Enzyme expression is increased during acute tubular necrosis in transplanted kidneys
-
manganese treatment causes significant increase of lysosomal enzyme cathepsin D
-
Streptomyces pneumonia (strain D39) triggers activation of cathepsin D in macrophages about 2fold
-
the enzyme expression is significantly upregulated in response to oxygen-glucose deprivation/reperfusion exposure
-
there is a positive relationship between the expression and presence of cathepsin D at the extracellular compartment of the maternal-fetal interface and the invasiveness of the trophoblast during the postimplantation period
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
enzyme contributes to antigen-dependent processing defect in DELTA9-tetrahydrocannabinol-exposed macrophages
medicine
-
mice deficient in enzyme show progressive atrophy of intestinal mucosa, a massive destruction of lymphoid organs, and a profound accumulation of ceroid lipofuscin
medicine
-
a new proapoptotic pathway is shown in which caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation
medicine
-
the results demonstrate an important role for CTSD in intracellular cholesterol trafficking and ABCA1-mediated efflux. Decreased CTSD expression may contribute to low plasma HDL-C levels
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Blum, J.S.; Fiani, M.L.; Stahl, P.D.
Localization of cathepsin D in endosomes: characterization and biological importance
Struct. Funct. Asp. Proteinases (Dunn, Ben M. ; ed. ) Plenum Press, New York
281-287
1991
Oryctolagus cuniculus, Mus musculus
Bowers, W.E.; Beyer, C.F.; Yago, N.
Cathepsin D of mouse leukemia L12010 cells. Unusual intracellular localization and biochemical properties
Biochim. Biophys. Acta
497
272-279
1977
Mus musculus
Partanen, S.; Storch, S.; Loeffler, H.G.; Hasilik, A.; Tyynelae, J.; Braulke, T.
A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells
Biochem. J.
369
55-62
2003
Mus musculus
Matveyeva, M.; Hartmann, C.B.; Harrison, M.T.; Cabral, G.A.; McCoy, K.L.
DELTA(9)-tetrahydrocannabinol selectively increases aspartyl cathepsin D proteolytic activity and impairs lysozyme processing by macrophages
Int. J. Immunopharmacol.
22
373-381
2000
Mus musculus
Tsukuba, T.; Okamoto, K.; Yasuda, Y.; Morikawa, W.; Nakanishi, H.; Yamamoto, K.
New functional aspects of cathepsin D and cathepsin E
Mol. Cells
10
601-611
2000
Homo sapiens, Mus musculus
Haidar, B.; Kiss, R.S.; Sarov-Blat, L.; Brunet, R.; Harder, C.; McPherson, R.; Marcel, Y.L.
Cathepsin D, a lysosomal protease, regulates ABCA1-mediated lipid efflux
J. Biol. Chem.
281
39971-39981
2006
Homo sapiens, Mus musculus
Conus, S.; Perozzo, R.; Reinheckel, T.; Peters, C.; Scapozza, L.; Yousefi, S.; Simon, H.U.
Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation
J. Exp. Med.
205
685-698
2008
Homo sapiens, Mus musculus
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)
Sevlever, D.; Jiang, P.; Yen, S.H.
Cathepsin D is the main lysosomal enzyme involved in the degradation of alpha-synuclein and generation of its carboxy-terminally truncated species
Biochemistry
47
9678-9687
2008
Homo sapiens (P07339), Mus musculus (P10605)
Qiao, L.; Hamamichi, S.; Caldwell, K.A.; Caldwell, G.A.; Yacoubian, T.A.; Wilson, S.; Xie, Z.L.; Speake, L.D.; Parks, R.; Crabtree, D.; Liang, Q.; Crimmins, S.; Schneider, L.; Uchiyama, Y.; Iwatsubo, T.; Zhou, Y.; Peng, L.; Lu, Y.; Standaert, D.G.; Walls, K.C.; Shacka, J.J.; Roth, K.A.; Zhang, J.
Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity
Mol. Brain
1
17
2008
Caenorhabditis elegans, Mus musculus (P18242), Mus musculus
Cullen, V.; Lindfors, M.; Ng, J.; Paetau, A.; Swinton, E.; Kolodziej, P.; Boston, H.; Saftig, P.; Woulfe, J.; Feany, M.B.; Myllykangas, L.; Schlossmacher, M.G.; Tyynelae, J.
Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo
Mol. Brain
2
5-5
2009
Mus musculus, Rodentia sp.
Mutka, A.L.; Haapanen, A.; Kaekelae, R.; Lindfors, M.; Wright, A.K.; Inkinen, T.; Hermansson, M.; Rokka, A.; Corthals, G.; Jauhiainen, M.; Gillingwater, T.H.; Ikonen, E.; Tyynelae, J.
Murine cathepsin D deficiency is associated with dysmyelination/myelin disruption and accumulation of cholesteryl esters in the brain
J. Neurochem.
112
193-203
2010
Mus musculus
Fan, X.; Luo, G.; Yang, D.; Ming, M.; Liu, H.; Pu, P.; Le, W.
Critical role of lysosome and its associated protein cathepsin D in manganese-induced toxicity in cultured midbrain astrocyte
Neurochem. Int.
56
291-300
2010
Mus musculus
Amarante-Paffaro, A.M.; Hoshida, M.S.; Yokota, S.; Goncalves, C.R.; Joazeiro, P.P.; Bevilacqua, E.; Yamada, A.T.
Localization of cathepsins D and B at the maternal-fetal interface and the invasiveness of the trophoblast during the postimplantation period in the mouse
Cells Tissues Organs
193
417-425
2011
Mus musculus
Grimm, S.; Ernst, L.; Groetzinger, N.; Hoehn, A.; Breusing, N.; Reinheckel, T.; Grune, T.
Cathepsin D is one of the major enzymes involved in intracellular degradation of AGE-modified proteins
Free Radic. Res.
44
1013-1026
2010
Mus musculus
Asuvapongpatana, S.; Saewu, A.; Chotwiwatthanakun, C.; Vanichviriyakit, R.; Weerachatyanukul, W.
Localization of cathepsin D in mouse reproductive tissues and its acquisition onto sperm surface during epididymal sperm maturation
Acta Histochem.
115
425-433
2013
Mus musculus
Liu, J.; Yang, L.; Tian, H.; Ma, Q.
Cathepsin D is involved in the oxygen and glucose deprivation/reperfusion-induced apoptosis of astrocytes
Int. J. Mol. Med.
38
1257-1263
2016
Mus musculus
Aghdassi, A.A.; John, D.S.; Sendler, M.; Weiss, F.U.; Reinheckel, T.; Mayerle, J.; Lerch, M.M.
Cathepsin D regulates cathepsin B activation and disease severity predominantly in inflammatory cells during experimental pancreatitis
J. Biol. Chem.
293
1018-1029
2018
Mus musculus
Cocchiaro, P.; Fox, C.; Tregidgo, N.W.; Howarth, R.; Wood, K.M.; Situmorang, G.R.; Pavone, L.M.; Sheerin, N.S.; Moles, A.
Lysosomal protease cathepsin D; a new driver of apoptosis during acute kidney injury
Sci. Rep.
6
27112
2016
Mus musculus
Houben, T.; Oligschlaeger, Y.; Hendrikx, T.; Bitorina, A.V.; Walenbergh, S.M.A.; van Gorp, P.J.; Gijbels, M.J.J.; Friedrichs, S.; Plat, J.; Schaap, F.G.; Luetjohann, D.; Hofker, M.H.; Shiri-Sverdlov, R.
Cathepsin D regulates lipid metabolism in murine steatohepatitis
Sci. Rep.
7
3494
2017
Mus musculus
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