Information on EC 1.1.1.300 - NADP-retinol dehydrogenase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.1.1.300
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RECOMMENDED NAME
GeneOntology No.
NADP-retinol dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
retinol + NADP+ = retinal + NADPH + H+
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
retinol biosynthesis
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the visual cycle I (vertebrates)
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SYSTEMATIC NAME
IUBMB Comments
retinol:NADP+ oxidoreductase
Greater catalytic efficiency in the reductive direction. This observation, and the enzyme's localization at the entrance to the mitochondrial matrix, suggest that it may function to protect mitochondria against oxidative stress associated with the highly reactive retinal produced from dietary beta-carotene by EC 1.13.11.63 (beta-carotene 15,15'-dioxygenase) [2]. Km-values for NADP+ and NADPH are at least 800-fold lower than those for NAD+ and NADH [1,4]. This enzyme differs from EC 1.1.1.105, retinol dehydrogenase, which prefers NAD+ and NADH.
CAS REGISTRY NUMBER
COMMENTARY hide
90033-53-8
cf. EC 1.1.1.105
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
gene harbours two initiation sites, one of which encodes a 279 and the other a 260 amino acids protein
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
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RDHs that catalyze the interconversion of retinal and retinol involved in rhodopsin turnover are members of the family of short chain dehydrogenase/reductases
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(E)-4-hydroxy-2-nonenal + NADPH + H+
(E)-4-hydroxy-2-nonenol + NADP+
show the reaction diagram
11-cis-retinal + NADH + H+
11-cis-retinol + NAD+
show the reaction diagram
NADH much less efficient than NADPH
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r
11-cis-retinal + NADPH + H+
11-cis-retinol + NADP+
show the reaction diagram
11-cis-retinol + NADP+
11-cis-retinal + NADPH
show the reaction diagram
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-
-
?
11-cis-retinol + NADP+
11-cis-retinal + NADPH + H+
show the reaction diagram
possibly involved in the production of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pigments
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r
13-cis-retinal + NADPH
13-cis-retinol + NADP+
show the reaction diagram
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r
13-cis-retinal + NADPH + H+
13-cis-retinol + NADP+
show the reaction diagram
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4fold lower activity than with all-trans-retinal
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-
?
13-cis-retinol + NADP+
13-cis-retinal + NADPH + H+
show the reaction diagram
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r
9-cis-retinal + NADPH
9-cis-retinol + NADP+
show the reaction diagram
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r
9-cis-retinal + NADPH + H+
9-cis-retinol + NADP+
show the reaction diagram
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60fold lower activity than with all-trans-retinal
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-
?
9-cis-retinol + NADP+
9-cis-retinal + NADPH + H+
show the reaction diagram
all-trans retinal + NADH + H+
all-tans-retinol + NAD+
show the reaction diagram
NADH much less efficient than NADPH
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r
all-trans retinal + NADH + H+
all-trans-retinol + NAD+
show the reaction diagram
prefers NADP+ and NADPH as cofactors
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r
all-trans retinal + NADPH + H+
all-tans-retinol + NADP+
show the reaction diagram
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r
all-trans retinal + NADPH + H+
all-trans-retinol + NADP+
show the reaction diagram
prefers NADP+ and NADPH as cofactors
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r
all-trans-3-hydroxyretinal + NADH + H+
all-trans-3-hydroxyretinol + NAD+
show the reaction diagram
catalytic efficiency towards all-trans-3-hydroxyretinal is lower than that towards all-trans retinal, prefers NADP+ and NADPH as cofactors
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-
?
all-trans-3-hydroxyretinal + NADPH + H+
all-trans-3-hydroxyretinol + NADP+
show the reaction diagram
catalytic efficiency towards all-trans-3-hydroxyretinal is lower than that towards all-trans retinal, prefers NADP+ and NADPH as cofactors
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-
?
all-trans-retinal + NAD(P)H + H+
all-trans-retinol + NAD(P)+
show the reaction diagram
all-trans-retinal + NADH + H+
all-trans-retinol + NAD+
show the reaction diagram
all-trans-retinal + NADPH + H+
all-tans-retinol + NADP+
show the reaction diagram
all-trans-retinal + NADPH + H+
all-trans-retinol + NADP+
show the reaction diagram
all-trans-retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
low activity with NAD+ as cofactor
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r
all-trans-retinol + NADP+
all-trans-retinal + NADPH + H+
show the reaction diagram
cis-6-nonenal + NADPH + H+
?
show the reaction diagram
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good substrate of RDH11 and RDH12, while RHD10 has very low activity towards this substrate
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?
estrone + NADH + H+
estradiol + NAD+
show the reaction diagram
n-nonanal + NADPH + H+
n-nonanol + NADP+
show the reaction diagram
retinal + NADH
retinol + NAD+
show the reaction diagram
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?
retinal + NADPH + H+
retinol + NADP+
show the reaction diagram
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?
retinol + NAD+
retinal + NADH
show the reaction diagram
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?
retinol + NADP+
retinal + NADPH
show the reaction diagram
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?
retinol + NADP+
retinal + NADPH + H+
show the reaction diagram
retinol bound to cellular retinol binding protein + NADP+
retinal bound to cellular retinol binding protein + NADPH
show the reaction diagram
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trans-2-nonenal + NADPH + H+
?
show the reaction diagram
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good substrate of RDH11 and RDH12, while RHD10 has very low activity towards this substrate
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?
additional information
?
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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
11-cis-retinal + NADPH + H+
11-cis-retinol + NADP+
show the reaction diagram
Q96NR8
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r
11-cis-retinol + NADP+
11-cis-retinal + NADPH + H+
show the reaction diagram
Q96NR8, Q9HBH5
possibly involved in the production of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pigments
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r
9-cis-retinol + NADP+
9-cis-retinal + NADPH + H+
show the reaction diagram
Q96NR8, Q9HBH5
possibly involved in the first step of 9-cis-retinoic acid production
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r
all-trans retinal + NADPH + H+
all-tans-retinol + NADP+
show the reaction diagram
Q96NR8
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r
all-trans-retinal + NADPH + H+
all-tans-retinol + NADP+
show the reaction diagram
Q9GKX2
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?
all-trans-retinal + NADPH + H+
all-trans-retinol + NADP+
show the reaction diagram
all-trans-retinol + NADP+
all-trans-retinal + NADPH + H+
show the reaction diagram
n-nonanal + NADPH + H+
n-nonanol + NADP+
show the reaction diagram
Q96NR8
might play a role in detoxification of lipid peroxidation products
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r
retinol + NADP+
retinal + NADPH + H+
show the reaction diagram
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(3beta)-3-[(3-carboxypropanoyl)oxy]-11-oxoolean-12-en-30-oic acid
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0.5 mM, 60% of inhibition
1,2-diheptanoyl-sn-glycero-3-phosphocholine
substitution of the detergent 1,2-diheptanoyl-sn-glycero-3-phosphocholine for Tween-20 results in complete inactivation of the enzyme
9-cis-retinoic acid
;
Nonanal
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inhibits the activity towards retinaldehyde
Phenylarsine oxide
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1 mM, 85% of inhibition
additional information
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not inhibitory: methylpyrazole, phenylmethylsulfonylfluoride
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0001
11-cis-retinal
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pH 7.4, 37C
0.0016
11-cis-retinol
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pH 7.4, 37C
0.62
13-cis-retinal
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pH 7.4, 37C, determined with NADP+
0.00014 - 0.19
9-cis-retinal
0.0016
9-cis-retinol
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pH 7.4, 37C
0.0032 - 0.0044
all-trans-3-hydroxyretinal
0.00006 - 0.5
all-trans-retinal
0.0006 - 1.3
all-trans-retinol
0.0096 - 0.0307
estrone
7.75 - 680
NAD+
2.22 - 1300
NADH
0.0004 - 0.8
NADP+
0.00047 - 0.23
NADPH
additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00012 - 0.4
all-trans-retinal
0.0006 - 0.2
all-trans-retinol
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001
9-cis-retinoic acid
pH 7.4
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.63
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eluate after purification, the specific activity of the purified enzyme with all-trans-retinal as substrate is 13fold higher than that of the microsomal preparation of wild-type
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.67
calculated from the deduced amino acid sequence
9.32
calculated from the deduced amino acid sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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squamos cell carcinoma, SCC tumor
Manually annotated by BRENDA team
detected in 54% of cervical tumor tissue samples but not in normal cervical tissue; detected in cervical tumor tissue samples where NRDRB1 could not be detected; normal and neoplastic cervical tissue samples
Manually annotated by BRENDA team
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RRD mRNA expression is initiated on embryo day 7
Manually annotated by BRENDA team
moderate expression level
Manually annotated by BRENDA team
moderate expression level
Manually annotated by BRENDA team
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and foreskin
Manually annotated by BRENDA team
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low mRNA expression
Manually annotated by BRENDA team
additional information
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not: skeletal muscle and heart
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
RDH13 is localized on the outer side of the inner mitochondrial membrane
Manually annotated by BRENDA team
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isoform RDH13
Manually annotated by BRENDA team
additional information
not detected in the peroxisome
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Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35400
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60000
gel filtration
365000
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molecular mass of RDH12-His6
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 23917, calculated from the deduced amino acid sequence; x * 27572, calculated from the deduced amino acid sequence
dimer
2 * 27000, SDS-PAGE, native mass by gel filtration; 2 * 27368, MALDI-TOF MS, native mass by gel filtration; 2 * 27430, calculated from the deduced amino acid sequence, native mass by gel filtration
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
no glycoprotein
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the wild-type enzyme is not glycosylated
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
alignment of Streptomyces hydrogenans 20beta-hydroxysteroid dehydrogenase with rat retinol dehydrogenase and cow 11-cis retinol dehydrogenase. Lysine64 of the rat enzyme is important in stabilizing binding of 2'-phosphate on NADP+ in two ways: lysine's positively charged side chain has a coulombic attraction to the 2'-phosphate and partially compensates for the negative charge of aspartic acid-38. Cow 11-cis retinol dehydrogenase has threonine61 at the position homologous to lysine64. Threonine61 does not have a stabilizing coulombic interaction with NADP+, nor can threonine61 counteract the repulsive interaction between NADP+ and aspartic acid37 in 11-cis retinol dehydrogenase
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
partially inactivated after 20 min
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
requires reducing conditions to stay active
686690
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80C, buffer containing 1 mM 1,2-diheptanoyl-sn-glycero-3-phosphocholine, stable for several months
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8C, in a refrigerator, the enzyme is nearly fully active for at least one month
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified to homogeneity
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recombinant enzyme
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recombinant enzyme from HEK-293 cell microsomes
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recombinant protein from Escherichia coli
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned as a gene regulated by the transcription factor sterol regulatory element binding proteins and previously named SCALD for short chain aldehyde reductase
expressed in native, soluble form in Escherichia coli BL21-AI and as GFP-fusion protein in HeLa-cells; GFP-fusion protein in HeLa-cells
expression in CHO-K1 cells
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expression in HEK-293 cell
expression in HeLa cell and 293T cell
expression in Sf9 cells
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expression in Sf9 cells; expression in Sf9 cells; expression in Sf9 cells; expression in Sf9 cells
full-length short-chain dehydrogenase/reductase cDNA expressed in Escherichia coli, truncated cDNA expressed in SF9 insect cells, enzyme belongs to the short-chain dehydrogenase/reductase superfamily
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production of recombinant His6-tagged enzyme in insect cells
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recombinant expression in HEK-293 cell microsomes
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stable transfection of HEK-293 cells; stable transfection of HEK-293 cells
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
M146G
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mutation in isoform prRDH1, gain-of-function mutant, enables estrone to bind and be reduced as an additional substrate
M147G
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mutation in isoform prRDH2, gain-of-function mutant, enables estrone to bind and be reduced as an additional substrate
L99I
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site-directed mutagenesis, about 30% of wild-type activity
M144G
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gain-of-function mutant, enables estrone to bind and be reduced as an additional substrate
Q189X
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mutation found in an individual affected by autosomal recessive childhood-onset severe retinal dystrophy
R25G/K26I
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The mutation allows the enzyme to flip its orientation in the membrane. The mutant is glycosylated in intact cells.
R62X
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mutation found in an individual affected by autosomal recessive childhood-onset severe retinal dystrophy
S175P
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site-directed mutagenesis, no catalytic activity. Protein is stable and abundantly expressed
Y226C
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mutation present in all individuals affected by autosomal recessive childhood-onset severe retinal dystrophy from three Austrian kindreds, enzyme expressed in COS-7 cells shows diminished activity
T49M
inactive. Mutation is associated with Lebr congenital amaurosis. Mutant is not able to detoxify 4-hydroxynonenal in cells
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine