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Information on EC 1.1.1.184 - carbonyl reductase (NADPH) and Organism(s) Mus musculus and UniProt Accession P48758

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EC Tree
IUBMB Comments
Acts on a wide range of carbonyl compounds, including quinones, aromatic aldehydes, ketoaldehydes, daunorubicin and prostaglandins E and F, reducing them to the corresponding alcohol. Si-specific with respect to NADPH [cf. EC 1.1.1.2 alcohol dehydrogenase (NADP+)].
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This record set is specific for:
Mus musculus
UNIPROT: P48758
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Word Map
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Synonyms
ketoreductase, carbonyl reductase 1, aldehyde reductase i, nadph-dependent carbonyl reductase, carbonyl reductase 3, hcbr1, tetrameric carbonyl reductase, tm1743, prostaglandin 9-ketoreductase, chcr3, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carbonyl reductase 1
-
15-hydroxyprostaglandin dehydrogenase [NADP+]
-
-
-
-
Adipocyte P27 protein
-
-
-
-
aldehyde reductase 1
-
-
-
-
aldehyde reductase I
-
-
-
-
ALR3
-
-
-
-
AP27
-
-
-
-
carbonyl reductase
-
-
-
-
carbonyl reductase (NADPH)
-
-
-
-
carbonyl reductase 3
-
LCR
-
-
-
-
NADPH-carbonyl reductase
-
-
-
-
NADPH-dependent carbonyl reductase
-
-
-
-
nonspecific NADPH-dependent carbonyl reductase
-
-
-
-
prostaglandin 9-ketoreductase
-
-
-
-
Prostaglandin-E2 9-reductase
-
-
-
-
reductase, carbonyl
-
-
-
-
xenobiotic ketone reductase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
secondary-alcohol:NADP+ oxidoreductase
Acts on a wide range of carbonyl compounds, including quinones, aromatic aldehydes, ketoaldehydes, daunorubicin and prostaglandins E and F, reducing them to the corresponding alcohol. Si-specific with respect to NADPH [cf. EC 1.1.1.2 alcohol dehydrogenase (NADP+)].
CAS REGISTRY NUMBER
COMMENTARY hide
77106-95-7
-
89700-36-7
-
89700-37-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
cortisol + NADPH + H+
20beta-dihydrocortisol + NADP+
show the reaction diagram
-
-
-
?
doxorubicin + NADPH + H+
doxorubicinol + NADP+
show the reaction diagram
-
-
-
?
cyclohex-2-en-1-ol + NADPH
cyclohex-2-en-1-one + NADP+
show the reaction diagram
-
-
-
-
?
doxorubicin + NADPH + H+
doxorubicinol + NADP+
show the reaction diagram
-
-
-
?
pyridine-3-aldehyde + NADPH
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
cortisol + NADPH + H+
20beta-dihydrocortisol + NADP+
show the reaction diagram
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
-
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
quercetin
-
2-mercaptoethanol
-
-
dithiothreitol
-
-
FeSO4
-
-
Isobutyramide
-
-
pyrazole
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.13
doxorubicin
isoform Cbr1, at pH 7.0 and 37°C
0.099
NADPH
isoform Cbr1, at pH 7.0 and 37°C
0.041
doxorubicin
isoform Cbr3, at pH 7.0 and 37°C
0.074
NADPH
isoform Cbr3, at pH 7.0 and 37°C
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.015
doxorubicin
isoform Cbr1, at pH 7.0 and 37°C
0.036
NADPH
isoform Cbr1, at pH 7.0 and 37°C
0.0014
doxorubicin
isoform Cbr3, at pH 7.0 and 37°C
0.0001
NADPH
isoform Cbr3, at pH 7.0 and 37°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.12
doxorubicin
isoform Cbr1, at pH 7.0 and 37°C
0.36
NADPH
isoform Cbr1, at pH 7.0 and 37°C
0.035
doxorubicin
isoform Cbr3, at pH 7.0 and 37°C
0.0013
NADPH
isoform Cbr3, at pH 7.0 and 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 6
-
NADH + 4-nitroacetophenone
5.2
-
NADPH + 4-nitroacetophenone
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
-
overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
pharmacological inhibition of carbonyl reductase 1 in diet-induced obesity in mice results in more marked glucose intolerance with evidence for enhanced hepatic glucocorticoid receptor signaling
metabolism
carbonyl reductase 1 generating 20beta-dihydrocortisol is a pathway modulating glucocorticoid receptor activation and providing enzymatic protection against excessive GR activation in obesity
physiological function
CBR1 is upregulated at the transcript level during cell differentiation. CBR1 expression is increased during skeletal muscle regeneration in tibialis anterior muscle after injury induced by cardiotoxin. Intracellular reactice levels and lipid peroxidation are increased incells transfected with CBR1 siRNA
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CBR1_MOUSE
277
0
30641
Swiss-Prot
Mitochondrion (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23000
-
4 * 23000, mouse, SDS-PAGE
90000
-
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
tetramer
-
4 * 23000, mouse, SDS-PAGE
additional information
-
overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
TALON metal affinity resin column chromatography
TALON metal affinity resin column chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21 cells
expressed in Escherichia coli BL21 cells
mutation leads to change in coenzyme specificity
-
overview
-
site directed mutagenesis
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
CBR1 is upregulated at the transcript level during cell differentiation. CBR1 expression is increased during skeletal muscle regeneration in tibialis anterior muscle after injury induced by cardiotoxin. The transcriptional upregulation of CBR1 is controlled by nuclear factor erythroid 2-related factor 2 (Nrf2), and Nrf2 knockdown with specific siRNA inhibits muscle differentiation
the enzyme is up-regulated in adipose tissue in obesity
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Nakayama, T.; Yashiro, K.; Inoue, Y.; Matsuura, K.; Ichikawa, H.; Hara, A.; Sawada, H.
Characterization of pulmonary carbonyl reductase of mouse and guinea pig
Biochim. Biophys. Acta
882
220-227
1986
Cavia porcellus, Mus musculus
Manually annotated by BRENDA team
Nakanishi, M.; Matsuura, K.; Kaibe, H.; Tanaka, N.; Nonaka, T.; Mitsui, Y.; Hara, A.
Switch of coenzyme specificity of mouse lung carbonyl reductase by substitution of threonine 38 with aspartic acid
J. Biol. Chem.
272
2218-2222
1997
Mus musculus
Manually annotated by BRENDA team
Nakanishi, M.; Kakumoto, M.; Matsuura, K.; Deyashiki, Y.; Tanaka, N.; Nonaka, T.; Mitsui, Y.; Hara, A.
Involvement of two basic residues (Lys-17 and Arg-39) of mouse lung carbonyl reductase in NADP(H)-binding and fatty acid activation: site-directed mutagenesis and kinetic analyses
J. Biochem.
120
257-263
1996
Mus musculus
Manually annotated by BRENDA team
Forrest, G.L.; Gonzalez, B.
Carbonyl reductase
Chem. Biol. Interact.
129
21-40
2000
Cavia porcellus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Tanaka, N.; Nonaka, T.; Nakanishi, M.; Deyashiki, Y.; Hara, A.
Crystallization of mouse lung carbonyl reductase complexed with NADPH and analysis of symmetry of its tetrameric molecule
J. Biochem.
118
871-873
1995
Mus musculus
Manually annotated by BRENDA team
Lim, S.; Shin, J.Y.; Jo, A.; Jyothi, K.R.; Nguyen, M.N.; Choi, T.G.; Kim, J.; Park, J.H.; Eun, Y.G.; Yoon, K.S.; Ha, J.; Kim, S.S.
Carbonyl reductase 1 is an essential regulator of skeletal muscle differentiation and regeneration
Int. J. Biochem. Cell Biol.
45
1784-1793
2013
Mus musculus (P48758)
Manually annotated by BRENDA team
Breysse, D.H.; Boone, R.M.; Long, C.M.; Merrill, M.E.; Schaupp, C.M.; White, C.C.; Kavanagh, T.J.; Schmidt, E.E.; Merrill, G.F.
Carbonyl reductase 1 plays a significant role in converting doxorubicin to cardiotoxic doxorubicinol in mouse liver, but the majority of the doxorubicinol-forming activity remains unidentified
Drug Metab. Dispos.
48
187-197
2020
Mus musculus (P48758), Mus musculus (Q8K354), Mus musculus
Manually annotated by BRENDA team
Morgan, R.A.; Beck, K.R.; Nixon, M.; Homer, N.Z.M.; Crawford, A.A.; Melchers, D.; Houtman, R.; Meijer, O.C.; Stomby, A.; Anderson, A.J.; Upreti, R.; Stimson, R.H.; Olsson, T.; Michoel, T.; Cohain, A.; Ruusalepp, A.; Schadt, E.E.; Bjoerkegren, J.L.M.; Andrew, R.; Kenyon, C.J.; Hadoke, P.W.F.; Odermatt, A.; Keen, J.
Carbonyl reductase 1 catalyzes 20beta-reduction of glucocorticoids, modulating receptor activation and metabolic complications of obesity
Sci. Rep.
7
10633
2017
Equus caballus, Homo sapiens (P16152), Homo sapiens, Mus musculus (P48758)
Manually annotated by BRENDA team