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Information on EC 1.3.1.70 - DELTA14-sterol reductase
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1.3.1.70 DELTA14-sterol reductaseIUBMB Comments
This enzyme acts on a range of steroids with a 14(15)-double bond.
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Word Map
- 1.3.1.70
- lamins
- envelope
- chromatin
- heterochromatin
- nucleoplasm
- lanosterol
-
emerin
-
lamina-associated
- ergosterol
-
greenberg
-
laminopathies
-
chromatin-binding
- pharmacology
-
ff-mas
-
hypolobulated
-
14alpha-demethylase
- agriculture
- fenpropimorph
- analysis
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
14-reductase, 14-SR, 3 beta-hydroxysterol-DELTA14-reductase, 3beta-hydroxysterol DELTA14-reductase, C-14 reductase, C-14 sterol reductase, C14-SR, C14SR, DELTA14-reductase, DELTA14-SR, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
14-reductase
-
-
-
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3beta-hydroxysterol DELTA14-reductase
C-14 reductase
C-14 sterol reductase
-
-
-
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C14SR
DELTA14-reductase
DELTA14-SR
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DELTA14SR
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DELTA7,14-steroid 14-reductase
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DELTA7,14-sterol 14-reductase
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DELTA7,14-sterol DELTA14-reductase
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DELTA7,14-sterol-14-reductase
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DELTA8,14-hydroxy steroid DELTA14(15)-reductase
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DELTA8,14-steroid 14-reductase
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DELTA8,14-sterol 14-reductase
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DELTA8,14-sterol DELTA14-reductase
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DELTA8,14-sterol-14-reductase
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ERG24
FACKEL protein
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-
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integral membrane sterol reductase
MaSR1
reductase, DELTA8,14-hydroxy steroid DELTA14(15)-
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-
-
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sterol 14-reductase
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-
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sterol C-14 reductase
sterol C14-reductase
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sterol DELTA14,15-reductase
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sterol DELTA14-reductase
TM7SF2
3beta-hydroxysterol DELTA14-reductase
-
besides the endoplasmic reticulum 3beta-hydroxysterol DELTA14-reductase (C14SR) encoded by TM7SF2 gene, the lamin B receptor (LBR) of the inner nuclear membrane possesses 3beta-hydroxysterol DELTA14-reductase activity
C-14 reductase
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-
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DELTA14-reductase
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sterol C-14 reductase
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sterol DELTA14-reductase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
mechanism
-
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
mechanism
-
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
mechanism
-
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
regulation, regulatory mechanism, enzyme induction and suppression, dietary induction
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4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
this enzyme acts on a range of steroids with a 14(15)-double bond
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-
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4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
reduction of 14-double bond of conjugated DELTA8,14-sterols and DELTA7,14-sterols
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4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
determination of residues critical for activity, overview
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4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
residues G225, Y317, and E475 are not essential for activity
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4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+ = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
mechanism
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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redox reaction
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reduction
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DELTA14-reduction in steroids
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PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
cholesterol biosynthesis (algae, late side-chain reductase), cholesterol biosynthesis (plants, early side-chain reductase), cholesterol biosynthesis I, cholesterol biosynthesis II (via 24,25-dihydrolanosterol), ergosterol biosynthesis II, phytosterol biosynthesis (plants), sterol biosynthesis (methylotrophs), zymosterol biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol:NADP+ DELTA14-oxidoreductase
This enzyme acts on a range of steroids with a 14(15)-double bond.
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CAS REGISTRY NUMBER
COMMENTARY
69403-07-2
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4,4-dimethyl-5alpha-cholesta-7,14-dien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-7-en-3beta-ol + NADP+
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + NADPH + H+
4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + NADPH + H+
4alpha-methylfecosterol + NADP+
4alpha-methyl-8,14,24(28)-ergostatrien-3beta-ol + NADPH
4alpha-methyl-8,24(28)-ergostadien-3beta-ol + NADP+
5alpha-cholesta-7,14-dien-3beta-ol + NADPH
5alpha-cholesta-7-en-3beta-ol + NADP+
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43% activity compared with 4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol
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-
?
5alpha-ergosta-8,14,24(28)-trien-3beta-ol + NADPH
5alpha-ergosta-8,24(28)-dien-3beta-ol + NADP+
ergosta-8,14-dien-3beta-ol + NADPH
ergosta-8-en-3beta-ol + NADP+
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DELTA8,14-sterol, ignosterol
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?
follicular fluid meiosis-activating sterol + NADPH
testicular meiosis-activating sterol + NADP+
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-
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?
4,4-dimethyl-5alpha-cholesta-7,14-dien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-7-en-3beta-ol + NADP+
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-
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?
4,4-dimethyl-5alpha-cholesta-7,14-dien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-7-en-3beta-ol + NADP+
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64% activity compared with 4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol
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-
?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
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C29DELTA8,14,24
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?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
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-
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?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
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-
-
-
?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
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probably the natural substrate
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?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
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-
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?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
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probably the natural substrate
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?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
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?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
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?
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
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?
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
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-
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?
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
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best substrate, probably natural substrate
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?
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
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presumably the natural substrate
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?
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + NADPH + H+
4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
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-
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?
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + NADPH + H+
4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
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?
4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + NADPH + H+
4alpha-methylfecosterol + NADP+
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?
4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + NADPH + H+
4alpha-methylfecosterol + NADP+
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step in the biosynthesis of the brassicasterol phytohormones, catalyzed by enzyme FK
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?
4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + NADPH + H+
4alpha-methylfecosterol + NADP+
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?
4alpha-methyl-8,14,24(28)-ergostatrien-3beta-ol + NADPH
4alpha-methyl-8,24(28)-ergostadien-3beta-ol + NADP+
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4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol
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?
4alpha-methyl-8,14,24(28)-ergostatrien-3beta-ol + NADPH
4alpha-methyl-8,24(28)-ergostadien-3beta-ol + NADP+
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4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADP+
5alpha-cholesta-8-en-3beta-ol + NADP+
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LBR
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADP+
5alpha-cholesta-8-en-3beta-ol + NADP+
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TM7SF2
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
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DELTA8,14-cholestadien-3beta-ol
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
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C27DELTA8,14
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
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DELTA8,14-cholestadien-3beta-ol
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
the substrate accumulates in patients suffering autosomal recessive HEM/Greenberg skeletal dysplasia
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
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DELTA8,14-cholestadien-3beta-ol
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
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53% activity compared with 4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
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DELTA8,14-cholestadien-3beta-ol
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADPH + H+
5alpha-cholesta-8-en-3beta-ol + NADP+
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-
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?
5alpha-cholesta-8,14-dien-3beta-ol + NADPH + H+
5alpha-cholesta-8-en-3beta-ol + NADP+
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-
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?
5alpha-ergosta-8,14,24(28)-trien-3beta-ol + NADPH
5alpha-ergosta-8,24(28)-dien-3beta-ol + NADP+
-
-
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?
5alpha-ergosta-8,14,24(28)-trien-3beta-ol + NADPH
5alpha-ergosta-8,24(28)-dien-3beta-ol + NADP+
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-
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?
isofucosterol + NADPH
sitosterol + NADP+
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step in the biosynthesis of the brassicasterol phytohormones, catalyzed by bifunctinal enzyme DIM1/CBB1/DWF1
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?
additional information
?
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brassicasterols have regulatory function in the plants concerning growth and development, the enzyme is up-regulated by several growth-promoting hormones including brassinolide and auxin, overview
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?
additional information
?
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enzyme acts on a range of steroids with a 14(15)-double bond
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?
additional information
?
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14-reductase has a important regulatory role in the overall cholesterol synthetic pathway
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?
additional information
?
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important essential enzyme of cholesterol biosynthesis from lanosterol
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?
additional information
?
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enzyme plays a key role in sterol biosynthesis, sterol content in vivo
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?
additional information
?
-
-
enzyme acts on a range of steroids with a 14(15)-double bond
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?
additional information
?
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enzyme involved in sterol, phytosterol, biosynthesis, DELTA8,14-sterols are intermediates in the biosynthesis of higher plant sterols, phytosterols
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?
additional information
?
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enzyme acts on a range of steroids with a 14(15)-double bond
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?
additional information
?
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14-reductase has a important regulatory role in the overall cholesterol synthetic pathway
-
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?
additional information
?
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important essential enzyme of cholesterol biosynthesis from lanosterol
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?
additional information
?
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enzyme plays a key role in sterol biosynthesis, sterol content in vivo
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?
additional information
?
-
enzyme-deficiency causes the lethal autosomal recessive HEM/Greenberg skeletal dysplasia, characterized by short limbs, fetal hydrops, abnormal chondro-osseous calcification
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?
additional information
?
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enzyme-deficiency causes the lethal autosomal recessive HEM/Greenberg skeletal dysplasia, characterized by short limbs, fetal hydrops, abnormal chondro-osseous calcification
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?
additional information
?
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enzyme-deficiency causes the lethal autosomal recessive HEM/Greenberg skeletal dysplasia, characterized by short limbs, fetal hydrops, abnormal chondro-osseous calcification
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?
additional information
?
-
-
C14SR is encoded by the TM7SF2 gene. TM7SF2 but not LBR, gene expression is regulated by cell sterol levels in HepG2 (human) and H-35 (rat) hepatoma cells. Primary role of C14SR in human cholesterol biosynthesis
-
-
?
additional information
?
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-
role of LBR in the cholesterol biosynthesis pathway is unclear
-
-
?
additional information
?
-
enzyme MaSR1 can reduce the double bond of a cholesterol biosynthetic intermediate analogously to the human enzyme
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?
additional information
?
-
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enzyme MaSR1 can reduce the double bond of a cholesterol biosynthetic intermediate analogously to the human enzyme
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?
additional information
?
-
enzyme MaSR1 can reduce the double bond of a cholesterol biosynthetic intermediate analogously to the human enzyme
-
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?
additional information
?
-
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enzyme MaSR1 can reduce the double bond of a cholesterol biosynthetic intermediate analogously to the human enzyme
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?
additional information
?
-
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enzyme plays a key role in sterol biosynthesis
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?
additional information
?
-
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enzyme plays a key role in sterol biosynthesis, sterol content in vivo
-
-
?
additional information
?
-
-
the charge and geometry given via residues E233, R235, D289, K351, R458, and R461 is important for enzyme activity
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?
additional information
?
-
-
enzyme acts on a range of steroids with a 14(15)-double bond
-
-
?
additional information
?
-
-
enzyme acts on a range of steroids with a 14(15)-double bond
-
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?
additional information
?
-
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reduction of 14-double bond of conjugated DELTA8,14-diene sterols and DELTA7,14-diene sterols
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?
additional information
?
-
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anaerobic conditions yield maximal rates of reduction
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?
additional information
?
-
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4-nor-methyldiene sterols, 5alpha-cholesta-8,14-dien-3beta-ol, and 5alpha-cholesta-7,14-dien-3beta-ol are reduced at about 50% of the rate of the corresponding 4-gem-dimethyldiene sterols, for both the C27-sterol and C29-sterol, the higher reaction rate of the 8,14-diene system is consistently observed over the isomeric 7,14-diene
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-
?
additional information
?
-
-
catalyzes anaerobically NADPH-dependent reduction of 14-double bond of 8,14-diene or 7,14-diene sterols that are sterol intermediates formed during C-32 demethylation in cholesterol biosynthesis from lanosterol in mammals
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?
additional information
?
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catalyzes anaerobically NADPH-dependent reduction of 14-double bond of 8,14-diene or 7,14-diene sterols that are sterol intermediates formed during C-32 demethylation in cholesterol biosynthesis from lanosterol in mammals
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?
additional information
?
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reduction of 14-double bond of sterol-conjugated dienes
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?
additional information
?
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14-reductase has a important regulatory role in the overall cholesterol synthetic pathway
-
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?
additional information
?
-
-
microsomal enzyme of cholesterol biosynthesis from lanosterol
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-
?
additional information
?
-
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important essential enzyme of cholesterol biosynthesis from lanosterol
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?
additional information
?
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enzyme acts on a range of steroids with a 14(15)-double bond
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?
additional information
?
-
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reduction of DELTA8,14-intermediate in ergosterol biosynthetic pathway to DELTA8-intermediate occurs by the trans addition of two hydrogens to the 14alpha- and 15beta-positions
-
-
?
additional information
?
-
-
enzyme of biosynthetic pathways of ergosterol, major sterol in yeast, and cholesterol including a DELTA8,14-sterol intermediate as result of demethylation of lanosterol at C-14
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-
?
additional information
?
-
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essential enzyme of ergosterol, yeast sterol, biosynthesis from lanosterol
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-
?
additional information
?
-
-
essential enzyme of ergosterol, yeast sterol, biosynthesis from lanosterol
-
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?
additional information
?
-
-
enzyme acts on a range of steroids with a 14(15)-double bond
-
-
?
additional information
?
-
-
reduction of DELTA8,14-intermediate in ergosterol biosynthetic pathway to DELTA8-intermediate occurs by the trans addition of two hydrogens to the 14alpha- and 15beta-positions
-
-
?
additional information
?
-
-
enzyme of biosynthetic pathways of ergosterol, major sterol in yeast, and cholesterol including a DELTA8,14-sterol intermediate as result of demethylation of lanosterol at C-14
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-
?
additional information
?
-
-
essential enzyme of ergosterol, yeast sterol, biosynthesis from lanosterol
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-
?
additional information
?
-
-
enzyme is involved in de novo synthesis of progesterone from lanosterol via cholesterol, pathway overview
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?
additional information
?
-
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enzyme acts on a range of steroids with a 14(15)-double bond
-
-
?
additional information
?
-
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DELTA8,14 derivatives are the only substrates to be transformed under normal biosynthetic conditions
-
-
?
additional information
?
-
-
no activity with 5alpha-cholesta-7,14-dien-3beta-ol, 7,14-cholestadien-3beta-ol or 5alpha-cholest-14-en-3beta-ol, 14-cholesten-3beta-ol
-
-
?
additional information
?
-
-
important roles of 4alpha-methyl group and side-chain substitution for recognition but not for catalysis, presence of DELTA8(9) unsaturation is compulsory for catalysis
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8-en-3beta-ol + NADP+
-
presumably the natural substrate
-
-
?
4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + NADPH + H+
4alpha-methylfecosterol + NADP+
-
step in the biosynthesis of the brassicasterol phytohormones, catalyzed by enzyme FK
-
-
?
4alpha-methyl-8,14,24(28)-ergostatrien-3beta-ol + NADPH
4alpha-methyl-8,24(28)-ergostadien-3beta-ol + NADP+
5alpha-cholesta-8,14-dien-3beta-ol + NADPH
5alpha-cholesta-8-en-3beta-ol + NADP+
the substrate accumulates in patients suffering autosomal recessive HEM/Greenberg skeletal dysplasia
-
-
?
follicular fluid meiosis-activating sterol + NADPH
testicular meiosis-activating sterol + NADP+
-
-
-
-
?
isofucosterol + NADPH
sitosterol + NADP+
-
step in the biosynthesis of the brassicasterol phytohormones, catalyzed by bifunctinal enzyme DIM1/CBB1/DWF1
-
-
?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
-
-
-
-
?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
-
probably the natural substrate
-
-
?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
-
probably the natural substrate
-
-
?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
-
-
-
?
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + NADPH + H+
4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + NADP+
-
-
-
?
4alpha-methyl-8,14,24(28)-ergostatrien-3beta-ol + NADPH
4alpha-methyl-8,24(28)-ergostadien-3beta-ol + NADP+
-
4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol
-
-
?
4alpha-methyl-8,14,24(28)-ergostatrien-3beta-ol + NADPH
4alpha-methyl-8,24(28)-ergostadien-3beta-ol + NADP+
-
4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol
-
-
?
additional information
?
-
-
brassicasterols have regulatory function in the plants concerning growth and development, the enzyme is up-regulated by several growth-promoting hormones including brassinolide and auxin, overview
-
-
?
additional information
?
-
-
14-reductase has a important regulatory role in the overall cholesterol synthetic pathway
-
-
?
additional information
?
-
-
important essential enzyme of cholesterol biosynthesis from lanosterol
-
-
?
additional information
?
-
-
enzyme plays a key role in sterol biosynthesis, sterol content in vivo
-
-
?
additional information
?
-
-
enzyme involved in sterol, phytosterol, biosynthesis, DELTA8,14-sterols are intermediates in the biosynthesis of higher plant sterols, phytosterols
-
-
?
additional information
?
-
-
14-reductase has a important regulatory role in the overall cholesterol synthetic pathway
-
-
?
additional information
?
-
-
important essential enzyme of cholesterol biosynthesis from lanosterol
-
-
?
additional information
?
-
-
enzyme plays a key role in sterol biosynthesis, sterol content in vivo
-
-
?
additional information
?
-
enzyme-deficiency causes the lethal autosomal recessive HEM/Greenberg skeletal dysplasia, characterized by short limbs, fetal hydrops, abnormal chondro-osseous calcification
-
-
?
additional information
?
-
enzyme-deficiency causes the lethal autosomal recessive HEM/Greenberg skeletal dysplasia, characterized by short limbs, fetal hydrops, abnormal chondro-osseous calcification
-
-
?
additional information
?
-
-
enzyme-deficiency causes the lethal autosomal recessive HEM/Greenberg skeletal dysplasia, characterized by short limbs, fetal hydrops, abnormal chondro-osseous calcification
-
-
?
additional information
?
-
-
C14SR is encoded by the TM7SF2 gene. TM7SF2 but not LBR, gene expression is regulated by cell sterol levels in HepG2 (human) and H-35 (rat) hepatoma cells. Primary role of C14SR in human cholesterol biosynthesis
-
-
?
additional information
?
-
-
role of LBR in the cholesterol biosynthesis pathway is unclear
-
-
?
additional information
?
-
-
enzyme plays a key role in sterol biosynthesis
-
-
?
additional information
?
-
-
enzyme plays a key role in sterol biosynthesis, sterol content in vivo
-
-
?
additional information
?
-
-
catalyzes anaerobically NADPH-dependent reduction of 14-double bond of 8,14-diene or 7,14-diene sterols that are sterol intermediates formed during C-32 demethylation in cholesterol biosynthesis from lanosterol in mammals
-
-
?
additional information
?
-
-
catalyzes anaerobically NADPH-dependent reduction of 14-double bond of 8,14-diene or 7,14-diene sterols that are sterol intermediates formed during C-32 demethylation in cholesterol biosynthesis from lanosterol in mammals
-
-
?
additional information
?
-
-
reduction of 14-double bond of sterol-conjugated dienes
-
-
?
additional information
?
-
-
14-reductase has a important regulatory role in the overall cholesterol synthetic pathway
-
-
?
additional information
?
-
-
microsomal enzyme of cholesterol biosynthesis from lanosterol
-
-
?
additional information
?
-
-
important essential enzyme of cholesterol biosynthesis from lanosterol
-
-
?
additional information
?
-
-
reduction of DELTA8,14-intermediate in ergosterol biosynthetic pathway to DELTA8-intermediate occurs by the trans addition of two hydrogens to the 14alpha- and 15beta-positions
-
-
?
additional information
?
-
-
enzyme of biosynthetic pathways of ergosterol, major sterol in yeast, and cholesterol including a DELTA8,14-sterol intermediate as result of demethylation of lanosterol at C-14
-
-
?
additional information
?
-
-
essential enzyme of ergosterol, yeast sterol, biosynthesis from lanosterol
-
-
?
additional information
?
-
-
essential enzyme of ergosterol, yeast sterol, biosynthesis from lanosterol
-
-
?
additional information
?
-
-
reduction of DELTA8,14-intermediate in ergosterol biosynthetic pathway to DELTA8-intermediate occurs by the trans addition of two hydrogens to the 14alpha- and 15beta-positions
-
-
?
additional information
?
-
-
enzyme of biosynthetic pathways of ergosterol, major sterol in yeast, and cholesterol including a DELTA8,14-sterol intermediate as result of demethylation of lanosterol at C-14
-
-
?
additional information
?
-
-
essential enzyme of ergosterol, yeast sterol, biosynthesis from lanosterol
-
-
?
additional information
?
-
-
enzyme is involved in de novo synthesis of progesterone from lanosterol via cholesterol, pathway overview
-
-
?
additional information
?
-
-
DELTA8,14 derivatives are the only substrates to be transformed under normal biosynthetic conditions
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
the binding pocket for NADPH is localized to the C-terminal domain transmembrane segments TM6-10
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
no activation by Mg2+ or Ca2+, 0.5-20 mM, but slight inhibition
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3beta-(2-(diethylamino)ethoxy)androst-5-en-17-one
-
U18666A, IC50: 0.004 mM
4-(3-[[1-(4-bromophenyl)piperidin-4-yl](methyl)amino]-1-methoxypropyl)benzonitrile
-
using a genetic aproach in Saccharomyces cerevisiae it is shown that ERG24 is the target enzyme of compound 4-(3-[[1-(4-bromophenyl)piperidin-4-yl](methyl)amino]-1-methoxypropyl)benzonitrile
AY9944-A-7
-
enzyme-specific inhibitor, leads to apoptosis in vivo at high concentrations in cumulus cells of oocytes
brefeldin
-
inhibition of growth of mutant strains NJ25, NJ50, NJ51, and NJ55, not of wild-type strain and mutant NJ25, overview
cerulenin
-
inhibition of growth of mutant strains NJ25, NJ50, NJ51, and NJ55, not of wild-type strain and mutant NJ25, overview
cholesterol
-
enzyme suppressed by feeding 5% cholesterol, 70% decrease in enzyme activity
clotrimazole
-
inhibition of growth of wild-type and mutant strains NJ25, NJ50, NJ51, and NJ55, overview
fluconazole
-
inhibition of growth of wild-type and mutant strain NJ25, only slightly of mutant strains NJ50, NJ51, and NJ55, overview
fluphenazine
-
inhibition of growth of mutant strains NJ25, NJ50, NJ51, and NJ55, not of wild-type strain and mutant NJ25, overview
HgCl2
-
3 mM: more than 99% inhibition, inhibition negligible in the presence of 10 mM glutathione
itraconazole
-
inhibition of growth of wild-type and mutant strain NJ25, only slightly of mutant strains NJ50, NJ51, and NJ55, overview
ketoconazole
-
inhibition of growth of wild-type and mutant strains NJ25, NJ50, NJ51, and NJ55, overview
N-ethylmaleimide
-
5 mM: 53% inhibition, inhibition negligible in the presence of 10 mM glutathione
NADP+
-
in the absence of NADPH-regenerating system, Ki: 0.45 mM; no inhibition by NAD+
Nystatin
-
inhibition of growth of wild-type and mutant strain NJ25, not of mutants strains NJ50, NJ51, and NJ55, overview
Phospholipase A2
-
very high inhibition by very small concentrations, activity not restored by addition of phospholipids or any components presumed to be released from treated microsomes. Various concentration ranges of potential cofactors including FMN, FAD, AMP, ADP, ATP, coenzyme Q, Coenzyme A, and hemin, plus heat-treated microsomes, and lipid extracts of microsomes does not restore microsomal 14-reductase of phospholipase A2-treated microsomes
-
terbinafine
-
inhibition of growth of mutant strains NJ25, NJ50, NJ51, and NJ55, not of wild-type strain and mutant NJ25, overview
Triparanol
-
4-chloro-alpha-[4-[2-diethylaminoethoxy]phenyl]-alpha-(4-methylphenyl)benze-methanol, slight inhibition
Tris-HCl
-
Tris-HCl buffer, 28% inhibition, not restored by addition of KCl at various concentrations
15-aza-24-methylene-D-homocholestadiene-3beta-ol
-
A25822B, extremely potent inhibitor
15-aza-24-methylene-D-homocholestadiene-3beta-ol
-
A25822B, extremely potent inhibitor
15-azasterol
-
15-aza-24-methylene-D-homocholestadiene; potent antimycotic agent, designated A258223, non-competitively inhibition at very low concentrations, Ki: 0.000002 mM
Ca2+
-
slight inhibition of growth of the wild-type strain, increased inhibition of growth of erg24 mutant strains
cyanide
-
cyanide ion, membrane-bound enzyme, modest inhibition at high concentrations, greater than 1 mM, partial purified enzyme, sodium cyanide, no or very poor inhibition, 10 mM: 3.5% inhibition
cycloheximide
-
inhibition of growth of mutant strains NJ25, NJ50, NJ51, and NJ55, not of wild-type strain and mutant NJ25, overview
cycloheximide
-
the 2.5fold increase in enzymic activity due to the diurnal rhythm is completely abolished by cycloheximide
fenpropidin
-
fungicide, very potent inhibitor; IC50: 0.0018 mM; N-[3-(p-tert-butylphenyl)-2-methylpropyl]-piperidine
fenpropidin
-
fungicide, very potent inhibitor; N-[3-(p-tert-butylphenyl)-2-methylpropyl]-piperidine
fenpropimorph
-
impairs cell expansion and affects gene expression in vivo, the effects cannot be reversed by addition of exogenous brassicasterols, changes sterol composition, phenotype is similar to fk-mutant plants, molecular mechanism
fenpropimorph
-
inhibition of growth of wild-type and mutant strains NJ25, NJ50, NJ51, and NJ55, overview
fenpropimorph
-
fungicide, very potent inhibitor; IC50: 0.0023 mM; N-[3-(p-tert-butylphenyl)-2-methylpropyl]-cis-2,6-dimethylmorpholine
fenpropimorph
-
fungicide, very potent inhibitor; N-[3-(p-tert-butylphenyl)-2-methylpropyl]-cis-2,6-dimethylmorpholine
N(1,5,9-trimethyldecyl)-4alpha,10-dimethyl-8-aza-trans-decal-3beta-ol
-
extremely potent inhibitor
N(1,5,9-trimethyldecyl)-4alpha,10-dimethyl-8-aza-trans-decal-3beta-ol
-
extremely potent inhibitor
N-Benzyl-8-aza-4alpha,10-dimethyl-trans-decal-3beta-ol
-
extremely potent inhibitor
N-dodecyl-8-aza-4alpha,10-dimethyl-trans-decal-3beta-ol
-
extremely potent inhibitor
N-dodecyl-8-aza-4alpha,10-dimethyl-trans-decal-3beta-ol
-
extremely potent inhibitor
N-[(3)-4-tert-butylphenyl-(2-methyl)propyl]-8-aza-4alpha,10-dimethyl-trans-decal-3beta-ol
-
extremely potent inhibitor
N-[(3)-4-tert-butylphenyl-(2-methyl)propyl]-8-aza-4alpha,10-dimethyl-trans-decal-3beta-ol
-
extremely potent inhibitor
trans-1,4-bis(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride
-
AY-9944, strong inhibition, 0.0003 mM: 50% inhibition, 0.0005 mM: 65% inhibition
trans-1,4-bis(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride
-
0.01% AY-9944: suppression and inhibition; AY-9944, competitive inhibitor, strong inhibition, Ki: 0.00026; AY-9944, direct inhibitory effects of sterol 14-reductase; hepatocyte, IC50: 0.00025 mM, microsomes, IC50: 0.0003 mM
trans-1,4-bis(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride
-
AY 9944, very slight inhibition, IC50: 0.04 mM
tridemorph
-
inhibition of growth of wild-type and mutant strains NJ25, NJ50, NJ51, and NJ55, overview
tridemorph
-
2,6-dimethyl-N-tridecylmorpholine; fungicide; slight inhibitor, IC50: 0.098 mM
additional information
-
inhibition by a series of ammonium-ion-containing fungicides
-
additional information
-
no direct inhibition by 3beta-hydroxy-4,4-dimethyl-5alpha-cholest-8(14)-en-15-one, even when concentration is increased to level of Km for substrate; no inhibition by trypsin
-
additional information
-
kinetic pattern of inhibition; no inhibition by lovastatin, mevalonolactone, Squalestatin 1, (E)-N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-((3,3'-bithiophen-5-yl)methoxy)benzenemethanamine, NB-598
-
additional information
-
no inhibition by ergosterol, up to 0.2 mM
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cholestyramine
-
11fold induction and activation by feeding 5% cholestyramine plus 0.1% lovastatin, CL-diet. 2fold induction and activation by feeding 5% cholestyramine alone
liposome
-
activity of purified enzyme totally dependent on the presence of liposome and NADPH
-
lovastatin
-
11fold induction and activation by feeding 5% cholestyramine plus 0.1% lovastatin, CL-diet. 4fold induction and activation by feeding 0.1% lovastatin alone
phosphatidylcholine
-
liposomal phosphatidylcholine, egg yolk: 1.4fold activation
additional information
-
brassicasterols have regulatory function in the plants concerning growth and development, the enzyme is up-regulated by several growth-promoting hormones including brassinolide and auxin, overview
-
additional information
-
the 2.5fold increase in enzymic activity due to the diurnal rhythm is completely abolished by cycloheximide
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Acute Kidney Injury
The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury.
Adenoma
Differential gene expression profiling of aggressive and nonaggressive follicular carcinomas.
Alzheimer Disease
Quantitation of glycogen synthase kinase-3 sensitive proteins in neuronal membrane rafts.
Bone Diseases, Developmental
A new case of Greenberg dysplasia and literature review suggest that Greenberg dysplasia, dappled diaphyseal dysplasia, and Astley-Kendall dysplasia are allelic disorders.
Breast Neoplasms
Spatiotemporal Mislocalization of Nuclear Membrane-Associated Proteins in ?-Irradiation-Induced Senescent Cells.
Breast Neoplasms
The clinicopathological significance of lamin A/C, lamin B1 and lamin B receptor mRNA expression in human breast cancer.
Candidiasis
ERG2 and ERG24 Are Required for Normal Vacuolar Physiology as Well as Candida albicans Pathogenicity in a Murine Model of Disseminated but Not Vaginal Candidiasis.
Carcinoma
Differential gene expression profiling of aggressive and nonaggressive follicular carcinomas.
Carcinoma
Distinct cellular responses to replication stress leading to apoptosis or senescence.
Carcinoma
Spatiotemporal Mislocalization of Nuclear Membrane-Associated Proteins in ?-Irradiation-Induced Senescent Cells.
Chondrodysplasia Punctata
Genetic disorders of cholesterol biosynthesis in mice and humans.
Colonic Neoplasms
Comprehensive analysis of metastasis-related genes reveals a gene signature predicting the survival of colon cancer patients.
delta14-sterol reductase deficiency
Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3 beta-hydroxysterol delta 14-reductase deficiency due to mutations in the lamin B receptor gene.
delta14-sterol reductase deficiency
HEM dysplasia and ichthyosis are likely laminopathies and not due to 3beta-hydroxysterol Delta14-reductase deficiency.
delta14-sterol reductase deficiency
Impaired cell proliferation in regenerating liver of 3 ?-hydroxysterol ?14-reductase (TM7SF2) knock-out mice.
Herpes Simplex
A three-residue signal confers localization of a reporter protein in the inner nuclear membrane.
Herpes Simplex
Fate of the inner nuclear membrane protein lamin B receptor and nuclear lamins in herpes simplex virus type 1 infection.
Ichthyosis
HEM dysplasia and ichthyosis are likely laminopathies and not due to 3beta-hydroxysterol Delta14-reductase deficiency.
Ichthyosis
Mutations at the mouse ichthyosis locus are within the lamin B receptor gene: a single gene model for human Pelger-Huët anomaly.
Infections
Characterization of lamin B receptor of Sf9 cells and its fate during Autographa californica nucleopolyhedrovirus infection.
Infections
Fate of the inner nuclear membrane protein lamin B receptor and nuclear lamins in herpes simplex virus type 1 infection.
Laminopathies
HEM dysplasia and ichthyosis are likely laminopathies and not due to 3beta-hydroxysterol Delta14-reductase deficiency.
Liver Cirrhosis, Biliary
Autoantibodies from patients with primary biliary cirrhosis recognize a region within the nucleoplasmic domain of inner nuclear membrane protein LBR.
Liver Cirrhosis, Biliary
Identification and characterization of autoantibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis.
Metabolism, Inborn Errors
Genetic disorders of cholesterol biosynthesis in mice and humans.
Mevalonate Kinase Deficiency
Genetic disorders of cholesterol biosynthesis in mice and humans.
Neoplasms
Candidate diagnostic markers and tumor suppressor genes for adrenocortical carcinoma by expression profile of genes on chromosome 11q13.
Neoplasms
Differential gene expression profiling of aggressive and nonaggressive follicular carcinomas.
Osteosarcoma
Spatiotemporal Mislocalization of Nuclear Membrane-Associated Proteins in ?-Irradiation-Induced Senescent Cells.
Pelger-Huet Anomaly
Alterations in nuclear structure promote lupus autoimmunity in a mouse model.
Pelger-Huet Anomaly
Mouse neutrophils lacking lamin B-receptor expression exhibit aberrant development and lack critical functional responses.
Pelger-Huet Anomaly
Mutations at the mouse ichthyosis locus are within the lamin B receptor gene: a single gene model for human Pelger-Huët anomaly.
Renal Insufficiency
The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0294
4,4-dimethyl-5alpha-cholesta-7,14-dien-3beta-ol
-
membrane-bound enzyme, Lineweaver-Burk
0.0345
4,4-dimethyl-5alpha-cholesta-7,14-dien-3beta-ol
-
microsomal-bound enzyme
additional information
additional information
-
kinetic pattern of inhibition
-
additional information
additional information
-
Km for 4,4-dimethylcholesta-8,14,24-trienol, probably the natural substrate of DELTA14-reductase in yeast, may be different because of interactions of enzyme with C-4 methyl groups
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.004
3beta-(2-(diethylamino)ethoxy)androst-5-en-17-one
Rattus norvegicus
-
U18666A, IC50: 0.004 mM
0.0003
trans-1,4-bis(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride
Rattus norvegicus
-
hepatocyte, IC50: 0.00025 mM, microsomes, IC50: 0.0003 mM
0.04
trans-1,4-bis(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride
Zea mays
-
AY 9944, very slight inhibition, IC50: 0.04 mM
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7
-
DELTA8,14-streol DELTA14-reductase has relatively broad pH profile in the basic region with optimal pH at pH 7.8, activity decreases rapidly at pH below 7
7.8
-
14-reductase has relatively broad pH profile in acidic region, activity drastically decreases with only moderate elevation of pH above 7.8
additional information
additional information
-
14-reductase has relatively broad pH profile in acidic region, activity drastically decreases with only moderate elevation of pH above 7.8
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene erg-3, strain 74-OR23-1 mat, and enzyme-deficient mutant strains OR8-1 mat a and erg-3 mat a
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
of an 18-weeks-old fetus with autosomal recessive HEM/Greenberg skeletal dysplasia showing enzyme-deficiency
brenda
additional information
-
in foetal heart the expression is much lower then in the adult heart, TM7SF2
brenda
-
in foetal thymus expression is much higher than in the adult thymus, TM7SF2
brenda
additional information
-
fk gene expression pattern in wild-type and mutant strains, regulatory effects of sterols, overview
brenda
additional information
-
growth of wild-type and disruption mutant strains with various media and temperature conditions, overview
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
integral membrane enzyme, the enzyme contains ten transmembrane segments, TM1-10
brenda
-
integral membrane enzyme, the enzyme contains ten transmembrane segments, TM1-10
-
brenda
additional information
-
enzyme non-mitochondrial, greatest activity in hard protein pellet, suggesting that enzyme is an insoluble protein
-
brenda
additional information
-
enzyme non-mitochondrial, greatest activity in hard protein pellet, suggesting that enzyme is an insoluble protein
-
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
the enzyme belongs to the sterol reductase family
malfunction
-
FgERG24A and FgERG24B are deleted in Fusarium graminearum. Compared to the wild-type strain HN9-1, FgERG24A and FgERG24B deletion mutants do not show recognizable phenotypic changes in mycelial growth on potato dextrose agar or in virulence on wheat heads. FgERG24B deletion mutants exhibit significantly increased sensitivity to amine fungicides, including tridemorph, fenpropidin and spiroxamine. FgERG24A deletion mutants do not show changed sensitivity to any amine tested. The resistance of the FgERG24B deletion mutant to amines is restored by genetic complementation of the mutant with wild-type FgERG24B
malfunction
Arabidopsis thaliana weak mutant allele fk-J3158, impaired in the FACKEL (FK) gene, which encodes the C-14 reductase, has a long life cycle and delayed flowering time in different photoperiods. Enzyme overexpression lines display an earlier flowering phenotype than that of the wild-type, flowering time of fk-J3158 flc double mutant is significantly earlier than that of fk-J3158 under the long-day conditions. These processes might be independent of the downstream brassinosteroid pathway and the autonomous pathway. The fk-J3158 plants are more sensitive than wild-type in reducing the bolting days and total leaf number under gibberellic acid treatment. Enzyme mutation leads to an absence of endogenous gibberellic acids in fk-J3158 and FK gene expression also affected under gibberellic acid and paclobutrazol treatment. The delayed flowering time of fk-J3158 is rescued by a 3-week vernalization treatment, and the expression of flowering locus C C (FLC) is accordingly downregulated in fk-J3158. Flowering time of fk-J3158 flc double mutant is significantly earlier than that of fk-J3158 under the long-day conditions. Phenotypes, detailed overview
malfunction
Tm7sf2 deficiency during liver regeneration alters lipid metabolism and generates a stress condition, which, in turn, transiently unbalances hepatocytes cell cycle progression. Tm7sf2 knockout mice show no alteration in cholesterol content, but accumulation and delayed catabolism of hepatic triglycerides is observed, resulting in persistent steatosis at all times post hepatectomy. Delayed cell cycle progression to the G1/S phase is observed in Tm7sf2 knockout mice, resulting in reduced cell division at the time points examined associated to abnormal endoplasmic reticulum stress response, leading to alteration in p53 content and, consequently, induction of p21 expression in Tm7sf2 knockout mice. Tm7sf2 knockout mice exhibit a high-degree of transient hepatic steatosis during liver regeneration after partial hepatectomy. Hepatocytes from Tm7sf2 KO mice have a defective progression through the G1/S phase, associated to delayed and/or reduced expression of central regulators of the cell cycle such as cyclin D1, cyclin A, cyclin E1 and CDK4
metabolism
-
an inverse upregulation of lanosterol 14alpha-demethylase, CYP51, and downregulation of 14-SR expression under luteinizing hormone/follicle stimulating hormone stimulation functions as the machinery for FF-MAS accumulation in preovulatory follicles prior to ovulation in the rabbit, overview
metabolism
the enzyme is involved in the cholesterol biosynthesis pathway
metabolism
-
the enzyme is involved in the cholesterol biosynthesis pathway
-
physiological function
-
FgERG24B controls the intrinsic resistance of Fusarium graminearum to amines
physiological function
the enzyme catalyzes the reduction of C14-unsaturated sterols during cholesterol biosynthesis from lanosterol. Role of C14-SR in vivo during cell proliferation by evaluating liver regeneration in Tm7sf2 knockout and wild-type mice, overview
physiological function
the enzyme is involved in sterol biosynthesis, but is also involved in the flowering of Arabidopsis mainly via the gibberellin pathway and vernalization pathway. This function of the enzyme is partially dependent on the FLOWERING LOCUS C (FLC)
additional information
TM7SF2 gene expression is controlled by cell sterol levels through the SREBP-2, motifs of TM7SF2 promoter responsible for activation by SREBP-2 are the SRE motif, and both the inverted CCAAT-box and GC-box2, which are essential for full promoter activation by SREBP-2, overview. Binding of SREBP-2 to SRE produces approximately 26fold promoter activation, whereas mutation of the SRE motif causes a dramatic decrease of transactivation by SREBP-2
additional information
the enzyme contains ten transmembrane segments (TM1-10). Its catalytic domain comprises the carboxy-terminal half (containing TM6-10) and envelops two interconnected pockets, one of which faces the cytoplasm and houses NADPH, while the other one is accessible from the lipid bilayer. The reducing end of NADPH meets the sterol substrate at the juncture of the two pockets
additional information
-
the enzyme contains ten transmembrane segments (TM1-10). Its catalytic domain comprises the carboxy-terminal half (containing TM6-10) and envelops two interconnected pockets, one of which faces the cytoplasm and houses NADPH, while the other one is accessible from the lipid bilayer. The reducing end of NADPH meets the sterol substrate at the juncture of the two pockets
additional information
-
the enzyme contains ten transmembrane segments (TM1-10). Its catalytic domain comprises the carboxy-terminal half (containing TM6-10) and envelops two interconnected pockets, one of which faces the cytoplasm and houses NADPH, while the other one is accessible from the lipid bilayer. The reducing end of NADPH meets the sterol substrate at the juncture of the two pockets
-
Show AA Sequence and Transmembrane Helices (465 entries)
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
38000
46750
-
cloned cDNA, calculated from amino-acid sequence. The discrepancy between the apparent molecular mass of 38000 Da estimated by SDS-PAGE and the calculated molecular mass may be due to an aberrant electrophoretic migration
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the enzyme contains ten transmembrane segments (TM1-10). Its catalytic domain comprises the carboxy-terminal half (containing TM6-10) and envelops two interconnected pockets, one of which faces the cytoplasm and houses NADPH, while the other one is accessible from the lipid bilayer
additional information
-
the enzyme contains ten transmembrane segments (TM1-10). Its catalytic domain comprises the carboxy-terminal half (containing TM6-10) and envelops two interconnected pockets, one of which faces the cytoplasm and houses NADPH, while the other one is accessible from the lipid bilayer
additional information
-
the enzyme contains ten transmembrane segments (TM1-10). Its catalytic domain comprises the carboxy-terminal half (containing TM6-10) and envelops two interconnected pockets, one of which faces the cytoplasm and houses NADPH, while the other one is accessible from the lipid bilayer
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified wild-type and mutant enzymes in complex with NADPH, hanging drop vapour diffusion method, mixing of protein solution containing 2 mM NADPH with reservoir solution containing 0.1 M Tris-HCl, pH 7.0, 0.2 M NH4Ac, and 30% v/v pentaerythritol ethoxylate, 5 days, 20°C, platinum-derivatives are obtained by soaking native crystals for 12 h in mother liquor plus 10 mg/ml K2Pt(NO2)4, X-ray diffraction structure determination and analysis at 2.74-4.3 A resolution, selenium-based single-wavelength anomalous dispersion, modeling
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D207N
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
D227N
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
D276N
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
D289E
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
D289N
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
D293N
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
D394N
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
D462N
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
D463N
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
E22Q
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
E233D
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
E233Q
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
E475Q
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
G225C
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
H388A
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
H457A
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
K229A
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
K351A
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
K351R
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
K469A
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
R212A
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
R217A
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
R235A
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
R235K
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
R345A
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
R355A
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
R458A
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
R458K
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
R461A
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
R461K
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
T371A
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
Y124F
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
Y273F
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
Y317F
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
Y391F
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
Y445F
-
site-directed mutagenesis, mutant cannot complement enzyme-deficient erg-3 mutant strain mat a
Y447F
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
Y470F
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
Y477F
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
Y490F
-
site-directed mutagenesis, mutant can complement enzyme-deficient erg-3 mutant strain mat a
additional information
additional information
-
mutational blockage of the enzyme leads to accumulation of atypical products from substrate 4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol in vivo, i.e. 5alpha-cholesta-8,14-dien-3beta-ol, (24R)-5alpha-ergosta-8,14-dien-3beta-ol, and (24R)-5alpha-stigmasta-8,14-dien-3beta-ol
additional information
-
erg24 gene disruption mutant strains, i.e. strain NJ25, NJ50, NJ51, and NJ55, show growth, but altered phenotypes, e.g. increased sensitivity against an allylamine antifungal compound, overview
additional information
enzyme deficiency due to mutations in the lamin B receptor gene causes autosomal recessive HEM/Greenberg skeletal dysplasia
additional information
enzyme deficiency due to mutations in the lamin B receptor gene causes autosomal recessive HEM/Greenberg skeletal dysplasia
additional information
-
enzyme deficiency due to mutations in the lamin B receptor gene causes autosomal recessive HEM/Greenberg skeletal dysplasia
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
detergents such as Lubrol-WX, Emulgen 911, Triton X-100, Triton WR-1339, and their combinations with ionic detergents such as taurodeoxycholate, cholate, and Na+ salts destroy enzyme even at low concentration, 0.1-0.5%, w/v
-
enzyme very labile
very labile membrane-bound enzyme, totally dependent on the presence of liposome and NADPH
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His8-tagged, seleniummethionine-labeled wild-type and mutant enzymes from Escherichia coli strain C43(DE3) by nickel affinity chromatography and gel filtration
solubilization with combined octylglucoside and sodium taurodeoxycholate system and partial purification
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
14-SR, DNA and amino acid sequence determination and analysis, expression pattern, overview
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a Neurospora crassa enzyme-deficient erg-3 mutant strain mat a and a yeast erg-4 mutant strain AP2 cannot be complemented by expression of 6 chimeric enzyme mutants variants constructed from the enzyme encoded by gene TM7SF2 and the Neurospora crassa gene erg-3 encoded enzyme
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an enzyme-deficient erg-3 mutant strain mat a and a yeast erg-4 mutant strain AP2 cannot be complemented by expression of 6 chimeric enzyme mutants variants constructed from the enzyme encoded by erg-3 and the human gene TM7SF2 encoding the SR-1 protein
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DNA and amino acid sequence determination and analysis of 2 mutants, i.e. TM7SF2 and LBR, with autosomal recessive HEM/Greenberg skeletal dysplasia expressing a defective, truncated enzyme
gene erg24, DNA and amino acid sequence determination, subcloning in Escherichia coli strain DH5alpha, complementation of the enzyme-deficient Saccharomyces cerevisiae erg24 mutant strain AP2
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gene TM7SF2, promoter analysis, the promoter contains a 5'-ATTGG-3' sequence, an inverted CCAAT-box, 14 bp upstream the -73/-64 SRE-like motif, and is a region responsible for promoter regulation by sterols and by coexpressed SREBP-2, expression analysis, overview
sequence comparisons, recombinant FLAG-tagged enzyme expression in human HEK-293 cells, recombinant expression of His8-tagged, seleniummethionine-labeled wild-type and mutant enzymes in Escherichia coli strain C43(DE3)
sterol DELTA14-reductase mRNA expression in bovine tisssues, high levels in liver and brain
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
2-amino-nonyl-6-methoxyl-tetralin muriate increases mRNA levels of sterol metabolism genes such as ERG24
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luteinizing hormone and follicle stimulating hormone both downregulates expression of 14-SR with the progression of antral follicular development
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TM7SF2 gene expression is controlled by cell sterol levels through the SREBP-2, motifs of TM7SF2 promoter responsible for activation by SREBP-2 are the SRE motif, and both the inverted CCAAT-box and GC-box2, which are essential for full promoter activation by SREBP-2, overview. Binding of SREBP-2 to SRE produces approximately 26fold promoter activation
TM7SF2 gene expression is controlled by cell sterol levels through the SREBP-2, mutation of the SRE motif causes a dramatic decrease of transactivation by SREBP-2
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
agriculture
-
target for important antifungal agents for use in the control of plant diseases
analysis
-
partial purified enzyme suitable for reconstitution studies, reconstitution of isolated, soluble enzymes involved in cholesterol biosynthesis from lanosterol
pharmacology
-
enzyme is a potential antifungal target site, development of antifungal compounds
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bottema, C.K.; Parks, L.W.
DELTA14-Sterol reductase in Saccharomyces cerevisiae
Biochim. Biophys. Acta
531
301-307
1978
Saccharomyces cerevisiae, Saccharomyces cerevisiae 3701B
brenda
Paik, Y.K.; Trzaskos, J.M.; Shafiee, A.; Gaylor, J.L.
Microsomal enzymes of cholesterol biosynthesis from lanosterol. Characterization, solubilization, and partial purification of NADPH-dependent DELTA8,14-steroid 14-reductase
J. Biol. Chem.
259
13413-13423
1984
Rattus norvegicus
brenda
Kim, C.K.; Jeon, K.I.; Lim, D.M.; Johng, T.N.; Trzaskos, J.M.; Gaylor, J.L.; Paik, Y.K.
Cholesterol biosynthesis from lanosterol: regulation and purification of rat hepatic sterol 14-reductase
Biochim. Biophys. Acta
1259
39-48
1995
Rattus norvegicus
brenda
Roberti, R.; Bennati, A.M.; Galli, G.; Caruso, D.; Maras, B.; Aisa, C.; Beccari, T.; Della Fazia, M.A.; Servillo, G.
Cloning and expression of sterol DELTA14-reductase from bovine liver
Eur. J. Biochem.
269
283-290
2002
Bos taurus, Homo sapiens
brenda
Taton, M.; Benveniste, P.; Rahier, A.
Microsomal DELTA8,14-sterol DELTA14-reductase in higher plants. Characterization and inhibition by analogues of a presumptive carbocationic intermediate of the reduction reaction
Eur. J. Biochem.
185
605-614
1989
Embryophyta, Zea mays
brenda
Lorenz, R.T.; Parks, L.W.
Cloning, sequencing, and disruption of the gene encoding sterol C-14 reductase in Saccharomyces cerevisiae
DNA Cell Biol.
11
685-692
1992
Saccharomyces cerevisiae
brenda
Baloch, R.I.; Mercer, E.I.
Inhibition of sterol DELTA8 -> DELTA7-isomerase and DELTA14-reductase by fenpropimorph, tridemorph and fenpropidin in cell-free enzyme systems from Saccharomyces cerevisiae
Phytochemistry
26
663-668
1987
Saccharomyces cerevisiae, Ustilago maydis, Saccharomyces cerevisiae NCYC 739
-
brenda
Waterham, H.R.; Koster, J.; Mooyer, P.; Noort Gv, G.; Kelley, R.I.; Wilcox, W.R.; Wanders, R.J.; Hennekam, R.C.; Oosterwijk, J.C.
Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3beta-hydroxysterol DELTA14-reductase deficiency due to mutations in the lamin B receptor gene
Am. J. Hum. Genet.
72
1013-1017
2003
Homo sapiens (O76062), Homo sapiens (Q14739), Homo sapiens
brenda
Jia, N.; Arthington-Skaggs, B.; Lee, W.; Pierson, C.A.; Lees, N.D.; Eckstein, J.; Barbuch, R.; Bard, M.
Candida albicans sterol C-14 reductase, encoded by the ERG24 gene, as a potential antifungal target site
Antimicrob. Agents Chemother.
46
947-957
2002
Candida albicans
brenda
Yamashita, Y.; Nishibori, M.; Terada, T.; Isobe, N.; Shimada, M.
Gonadotropin-induced DELTA14-reductase and DELTA7-reductase gene expression in cumulus cells during meiotic resumption of porcine oocytes
Endocrinology
146
186-194
2005
Sus scrofa
brenda
Prakash, A.; Kasbekar, D.P.
Genes encoding chimeras of Neurospora crassa erg-3 and human TM7SF2 proteins fail to complement Neurospora and yeast sterol C-14 reductase mutants
J. Biosci.
27
105-112
2002
Homo sapiens, Neurospora crassa
brenda
Prakash, A.; Kasbekar, D.P.
The sterol C-14 reductase encoded by the Neurospora crassa erg-3 gene: essential charged and polar residues identified by site-specific mutagenesis
Mol. Genet. Genomics
266
787-795
2002
Neurospora crassa
brenda
He, J.X.; Fujioka, S.; Li, T.C.; Kang, S.G.; Seto, H.; Takatsuto, S.; Yoshida, S.; Jang, J.C.
Sterols regulate development and gene expression in Arabidopsis
Plant Physiol.
131
1258-1269
2003
Arabidopsis thaliana
brenda
Bennati, A.M.; Castelli, M.; Della Fazia, M.A.; Beccari, T.; Caruso, D.; Servillo, G.; Roberti, R.
Sterol dependent regulation of human TM7SF2 gene expression: role of the encoded 3beta-hydroxysterol DELTA14-reductase in human cholesterol biosynthesis
Biochim. Biophys. Acta
1761
677-685
2006
Homo sapiens
brenda
Shah Alam Bhuiyan, M.; Eckstein, J.; Barbuch, R.; Bard, M.
Synthetically lethal interactions involving loss of the yeast ERG24: the sterol C-14 reductase gene
Lipids
42
69-76
2007
Saccharomyces cerevisiae
brenda
Schiavoni, G.; Bennati, A.M.; Castelli, M.; Fazia, M.A.; Beccari, T.; Servillo, G.; Roberti, R.
Activation of TM7SF2 promoter by SREBP-2 depends on a new sterol regulatory element, a GC-box, and an inverted CCAAT-box
Biochim. Biophys. Acta
1801
587-592
2010
Homo sapiens (O76062)
brenda
Wang, F.; Yang, J.; Wang, H.; Xia, G.
Gonadotropin-regulated expressions of lanosterol 14alpha-demethylase, sterol DELTA14-reductase and C-4 sterol methyl oxidase contribute to the accumulation of meiosis-activating sterol in rabbit gonads
Prostaglandins Other Lipid Mediat.
92
25-32
2010
Oryctolagus cuniculus
brenda
Liang, R.M.; CAO, YB.; Fan, K.H.; Xu, Y.; Gao, P.H.; Zhou, Y.J.; Tang, H.; Liu, H.T.; Jiang, Y.Y.
2-Amino-nonyl-6-methoxyl-tetralin muriate inhibits sterol C-14 reductase in the ergosterol biosynthetic pathway
Acta Pharmacol. Sin.
30
1709
2009
Candida albicans
brenda
Hata, M.; Ishii, Y.; Watanabe, E.; Uoto, K.; Kobayashi, S.; Yoshida, K.; Otani, T.; Ando, A.
Inhibition of ergosterol synthesis by novel antifungal compounds targeting C-14 reductase
Med. Mycol.
48
613-621
2010
Candida albicans
brenda
Liu, X.; Fu, J.; Yun, Y.; Yin, Y.; Ma, Z.
A sterol C-14 reductase encoded by FgERG24B is responsible for the intrinsic resistance of Fusarium graminearum to amine fungicides
Microbiology
157
1665-1675
2011
Fusarium graminearum
brenda
Bartoli, D.; Piobbico, D.; Bellet, M.M.; Bennati, A.M.; Roberti, R.; Della Fazia, M.A.; Servillo, G.
Impaired cell proliferation in regenerating liver of 3beta-hydroxysterol DELTA14-reductase (TM7SF2) knock-out mice
Cell Cycle
15
2164-2173
2016
Mus musculus (Q71KT5)
brenda
Li, X.; Roberti, R.; Blobel, G.
Structure of an integral membrane sterol reductase from Methylomicrobium alcaliphilum
Nature
517
104-107
2015
Methylomicrobium alcaliphilum (G4SW86), Methylomicrobium alcaliphilum, Methylomicrobium alcaliphilum 20Z (G4SW86), Methylomicrobium alcaliphilum 20Z
brenda
Huang, B.; Qian, P.; Gao, N.; Shen, J.; Hou, S.
Fackel interacts with gibberellic acid signaling and vernalization to mediate flowering in Arabidopsis
Planta
245
939-950
2017
Arabidopsis thaliana (Q9LDR4)
brenda
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