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Information on EC 1.3.1.72 - DELTA24-sterol reductase and Organism(s) Homo sapiens and UniProt Accession Q15392

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IUBMB Comments
Acts on a range of steroids with a 24(25)-double bond, including lanosterol, desmosterol and zymosterol.
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Homo sapiens
UNIPROT: Q15392
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
dhcr24, seladin-1, dwarf1, 24-dehydrocholesterol reductase, 24-reductase, dehydrocholesterol reductase, diminuto/dwarf1, delta24-reductase, zmdwf1, desmosterol reductase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3 beta-hydroxysteroid-DELTA 24 reductase
-
3-beta-hydroxysterol-DELTA24-reductase
-
3beta-hydroxysteroid-DELTA24 reductase
-
3beta-hydroxysterol DELTA24-reductase
-
dehydrocholesterol reductase
-
DHCR24
seladin-1
sterol DELTA24-reductase
-
24,25-reductase
-
-
-
-
24,25-sterol reductase
-
-
-
-
24-dehydrocholesterol reductase
-
-
24-reductase
-
-
-
-
3beta-hydroxysterol DELTA24-reductase
-
-
3beta-hydroxysterol-delta24 reductase
-
-
C-24 reductase
-
-
-
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DELTA24 reductase
-
-
-
-
DELTA24-dehydrocholesterol reductase
-
-
DELTA24-reductase
-
-
-
-
desmosterol reductase
hydroxy steroid DELTA24-reductase
-
-
-
-
lanosterol 24-reductase
-
-
-
-
lanosterol DELTA24-reductase
-
-
-
-
lanosterol reductase
reductase, hydroxy steroid DELTA24-
-
-
-
-
sterol 24,25-reductase
-
-
-
-
sterol 24-reductase
-
-
-
-
sterol 24DELTA-reductase
-
-
sterol DELTA24 reductase
-
-
-
-
sterol DELTA24-reductase
-
-
-
-
sterol-DELTA24-reductase
-
-
-
-
additional information
-
enzyme belongs to the family of flavin adenine dinucleotide-dependent oxidoreductases
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
sterol:NADP+ DELTA24-oxidoreductase
Acts on a range of steroids with a 24(25)-double bond, including lanosterol, desmosterol and zymosterol.
CAS REGISTRY NUMBER
COMMENTARY hide
9033-57-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + NADP+
show the reaction diagram
-
-
-
?
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
show the reaction diagram
-
-
-
?
5alpha-cholesta-7,24-dien-3beta-ol + NADPH
5alpha-cholest-7-en-3beta-ol + NADP+
show the reaction diagram
-
-
-
?
7-dehydrodesmosterol + NADPH
7-dehydrocholesterol + NADP+
show the reaction diagram
-
-
-
?
cholesta-5,24-dien-3beta-ol + NADPH + H+
cholest-5-en-3beta-ol + NADP+
show the reaction diagram
desmosterol + FADH2
cholesterol + FAD + H+
show the reaction diagram
-
-
-
?
lanosterol + NADPH + H+
24-dihydrolanosterol + NADP+
show the reaction diagram
-
-
-
?
zymosterol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
show the reaction diagram
-
-
-
?
5alpha-cholest-7-en-3beta-ol + NADP+
5alpha-cholesta-7,24-dien-3beta-ol + NADPH + H+
show the reaction diagram
-
-
-
-
?
5alpha-cholesta-7,24-dien-3beta-ol + NADPH
5alpha-cholest-7-en-3beta-ol + NADP+
show the reaction diagram
cholesta-5,7,24-trien-3beta-ol + NADPH
cholest-5,7-dien-3beta-ol + NADP+
show the reaction diagram
cholesta-5,7,24-trien-3beta-ol + NADPH + H+
7-dehydrocholesterol + NADP+
show the reaction diagram
-
-
-
-
?
cholesta-7,24-dien-3beta-ol + NADPH + H+
lathosterol + NADP+
show the reaction diagram
-
-
-
-
?
desmosterol + NADPH
cholesterol + NADP+
show the reaction diagram
desmosterol + NADPH + H+
cholesterol + NADP+
show the reaction diagram
-
-
-
-
?
lanosterol + NADPH
24-dihydrolanosterol + NADP+
show the reaction diagram
lanosterol + NADPH
4,4,14alpha-trimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
show the reaction diagram
-
4,4',14alpha-trimethyl-5alpha-cholesta-8,24-dien-3beta-ol
-
-
?
lanosterol + NADPH + H+
4,4,14alpha-trimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
show the reaction diagram
-
-
-
-
?
zymosterol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
show the reaction diagram
-
-
-
-
?
zymosterol + NADPH + H+
zymostenol + NADP+
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
cholesta-5,24-dien-3beta-ol + NADPH + H+
cholest-5-en-3beta-ol + NADP+
show the reaction diagram
5alpha-cholest-7-en-3beta-ol + NADP+
5alpha-cholesta-7,24-dien-3beta-ol + NADPH + H+
show the reaction diagram
-
-
-
-
?
5alpha-cholesta-7,24-dien-3beta-ol + NADPH
5alpha-cholest-7-en-3beta-ol + NADP+
show the reaction diagram
cholesta-5,7,24-trien-3beta-ol + NADPH
cholest-5,7-dien-3beta-ol + NADP+
show the reaction diagram
cholesta-5,7,24-trien-3beta-ol + NADPH + H+
7-dehydrocholesterol + NADP+
show the reaction diagram
-
-
-
-
?
cholesta-7,24-dien-3beta-ol + NADPH + H+
lathosterol + NADP+
show the reaction diagram
-
-
-
-
?
desmosterol + NADPH
cholesterol + NADP+
show the reaction diagram
desmosterol + NADPH + H+
cholesterol + NADP+
show the reaction diagram
-
-
-
-
?
lanosterol + NADPH
24-dihydrolanosterol + NADP+
show the reaction diagram
-
step in the biosynthesis of cholesterol from lanosterol
-
-
?
lanosterol + NADPH + H+
4,4,14alpha-trimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
show the reaction diagram
-
-
-
-
?
zymosterol + NADPH + H+
zymostenol + NADP+
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
FAD
-
dependent on, noncovalent binding
NADPH
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
brassicasterol
competitive
ergosterol
competitive
stigmasterol
competitive
U18666A
an inhibitor of DHCR24 activity, prevents ACTH-induced translocation of the enzyme to the nucleus in adrenal cells but not in prostate cancer cells
(1R,3aR,5aS,7S,9aS,9bR,11aR)-9a,11a-dimethyl-1-[(2R,3E)-4-phenylbut-3-en-2-yl]-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-ol
-
-
-
(1R,3aR,5aS,7S,9aS,9bR,11aR)-9a,11a-dimethyl-1-[(2S)-1-oxopropan-2-yl]-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-yl acetate
-
-
-
(20S)-pregn-5-ene-3,20-diol
-
-
-
(2S)-2-((3S,5S,10S,13R,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-N-methylpropanamide
-
1 microM, 58% inhibition of total cholesterol production. Acts both on sterol reductoase and lathosterol oxidase
(2S)-2-((3S,5S,10S,13R,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-N-propylpropanamide
-
1 microM, 45% inhibition of total cholesterol production. Acts both on sterol reductoase and lathosterol oxidase
(2S)-2-((3S,5S,10S,13R,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)propanamide
-
1 microM, 75% inhibition of total cholesterol production
(2S)-2-[(1R,3aR,5aS,7S,9aS,9bR,11aR)-7-(acetyloxy)-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-1-yl]propanoic acid
-
-
-
(2S)-2-[(1R,3aR,5aS,7S,9aS,9bR,11aR)-7-hydroxy-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-1-yl]-N-methylpropanamide
-
-
-
(2S)-N-ethyl-2-((3S,5S,10S,13R,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)propanamide
-
1 microM, 61% inhibition of total cholesterol production
(3S,20S)-20-(aminomethyl)-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-(ethoxyaminocarbonyl)-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-(hydroxycarbamoyl)-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-(hydroxymethyl)-pregn-7-en-3-ol
-
-
-
(3S,20S)-20-(methoxyaminocarbonyl)-pregn-7-en-3-ylacetate
-
-
-
(3S,20S)-20-(methyl-carbamoyl)-pregn-7-en-3beta-ol
-
i.e. MGI-21
-
(3S,20S)-20-(N,N-dimethylaminocarbonyl)-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-[((E)-2-methylbut-2-enoyloxy)methyl]-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-[((E)-but-2-enoyloxy)methyl]-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-[(butanoylamino)methyl]-pregn-7-en-3-ylacetate
-
-
-
(3S,20S)-20-[(dimethylamino)acetoxymethyl]-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-[(formyloxy)methyl]-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-[(N-methyl-N-butanoylamino)methyl]-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-[(N-methyl-N-propanoylamino)methyl]-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-[(propanylamino)methyl]-pregn-7-en-3-yl acetate
-
-
-
(3S,20S)-20-[N-methyl-N-(2-methylpropyl)-aminocarbonyl]-pregn-7-en-3-yl acetate
-
-
-
(3S,5S,10S,13R,17R)-10,13-dimethyl-17-((S)-1-(methylamino)-1-oxopropan-2-yl)-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate
-
1 microM, 84% inhibition of total cholesterol production. Acts both on sterol reductoase and lathosterol oxidase
(3S,5S,10S,13R,17R)-10,13-dimethyl-17-((S)-1-oxo-1-(propylamino)propan-2-yl)-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate
-
1 microM, 71% inhibition of total cholesterol production. Acts both on sterol reductoase and lathosterol oxidase
(3S,5S,10S,13R,17R)-17-((S)-1-(ethylamino)-1-oxopropan-2-yl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate
-
1 microM, 97% inhibition of total cholesterol production
(3S,5S,10S,13R,17R)-17-((S)-1-amino-1-oxopropan-2-yl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate
-
1 microM, 94% inhibition of total cholesterol production
(7S,9aR,11aS)-1-[(2S)-1-hydroxypropan-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-ol
-
-
-
(7S,9aS,11aR)-1-[(2S)-1-hydroxypropan-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-yl acetate
-
-
-
24(S),25-epoxycholesterol
-
incubation with 24(S),25-epoxycholesterol results in accumulation of desmosterol at the expense of cholesterol, consistent with inhibition of DHCR24 activity
3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one
-
-
3beta-[2-(diethylamino)ethoxy]androst-5-en-17-one
-
i.e. U18666A
4-[(E)-2-((3S,20R)-3-hydroxypregn-7-en-20-yl)-ethenyl]-1-methylpyridinium iodide
-
i.e. DR 258
-
5,22-cholestedien-3beta-ol
-
desmosterol isomer, competitive inhibition
6-(6-aminohexyl)-5-chloronaphthalene-1-sulfonamide
-
brassicasterol
-
DELTA22-unsaturated phytosterol, competitive inhibition
Calmodulin antagonists
-
ergosterol
-
DELTA22-unsaturated phytosterol, competitive inhibition
N,N-dimethyl-3beta-hydroxy-cholenamide
-
-
-
N,N-dimethyl-3beta-hydroxycholenamide
-
-
-
N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide
-
W-7, specific, dose-dependent inhibition
stigmasterol
-
DELTA22-unsaturated phytosterol, competitive inhibition
Trifluoperazine
-
specific, dose-dependent inhibition
trifluoroperazine
-
-
Triparanol
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cholesterol
-
high levels of DHCR24 are associated with elevated cholesterol concentrations
FAD
-
activate 2fold when added to the assay
H2O2
-
DHCR24 mRNA levels increase in response to oxidative stress (0.1 mM H2O2) in a time-dependent manner, reaching the maximum after 4 h
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0000029
(1R,3aR,5aS,7S,9aS,9bR,11aR)-9a,11a-dimethyl-1-[(2R,3E)-4-phenylbut-3-en-2-yl]-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-ol
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.000823
(2S)-2-[(1R,3aR,5aS,7S,9aS,9bR,11aR)-7-hydroxy-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-1-yl]-N-methylpropanamide
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.000198
(3S,20S)-20-(aminomethyl)-pregn-7-en-3-yl acetate
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.0000001
(3S,20S)-20-(hydroxymethyl)-pregn-7-en-3-ol
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.000805
(3S,20S)-20-(methoxyaminocarbonyl)-pregn-7-en-3-ylacetate
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.000203
(3S,20S)-20-[((E)-2-methylbut-2-enoyloxy)methyl]-pregn-7-en-3-yl acetate
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.0000063
(3S,20S)-20-[((E)-but-2-enoyloxy)methyl]-pregn-7-en-3-yl acetate
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.0169
(3S,20S)-20-[(butanoylamino)methyl]-pregn-7-en-3-ylacetate
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.0000055
(3S,20S)-20-[(dimethylamino)acetoxymethyl]-pregn-7-en-3-yl acetate
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.0000042
(3S,20S)-20-[(formyloxy)methyl]-pregn-7-en-3-yl acetate
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.0000025
(7S,9aR,11aS)-1-[(2S)-1-hydroxypropan-2-yl]-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-ol
Homo sapiens
-
at 37°C, pH not specified in the publication
-
0.0000033
(7S,9aS,11aR)-1-[(2S)-1-hydroxypropan-2-yl]-9a,11a-dimethyl-2,3,3a,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[a]phenanthren-7-yl acetate
Homo sapiens
-
at 37°C, pH not specified in the publication
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
-
assay at
7.6
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
DHCR24 is specifically expressed on the surface of HCC cell lines
Manually annotated by BRENDA team
-
intestinal mucosa cells
Manually annotated by BRENDA team
-
fibroblast from skin
Manually annotated by BRENDA team
-
BE(2)C cell line
Manually annotated by BRENDA team
-
a human hepatoblastoma-derived cell line
Manually annotated by BRENDA team
-
human skin fibroblast
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
hepatocellular carcinoma cells, hepatoblastoma cell line, and cervical adenocarcinoma-derived cell line
Manually annotated by BRENDA team
-
a predicted transmembrane (TM) domain-deleted DHCR24 mutation is localized to the cytoplasm
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
malfunction
additional information
-
the hepatitis C virus-expressing hepatoblastoma-derived cell line, RzM6-LC, shows augmented tumorigenicity. DHCR24 expression reflects tumorigenicity, overview. Ectopic or HCV-induced DHCR24 overexpression results in resistance to oxidative stress-induced apoptosis and suppressed p53 activity. DHCR24 overexpression in these cells paralleles the increased interaction between p53 and MDM2, a p53-specific E3 ubiquitin ligase, in the cytoplasm. Persistent DHCR24 overexpression does not alter the phosphorylation status of p53 but results in decreased acetylation of p53 at Lys residues 373 and 382 in the nucleus after treatment with H2O2. DHCR24 overexpression inhibits polyubiquitination in RzM6-LC cells and H358, p53 null, cells. Ectopic expression of DHCR24 does not inhibit apoptotic response to H2O2 in WI38 cells
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
DHC24_HUMAN
516
2
60101
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60000
-
SDS-PAGE
60100
-
x * 60100, sequence calculation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 60100, about, sequence calculation
?
-
x * 60100, sequence calculation
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
protein kinase C (PKC) activates DHCR24 activity through reversible phosphorylation. PKC inhibitors, BIM and Ro-318220, reduce cholesterol levels and accumulate desmosterol within 4 h, indicating decreased DHCR24 activity. Phosphorylation at T110 modulates DHCR24 activity
additional information
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E191K
E480K
site-directed mutagenesis, mutation of a C-terminal domain residue, about 50% of wild-type activity remain
K306N
N294T
R103C
site-directed mutagenesis, mutation of a FAD binding domain residue
R94H
site-directed mutagenesis, mutation of a FAD binding domain residue, about 20% of wild-type activity remain
T110A
site-directed mutagenesis, mutation and inactivation of the phosphorylation site results in 60% loss of activity compared to wild-type
T110E
site-directed mutagenesis, DHCR24 activity of the phosphomimetic T110E mutant is similar to wild-type activity
Y299F
site-directed mutagenesis, compared with wild-type DHCR24, the mutant Y299F stable cells contain reduced DHCR24 mRNA expression while having comparable DHCR24 protein levels, the mutant enzyme activity is reduced by 40% compared to the wild-type
Y300F
site-directed mutagenesis, compared with wild-type DHCR24, the mutant Y299F stable cells contain comparable DHCR24 mRNA expression while having reduced DHCR24 protein levels, the mutant enzyme activity is similar to the wild-type
Y321F
site-directed mutagenesis, the mutant enzyme activity is similar to the wild-type
Y471S
Y507F
site-directed mutagenesis, the mutant enzyme activity is reduced by 60% compared to the wild-type
E191K
-
natural mutant, 20% residual enzyme activity
K306N
-
natural mutant, 50% residual enzyme activity
N294T
-
natural mutant, 14.4% residual enzyme activity
N294T/K306N
additional information
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
seladin-1 expression is up-regulated in an acute response and down-regulated in a chronic response to oxidative stress
-
688975
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
partially from transgenic CHO cells by subcellular fractionation and membrane isolation
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
construction of a recombinant adenovirus driving DHCR24 expression vector specific for neurons with neuron-specific promoter, synapsin-1 (SYN1), cloning of a SYN1 promoter DNA fragment of human enzyme DHCR24, and transfection of recombinant Ad-hSYN1-DHCR24 into HEK AD-293, N2A (mouse neuroblastoma), and MIN6 (mouse pancreatic carcinoma) cells. DHCR24 is specially expressed in HEK AD-293 and N2A cells, but not in MIN6 cells. Adenovirus transfection inhibits apoptosis through scavenging excess reactive oxygen species, and recombinant DHCR24 adenoviruse induces neuron-specific DHCR24 expression
ectopic expression of wild-type and mutant human DHCR24s in CHO-7 cells that are deficient for DHCR24 through specific siRNA knockout, quantitative real-time RT-PCR enzyme expression analysis
generation of plasmids pcDNA5-DHCR7-myc/FRT and pcDNA5-DHCR24-V5/FRT, and of DHCR24 mutant plasmid pcDNA5-DHCR24 Y471S-V5/FRT, the latter is stably recombinantly expressed in CHO-7 cells, stable overexpression of inactive DHCR24 mutant Y471S in CHO-7 cells, quantitative real-time PCR expression analysis
recombinant expression of truncated DHCR24 (DELTA23 DHCR24) with a V5 epitope tag at either the N-terminus (V5-DHCR24) or C-terminus (DHCR24-V5) in CHO-7 cells, and the cellular localization of DELTA23 DHCR24 is primarily to the membrane fraction like the wild-type
the DHCR24 gene locus is 1p32.3, spans about 46.4 kb, and comprises eight introns and nine exons, promoter map of human DHCR24, phylogenetic tree
expressed as a EGFP-fusion protein in murine neuroblastoma cell line N2A
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expressed in CHO cells
-
gene DHCR24, DNA and amino acid sequence determination and analysis of wild-type and natural desmosterolysis mutant genes, chromosomal mapping to 1p31.1-p33, functional expression of wild-type and mutant enzymes in Saccharomyces cerevisiae
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RzM6-0d cells are transduced with DHCR24 lentivirus. Expression of DHCR24 from pGEM-T easy vector via in vitro translation using reticulocyte lysate. Expression of HA- or FLAG-tagged DHCR24 in RzM6 or HepG2 cells. Expression of GFP- and FLAG-tagged DHCR24 in 293FT cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
DHCR24 is overexpressed in hepatitis C virus-related hepatocellular carcinoma specifically induced by hepatitis C virus
DHCR24 is transcriptionally regulated by sterols via the sterol-regulatory element-binding protein-2 transcription factor
histone acetylation also regulates DHCR24 expression, with a reduction in DHCR24 transcription correlating with recruitment of acetylated histones H3 and H4 to its promoter
the enzyme is regulated by the following transcription factors/proteins: sterol regulatory element binding protein 2, nuclear factor Y (via methylation), specificity protein 1, estrogen receptor, androgen receptor, thyroid hormone receptor, constitutive androstane receptor, and pregnane X receptor. Transcriptional regulation of DHCR24, detailed overview
the sterol-regulated region is extremely GC rich and lies within a CpG island, a region of DNA with a high G and C content and a high frequency of CpG dinucleotides, which is conserved in mammals. In addition to containing a specificity protein 1 (Sp1) site required for augmentation of DHCR24 in HCV infection, this region is also important in epigenetic regulation of DHCR24. Methylation of this region decreases DHCR24 expression, with pronounced methylation occurring in cell types with low DHCR24 levels. Sex steroids, such as estrogens and androgens, are positive regulators of DHCR24, increasing gene expression via activation of their respective nuclear receptors, estrogen receptor and androgen receptor, overview. Adrenocorticotropic hormone (ACTH) stimulates the enzyme expression in adrenal gland
activation of constitutive androstane receptor (CAR) in cultured human hepatocytes increases mRNA levels of mouse Dhcr24 and human DHCR24. A CAR-responsive element is identified in the promoter of human DHCR24
-
expression of DHCR24 is mediated by two sterol regulatory elements (SREs) in the promoter of the gene, assisted by two nearby NF-Y binding sites
-
hepatitis C virus induces the DHCR24 overexpression in human hepatocytes
-
vascular endothelial cells have the capacity to instruct vascular smooth muscle cells to shut down the expression of the enzyme thereby limiting their cholesterol biosynthesis
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
pharmacology
3beta-hydroxysterol DELTA24-reductase on the surface of hepatitis C virus-related hepatocellular carcinoma cells can be a target for molecular targeting therapy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Filipovic, I.; Buddecke, E.
Calmodulin antagonists suppress cholesterol synthesis by inhibiting sterol DELTA24 reductase
Lipids
22
261-265
1987
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Waterham, H.R.; Koster, J.; Romeijn, G.J.; Hennekam, R.C.M.; Vreken, P.; Andersson, H.C.; FitzPatrick, D.R.; Kelley, R.I.; Wanders, R.J.A.
Mutations in the 3beta-hydroxysterol DELTA24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis
Am. J. Hum. Genet.
69
685-694
2001
Homo sapiens
Manually annotated by BRENDA team
Fernandez, C.; Suarez, Y.; Ferruelo, A.J.; Gomez-Coronado, D.; Lasuncion, M.A.
Inhibition of cholesterol biosynthesis by DELTA22-unsaturated phytosterols via competitive inhibition of sterol DELTA24-reductase in mammalian cells
Biochem. J.
366
109-119
2002
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Giera, M.; Renard, D.; Ploessl, F.; Bracher, F.
Lathosterol side chain amidesa new class of human lathosterol oxidase inhibitors
Steroids
73
299-308
2008
Homo sapiens
Manually annotated by BRENDA team
Kuehnle, K.; Crameri, A.; Kaelin, R.E.; Luciani, P.; Benvenuti, S.; Peri, A.; Ratti, F.; Rodolfo, M.; Kulic, L.; Heppner, F.L.; Nitsch, R.M.; Mohajeri, M.H.
Prosurvival effect of DHCR24/seladin-1 in acute and chronic responses to oxidative stress
Mol. Cell. Biol.
28
539-550
2008
Homo sapiens
Manually annotated by BRENDA team
Pedretti, A.; Bocci, E.; Maggi, R.; Vistoli, G.
Homology modelling of human DHCR24 (seladin-1) and analysis of its binding properties through molecular docking and dynamics simulations
Steroids
73
708-719
2008
Homo sapiens (Q15392), Homo sapiens
Manually annotated by BRENDA team
Nishimura, T.; Kohara, M.; Izumi, K.; Kasama, Y.; Hirata, Y.; Huang, Y.; Shuda, M.; Mukaidani, C.; Takano, T.; Tokunaga, Y.; Nuriya, H.; Satoh, M.; Saito, M.; Kai, C.; Tsukiyama-Kohara, K.
Hepatitis C virus impairs p53 via persistent overexpression of 3beta-hydroxysterol DELTA24-reductase
J. Biol. Chem.
284
36442-36452
2009
Homo sapiens
Manually annotated by BRENDA team
Zerenturk, E.J.; Kristiana, I.; Gill, S.; Brown, A.J.
The endogenous regulator 24(S),25-epoxycholesterol inhibits cholesterol synthesis at DHCR24 (Seladin-1)
Biochim. Biophys. Acta
1821
1269-1277
2012
Cricetulus griseus, Homo sapiens
Manually annotated by BRENDA team
Zerenturk, E.J.; Sharpe, L.J.; Brown, A.J.
Sterols regulate 3beta-hydroxysterol DELTA24-reductase (DHCR24) via dual sterol regulatory elements: cooperative induction of key enzymes in lipid synthesis by Sterol Regulatory Element Binding Proteins
Biochim. Biophys. Acta
1821
1350-1360
2012
Homo sapiens
Manually annotated by BRENDA team
Lu, X.; Li, Y.; Liu, J.; Cao, X.; Wang, X.; Wang, D.; Seo, H.; Gao, B.
The membrane topological analysis of 3beta-hydroxysteroid-DELTA24 reductase (DHCR24) on endoplasmic reticulum
J. Mol. Endocrinol.
48
1-9
2012
Homo sapiens
Manually annotated by BRENDA team
Yoshinari, K.; Ohno, H.; Benoki, S.; Yamazoe, Y.
Constitutive androstane receptor transactivates the hepatic expression of mouse Dhcr24 and human DHCR24 encoding a cholesterogenic enzyme 24-dehydrocholesterol reductase
Toxicol. Lett.
208
185-191
2012
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Zerenturk, E.J.; Sharpe, L.J.; Brown, A.J.
DHCR24 associates strongly with the endoplasmic reticulum beyond predicted membrane domains implications for the activities of this multi-functional enzyme
Biosci. Rep.
34
e00098
2014
Homo sapiens (Q15392)
Manually annotated by BRENDA team
Wu, B.; Chen, K.; Shrestha, S.; Ong, K.; Barter, P.; Rye, K.
High-density lipoproteins inhibit vascular endothelial inflammation by increasing 3beta-hydroxysteroid-DELTA24 reductase expression and inducing heme oxygenase-1
Circ. Res.
112
278-288
2013
Homo sapiens (Q15392)
Manually annotated by BRENDA team
Luu, W.; Zerenturk, E.J.; Kristiana, I.; Bucknall, M.P.; Sharpe, L.J.; Brown, A.J.
Signaling regulates activity of DHCR24, the final enzyme in cholesterol synthesis
J. Lipid Res.
55
410-420
2014
Homo sapiens (Q15392), Homo sapiens
Manually annotated by BRENDA team
Luu, W.; Hart-Smith, G.; Sharpe, L.J.; Brown, A.J.
The terminal enzymes of cholesterol synthesis, DHCR24 and DHCR7, interact physically and functionally
J. Lipid Res.
56
888-897
2015
Homo sapiens (Q15392), Homo sapiens
Manually annotated by BRENDA team
Lu, X.; Jia, D.; Zhao, C.; Wang, W.; Liu, T.; Chen, S.; Quan, X.; Sun, D.; Gao, B.
Recombinant adenovirus-mediated overexpression of 3beta-hydroxysteroid-DELTA24 reductase
Neural Regen. Res.
9
504-512
2014
Homo sapiens (Q15392), Homo sapiens, Rattus norvegicus (Q5BQE6)
Manually annotated by BRENDA team
Saito, M.; Takano, T.; Nishimura, T.; Kohara, M.; Tsukiyama-Kohara, K.
3beta-hydroxysterol DELTA24-reductase on the surface of hepatitis C virus-related hepatocellular carcinoma cells can be a target for molecular targeting therapy
PLoS ONE
10
e0124197
2015
Homo sapiens (Q15392)
Manually annotated by BRENDA team
Lu, X.; Li, Y.; Wang, W.; Chen, S.; Liu, T.; Jia, D.; Quan, X.; Sun, D.; Chang, A.K.; Gao, B.
3 beta-hydroxysteroid-DELTA 24 reductase (DHCR24) protects neuronal cells from apoptotic cell death induced by endoplasmic reticulum (ER) stress
PLoS ONE
9
e86753
2014
Homo sapiens (Q15392)
Manually annotated by BRENDA team
Zerenturk, E.J.; Sharpe, L.J.; Ikonen, E.; Brown, A.J.
Desmosterol and DHCR24 unexpected new directions for a terminal step in cholesterol synthesis
Prog. Lipid Res.
52
666-680
2013
Arabidopsis thaliana, Bombyx mori, Homo sapiens (Q15392), Homo sapiens
Manually annotated by BRENDA team
Kohlhaas, J.; Jaeger, M.; Lust, L.; De La Torre, C.; Hecker, M.; Korff, T.
Endothelial cells control vascular smooth muscle cell cholesterol levels by regulating 24-dehydrocholesterol reductase expression
Exp. Cell Res.
399
112446
2021
Homo sapiens
Manually annotated by BRENDA team
Mueller, C.; Hemmers, S.; Bartl, N.; Plodek, A.; Koerner, A.; Mirakaj, V.; Giera, M.; Bracher, F.
New chemotype of selective and potent inhibitors of human delta 24-dehydrocholesterol reductase
Eur. J. Med. Chem.
140
305-320
2017
Homo sapiens
Manually annotated by BRENDA team