Information on EC 1.1.1.315 - 11-cis-retinol dehydrogenase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.1.1.315
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RECOMMENDED NAME
GeneOntology No.
11-cis-retinol dehydrogenase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
11-cis-retinol-[retinal-binding-protein] + NAD+ = 11-cis-retinal-[retinol-binding-protein] + NADH + H+
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
the visual cycle I (vertebrates)
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SYSTEMATIC NAME
IUBMB Comments
11-cis-retinol:NAD+ oxidoreductase
This enzyme, abundant in the retinal pigment epithelium, catalyses the reduction of 11-cis-retinol to 11-cis-retinal [1] while the substrate is bound to the retinal-binding protein [4]. This is a crucial step in the regeneration of 11-cis-retinal, the chromophore of rhodopsin. The enzyme can also accept other cis forms of retinol [2].
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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11-cis retinol oxidation occurs at a reduced rate in retinal pigment epithelium membranes from Rdh5-/- mice
metabolism
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RDH11, which can can utilize both cis and trans-retinoid substrates, plays a minor but complementary role to RDH5 in the flow of retinoids during dark adaptation
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
11-cis-retinal-[cellular retinaldehyde binding protein] + NADH + H+
11-cis-retinol-[cellular retinaldehyde binding protein] + NAD+
show the reaction diagram
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in presence of excess NADH, wild-type catalyzes the reduction of 11-cis-retinal
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r
11-cis-retinol + NAD+
11-cis-retinal + NADH
show the reaction diagram
11-cis-retinol + NAD+
11-cis-retinal + NADH + H+
show the reaction diagram
11-cis-retinol + NADP+
11-cis-retinal + NADPH
show the reaction diagram
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-
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?
11-cis-retinol + NADP+
11-cis-retinal + NADPH + H+
show the reaction diagram
11-cis-retinol-[cellular retinaldehyde binding protein] + NAD+
11-cis-retinal-[cellular retinaldehyde binding protein] + NADH + H+
show the reaction diagram
11-cis-retinol-[cellular retinaldehyde binding protein] + NADP+
11-cis-retinal-[cellular retinaldehyde binding protein] + NADPH + H+
show the reaction diagram
11-cis-retinol-[retinal-binding-protein] + NAD+
11-cis-retinal-[retinol-binding-protein] + NADH + H+
show the reaction diagram
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-
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?
13-cis-retinol + NAD+
13-cis-retinal + NADH
show the reaction diagram
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?
13-cis-retinol + NAD+
13-cis-retinal + NADH + H+
show the reaction diagram
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-
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?
9-cis-retinol + NAD+
9-cis-retinal + NADH
show the reaction diagram
9-cis-retinol + NAD+
9-cis-retinal + NADH + H+
show the reaction diagram
9-cis-retinol + NADP+
9-cis-retinal + NADPH
show the reaction diagram
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-
-
?
9-cis-retinol + NADP+
9-cis-retinal + NADPH + H+
show the reaction diagram
all-trans retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
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no significant difference in the binding constants of NADP+ and NADPH versus NAD+ and NADH
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r
all-trans retinol + NADP+
all-trans-retinal + NADPH + H+
show the reaction diagram
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no significant difference in the binding constants of NADP+ and NADPH versus NAD+ and NADH
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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-retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
all-trans-retinol + NADP+
all-trans-retinal + NADPH + H+
show the reaction diagram
all-trans-retinol + NADPH
all-trans-retinal + NADP+
show the reaction diagram
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r
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-retinol + NAD+
11-cis-retinal + NADH
show the reaction diagram
Q92781
Rdh5 catalyses 9-cis-retinol metabolism equally efficiently as 11-cis-retinol metabolism. Substrate specificity and expression locus of Rdh5 suggest that it could serve as both an 11-cis-retinol dehydrogenase in the RPE and a 9-cis-retinol dehydrogenase and/or an androgen dehydrogenase outside of the retinal pigment epithelium
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11-cis-retinol + NAD+
11-cis-retinal + NADH + H+
show the reaction diagram
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RDH10 can utilize both NAD+ and NADP+ as cofactors for 11-cis-retinol dehydrogenase activity. NAD+ cofactor confers more robust activity. RDH10 may function in the RPE retinoid visual cycle as an 11-cis-retinol dehydrogenase, and thereby partially compensate for the loss of RDH5 function in human patients with fundus albipunctatus
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?
11-cis-retinol + NADP+
11-cis-retinal + NADPH + H+
show the reaction diagram
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RDH10 can utilize both NAD+ and NADP+ as cofactors for 11-cis-retinol dehydrogenase activity. NAD+ cofactor confers more robust activity. RDH10 may function in the RPE retinoid visual cycle as an 11-cis-retinol dehydrogenase, and thereby partially compensate for the loss of RDH5 function in human patients with fundus albipunctatus
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?
11-cis-retinol-[cellular retinaldehyde binding protein] + NAD+
11-cis-retinal-[cellular retinaldehyde binding protein] + NADH + H+
show the reaction diagram
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?
11-cis-retinol-[cellular retinaldehyde binding protein] + NADP+
11-cis-retinal-[cellular retinaldehyde binding protein] + NADPH + H+
show the reaction diagram
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?
11-cis-retinol-[retinal-binding-protein] + NAD+
11-cis-retinal-[retinol-binding-protein] + NADH + H+
show the reaction diagram
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?
9-cis-retinol + NAD+
9-cis-retinal + NADH
show the reaction diagram
Q92781
Rdh5 catalyses 9-cis-retinol metabolism equally efficiently as 11-cis-retinol metabolism
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?
9-cis-retinol + NAD+
9-cis-retinal + NADH + H+
show the reaction diagram
O54909
the multifunctional cis-retinol/3alpha-hydroxysterol short-chain dehydrogenase may catalyze the first step in an enzymatic pathway from 9-cis-retinol to generate the retinoid X receptor ligand 9-cis-retinoic acid and/or may regenerate dihydrotestosterone from its catabolite 5alpha-androstan-3alpha,17beta-diol
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?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADP+
NADPH
additional information
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
11-cis-retinol
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substrate inhibition above 0.005 mM
4-Methylpyrazole
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9-cis-retinol
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substrate inhibition above 0.001 mM
all-trans-retinol
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substrate inhibition
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cellular retinaldehyde-binding protein
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RDH10 oxidizes 11-cis-retinol to generate 11-cis-retinaldehyde in vitro in the presence of cellular retinaldehyde-binding protein
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0063 - 0.06
11-cis-retinol
0.0025 - 0.0067
11-cis-retinol-[cellular retinaldehyde binding protein]
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0.0066 - 6
9-cis-retinol
0.57
all-trans retinal
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pH 7.4, 37°C, wild-type enzyme
0.00018 - 0.0041
all-trans retinol
0.4
all-trans-retinal
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; microsomal preparations of RDH10
0.035
all-trans-retinol
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; microsomal preparations of RDH10, cofactor: NAD+
0.002 - 0.1
NAD+
0.11
NADH
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pH 7.4, 37°C, wild-type enzyme
0.00069 - 0.027
NADP+
0.015
NADPH
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pH 7.4, 37°C, wild-type enzyme
additional information
additional information
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.4
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wild-type, pH not specified in the publication, temperature not specified in the publication
24000
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substrate 11-cis-retinol, pH 7.4, 37°C
81000
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substrate 9-cis-retinol, pH 7.4, 37°C
124000
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substrate all-trans-retinol, pH 7.4, 37°C
additional information
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specific activity is sevenfold higher in the presence of NAD+ cofactor, 69.44 picomoles/mg membrane protein/min, than in the presence of NADP+ cofactor, 9.66 picomoles/mg membrane protein/min, pH 7.4, 37°C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
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calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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17% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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5% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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26% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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29% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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11% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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9% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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9% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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6% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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5% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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45% mRNA expression of Rdh5 compared to liver; 45% of the expression in liver
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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fetal brain (5% mRNA expression of Rdh5 compared to adult liver), fetal heart (6% mRNA expression of Rdh5 compared to adultliver), fetal kidney (17% mRNA expression of Rdh5 compared to adult liver), fetal liver (20% mRNA expression of Rdh5 compared to adult liver), fetal spleen (5% mRNA expression of Rdh5 compared to adult liver), fetal thymus (7% mRNA expression of Rdh5 compared to adult liver), fetal lung (14% mRNA expression of Rdh5 compared to liver)
Manually annotated by BRENDA team
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3% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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7% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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9% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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21% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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97% mRNA expression of Rdh5 compared to liver; 97% of the expression in liver
Manually annotated by BRENDA team
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7% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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8% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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25% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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20% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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21% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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10% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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24% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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28% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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21% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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11% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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9% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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6% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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22% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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7% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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43% mRNA expression of Rdh5 compared to liver; 43% of the expression in liver
Manually annotated by BRENDA team
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9% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
-
17% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
-
25% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
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24% mRNA expression of Rdh5 compared to liver
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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pronounced 11-cis-retinol dehydrogenase activity is associated with both endoplasmic reticulum- and plasma membrane-enriched membrane fractions. In contrast, 11-cis-retinyl ester hydrolase activity is mostly recovered in plasma membrane-enriched fractions, while lecithin retinol acyl transferase LRAT activity is found only in endoplasmic reticulum-enriched membranes
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
38087
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x * 38087, calculated from sequence
38090
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calculated from sequence
39600
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x * 39600, SDS-PAGE and calculated
60000
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chemical cross-linking
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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2 * 32000, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
N-terminal 18 amino acids of sequence have the characteristics of a classigal signal sequence
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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modeling of the amino acid sequence of human RDH5 into the known three-dimensional structure of 17-hydroxysteroid dehydrogenase, Protein Data Bank code 1bhs
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, some loss of activity after repeated freeze-thawing cycles
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme copurifies with retinal G protein coupled receptor from microsomes
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purification of His-tagged enzyme using nickel affinity chromatography results in an inactive enzyme
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in CHO cells
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expressed in COS1 cells; expression in Cos-1 cells
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expression in CHO cells; expression in CHO-K1 cells
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expression in Cos-1 cells
expression in HEK-293 cell
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expression in Hi-5 insect cells
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expression in Sf9 cell
expression in Sf9 cell; RDH10 is expressed the enzyme in insect Sf9 cells using the Baculovirus expression system. Purification of RDH10-His6 from Sf9 cells using nickel affinity chromatography produces an inactive enzyme. Therefore, microsomal preparations of RDH10 are used for its kinetic characterization
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RDH10 is expressed in COS cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DELTA289-318
results show that the N-terminal hydrophobic domain is a membrane-anchoring domain
A294P
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naturally occuring mutation, 52% of wild-type activity in cell-reporter assay, active in vitro
D128N 
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naturally occuring mutation, less than 1% of wild-type activity in cell-reporter assay
D169A
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mutant enzyme completely loses enzymatic activity
D169N
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mutant enzyme completely loses enzymatic activity
G35S
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naturally occuring mutation, 1.7% of wild-type activity in cell-reporter assay
G43A/G47A/G49A
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mutant enzyme completely loses enzymatic activity
K214A
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mutant enzyme completely loses enzymatic activity
K214R
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mutant enzyme completely loses enzymatic activity
L105I
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naturally occuring mutation, 1% of wild-type activity in cell-reporter assay
L310EV
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naturally occuring mutation, 4% of wild-type activity in cell-reporter assay, no activity in vitro
R157W
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naturally occuring mutation, less than 1% of wild-type activity in cell-reporter assay
R280H
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naturally occuring mutation, 4% of wild-type activity in cell-reporter assay, no activity in vitro
S197A
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mutation does not abolish activity
S197C
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mutant enzyme completely loses enzymatic activity
S197G
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mutation does not abolish activity
S197T
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mutant enzyme completely loses enzymatic activity
S197V
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mutant enzyme completely loses enzymatic activity
V212
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naturally occuring mutation with 4bp deletion, frame shift mutant with premature stop codon at position 246
V264G
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naturally occuring mutation, 4% of wild-type activity in cell-reporter assay
Y210A
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mutant enzyme completely loses enzymatic activity
Y210F
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mutant enzyme completely loses enzymatic activity
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine