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Information on EC 1.1.1.105 - all-trans-retinol dehydrogenase (NAD+) and Organism(s) Homo sapiens and UniProt Accession Q8N3Y7

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IUBMB Comments
The enzyme recognizes all-trans-retinol and all-trans-retinal as substrates and exhibits a strong preference for NAD+/NADH as cofactors. Recognizes the substrate both in free form and when bound to cellular-retinol-binding-protein (CRBP1), but has higher affinity for the bound form . No activity with 11-cis-retinol or 11-cis-retinal (cf. EC 1.1.1.315, 11-cis retinol dehydrogenase). Also active with 3alpha-hydroxysteroids .
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Select one or more organisms in this record:
This record set is specific for:
Homo sapiens
UNIPROT: Q8N3Y7
Word Map
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The taxonomic range for the selected organisms is: Homo sapiens
Reaction Schemes
all-trans-retinol-[cellular-retinol-binding-protein]
+
=
all-trans-retinal-[cellular-retinol-binding-protein]
+
+
Synonyms
ADH, alcohol dehydrogenase, all-trans retinol dehydrogenase, all-trans-retinol dehydrogenase, dehydrogenase, retinol, DHRS9, epidermal retinol dehydrogenase 2, LOC100185899, MDR, microsomal retinol dehydrogenase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
all-trans retinol dehydrogenase
-
-
-
-
all-trans-retinol dehydrogenase
247
-
dehydrogenase, retinol
-
-
-
-
epidermal retinol dehydrogenase 2
285473
-
MDR
-
-
-
-
microsomal retinol dehydrogenase
-
-
-
-
NAD+-dependent retinoid-active short-chain dehydrogenase/reductase
247
-
P32
-
-
-
-
RDH-E2
285473
-
RDH-like SDR
247
-
RDH10
RDH12
275890
-
RDH16
RDH8
247
-
RDHE2
285473
-
RDHE2S
247
-
RDHL
247
-
retinal reductase
-
-
-
-
retinene reductase
-
-
-
-
retinol dehydrogenase (vitamin A1)
-
-
-
-
retinol dehydrogenase 10
retinol dehydrogenase 12
275890
-
retinol dehydrogenase 2
285473
-
retinol dehydrogenase 4
retinol dehydrogenase epidermal 2-similar
247
-
RL-HSD
247
-
RoDH-4
RoDH-like 3alpha-hydroxysteroid dehydrogenase
247
-
RoDH4
247
-
SDR16C5
285473
-
SDR16C6
247
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
all-trans retinol:NAD+ oxidoreductase
The enzyme recognizes all-trans-retinol and all-trans-retinal as substrates and exhibits a strong preference for NAD+/NADH as cofactors. Recognizes the substrate both in free form and when bound to cellular-retinol-binding-protein (CRBP1), but has higher affinity for the bound form [2]. No activity with 11-cis-retinol or 11-cis-retinal (cf. EC 1.1.1.315, 11-cis retinol dehydrogenase). Also active with 3alpha-hydroxysteroids [2].
CAS REGISTRY NUMBER
COMMENTARY hide
9033-53-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
all-trans-retinal + NADH + H+
all-trans-retinol + NAD+
show the reaction diagram
-
-
-
?
all-trans-retinaldehyde + NADH + H+
?
show the reaction diagram
-
-
-
?
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
exhibits a strong preference for NAD+/NADH as cofactors. Activity with NAD+ is about 10fold higher than activity in presence of NADP+
-
-
r
11-cis-retinol + NAD+
?
show the reaction diagram
-
-
-
-
?
13-cis-retinol + NAD+
13-cis-retinal + NADH + H+
show the reaction diagram
3,4-didehydroretinol + NAD+
3,4-didehydroretinal + NADH
show the reaction diagram
-
60% of the efficiency against all-trans-retinol
-
-
?
5alpha-androstan-3alpha-ol-17-one + NAD+
? + NADH
show the reaction diagram
-
-
-
-
-
all-trans retinal + NADH + H+
all-trans-retinol + NAD+
show the reaction diagram
-
-
-
-
r
all-trans-retinal + NADH + H+
all-trans-retinol + NAD+
show the reaction diagram
all-trans-retinaldehyde + NADH + H+
all-trans-retinol + NAD+
show the reaction diagram
-
-
-
-
r
all-trans-retinol + NAD+
all-trans-retinal + NADH
show the reaction diagram
all-trans-retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
all-trans-retinol + NAD+
all-trans-retinaldehyde + NADH + H+
show the reaction diagram
-
-
-
-
r
all-trans-retinol-[cellular-retinol-binding-protein] + NAD+
all-trans-retinal-[cellular-retinol-binding-protein] + NADH + H+
show the reaction diagram
androsterone + NAD+
? + NADH
show the reaction diagram
-
-
-
-
?
retinol + NAD+
retinal + NADH
show the reaction diagram
retinol bound to cellular retinol binding protein + NAD+
retinal bound to cellular retinol binding protein + NADH
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
all-trans-retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
Q8N3Y7
exhibits a strong preference for NAD+/NADH as cofactors. Activity toward all-trans-retinal in the presence of NADH is 2fold lower than activity with all-trans-retinol and NAD+. The preference for NAD+ suggests that RDH-E2 is likely to function in the oxidative direction in vivo, further supporting its potential role in the oxidation of retinol to retinaldehyde for retinoic acid biosynthesis in human keratinocytes
-
-
r
13-cis-retinol + NAD+
13-cis-retinal + NADH + H+
show the reaction diagram
O75452
RoDH-4 can potentially contribute to the biosynthesis of two powerful modulators of gene expression: retinoic acid from retinol and dihydrotestosterone from 3alpha-androstane-diol
-
-
?
all-trans-retinol + NAD+
all-trans-retinal + NADH
show the reaction diagram
-
RoDH-4 is capable of contributing to the oxidation of retinol to retinaldehyde for retinoic acid biosynthesis in the cellular context
-
-
?
all-trans-retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
O75452
RoDH-4 can potentially contribute to the biosynthesis of two powerful modulators of gene expression: retinoic acid from retinol and dihydrotestosterone from 3alpha-androstane-diol
-
-
?
all-trans-retinol-[cellular-retinol-binding-protein] + NAD+
all-trans-retinal-[cellular-retinol-binding-protein] + NADH + H+
show the reaction diagram
-
-
-
-
ir
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD+
-
exhibits a strong preference for NAD+/NADH as cofactors. Activity with NAD+ is about 10fold higher than activity in presence of NADP+
NADH
-
exhibits a strong preference for NAD+/NADH as cofactors
NADP+
-
exhibits a strong preference for NAD+/NADH as cofactors. Activity with NAD+ is about 10fold higher than activity in presence of NADP+
NADPH
-
the enzyme has lower affinity for NADPH than for NADH
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
imidazole
-
; increasing the amount of imidazole in the reaction mixture with purified RDH-E2 from 25 to 225mM significantly decreases RDH-E2 activity
13-cis-retinoic acid
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-
3,4-didehydroretinoic acid
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-
3,4-didehydroretinol
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-
cellular retinol binding protein
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free form without retinol
-
additional information
-
all-trans-retinol and 13-cis-retinol inhibit RoDH-4 catalyzed oxidation of androsterone
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
retinoic acid-inducible dehydrogenase reductase 3
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00006
11-cis-retinol
-
pH and temperature not specified in the publication
0.00046
all-trans retinal
-
pH not specified in the publication, temperature not specified in the publication
0.57
all-trans-retinal
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wild type enzyme, in 100 mM sodium phosphate, pH 7.4
0.00046
all-trans-retinaldehyde
-
pH and temperature not specified in the publication
0.000039 - 0.0041
all-trans-retinol
0.0002
androsterone
-
pH 7.3, 37°C
0.00024 - 0.036
NAD+
0.011 - 0.11
NADH
0.027
NADP+
-
wild type enzyme, in 100 mM sodium phosphate, pH 7.4
0.0015
NADPH
-
wild type enzyme, in 100 mM sodium phosphate, pH 7.4
0.0027
retinol bound to cellular retinol binding protein
-
pH 7.3, 37°C
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02
all-trans-retinol
-
37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00021 - 0.0011
13-cis-retinoic acid
0.0035 - 0.0069
3,4-didehydroretinoic acid
0.0022 - 0.0025
3,4-didehydroretinol
0.00003
cellular retinol binding protein
-
pH 7.3, 37°C
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
retinal dehydrogenase 2 is significantly elevated in psoriatic skin
Manually annotated by BRENDA team
-
epidermal keratinocytes, gene is expressed predominantly in the differentiating spinous layers
Manually annotated by BRENDA team
-
significant amounts of RoDH-4 message is detected in fetal lung
Manually annotated by BRENDA team
the highest level of RDH12 expression is in the retina where it is localised to the inner segments and cell bodies of rod and cone photoreceptors
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
; RDH-E2 protein exhibits a punctuate localization pattern, surrounding the nucleus suggesting that RDH-E2 is associated with endoplasmic reticulum
Manually annotated by BRENDA team
-
of endoplasmic reticulum
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
RDHE2 does not partner with dehydrogenase/reductase DHRS3/SDR16C1 or cellular retinol binding protein type CRBP1
metabolism
-
the enzyme catalyzes the first step in all-trans-retinal biosynthesis, modeling of all-trans-retinal homeostasis, overview
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
RDHE2_HUMAN
309
0
34095
Swiss-Prot
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35000
calculated from amino acid sequence
36000
-
x * 36000, SDS-PAGE
40000
-
SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 36000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
no glycoprotein
-
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C201R
the loss of function mutant is associated with severe loss of retinal functionand early onset severe retinal dystrophy
DELTAM1-Y13
truncated RoDH-4 that lacks the first thirteen amino acids of the N-terminal segment is partially active and exhibits the apparent Km value for androsterone similar to that of the wild-type enzyme, truncated mutant behaves as an integral membrane protein
DELTAS295-L317
removal of 23 N-terminal hydrophobic amino acids results in significant loss of activity and a 14fold increase in the apparent Km value, truncated mutant behaves as an integral membrane protein
DELTAY291-L317
removal of the C-terminal 27 amino acid segment results in about 600fold increase in the apparent Km value, truncated mutant behaves as an integral membrane protein
G43A/G47A/G49A
-
the triple mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
K214A
-
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
K214R
-
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
N169A
-
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
N169D
-
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
S197A
-
mutant retains significant enzymatic activities, although lower than that of wild type enzyme
S197C
-
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
S197G
-
mutant retains significant enzymatic activities, although lower than that of wild type enzyme
S197T
-
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
S197V
-
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
Y210A
-
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
Y210F
-
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
gel-filtration of RDH-E2 preparation to remove imidazole results in significant loss of activity (about 90%) despite nearly complete recovery of the protein suggesting that RDH-E2 is sensitive to desalting
-
the enzyme is sensitive to desalting
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, reconstitution of enzyme into proteoliposomes, stable for at least 4 months
-
PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
Ni2+-NTA resin column chromatography; recombinant enzyme
-
preparation of RoDH-4 contains a minor contaminating protein band. Therefore, the exact concentration of RoDH-4 is determined based on the calibration curve constructed from several concentrations of BSA loaded on to the same SDS/PAGE gel
-
solubilized enzyme is extremely unstable and loses almost 80% of the initial activity even at partially purified stage, purification uses resistance of enzyme to proteolysis at 4°C in the presence of 1% Triton
-
CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
expressed in Sf9 insect cells and in HEK-293 cells; RDH-E2 is expressed in Sf9 insect cells as a fusion to the C-terminal His6-tag
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human RDHE2 exhibits a relatively low but reproducible activity when expressed in either HepG2 or HEK293 cells
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expressed in COS-1 cells
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expressed in HEK-293 cells and Sf9 insect cells
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expression in Sf9 cells, HepG2 and HEK293 cells
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human RDHE2S is unstable when expressed in HEK293 cells. RDHE2S protein produced in Sf9 cells is stable but has no detectable catalytic activity towards retinol
-
RDH8 gene is located on 19p13, DNA and amino acid sequence determination and analysis, RDH8 genotping and phenotyping in Han Chinese population
-
recombinant RoDH-4, expressed in microsomes of Sf9 insect cells
-
retinol dehydrogenase 4
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of the native RDHE2 is downregulated in the presence of elevated levels of all-trans-retinoic acid
-
insulin decreases Rdh10 and Rdh16 mRNA in HepG2 cells incubated in serum-free medium by inhibiting transcription and destabilizing mRNA
-
removing serum from the medium of the human hepatoma cell line HepG2 increases isoforms Rdh10 and Rdh16 mRNA expression 2-3-fold by 4 h, by increasing transcription and stabilizing mRNA
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
mutations in RDH12 are associated with Leber congenital amaurosis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Gough, W.H.; VanOoteghem, S.; Sint, T.; Kedishvili, N.Y.
cDNA cloning and characterization of a new human microsomal NAD+-dependent dehydrogenase that oxidizes all-trans-retinol and 3alpha-hydroxysteroids
J. Biol. Chem.
273
19778-19785
1998
Homo sapiens, Homo sapiens (O75452)
Manually annotated by BRENDA team
Jurukovski, V.; Markova, N.G.; Karaman-Jurukovska, N.; Randolph, R.K.; Su, J.; Napoli, J.L.; Simon, M.
Cloning and characterization of retinol dehydrogenase transcripts expressed in human epidermal keratinocytes
Mol. Genet. Metab.
67
62-73
1999
Homo sapiens
Manually annotated by BRENDA team
Karlsson, T.; Vahlquist, A.; Kedishvili, N.; Torma, H.
13-cis-retinoic acid competitively inhibits 3alpha-hydroxysteroid oxidation by retinol dehydrogenase RoDH-4: a mechanism for its anti-androgenic effects in sebaceous glands?
Biochem. Biophys. Res. Commun.
303
273-278
2003
Homo sapiens
Manually annotated by BRENDA team
Lapshina, E.A.; Belyaeva, O.V.; Chumakova, O.V.; Kedishvili, N.Y.
Differential recognition of the free versus bound retinol by human microsomal retinol/sterol dehydrogenases: characterization of the holo-CRBP dehydrogenase activity of RoDH-4
Biochemistry
42
776-784
2003
Homo sapiens
Manually annotated by BRENDA team
Gallego, O.; Belyaeva, O.V.; Porte, S.; Ruiz, F.X.; Stetsenko, A.V.; Shabrova, E.V.; Kostereva, N.V.; Farres, J.; Pares, X.; Kedishvili, N.Y.
Comparative functional analysis of human medium-chain dehydrogenases, short-chain dehydrogenases/reductases and aldo-keto reductases with retinoids
Biochem. J.
399
101-109
2006
Homo sapiens, Homo sapiens (O75452)
Manually annotated by BRENDA team
Liden, M.; Eriksson, U.
Understanding retinol metabolism: Structure and function of retinol dehydrogenases
J. Biol. Chem.
281
13001-13004
2006
Bos taurus, Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Takahashi, Y.; Moiseyev, G.; Farjo, K.; Ma, J.X.
Characterization of key residues and membrane association domains in retinol dehydrogenase 10
Biochem. J.
419
113-122
2009
Homo sapiens (Q8IZV5)
Manually annotated by BRENDA team
Pares, X.; Farres, J.; Kedishvili, N.; Duester, G.
Medium- and short-chain dehydrogenase/reductase gene and protein families: Medium-chain and short-chain dehydrogenases/reductases in retinoid metabolism
Cell. Mol. Life Sci.
65
3936-3949
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Belyaeva, O.V.; Chetyrkin, S.V.; Kedishvili, N.Y.
Characterization of truncated mutants of human microsomal short-chain dehydrogenase/reductase RoDH-4
Chem. Biol. Interact.
143-144
279-287
2003
Homo sapiens, Homo sapiens (O75462)
Manually annotated by BRENDA team
Lee, S.A.; Belyaeva, O.V.; Kedishvili, N.Y.
Biochemical characterization of human epidermal retinol dehydrogenase 2
Chem. Biol. Interact.
178
182-187
2009
Homo sapiens, Homo sapiens (Q8N3Y7)
Manually annotated by BRENDA team
Moradi, P.; Mackay, D.; Hunt, D.; Moore, A.
Focus on molecules: Retinol dehydrogenase 12 (RDH12)
Exp. Eye Res.
87
160-161
2008
Homo sapiens (Q96NR8)
Manually annotated by BRENDA team
Napoli, J.L.
Physiological insights into all-trans-retinoic acid biosynthesis
Biochim. Biophys. Acta
1821
152-167
2012
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Yu, Y.S.; Wang, L.L.; Shen, Y.; Yap, M.K.; Yip, S.P.; Han, W.
Investigation of the association between all-trans-retinol dehydrogenase (RDH8) polymorphisms and high myopia in Chinese
J. Zhejiang Univ. Sci. B
11
836-841
2010
Homo sapiens
Manually annotated by BRENDA team
Adams, M.K.; Lee, S.A.; Belyaeva, O.V.; Wu, L.; Kedishvili, N.Y.
Characterization of human short chain dehydrogenase/reductase SDR16C family members related to retinol dehydrogenase 10
Chem. Biol. Interact.
276
88-94
2017
Homo sapiens, Homo sapiens (Q8N3Y7)
Manually annotated by BRENDA team
Adams, M.K.; Belyaeva, O.V.; Wu, L.; Kedishvili, N.Y.
The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis
J. Biol. Chem.
289
14868-14880
2014
Homo sapiens, Homo sapiens (Q8IZV5)
Manually annotated by BRENDA team
Obrochta, K.M.; Krois, C.R.; Campos, B.; Napoli, J.L.
Insulin regulates retinol dehydrogenase expression and all-trans-retinoic acid biosynthesis through FoxO1
J. Biol. Chem.
290
7259-7268
2015
Homo sapiens, Homo sapiens (O75452), Homo sapiens (Q8IZV5), Mus musculus, Mus musculus (Q8VIJ7)
Manually annotated by BRENDA team
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