Information on EC 1.3.1.21 - 7-dehydrocholesterol reductase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY hide
1.3.1.21
-
RECOMMENDED NAME
GeneOntology No.
7-dehydrocholesterol reductase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
cholesterol + NADP+ = cholesta-5,7-dien-3beta-ol + NADPH + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
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redox reaction
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-
-
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reduction
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
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cholesterol biosynthesis
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cholesterol biosynthesis I
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cholesterol biosynthesis II (via 24,25-dihydrolanosterol)
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cholesterol biosynthesis III (via desmosterol)
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Insect hormone biosynthesis
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Metabolic pathways
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plant sterol biosynthesis
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Steroid biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
cholesterol:NADP+ DELTA7-oxidoreductase
The enzyme is part of the cholesterol biosynthesis pathway.
CAS REGISTRY NUMBER
COMMENTARY hide
9080-21-1
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
strain 1S-4
SwissProt
Manually annotated by BRENDA team
strain 1S-4
SwissProt
Manually annotated by BRENDA team
Mus musculus C57BL/6
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-
-
Manually annotated by BRENDA team
maize
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-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
7-dehydrodesmosterol + NADPH
desmosterol + NADP+
show the reaction diagram
7-dehydrositosterol + NADPH
sitosterol + NADP+
show the reaction diagram
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25% of that with 7-dehydrocholesterol
-
?
cholesta-5,7-dien-3-beta-ol + NADPH
cholesterol + NADP+
show the reaction diagram
cholesta-5,7-dien-3alpha-ol + NADPH
epicholesterol + NADP+
show the reaction diagram
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i.e. 7-dehydroepicholesterol, 25% activity of that with 7-dehydrocholesterol
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-
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cholesta-5,7-dien-3beta-ol + NADPH
cholesterol + NADP+
show the reaction diagram
cholesta-7-en-3beta-ol + NADPH
?
show the reaction diagram
cholesterol + NADP+
cholesta-5,7-dien-3-beta-ol + NADPH + H+
show the reaction diagram
-
-
-
?
cholesterol + O2 + NAD(P)H + H+
cholesta-5,7-dien-3beta-ol + NAD(P)+ + 2 H2O
show the reaction diagram
ergosta-5,7,22-trien-3beta-ol + NADPH
ergosta-5,22-diene-3beta-ol + NADP+
show the reaction diagram
ergosta-5,7-diene-3beta-ol + NADPH
ergosta-5-ene-3beta-ol + NADP+
show the reaction diagram
ergosta-5,7-diene-3beta-ol + NADPH
ergosta-5-eneol + NADP+
show the reaction diagram
-
-
?
ergosta-5,7-dienol + NADPH
ergosta-5-enol + NADP+
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
7-dehydrodesmosterol + NADPH
desmosterol + NADP+
show the reaction diagram
cholesta-5,7-dien-3-beta-ol + NADPH
cholesterol + NADP+
show the reaction diagram
cholesta-5,7-dien-3beta-ol + NADPH
cholesterol + NADP+
show the reaction diagram
cholesterol + O2 + NAD(P)H + H+
cholesta-5,7-dien-3beta-ol + NAD(P)+ + 2 H2O
show the reaction diagram
Q17938
first committed step in biosynthesis of Caenorhabditis elegans bile acid-like steroids called dafachronic acids
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-
?
ergosta-5,7-diene-3beta-ol + NADPH
ergosta-5-ene-3beta-ol + NADP+
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADH
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low activity
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Iron
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iron-dependent
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,4-bis-[2-chlorobenzylaminomethyl]-cyclohexane
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AY-9944
1-[p-(beta-Diethylaminoethoxy) phenyl]1-(p-tolyl)-2-(p-chlorophenyl)ethanol
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i.e. MER-29 or triparanol
2-[2-(4-chlorophenyl)ethyl]-6-hydroxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline
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strong and selective inhibition of 7-dehydrocholesterol reductase, stronger inhibition of overall cholesterol biosynthesis than BM 15.766, presently the most selective known inhibitor of 7-DHCR
20,25-Diazacholesterol
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3beta-[2-(diethylamino)ethoxy]androst-5-en-17-one
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i.e. U18666A
4-(2-[1-(n-chlorocinnamyl) piperazin-4-yl] ethyl) benzoic acid
6,7-diaza-5alpha-cholest-8(14)-en-3beta-ol
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6,7-diaza-5beta-cholest-8(14)-en-3beta-ol
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6-aza-B-homo-5alpha-cholest-7-en-3beta-ol
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6-aza-B-homo-5alpha-cholest-8-en-3beta-ol
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7-dehydrocholesterol
8beta-cyano-6,7-diaza-5alpha-cholest-5,8(14)-dien-3beta-ol
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AY9944
BM 15.766
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BM15.766
brassicasterol
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higher concentration, competitive
cholest-5,7-dien-3beta-ol
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EDTA
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epicholesterol
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higher concentration, competitive
ergosterol
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non-competetively, concentration 0.025 mM
N-(1,5,9-trimethyldecyl-)-4alpha,10-dimethyl-8-aza-trans-decalin-3beta-ol
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sitosterol
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higher concentration, competitive
trans-1,4-Bis-(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride
Triparanol
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-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Lipid transfer protein
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cytosolic, activity enhancement which is inhibited by addition of Tween 80, probably identical with sterol carrier protein
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Sterol carrier protein
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from cytosol, required for activity, probably identical with lipid transfer protein
sterol regulatory element-binding protein cleavage-activating protein
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Tween 80
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can substitute carrier protein
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.14
7-dehydrocholesterol
0.21
ergosterol
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0014
20,25-Diazacholesterol
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-
0.00005
6,7-diaza-5alpha-cholest-8(14)-en-3beta-ol
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0.00007
6-aza-B-homo-5alpha-cholest-7-en-3beta-ol
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0.5
cholest-5,7-dien-3beta-ol
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0.000109 - 0.00024
trans-1,4-Bis-(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride
0.047 - 0.083
Triparanol
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0005
2-[2-(4-chlorophenyl)ethyl]-6-hydroxy-7-methoxy-1,2,3,4-tetrahydroisoquinoline
Homo sapiens
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whole-cell assay, pH not specified in the publication, temperature not specified in the publication
0.0000023
BM 15.766
Homo sapiens
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whole-cell assay, pH not specified in the publication, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00011
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testis enzyme, extract
0.000605
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0.000756
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0.00108
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solubilized by 1.5% 3-[3-(cholamidopropyl)-dimethylammonio]-1-propanesulfonate, i.e. CHAPS, from microsomes
0.0023
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liver enzyme, extract
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.6
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acetate buffer
6.2
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citrate buffer
6.8
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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of healthy persons, heterozygous persons, and Smith-Lemli-Opitz syndrome patients
Manually annotated by BRENDA team
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exocrine, high desmosterol synthesis
Manually annotated by BRENDA team
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of healthy persons, heterozygous persons, and Smith-Lemli-Opitz syndrome patients
Manually annotated by BRENDA team
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coexpression of enzyme and Sonic Hedgehog, Shh, during midline development in embryo. Enzyme functions as an negative regulator in Hedghog signaling at the level or downstream of Smoothend and affects intracellular Hedgehog signaling
Manually annotated by BRENDA team
with holoprosencephaly at gestation age of 21 to 33 weeks
Manually annotated by BRENDA team
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progenitor cells, immature cells, and adult cells, differentially expressed transcripts and enzyme expression levels during development and differentiation, overview
Manually annotated by BRENDA team
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15-20% of total activiy in brain, lipid exchange between microsomes and myelin
Manually annotated by BRENDA team
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during early embryonic development, the expression of Xdhcr7 is first of all spatially restricted to the Spemann’s organizer and later to the notochord. In both tissues, Xdhcr7 is coexpressed with Sonic hedgehog, Shh
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
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during early embryonic development, the expression of Xdhcr7 is first of all spatially restricted to the Spemann’s organizer and later to the notochord. In both tissues, Xdhcr7 is coexpressed with Sonic hedgehog, Shh
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
Dhcr7 is a nine-pass transmembrane protein in the endoplasmic reticulum
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
53970
calculated from amino acid sequence
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Tween 80 stabilizes during enzyme assay
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
analysis of differentially expressed transcripts of gene dhcr7 in progenitor Leydig cells and in immature Leydig cells, increased expression of the enzyme during differentiation process
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DNA and amino acid sequence determination and polymorphism analysis of DNA from fetae with holoprosencephaly, naturally occurring mutations involved in pathogenesis are G344D, R404C, and G410S, overexpression of wild-type and mutant enzymes in Saccharomyces cerevisiae as myc-tagged proteins
DNA and amino acid sequence determination, gene structure and organization, gene dhcr7 maps to chromosome 11q12-13
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DNA and amino acid sequence determination, gene structure and organization, gene dhcr7 maps to chromosome 7F5
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DNA and amino acid sequence determination, gene structure and organization, gene dhcr7 maps to chromosome 8q2.1
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expressed in Saccharomyces cerevisiae
expression in S2 cell
expression in Saccharomyces cerevisiae cells; full length cDNA and 5'-terminal truncated cDNA, for the latter M59 is the first encountered, gene characterization
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expression in Saccharomyces cerevisiae with c-myc epitope
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expression in Sf9 cell
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expression of cDNA in Saccharomyces cerevisiae and overexpression of recombinant protein Escherichia coli, sequence analysis
expression of mouse embryonic fibroblasts, and in GLI1-positive AsPC1 cells
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gene characterization
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gene Dhcr7, chromosome mapping to 8q2.1, DNA and amino acid sequence determination and analysis of the full-length gene and the splicing variants Dhcr7-AS-1-5, gene structure, physical map, 5 alternative splicing variants; gene Dhcr7, DNA and amino acid sequence determination and analysis, 1723 nucleotides, about 636 base pairs, gene structure, physical map, transcript half-life, alternative splicing variant 4; gene Dhcr7, DNA and amino acid sequence determination and analysis, gene structure, 1474 nucleotides, about 387 base pairs, physical map, transcript half-life, alternative splicing variant 1; gene Dhcr7, DNA and amino acid sequence determination and analysis, gene structure, 1595 nucleotides, about 508 base pairs, physical map, transcript half-life, alternative splicing variant 2
gene Dhcr7, DNA and amino acid sequence determination and analysis, no alternative splicing
gene dhcr7, maps to chromosome 11q13, determination of gene structure and organisation, DNA sequence determination and analysis of wild-type and natural mutant genes
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
trans-1,4-bis(2-chlorobenzaminomethyl)cyclohexane dihydrochloride, i.e. AY9944, is a competitive inhibitor of DHCR7 enzyme activity and inductor of DHCR7 expression. The DHCR7 expression is also activated by antipsychotic drugs, e.g. clozapine, chlorpromazine, haloperidol, and antidepressants such as imipramine, overview
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H190A
mutation within Rieske [2Fe-2S]-motif, complete loss of activity
H282A
mutation within non-heme Fe(II) binding motif, complete loss of activity
C122A
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mutation within Rieske [2Fe-2S]-motif, complete loss of activity
D234A
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mutation within non-heme Fe(II) binding motif, complete loss of activity
A247V
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natural mutant, Smith-Lemli-Opitz syndrome patient, 3.1% of wild-type enzyme activity, disease severity score is not directly correlated
C380Y
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natural mutant, Smith-Lemli-Opitz syndrome patient, 1.7% of wild-type enzyme activity, disease severity score is not directly correlated
E288K
mutation isolated in patient with severe form of Smith-Lemli-Opitz syndrome, carrying additional heterozygous mutation I251N
E448K
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natural mutation present in patient with Smith-Lemli-Opitz syndrome
F174S
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enzyme mutation in patients with Smith-Lemli-Opitz syndrome
G344D
site-directed mutagenesis, analogously to the naturally occurring mutation in holoprosencephaly, 50% reduced enzyme activity compared to the wild-type enzyme
G410S
site-directed mutagenesis, analogously to the naturally occurring mutation in holoprosencephaly, inactive mutant
H301R
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enzyme mutation in patients with Smith-Lemli-Opitz syndrome
I251N
mutation isolated in patient with severe form of Smith-Lemli-Opitz syndrome, carrying additional heterozygous mutation E288K
L99P
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natural mutation present in patient with Smith-Lemli-Opitz syndrome
N274K
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enzyme mutation in patients with Smith-Lemli-Opitz syndrome
P51H
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natural mutation present in patient with Smith-Lemli-Opitz syndrome
Q98X
-
enzyme mutation in patients with Smith-Lemli-Opitz syndrome
R404C
site-directed mutagenesis, analogously to the naturally occurring mutation in holoprosencephaly, inactive mutant
R466Q
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natural mutant, Smith-Lemli-Opitz syndrome patient, 1.0% of wild-type enzyme activity, disease severity score is not directly correlated
R540L
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natural mutation present in patient with Smith-Lemli-Opitz syndrome
S169L
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natural mutant, Smith-Lemli-Opitz syndrome patient, 6.2% of wild-type enzyme activity, disease severity score is not directly correlated
T154M
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natural mutant, Smith-Lemli-Opitz syndrome patient, 8.2% of wild-type enzyme activity, disease severity score is not directly correlated
W182L
-
enzyme mutation in patients with Smith-Lemli-Opitz syndrome
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine