Information on EC 1.2.1.36 - retinal dehydrogenase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.2.1.36
-
RECOMMENDED NAME
GeneOntology No.
retinal dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
retinal + NAD+ + H2O = retinoate + NADH + 2 H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dehydrogenation
-
;
oxidation
redox reaction
-
-
-
-
reduction
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
-
-
retinoate biosynthesis I
-
-
Retinol metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
retinal:NAD+ oxidoreductase
A metalloflavoprotein (FAD). Acts on both the 11-trans- and 13-cis-forms of retinal.
CAS REGISTRY NUMBER
COMMENTARY hide
37250-99-0
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
elephant shrew, Macroscelidea, protein of eye lens eta-crystallin is identified with retinal dehydrogenase
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
Ovis aries aries
sheep
-
-
Manually annotated by BRENDA team
deermouse
-
-
Manually annotated by BRENDA team
Sprague-Dawley, BR strain
-
-
Manually annotated by BRENDA team
Wistar strain
-
-
Manually annotated by BRENDA team
zebra finch
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
both isoforms Raldh1 and -2 contribute to atRA biosynthesis in hippocampus astrocytes
physiological function
-
retinaldehyde dehydrogenase 2 is required to activate retinoic acid signaling at the onset of gastrulation
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
13-cis-retinal + NAD+ + H2O
13-cis-retinoate + NADH
show the reaction diagram
13-cis-retinal + NAD+ + H2O
13-cis-retinoate + NADH + H+
show the reaction diagram
2,4-decadienal + NAD+ + H2O
2,4-decadienoate + NADH + H+
show the reaction diagram
3-deoxyglucosone + NAD+ + H2O
2-keto-3-deoxygluconate + NADH + H+
show the reaction diagram
9-cis-retinal + NAD+ + H2O
9-cis-retinoate + NADH
show the reaction diagram
9-cis-retinal + NAD+ + H2O
9-cis-retinoate + NADH + H+
show the reaction diagram
acetaldehyde + NAD+ + H2O
acetate + NADH + H+
show the reaction diagram
aldophosphoamide + NAD+ + H2O
?
show the reaction diagram
-
-
-
-
?
all-trans retinal + NAD+ + H2O
all-trans-retinoate + NADH + H+
show the reaction diagram
-
RALDH3 oxidizes all-trans retinal with high catalytic efficiency
-
-
?
all-trans retinal + NAD+ + H2O
retinoate + NADH + H+
show the reaction diagram
-
-
-
-
?
all-trans retinaldehyde + NAD+ + H2O
all-trans retinoic acid + NADH + H+
show the reaction diagram
-
-
-
-
?
all-trans-retinal + NAD+ + H2O
all-trans-retinoate + NADH
show the reaction diagram
all-trans-retinal + NAD+ + H2O
all-trans-retinoic acid + NADH
show the reaction diagram
all-trans-retinaldehyde + NAD(P)H
NAD(P)+ + H2O + all-trans-retinoate
show the reaction diagram
-
-
-
-
?
all-trans-retinol + NAD(P)H
NAD(P)+ + H2O + all-trans-retinaldehyde
show the reaction diagram
-
-
-
-
?
benzaldehyde + NAD+ + H2O
benzoate + NADH + H+
show the reaction diagram
citral + NAD+ + H2O
citric acid + NADH + H+
show the reaction diagram
decanal + NAD+ + H2O
decanoate + NADH
show the reaction diagram
-
-
-
-
?
decanal + NAD+ + H2O
decanoate + NADH + H+
show the reaction diagram
decanal + NAD+ + H2O
decanoic acid + NADH
show the reaction diagram
hexanal + NAD+ + H2O
hexanoate + NADH + H+
show the reaction diagram
octanal + NAD+ + H2O
octanoate + NADH
show the reaction diagram
octanal + NAD+ + H2O
octanoate + NADH + H+
show the reaction diagram
-
-
-
?
propanal + NAD+ + H2O
propanoate + NADH + H+
show the reaction diagram
-
-
-
?
propanal + NAD+ + H2O
propionate + NADH
show the reaction diagram
-
-
-
-
?
retinal + NAD+ + H2O
retinoate + NADH
show the reaction diagram
retinal + NAD+ + H2O
retinoate + NADH + H+
show the reaction diagram
retinal + NAD+ + H2O
retinoic acid + NADH
show the reaction diagram
-
-
-
-
?
retinal + NAD+ + H2O
retinoic acid + NADH + H+
show the reaction diagram
retinol + NAD+ + H2O
? + NADH + H+
show the reaction diagram
retinol + NAD+ + H2O
all-trans-retinoic acid + NADH + H+
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
13-cis-retinal + NAD+ + H2O
13-cis-retinoate + NADH
show the reaction diagram
-
type-2 isozyme
-
-
?
9-cis-retinal + NAD+ + H2O
9-cis-retinoate + NADH
show the reaction diagram
all-trans-retinal + NAD+ + H2O
all-trans-retinoate + NADH
show the reaction diagram
all-trans-retinal + NAD+ + H2O
all-trans-retinoic acid + NADH
show the reaction diagram
-
key enzyme in retinoic acid biosynthesis, essential in developing diaphragm, enzyme inhibition or disfunction causes the serious developmental anomaly congenital diaphragmatic hernia, i.e. CDH
-
-
?
retinal + NAD+ + H2O
retinoate + NADH
show the reaction diagram
retinal + NAD+ + H2O
retinoate + NADH + H+
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
FAD
-
metalloflavoprotein, reaction rate is maximal with FAD
NADPH
-
prefers NADPH to NADH as a cofactor
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
-
reaction rate is maximal with Fe2+
Iron
-
metalloprotein, approximately 2 mol of iron per mol of enzyme
MgCl2
-
40% stimulation of enzyme activity with 2 mM MgCl2
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-Iodoacetamide
-
slight
3,3',5-tri-iodothyronine
-
-
3,3',5-Triiodothyroacetic acid
-
0.001 mM, 60% inhibition
4-biphenyl carboxylic acid
-
90% inhibition at 0.1 mM in cell culture in vivo, leads to posterolateral defects in the diaphragm in vivo
4-diethylaminobenzaldehyde
-
partial inhibition
acetaldehyde
all-trans-retinal
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9-cis-retinoic acid synthesis from 0.002 mM 9-cis-retinal is inhibited 50% by 0.005 mM all-trans-retinal
all-trans-retinol
-
competitive
alpha,alpha'-dipyridyl
-
slight
apo-CRBP
-
IC50 0.0014 mM
-
Atabrine
-
slight, FAD reverses inhibition
beta-ionone
-
; potent inhibitor of isoform RALDH4 activity, at 0.002 mM concentration 9-cis and 13-cis retinal oxidation is reduced by 53% and 63%, respectively
Ca2+
-
50% inhibition at 0.22 mM
Chloral hydrate
citral
D-3,3',5-triiodothyronine
-
0.001 mM, 65% inhibition
Disulfiram
estrogen
-
downregulates Raldh1 expression in the uterine glandular epithelium
ethanol
-
competitive inhibition
L-thyroxine
-
0.001 mM, 64% inhibition
Mn2+
-
50% inhibition at 0.024 mM
N,N'-octamethylenebis (dichloroacetamide)
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complete inhibition at very low concentration below 1 pM in cell culture in vivo, leads to posterolateral defects in the diaphragm in vivo
NADPH
-
0.2 mM, 79% inhibition
nitrofen
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90% inhibition at 0.1 mM in cell culture in vivo, leads to posterolateral defects in the diaphragm in vivo
p-chloromercuribenzoate
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-
p-hydroxymercuribenzoate
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complete inhibition at 1 mM in absence of DTT, 2 mM DTT protect nearly completely; strongly suppress enzyme reaction, reversed by addition of DTT
pravastatin sodium
-
cholesterol-lowering agent downregulates the expression of RALDH1,2 genes
retinal
retinol
-
40% uncompetitive inhibition of all-trans-retinal oxidation at 0.012 mM
SB-210661
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80% inhibition at 1 mM in cell culture in vivo, leads to posterolateral defects in the diaphragm in vivo
Zn2+
-
50% inhibition at 0.01 mM
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
apoCRABP
-
stimulates retinoic acid synthesis by about 30-50%
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cholecalciferol
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0.2 mM, activation to 136% of the control
cholesterol
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-
CRBP
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dithiothreitol
-
-
estrogen
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expression of Raldh2 is rapidly induced by stromal cells
glutathione
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0034
13-cis retinal
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; isoform RALDH4, in 100 mM HEPES buffer, pH 8.5, at 37C
0.0006 - 0.00062
13-cis-retinal
0.0063
2,4-decadienal
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wild type enzyme ALDH1A2, at pH 8.5 and 25C
0.095
3-deoxyglucosone
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partially purified recombinant ALDH1A1 at pH 7.1 and in the presence of 1 mM NAD
0.003
9-cis retinal
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; isoform RALDH4, in 100 mM HEPES buffer, pH 8.5, at 37C
0.00225 - 0.0087
9-cis-retinal
0.014 - 3.4
acetaldehyde
0.0039
all-trans retinal
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; isoform RALDH3, in 10 mM Tris-HCl buffer, pH 8.5, at 37C
0.0002 - 0.0116
all-trans-retinal
0.0032
all-trans-retinaldehyde
-
-
0.003
all-trans-retinol
-
-
0.0003 - 0.103
benzaldehyde
0.0029
citral
-
wild type enzyme ALDH1A2, at pH 8.5 and 25C
0.0003 - 0.01
decanal
0.0003 - 0.023
Hexanal
0.022 - 0.39
NAD+
6
NADH
-
-
0.0015
NADPH
-
-
0.0003 - 0.01
octanal
0.0066
propanal
-
-
0.0007 - 0.76
retinal
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.15
2,4-decadienal
Rattus norvegicus
-
wild type enzyme ALDH1A2, at pH 8.5 and 25C
0.2
benzaldehyde
Mus musculus
-
wild-type
0.1
citral
Rattus norvegicus
-
wild type enzyme ALDH1A2, at pH 8.5 and 25C
0.4 - 2.2
decanal
0.3 - 2
Hexanal
3.1 - 3.3
NAD+
4.8 - 5.4
octanal
0.008 - 13
retinal
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0377
3,3',5-tri-iodothyronine
-
-
0.049 - 0.53
acetaldehyde
0.00032 - 0.00061
beta-ionone
0.27 - 0.479
Ca2+
0.005 - 0.0126
Chloral hydrate
0.11 - 0.349
Mg2+
0.015 - 0.052
Mn2+
0.005 - 0.036
Zn2+
additional information
additional information
-
kinetics, recombinant isozyme type-1
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0014
apo-CRBP
Rattus norvegicus
-
IC50 0.0014 mM
-
0.001
citral
Rattus norvegicus
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IC50 about 0.001 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.047
-
-
0.13
-
-
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
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about, assay at
7.7
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in 0.1 M sodium phosphate buffer, rather broad pH curve with pH-otimum at approximately pH 7.7
7.8
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recombinant isozyme type-1 exhibits 2 pH-optima at pH 7.8 and pH 9.4 with substrates all-trans-retinal and 9-cis-retinal, respectively
9
-
all-trans-retinal oxidation; recombinant isozyme type-2
9.4
-
recombinant isozyme type-1 exhibits 2 pH-optima at pH 7.8 and pH 9.4 with substrates all-trans-retinal and 9-cis-retinal, respectively
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.1 - 9
-
-
7.5 - 9
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exhibits a broad pH optimum
8.4 - 8.6
-
on chromatofocusing column, major activity peak is eluted at pH range 8.4-8.6
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 37
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lower activity at 37C is also due to instability of the substrates
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.9
-
about
5.8 - 7.2
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Coomassie brilliant blue staining
additional information
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-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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lung cancer
Manually annotated by BRENDA team
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taenial amygdala
Manually annotated by BRENDA team
developing pituitary gland; developing pituitary gland; developing pituitary gland
Manually annotated by BRENDA team
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robust nucleus of the arcopallium, RA
Manually annotated by BRENDA team
at embryonic day 12.5, RALDH1 mRNA is present in the posterior region of oral ectoderm; at embryonic day 12.5, RALDH2 mRNA is present in part of the anterior oral ectoderm
Manually annotated by BRENDA team
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endocrine islets of Langerhans
Manually annotated by BRENDA team
-
epididymis capa, epididymis cauda
Manually annotated by BRENDA team
-
pancreas exocrine acini
Manually annotated by BRENDA team
raldh4 mRNA is present in developing intestine regions at 2 dpf embryos. Its expression level becomes very high in embryos from 3 dpf to 5 dpf. In 5 dpf embryos raldh4 is expressed in the epithelium of intestine. At 7 dpf, raldh4 mRNA is only weakly expressed in the epithelium of intestinal bulb
Manually annotated by BRENDA team
-
expresses endogenous RDH13 at high levels
Manually annotated by BRENDA team
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cell culture
Manually annotated by BRENDA team
-
submaxillary gland
Manually annotated by BRENDA team
-
uterine glandular epithelium; uterine glandular epithelium
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
36000
-
immunoblotting
53000
-
3 * 53000, SDS-PAGE
54407
x * 54407, calculation from nucleotide sequence
54600
-
4 * 54600
54700
-
4 * 54700, calculation from nucleotide sequence
58000
-
SDS-PAGE, recombinant protein
80000
-
thin layer chromatography, gel filtration
140000
-
standard deviation 3500, gel filtration
214000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homotetramer
-
4 * 55000, SDS-PAGE
tetramer
-
4 * 54600; 4 * 54700, calculation from nucleotide sequence
trimer
-
3 * 53000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
no glycoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion
recombinant isozyme type-2 mutant L459F/N460G in complex with NAD+ and in absence of substrate, hanging drop vapour diffusion method, 7.6 mg/ml enzyme with 2 mM NAD+ and about 14 mg/ml retinol, 0.002 ml protein solution plus equal volume of well solution containing 7% PEG 6000, 2% 2-methyl-2,4-pentanediol, and 0.1 M Tris, pH 7.5, X-ray diffraction structure determination and analysis at 3.3 A resolution
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dialysis against distilled water, several hours, about 29% loss of activity
-
DTT stabilizes isozyme type-2
-
quite unstable during extensive freezing and thawing
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70C, 20 mM Hepes, 2 mM DTT, 150 mM KCl, 15% glycerol, pH 8
-
-70C, at concentration of 0.078 mg/ml, 15% glycerol, stable for three months
-
dilution (1:5) with 100 mM phosphate buffer often results in loss of 80-90% of specific activity
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
after recombinant production in Escherichia coli BL-21DE3
-
after recombinant production in Escherichia coli BL-21DE3; recombinant isozyme type-2 as fusion protein from Escherichia coli by GST-affinity chromatography, cleavage by thrombin to eliminate the fusion tag
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by gel filtration, more than 400fold with a yield of about 1%, to near homogeneity
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Ni-affinity chromatography
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Ni-NTA column chromatography; on a Ni-NTA column; on a Ni-NTA column
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nickel-Sepharose column chromatography and Q-Sepharose column chromatography
partially by isoelectric focusing
-
RDH13-His6 purified by Ni2+ affinity chromatography, to homogeneity
-
recombinant isozyme type-1 as fusion protein from Escherichia coli by GST-affinity chromatography, cleavage by thrombin to eliminate the fusion tag
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recombinant wild-type and mutant isozyme type-2 from Escherichia coli strain Bl21(DE3), no usage of His-tag since it may influence the enzyme activity
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using a nickel-chelating Sepharose and a S300 HR gel-filtration column
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned into the pET28a vector. Expressed in Sf9 cells as a fusion with the C-terminal His6 tag
-
expressed in COS-1 cells
-
expressed in Escherichia coli BL21(DE3) cells as His-tagged enzyme; into the vector pET28a for expression in Escherichia coli BL21DE3 cells; into the vector pET28a for expression in Escherichia coli BL21DE3 cells
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expressed in Escherichia coli C41(DE3) cells
expression in Escherichia coli BL21 (DE3) as His-tag fusion protein
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expression in Escherichia coli; functional expression of wild-type and chimeric mutant enzymes in Escherichia coli strain BL21(DE3)
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expression of isozyme type-1 in Escherichia coli strain BL21(DE3) as N-terminally fusion protein to glutathione-S-transferase
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expression of isozyme type-2 in Escherichia coli strain BL21(DE3) as N-terminally fusion protein to glutathione-S-transferase; recombinant in Escherichia coli BL21(DE3)
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expression of xCTBP/xALDH1 in Escherichia coli
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into the cloning vector pGEM-T Easy and subcloned into the expression vector pET14b
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into the pGEM-T easy vector, 396-1002; into the pGEM-T easy vector, bp 1488-2079; into the pGEM-T easy vector, bp 935-1485
into the pKO-V901 plasmid
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ligated into a pCMV5 expression vector and overexpressed in HEK-293 cells
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overexpression of wild-type and mutant isozyme type-2 in Escherichia coli strain Bl21(DE3)
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recombinant in Escherichia coli (pLysS cells)
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recombinant in Escherichia coli BL21(DE3)
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
high retinoic acid levels inhibit Raldh1 gene expression by sequestering CCAAT/enhancer binding protein beta through its interaction to GADD153. A decrease in Raldh1 mRNA levels in the aryl hydrocarbon receptor-null liver relative to wild type mouse liver is observed
-
levels of RALDH1 gene expression and protein production markedly decrease after 1-week treatment with 17beta-estradiol in male rats. Treatment of isolated anterior pituitary cells with 17beta-estradiol (0.00001-10 nM) decreases expression of RALDH1 mRNA in a dose-dependent manner (about 55% RALDH1 mRNA level remaining 6 h after treatment with 10 nM 17beta-estradiol). 17beta-Estradiol-induced suppression of RALDH1 expression is completely blocked by the estrogen receptor antagonist ICI 182, 780. The ERalpha-selective agonist propylpyrazole triol (10 nM) mimicks the effect of 17beta-estradiol on RALDH1 expression, but the ERbeta-selective agonist diarylpropionitrile (10 nM) does not
mRNA expression is upregulated by p53 (44.3fold) and p63gamma (16.3fold) by binding to the retSDR1 promoter in vivo
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K127A
-
the mutant shows reduced activity compared to the wild type enzyme
N120A
-
the mutant shows reduced activity compared to the wild type enzyme
Y296A
-
the mutant shows reduced activity compared to the wild type enzyme
Y296V
-
the mutant shows reduced activity compared to the wild type enzyme
C301A
-
site-directed mutagenesis, catalytic residue mutation, reduced activity compared to the wild-type enzyme
F471L
-
mutant
L459F/N460G
-
site-directed mutagenesis, inactive mutant, still able to bind the cofactor NAD+
T1411C
-
mutant
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
degradation
medicine
additional information