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Information on EC 1.14.99.38 - cholesterol 25-monooxygenase and Organism(s) Homo sapiens and UniProt Accession P05177

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IUBMB 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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Homo sapiens
UNIPROT: P05177
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
cyp3a11, ch25h, cholesterol-25-hydroxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CH25H
cholesterol 25-hydroxylase
cholesterol 25-monooxygenase
-
cholesterol-25-hydroxylase
-
CYP27A1
EC 1.14.13.15
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
reduction
-
-
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 hide
60202-07-5
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
show the reaction diagram
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
show the reaction diagram
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
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
show the reaction diagram
lower 25-hydroxylation enzyme activity by CYP1A2 compared to marker enzyme CYP3A4
-
-
?
cholesterol + AH2 + O2
25-hydroxycholesterol + A + H2O
show the reaction diagram
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
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
the enzyme contains a di-iron cofactor
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
desmosterol
a potent inhibitor of CH25H
desmosterol
a potent inhibitor of CH25H
troleandomycin
specific inhibitor of CYP3A
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.77
sequence calculation
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene Ch25h
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
patients with chronic obstructive pulmonary disease have increased expression of cholesterol 25-hydroxylase in the lung
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
transmembrane enzyme, prediction of transmembrane structures for CH25H subunits, overview
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
additional information
the high concentrations of vitamin D3 metabolites required for upregulation of the cholesterol 25-hydroxylase gene makes it unlikely that these metabolites are important regulators of cholesterol 25-hydroxylase in vivo
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CP1A2_HUMAN
516
1
58407
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
31700
x * 31700
31745
x * 31745, sequence calculation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H242Q/H243Q
inactive
additional information
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression in insect cell microsomes via baculovirus transfection
expressed in Huh-7.5.1 cells
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 10, 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
recombinant expression in insect cell microsomes via baculovirus transfection
the gene encoding the enzyme is located on chromosome 10
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is not induced by interferons in human cells and knockdown of STAT-1 has no effect on the induction of the enzyme
-
exposure to DNA methyltransferase inhibitors and decitabine enhances enzyme mRNA expression in myelodysplasia/leukemia cell lines
the enzyme expression in primary human hepatocytes is primarily and transiently induced by type I interferon. Infection with hepatitis C virus causes up-regulation of the enzyme in vivo
the enzyme is upregulated upon poly(I:C) treatment or hepatitis C virus infection in hepatocytes
-
the enzyme mRNA expression level is originally low in myelodysplasia/leukemia cell lines. Enzyme knockdown partially protects the cells from decitabine-induced cell death
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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)
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team
Shibata, N.; Kawarai, T.; Lee, J.H.; Lee, H.S.; Shibata, E.; Sato, C.; Liang, Y.; Duara, R.; Mayeux, R.P.; St George-Hyslop, P.H.; Rogaeva, E.
Association studies of cholesterol metabolism genes (CH25H, ABCA1 and CH24H) in Alzheimer's disease
Neurosci. Lett.
391
142-146
2006
Homo sapiens
Manually annotated by BRENDA team
Papassotiropoulos, A.; Lambert, J.C.; Wavrant-De Vrieze, F.; Wollmer, M.A.; von der Kammer, H.; Streffer, J.R.; Maddalena, A.; Huynh, K.D.; Wolleb, S.; Lutjohann, D.; Schneider, B.; Thal, D.R.; Grimaldi, L.M.; Tsolaki, M.; Kapaki, E.; Ravid, R.; Konietzko, U.; Hegi, T.; Pasch, T.; Jung, H.; Braak, H.
Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimers disease
Neurodegener. Dis.
2
233-241
2005
Homo sapiens
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team
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)
Manually annotated by BRENDA team
Anggakusuma, G.; Romero-Brey, I.; Berger, C.; Colpitts, C.C.; Boldanova, T.; Engelmann, M.; Todt, D.; Perin, P.M.; Behrendt, P.; Vondran, F.W.; Xu, S.; Goffinet, C.; Schang, L.M.; Heim, M.H.; Bartenschlager, R.; Pietschmann, T.; Steinmann, E.
Interferon-inducible cholesterol-25-hydroxylase restricts hepatitis C virus replication through blockage of membranous web formation
Hepatology
62
702-714
2015
Homo sapiens (Q95992), Homo sapiens
Manually annotated by BRENDA team
Xiang, Y.; Tang, J.J.; Tao, W.; Cao, X.; Song, B.L.; Zhong, J.
Identification of cholesterol 25-hydroxylase as a novel host restriction factor and a part of the primary innate immune responses against hepatitis C virus infection
J. Virol.
89
6805-6816
2015
Homo sapiens
Manually annotated by BRENDA team
Chen, Y.; Wang, S.; Yi, Z.; Tian, H.; Aliyari, R.; Li, Y.; Chen, G.; Liu, P.; Zhong, J.; Chen, X.; Du, P.; Su, L.; Qin, F.X.; Deng, H.; Cheng, G.
Interferon-inducible cholesterol-25-hydroxylase inhibits hepatitis C virus replication via distinct mechanisms
Sci. Rep.
4
7242
2014
Homo sapiens (Q95992)
Manually annotated by BRENDA team
Tsujioka, T.; Yokoi, A.; Itano, Y.; Takahashi, K.; Ouchida, M.; Okamoto, S.; Kondo, T.; Suemori, S.; Tohyama, Y.; Tohyama, K.
Five-aza-2-deoxycytidine-induced hypomethylation of cholesterol 25-hydroxylase gene is responsible for cell death of myelodysplasia/leukemia cells
Sci. Rep.
5
16709
2015
Homo sapiens (Q95992)
Manually annotated by BRENDA team