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Information on EC 1.14.14.29 - 25/26-hydroxycholesterol 7alpha-hydroxylase and Organism(s) Homo sapiens and UniProt Accession O75881
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1.14.14.29 25/26-hydroxycholesterol 7alpha-hydroxylaseIUBMB Comments
A P-450 (heme-thiolate) protein. Unlike EC 1.14.14.26, 24-hydroxycholesterol 7alpha-monooxygenase, which is specific for its oxysterol substrate, this enzyme can also metabolize the oxysterols 24,25-epoxycholesterol, 22-hydroxycholesterol and 24-hydroxycholesterol, but to a lesser extent . The direct electron donor to the enzyme is EC 1.6.2.4, NADPH---hemoprotein reductase.
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Word Map
- 1.14.14.29
- oxysterols
- bile
- cyp27a1
- 27-hydroxycholesterol
- paraplegia
- dehydroepiandrosterone
-
neurosteroids
-
7alpha-hydroxylation
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27-hydroxylase
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interferon-stimulated
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lithogenic
- cholesterol-25-hydroxylase
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7alpha-hydroxy-dhea
- 5alpha-androstane-3beta,17beta-diol
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7-hydroxylation
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cyp2b9
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
cyp7b1, cyp7b, cholesterol 25-hydroxylase, oxysterol 7alpha-hydroxylase, oxysterol 7 alpha-hydroxylase, cypb1, cyp7b1 oxysterol 7alpha-hydroxylase, cytochome p450 7b1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
25-hydroxycholesterol 7alpha-hydroxylase
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-
-
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CYP7B
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-
-
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CYP7B1
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oxysterol 7alpha-hydroxylase
oxysterol 7alpha-hydroxylase
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PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
cholest-5-ene-3beta,25/26-diol,[NADPH-hemoprotein reductase]:oxygen oxidoreductase (7alpha-hydroxylating)
A P-450 (heme-thiolate) protein. Unlike EC 1.14.14.26, 24-hydroxycholesterol 7alpha-monooxygenase, which is specific for its oxysterol substrate, this enzyme can also metabolize the oxysterols 24,25-epoxycholesterol, 22-hydroxycholesterol and 24-hydroxycholesterol, but to a lesser extent [2]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH---hemoprotein reductase.
CAS REGISTRY NUMBER
COMMENTARY
149316-80-3
-
440356-82-1
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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
27-hydroxycholesterol + NADPH + H+ + O2
3beta,7alpha-dihydroxy-5-cholestenoic acid + NADP+ + H2O
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-
-
?
5alpha-androstane-3alpha,17beta-diol + NADPH + O2
? + NADP+ + H2O
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-
-
?
cholest-5-ene-3beta,25-diol + NADPH + H+ + O2
cholest-5-ene-3beta,7alpha,25-triol + NADP+ + H2O
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-
-
?
cholest-5-ene-3beta,27-diol + NADPH + H+ + O2
cholest-5-ene-3beta,7alpha,27-triol + NADP+ + H2O
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-
-
?
dehydroepiandrosterone + NADPH + H+ + o2
7alpha-hydroxy-dehydroepiandrosterone + NADP+ + H2O
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-
-
?
5alpha-androstane-3alpha,17beta-diol + NADPH + O2
5alpha-androstane-3alpha,7alpha,17beta-triol + NADP+ + H2O
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major product, plus some hydroxylation at position 6
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?
cholest-5-ene-3beta,25-diol + NADPH + H+ + O2
cholest-5-ene-3beta,7alpha,25-triol + NADP+ + H2O
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-
-
-
?
dehydroepiandrosterone + NADPH + H+ + o2
7alpha-hydroxy-dehydroepiandrosterone + NADP+ + H2O
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-
-
-
?
additional information
?
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regulation of CYP7B1 transcription by Sp1 may play a pivotal role in regulating oxysterol levels, which regulate cholesterol metabolism
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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
27-hydroxycholesterol + NADPH + H+ + O2
3beta,7alpha-dihydroxy-5-cholestenoic acid + NADP+ + H2O
-
-
-
?
dehydroepiandrosterone + NADPH + H+ + o2
7alpha-hydroxy-dehydroepiandrosterone + NADP+ + H2O
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-
-
?
additional information
?
-
-
regulation of CYP7B1 transcription by Sp1 may play a pivotal role in regulating oxysterol levels, which regulate cholesterol metabolism
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5alpha-androstane-3alpha,17beta-diol
inhibition of the reaction with dehydroepiandrosterone
5alpha-Androstane-3beta,17beta-diol
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inhibits hydroxylation of dehydroepiandrosterone by approximately 60-70% when both steroids are present at equimolar concentrations. A 10fold higher concentration of 5alpha-androstane-3beta,17beta-diol than of dehydroepiandrosterone in the incubation mixture results in the suppression of dehydroepiandrosterone hydroxylation by 80%. In HEK293 cells, the suppressive effect of 5alpha-androstane-3beta,17beta-diol on dehydroepiandrosterone metabolism is statistically significant also at a 10fold lower concentration of 5alpha-androstane-3beta,17beta-diol than of dehydroepiandrosterone in the incubation mixture
LY294002
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specific inhibitor of phosphatidylinositol 3-kinase, abolishes estrogen receptor-mediated upregulation of a CYP7B1 promoter-luciferase reporter in Hep-G2 cells but not in HEK-293 cells
PD98059
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markedly suppresses basal CYP7B1 promoter activity, abolishes upregulation of CYP7B1 by estrogen receptor in Hep-G2 cells
SP600125
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markedly suppresses basal CYP7B1 promoter activity, abolishes upregulation of CYP7B1 by estrogen receptor in Hep-G2 cells but not in HEK-293 cells
additional information
-
overexpression of Akt, in the absence of estrogen stimulation, suppresses basal CYP7B1 promoter activity by about 75%. Overexpression of dominant-negative mutant Akt abolishes estrogen receptor-mediated stimulation of CYP7B1 in Hep-G2 cells
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
estrogen
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overexpression of PI3K or Akt significantly increases estrogenic upregulation of CYP7B1 in Hep-G2 cells. Estrogen receptor interacts with the PI3K/Akt pathway without binding to the CYP7B1 gene. In HEK293 cells, CYP7B1 transcription is much less affected by Akt, indicating that the mechanism for upregulation of CYP7B1 is different in different cell types
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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CYP7B1 is overexpressed in high-grade prostatic intraepithelial neoplasia and in prostate cancer
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CYP7B1 is overexpressed in high-grade prostatic intraepithelial neoplasia and in prostate cancer
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CYP7B1 is overexpressed in high-grade prostatic intraepithelial neoplasia and in prostate cancer
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activity is detected in keratinocytes of the spinous and granula layers, and to lesser extent in the basal layer and basal cell bodies. High activity in hair follicle associated cells
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
CYP7B1 is an enzyme expressed in many human tissues and implicated in cholesterol metabolism. In the liver, this protein is part of the alternate/acidic pathway for primary bile acid production while in brain, CYP7B1 provides the primary metabolic route for cholesterol derivatives dehydroepiandrosterone and related hydroxysteroids via 7alpha-hydroxylation
physiological function
CYP7B1-mediated catalysis may play a role for control of the cellular levels of androgens, not only of estrogens
physiological function
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important role for CYP7B1 in cellular growth, particularly in connection with estrogenic signalling
additional information
additional information
spastic paraplegia type 5, SPG5, is caused by mutations in CYP7B1, a gene encoding the cytochrome P-450 oxysterol 7-alpha-hydroxylase, CYP7B1, an enzyme implicated in cholesterol metabolism. Mutations in CYP7B1 are found in both pure and complicated forms of the disease, clinical phenotypes, overview
additional information
-
spastic paraplegia type 5, SPG5, is caused by mutations in CYP7B1, a gene encoding the cytochrome P-450 oxysterol 7-alpha-hydroxylase, CYP7B1, an enzyme implicated in cholesterol metabolism. Mutations in CYP7B1 are found in both pure and complicated forms of the disease, clinical phenotypes, overview
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). CP7B1_HUMAN
506
2
58256
Swiss-Prot
Secretory Pathway (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G443A
c.1328G-C, naturally occuring mutation of CYP7B1 involved in spastic paraplegia type 5
G87V
c.260G-T, naturally occuring mutation of CYP7B1 involved in spastic paraplegia type 5
H285L
c.854A-T, naturally occuring mutation of CYP7B1 involved in spastic paraplegia type 5
R324H
c.971G-A, naturally occuring mutation of CYP7B1 involved in spastic paraplegia type 5
A316AA
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the mutation is associated with the SPG5A subtype of hereditary spastic paraplegia
G147D
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the mutation is associated with the SPG5A subtype of hereditary spastic paraplegia
R112X
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the mutation is associated with the SPG5A subtype of hereditary spastic paraplegia
R486C
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the mutation is associated with the SPG5A subtype of hereditary spastic paraplegia
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
CYP7B1 genotyping and screening for CYP7B1 mutations in a large cohort of 105 Italian HSP index patients, including 50 patients with a complicated phenotype and 55 with a pure form, overall mutation frequencies of CYP7B1, overview
14 deletion mutants of the regulatory sequences of CYP7B1/Luc reporter gene are constructed for transfection assays. The constructs are transiently transfected into HepG2, NT1088, and HEK 293 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of CYP7B1 by estrogen receptor can be mediated via the PI3K/Akt signal pathway. Overexpression of PI3K or Akt significantly increases estrogenic up-regulation of CYP7B1
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expression of CYP7B1 by estrogen receptor can be mediated via the PI3K/Akt signal pathway. Treatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase PI3K, abolishes estrogen-receptor-mediated up-regulation of a CYP7B1 promoter-luciferase reporter
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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identification of mutations in CYP7B1 associated with hereditary spastic paraplegias provide direct evidence for abnormalities in cholesterol metabolism in the pathogenesis of motor-neuron degeneration
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Russell, D.W.
The enzymes, regulation, and genetics of bile acid synthesis
Annu. Rev. Biochem.
72
137-174
2003
Homo sapiens (O75881), Mus musculus (Q60991)
Toll, A.; Wikvall, K.; Sudjana-Sugiaman, E.; Kondo, K.H.; Bjrhem, I.
7alpha-Hydroxylation of 25-hydroxycholesterol in liver microsomes. Evidence that the enzyme involved is different from cholesterol 7alpha-hydoxylase
Eur. J. Biochem.
224
309-316
1994
Homo sapiens, Rattus norvegicus, Sus scrofa
Wu, Z.; Chiang, J.Y.
Transcriptional regulation of human oxysterol 7alpha-hydroxylase gene (CYP7B1) by Sp1
Gene
272
191-197
2001
Homo sapiens
Li-Hawkins, J.; Lund, E.G.; Bronson, A.D.; Russell, D.W.
Expression cloning of an oxysterol 7alpha-hydroxylase selective for 24-hydroxycholesterol
J. Biol. Chem.
275
16543-16549
2000
Homo sapiens, Mus musculus
Wu, Z.; Martin, K.O.; Javitt, N.B.; Chiang, J.Y.
Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1
J. Lipid Res.
40
2195-2203
1999
Homo sapiens
Tsaousidou, M.K.; Ouahchi, K.; Warner, T.T.; Yang, Y.; Simpson, M.A.; Laing, N.G.; Wilkinson, P.A.; Madrid, R.E.; Patel, H.; Hentati, F.; Patton, M.A.; Hentati, A.; Lamont, P.J.; Siddique, T.; Crosby, A.H.
Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration
Am. J. Hum. Genet.
82
510-515
2008
Homo sapiens
Pettersson, H.; Holmberg, L.; Axelson, M.; Norlin, M.
CYP7B1-mediated metabolism of dehydroepiandrosterone and alpha-androstane-3beta,17beta-diol - potential role(s) for estrogen signaling
FEBS J.
275
1778-1789
2008
Homo sapiens, Sus scrofa
Hennebert, O.; Chalbot, S.; Alran, S.; Morfin, R.
Dehydroepiandrosterone 7alpha-hydroxylation in human tissues: possible interference with type 1 11beta-hydroxysteroid dehydrogenase-mediated processes
J. Steroid Biochem. Mol. Biol.
104
326-333
2007
Homo sapiens
Olsson, M.; Gustafsson, O.; Skogastierna, C.; Tolf, A.; Rietz, B.D.; Morfin, R.; Rane, A.; Ekstroem, L.
Regulation and expression of human CYP7B1 in prostate: overexpression of CYP7B1 during progression of prostatic adenocarcinoma
Prostate
67
1439-1446
2007
Homo sapiens
Pettersson, H.; Lundqvist, J.; Oliw, E.; Norlin, M.
CYP7B1-mediated metabolism of 5alpha-androstane-3alpha,17beta-diol (3alpha-Adiol): A novel pathway for potential regulation of the cellular levels of androgens and neurosteroids
Biochim. Biophys. Acta
1791
1206-1215
2009
Homo sapiens, Homo sapiens (O75881), Mus musculus (Q60991), Sus scrofa
Tang, W.; Pettersson, H.; Norlin, M.
Involvement of the PI3K/Akt pathway in estrogen-mediated regulation of human CYP7B1: identification of CYP7B1 as a novel target for PI3K/Akt and MAPK signalling
J. Steroid Biochem. Mol. Biol.
112
63-73
2008
Homo sapiens
Arnoldi, A.; Crimella, C.; Tenderini, E.; Martinuzzi, A.; D'Angelo, M.G.; Musumeci, O.; Toscano, A.; Scarlato, M.; Fantin, M.; Bresolin, N.; Bassi, M.T.
Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations
Clin. Genet.
81
150-157
2012
Homo sapiens (O75881), Homo sapiens
Roos, P.; Svenstrup, K.; Danielsen, E.R.; Thomsen, C.; Nielsen, J.E.
CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A
Acta Neurol. Scand.
129
330-334
2013
Homo sapiens
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