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Information on EC 1.14.99.38 - cholesterol 25-monooxygenase and Organism(s) Mus musculus and UniProt Accession Q9Z0F5
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1.14.99.38 cholesterol 25-monooxygenaseIUBMB Comments
Unlike most other sterol hydroxylases, this enzyme is not a cytochrome P-450. Instead, it uses diiron cofactors to catalyse the hydroxylation of hydrophobic substrates . The diiron cofactor can be either Fe-O-Fe or Fe-OH-Fe and is bound to the enzyme through interactions with clustered histidine or glutamate residues [4,5]. In cell cultures, this enzyme down-regulates cholesterol synthesis and the processing of sterol regulatory element binding proteins (SREBPs). cf. EC 1.17.99.10, cholesterol C-25 hydroxylase.
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Word Map
- 1.14.99.38
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pregnane
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cyp2b10
- 25-hydroxycholesterol
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androstane
- oxysterols
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drug-metabolizing
- phenobarbital
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cyp2c29
- ugt1a1
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interferon-stimulated
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cyp3a13
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apap-induced
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lithocholic
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acetaminophen-induced
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pxr-mediated
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cyp2a4
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pxr-null
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tcpobop
- medicine
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
cyp3a11, ch25h, cholesterol-25-hydroxylase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
cholesterol,hydrogen-donor:oxygen oxidoreductase (25-hydroxylating)
Unlike most other sterol hydroxylases, this enzyme is not a cytochrome P-450. Instead, it uses diiron cofactors to catalyse the hydroxylation of hydrophobic substrates [1]. The diiron cofactor can be either Fe-O-Fe or Fe-OH-Fe and is bound to the enzyme through interactions with clustered histidine or glutamate residues [4,5]. In cell cultures, this enzyme down-regulates cholesterol synthesis and the processing of sterol regulatory element binding proteins (SREBPs). cf. EC 1.17.99.10, cholesterol C-25 hydroxylase.
CAS REGISTRY NUMBER
COMMENTARY
60202-07-5
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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
additional information
?
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25-hydroxycholesterol is a secondary autoxidation product derived from 3beta-hydroxy-cholest-5-ene-25-hydroperoxide, a hydroperoxide identified in air-aged cholesterol. Thermal decomposition of 3beta-hydroxy-cholest-5-ene-25-hydroperoxide gives rise to 25-hydroxycholesterol
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-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
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-
-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
cholesterol 25-hydroxylase has the capacity to play an important role in regulating lipid metabolism by synthesizing a corepressor that blocks sterol regulatory element binding protein processing and ultimately leads to inhibition of gene transcription
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-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
the enzyme has the capacity to synthesize an active and potent regulator of the sterol response element binding protein pathway within the cell
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-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
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-
-
-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
the reaction might be catalyzed by CYP3A4
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-
?
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
additional information
?
-
25-hydroxycholesterol is a secondary autoxidation product derived from 3beta-hydroxy-cholest-5-ene-25-hydroperoxide, a hydroperoxide identified in air-aged cholesterol. Thermal decomposition of 3beta-hydroxy-cholest-5-ene-25-hydroperoxide gives rise to 25-hydroxycholesterol
-
-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
-
-
-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
cholesterol 25-hydroxylase has the capacity to play an important role in regulating lipid metabolism by synthesizing a corepressor that blocks sterol regulatory element binding protein processing and ultimately leads to inhibition of gene transcription
-
-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
the enzyme has the capacity to synthesize an active and potent regulator of the sterol response element binding protein pathway within the cell
-
-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
-
-
-
-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
the reaction might be catalyzed by CYP3A4
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe
Fe
diiron-containing enzyme. The iron is present as Fe-O-Fe or Fe-OH-Fe and is coordinated with clusters of conserved histidine residues
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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incubation with LPS derived from Escherichia coli or Salmonella enterica induces CH25H mRNA
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
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quantitative enzyme expression analysis in macrophages and dendritic cells, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
transmembrane enzyme, prediction of transmembrane structures for CH25H subunits, overview
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
loss of function of Ch25h leads to susceptibility to viral infections in vitro
physiological function
malfunction
mice with a disruption in the cholesterol 25-hydroxylase gene regulate cholesterol metabolism normally. Ch25h-/- mice have higher levels of mRNAs coding for immunoglobulin A and immunoglobulin J. Disruption in the Cyp7b1 gene leads to significantly increased levels of 25-hydroxycholesterol in the circulation, and to significantly lower levels of IgA compared to wild-type mice
physiological function
additional information
physiological function
cholesterol 25-hydroxylase plays an essential role in cholesterol metabolism in the body by catalysing the formation of 25-hydroxycholesterol from cholesterol which acts to repress cholesterol biosynthesis
physiological function
cholesterol-25-hydroxylase acts as a broadly antiviral interferon-stimulated gene. CH25H converts cholesterol to a soluble antiviral factor, 25-hydroxycholesterol. 25-Hydroxycholesterol treatment in cultured cells broadly inhibits growth of enveloped viruses including VSV, HSV, HIV, and MHV68 and acutely pathogenic EBOV, RVFV, RSSEV, and Nipah viruses. The compound inhibits cell entry of viruses HIV and VSV, and inhibits viral protein-mediated cell-cell membrane fusion of virus NIV. 25-Hydroxycholesterol directly modifies membranes
physiological function
important role for 25-hydroxycholesterol in the immune system. High concentrations of 25-hydroxycholesterol induce apoptosis in a mouse oligodendrocyte cell line 158N in an liver X receptor-independent manner. Treatment of these cells with 25-hydroxycholesterol results in enhanced secreted phospholipase A2 activity
physiological function
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adenovirus-mediated enzyme overexpression in mice improves glucose tolerance and insulin sensitivity and lowers the homeostatic model assessment for insulin resistance score
additional information
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Ch25h expression is controlled primarily by type I IFN signaling, type1 IFN-mediated Ch25h expression is IFNR-dependent, overview
additional information
25-hydroxycholesterol does not stimulate the sPLA2-IIA promoter in the mouse Schwann cell line MSC80
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). CH25H_MOUSE
298
3
34672
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in COS cells, expression of cholesterol 25-hydroxylase in transfected cells reduces the biosynthesis of cholesterol from acetate and suppresses the cleavage of sterol regulatory element binding protein-1 and -2
intronless gene CH25H is located on chromosome 19, DNA and amino acid sequence deterination and analysis, sequence comparisons, gene structures and tandem locations for the human CH25H and LIPA, EC 3.1.1.13, genes on chromosome 10
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
both IFN-alpha- and IFN-gamma induce the enzyme in bone marrow-derived macrophages
induction of CYP3A by pregnenolone-16 alpha-carbonitrile causes accumulation of 25-hydroxycholesterol in cell line AML12 derived from mouse liver, the induction is not suppressed by the addition of desmosterol. Although the transcription of Ch25h is also upregulated by addition of pregnenolone-16 alpha-carbonitrile, the protein level of CH25H is not elevated. Desmosterol does not affect the expression of cellular CYP3A protein, but CH25H protein level is obviously decreased by desmosterol treatment
vasoprotective stimuli such as pulsatile shear stress and statins increase the expression of the enzyme via Krueppel-like factor 4
activation of the innate immune system by TLR ligands induces 25-hydroxycholesterol production which results in suppression of IgA class switching in B cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Russell, D.W.
Oxysterol biosynthetic enzymes
Biochim. Biophys. Acta
1529
126-135
2000
Homo sapiens (O95992), Mus musculus (Q9Z0F5)
Lund, E.G.; Kerr, T.A.; Sakai, J.; Li, W.P.; Russell, D.W.
cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism
J. Biol. Chem.
273
34316-34327
1998
Homo sapiens (O95992), Mus musculus (Q9Z0F5)
Diczfalusy, U.; Olofsson, K.; Carlsson, A.; Gong, M.; Golenbock, D.; Rooyackers, O.; Flring, U.; Bjrkbacka, H.
Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide
J. Lipid Res.
50
2258-2264
2009
Homo sapiens, Mus musculus
Bauman, D.R.; Bitmansour, A.D.; McDonald, J.G.; Thompson, B.M.; Liang, G.; Russell, D.W.
25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production
Proc. Natl. Acad. Sci. USA
106
16764-16769
2009
Mus musculus
Park, K.; Scott, A.L.
Cholesterol 25-hydroxylase production by dendritic cells and macrophages is regulated by type I interferons
J. Leukoc. Biol.
88
1081-1087
2010
Mus musculus, Mus musculus BALB/cJ
Holmes, R.S.; Vandeberg, J.L.; Cox, L.A.
Genomics and proteomics of vertebrate cholesterol ester lipase (LIPA) and cholesterol 25-hydroxylase (CH25H)
3 Biotech
1
99-109
2011
Bos taurus (Q0P599), Canis lupus familiaris, Equus caballus (F6T000), Gallus gallus, Homo sapiens (O95992), Homo sapiens, Macaca mulatta (F7EC50), Mus musculus (Q9Z0F5), Rattus norvegicus (Q4QQV7), Xenopus tropicalis
Diczfalusy, U.
On the formation and possible biological role of 25-hydroxycholesterol
Biochimie
95
455-460
2013
Rattus norvegicus, Sus scrofa, Homo sapiens (Q02318), Mus musculus (Q64459)
Liu, S.Y.; Aliyari, R.; Chikere, K.; Li, G.; Marsden, M.D.; Smith, J.K.; Pernet, O.; Guo, H.; Nusbaum, R.; Zack, J.A.; Freiberg, A.N.; Su, L.; Lee, B.; Cheng, G.
Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol
Immunity
38
92-105
2013
Mus musculus (Q9Z0F5)
Honda, A.; Miyazaki, T.; Ikegami, T.; Iwamoto, J.; Maeda, T.; Hirayama, T.; Saito, Y.; Teramoto, T.; Matsuzaki, Y.
Cholesterol 25-hydroxylation activity of CYP3A
J. Lipid Res.
52
1509-1516
2011
Homo sapiens (P05177), Homo sapiens (P08684), Homo sapiens (P10635), Homo sapiens (P11712), Mus musculus (Q9Z0F5)
Li, Z.; Martin, M.; Zhang, J.; Huang, H.Y.; Bai, L.; Zhang, J.; Kang, J.; He, M.; Li, J.; Maurya, M.R.; Gupta, S.; Zhou, G.; Sangwung, P.; Xu, Y.J.; Lei, T.; Huang, H.D.; Jain, M.; Jain, M.K.; Subramaniam, S.; Shyy, J.Y.
Krueppel-like factor 4 regulation of cholesterol-25-hydroxylase and liver X receptor mitigates atherosclerosis susceptibility
Circulation
136
1315-1330
2017
Mus musculus (Q9Z0F5)
Noebauer, B.; Jais, A.; Todoric, J.; Gossens, K.; Sutterluety-Fall, H.; Einwallner, E.
Hepatic cholesterol-25-hydroxylase overexpression improves systemic insulin sensitivity in mice
J. Diabetes Res.
2017
4108768
2017
Mus musculus
Mukherjee, P.; Hough, G.; Chattopadhyay, A.; Navab, M.; Fogelman, H.R.; Meriwether, D.; Williams, K.; Bensinger, S.; Moller, T.; Faull, K.F.; Lusis, A.J.; Iruela-Arispe, M.L.; Bostrom, K.I.; Tontonoz, P.; Reddy, S.T.; Fogelman, A.M.
Transgenic tomatoes expressing the 6F peptide and ezetimibe prevent diet-induced increases of IFN-beta and cholesterol 25-hydroxylase in jejunum
J. Lipid Res.
58
1636-1647
2017
Mus musculus
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