Any feedback?
Information on EC 1.14.14.17 - squalene monooxygenase and Organism(s) Homo sapiens
for references in articles please use BRENDA:EC1.14.14.17Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.14.14.17 squalene monooxygenaseIUBMB Comments
A flavoprotein (FAD). This enzyme, together with EC 5.4.99.7, lanosterol synthase, was formerly known as squalene oxidocyclase. The electron donor is EC 1.6.2.4, NADPH---hemoprotein reductase [5,7].
Specify your search results
Word Map
- 1.14.14.17
- cholesterol
- sterol
- terbinafine
- ergosterol
- trichophyton
- mevalonate
- lanosterol
- allylamine
- 2,3-oxidosqualene
- hmg-coa
- itraconazole
- mentagrophytes
- rubrum
- oxidosqualene
-
terbinafine-resistant
- tellurium
- tinea
- naftifine
- interdigitale
-
antimycotic
-
bloch
-
griseofulvin
-
dammarenediol
-
dermatophytoses
- cycloartenol
- beta-amyrin
- medicine
-
corporis
- drug development
- nutrition
- biotechnology
- pharmacology
-
cholesterogenic
- synthesis
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
Synonyms
squalene epoxidase, squalene monooxygenase, erg1p, erg1 protein, pgsqe1, pgsqe2, tksqe1, squalene mono-oxygenase, squalene epoxidase 1, squalene-2,3-epoxide cyclase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
hydroxylase, squalene
-
-
-
-
oxygenase, squalene mono-
-
-
-
-
SQLE
squalene 2,3-oxidocyclase
-
-
-
-
squalene epoxidase
squalene hydroxylase
-
-
-
-
squalene oxydocyclase
-
-
-
-
squalene-2,3-epoxidase
-
-
-
-
squalene-2,3-epoxide cyclase
-
-
-
-
squalene epoxidase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
epoxidation
-
-
-
-
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-
SYSTEMATIC NAME
IUBMB Comments
squalene,NADPH-hemoprotein:oxygen oxidoreductase (2,3-epoxidizing
A flavoprotein (FAD). This enzyme, together with EC 5.4.99.7, lanosterol synthase, was formerly known as squalene oxidocyclase. The electron donor is EC 1.6.2.4, NADPH---hemoprotein reductase [5,7].
CAS REGISTRY NUMBER
COMMENTARY
9029-62-3
-
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
squalene + reduced NADPH-cytochrome P450 reductase + O2
(3S)-2,3-epoxy-2,3-dihydrosqualene + oxidized NADPH-cytochrome P450 reductase + H2O
-
-
-
-
r
squalene + [reduced NADPH-hemoprotein reductase] + O2
(3S)-2,3-epoxy-2,3-dihydrosqualene + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
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
squalene + [reduced NADPH-hemoprotein reductase] + O2
(3S)-2,3-epoxy-2,3-dihydrosqualene + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
electron transfer partner NADPH-cytochrome P450 reductase
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(E)-N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[2-methyl-2-(3-thienylmethoxy)propyloxy]benzylamine hydrochloride
-
trivial name FR194738, 0.0000098 mM, 50% inhibition of enzyme activity in HepG2 cell homogenate
dimethyltelluride
-
approx. 0.0001 mM, 50% inhibition of recombinant enzyme, 0.1 mM, complete inhibition, preincubation with 1 mM glutathione maintains 50% of initial activity
dimethyltellurium dichloride
-
approx. 0.0001 mM, 50% inhibition of recombinant enzyme, 0.1 mM, complete inhibition, preincubation with 1 mM glutathione maintains 50% of initial activity
methylselenol
-
0.095 mM, 50% inhibition of recombinant enzyme, 1 mM, complete inhibition
Phenylarsine oxide
-
recombinant enzyme, glutathione and 2,3-dimercaptopropanol protect almost completely
Selenite
-
0.037 mM, 50% inhibition of recombinant enzyme, 2,3-dimercaptopropanol and dithiothreitol increase inhibition
tellurite
-
0.01 mM, 50% inhibition of recombinant enzyme, 10 mM, 95% inhibition, glutathione and 2,3-dimercaptopropanol protect almost completely
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000014
reduced NADPH-cytochrome P450 reductase
-
recombinant enzyme, Km for electron transfer partner NADPH-cytochrone P 450 reductase
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
enzyme downregulation inhibits the tumorigenicity of hepatocellular carcinoma cells in vitro and in vivo
metabolism
physiological function
-
squalene epoxidase promotes the growth and migration of the hepatocellular carcinoma cells
metabolism
Q9UNR6
enzyme undergoes cholesterol-dependent proteasomal degradation when cholesterol is in excess. The amphipathic helix within the first 100 amino acids of squalene monooxygenase attaches reversibly to the ER membrane depending on cholesterol levels. With excess, the helix is ejected and unravels, exposing a hydrophobic patch, which then serves as a degradation signal
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ERG1_HUMAN
574
4
63923
Swiss-Prot
Secretory Pathway (Reliability: 3)
B4DHX0_HUMAN
379
2
42604
TrEMBL
other Location (Reliability: 2)
H0YBN7_HUMAN
163
0
18433
TrEMBL
other Location (Reliability: 1)
B4DX34_HUMAN
479
2
52995
TrEMBL
other Location (Reliability: 5)
Q5HYI4_HUMAN
574
4
63794
TrEMBL
Secretory Pathway (Reliability: 3)
E7EVQ6_HUMAN
479
2
53068
TrEMBL
other Location (Reliability: 5)
E5RJH9_HUMAN
184
0
20352
TrEMBL
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
Q9UNR6
a 12-residue region (residues Gln-62Leu-73), is required for cholesterol-mediated turnover
additional information
-
a 12-residue region (residues Gln-62Leu-73), is required for cholesterol-mediated turnover
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Treatment with 0.1-0.2 mM unsaturated fatty acids such as oleate, but not saturated fatty acids, increases protein levels of the enzyme at the post-translational level
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
mRNA expression of squalene epoxidase is associated with ER+ 7p+/8q+ breast cancer (mRNA analysis of tumor patients)
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
Q9UNR6
breast, ovarian, and colorectal cancers show the highest copy number-driven gene expression among 8783 cases from 22 cancer types, with breast camcer presenting the strongest one. Squalene epoxidase overexpression is more prevalent in aggressive breast cancer, and is an independent prognostic factor of unfavorable outcome. Squalene epoxidase inhibition results in a copy-dosage correlated decrease in cell viability, and in a noticeable increase in replication time, only in lines with detectable Squalene epoxidase transcript
medicine
Q9UNR6
expression of squalene epoxidase mRNA and protein in lung squamous cancerous tissues is significantly higher than in pericarcinoma tissues. The positive expression rate of squalene epoxidase mRNA is not associated with gender, age, smoking, or tumor size but closely correlated with poor differentiation, clinical stages, and lymphatic metastasis. The expression of mRNA is negatively associated with overall survival rate
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Laden, B.P.; Tang, Y.; Porter, T.D.
Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase
Arch. Biochem. Biophys.
374
381-388
2000
Homo sapiens
Sawada, M.; Matsuo, M.; Hagihara, H.; Tenda, N.; Nagayoshi, A.; Okumura, H.; Washizuka, K.; Seki, J.; Goto, T.
Effect of FR194738, a potent inhibitor of squalene epoxidase, on cholesterol metabolism in HepG2 cells
Eur. J. Pharmacol.
431
11-16
2001
Homo sapiens
Laden, B.P.; Porter, T.D.
Inhibition of human squalene monooxygenase by tellurium compounds: evidence of interaction with vicinal sulfhydryls
J. Lipid Res.
42
235-240
2001
Homo sapiens
Gupta, N.; Porter, T.D.
Inhibition of human squalene monooxygenase by selenium compounds
J. Biochem. Mol. Toxicol.
16
18-23
2002
Homo sapiens
Helms, M.W.; Kemming, D.; Pospisil, H.; Vogt, U.; Buerger, H.; Korsching, E.; Liedtke, C.; Schlotter, C.M.; Wang, A.; Chan, S.Y.; Brandt, B.H.
Squalene epoxidase, located on chromosome 8q24.1, is upregulated in 8q+ breast cancer and indicates poor clinical outcome in stage I and II disease
Br. J. Cancer
99
774-780
2008
Homo sapiens
Seiki, S.; Frishman, W.H.
Pharmacologic inhibition of squalene synthase and other downstream enzymes of the cholesterol synthesis pathway: a new therapeutic approach to treatment of hypercholesterolemia
Cardiol. Rev.
17
70-76
2009
Canis lupus familiaris, Homo sapiens, Nicotiana sp.
Stevenson, J.; Luu, W.; Kristiana, I.; Brown, A.J.
Squalene mono-oxygenase, a key enzyme in cholesterol synthesis, is stabilized by unsaturated fatty acids
Biochem. J.
461
435-442
2014
Homo sapiens
Howe, V.; Chua, N.K.; Stevenson, J.; Brown, A.J.
The regulatory domain of squalene monooxygenase contains a re-entrant loop and senses cholesterol via a conformational change
J. Biol. Chem.
290
27533-27544
2015
Homo sapiens
Sui, Z.; Zhou, J.; Cheng, Z.; Lu, P.
Squalene epoxidase (SQLE) promotes the growth and migration of the hepatocellular carcinoma cells
Tumour Biol.
36
6173-6179
2015
Homo sapiens
Chua, N.K.; Howe, V.; Jatana, N.; Thukral, L.; Brown, A.J.
A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis
J. Biol. Chem.
292
19959-19973
2017
Homo sapiens (Q9UNR6), Homo sapiens
Brown, D.N.; Caffa, I.; Cirmena, G.; Piras, D.; Garuti, A.; Gallo, M.; Alberti, S.; Nencioni, A.; Ballestrero, A.; Zoppoli, G.
Squalene epoxidase is a bona fide oncogene by amplification with clinical relevance in breast cancer
Sci. Rep.
6
19435
2016
Homo sapiens (Q9UNR6)
EXTERNAL LINKS (specific for EC-Number 1.14.14.17)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
