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Information on EC 1.14.14.24 - vitamin D 25-hydroxylase and Organism(s) Mus musculus and UniProt Accession Q6VVW9

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IUBMB Comments
A microsomal enzyme isolated from human and mouse liver that bioactivates vitamin D3. While multiple isoforms (CYP27A1, CYP2J2/3, CYP3A4, CYP2D25 and CYP2C11) are able to catalyse the reaction in vitro, only CYP2R1 is thought to catalyse the reaction in humans in vivo . The direct electron donor to the enzyme is EC 1.6.2.4, NADPH---hemoprotein reductase.
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This record set is specific for:
Mus musculus
UNIPROT: Q6VVW9
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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
cyp2r1, cyp2j3, vitamin d 25-hydroxylase, cytochrome p450 2c11, cytochrome p450 2j2, cyp2d25, vitamin d-25-hydroxylase, cytochrome p450 2r1, cytochrome p450 2j3, vitamin d2 25-hydroxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cytochrome P450 2R1
-
vitamin D 25-hydroxylase
-
CYP2R1
-
-
-
-
vitamin D2 25-hydroxylase
-
-
-
-
vitamin D3 25-hydroxylase
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
calciol,NADPH-hemoprotein reductase:oxygen oxidoreductase (25-hydroxylating)
A microsomal enzyme isolated from human and mouse liver that bioactivates vitamin D3. While multiple isoforms (CYP27A1, CYP2J2/3, CYP3A4, CYP2D25 and CYP2C11) are able to catalyse the reaction in vitro, only CYP2R1 is thought to catalyse the reaction in humans in vivo [4]. The direct electron donor to the enzyme is EC 1.6.2.4, NADPH---hemoprotein reductase.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
calciol + O2 + [reduced NADPH-hemoprotein reductase]
calcidiol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
?
vitamin D3 + O2 + NADPH + H+
25-hydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
?
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
calciol + O2 + [reduced NADPH-hemoprotein reductase]
calcidiol + [oxidized NADPH-hemoprotein reductase] + H2O
show the reaction diagram
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
quantitative real-time PCR enzyme expression analysis, no or low expression in kidney and ovaries
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
enzyme-deficient Cyp2r1-/- mice show greater than 50% reduction in serum 25-hydroxyvitamin D3 level, while the 1alpha,25-dihydroxyvitamin D3 level in the serum remains unchanged. A double knockout of Cyp2r1 and Cyp27a1, the enzyme responsible for the 1alpha-hydroxylation step, maintain a similar circulating level of 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3
metabolism
the cross talk from the bone to the testis of the vitamin D 25-hydroxylase CYP2R1 involves osteocalcin, which is produced by the osteoblasts and stimulates the production of testosterone by the Leydig cells through its putative receptor GPRC6A, a cation-sensing G-protein-coupled receptor. Action of osteocalcin on CYP2R1 expression and 25-hydroxyvitamin D production in a mouse Leydig cell line MA-10
physiological function
physiological function
-
the absence of either of the two key hydroxylases, i.e., 25-hydroxylase and 1alpha-hydroxylase, neither inhibits nor enhances the development of experimental autoimmune encephalomyelitis in a mice model
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CP2R1_MOUSE
501
1
57313
Swiss-Prot
Secretory Pathway (Reliability: 1)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
construction of null mutant enzyme-deficient Cyp2r1-/- mice, that show greater than 50% reduction in serum 25-hydroxyvitamin D3 level, while the 1alpha,25-dihydroxyvitamin D3 level in the serum remains unchanged. A double knockout of Cyp2r1 and Cyp27a1, the enzyme responsible for the 1alpha-hydroxylation step, maintain a similar circulating level of 25-hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in HEK 293 cell
gene CYP2R1, quantitative real-time PCR enzyme expression analysis
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the luteinizing hormone induces the enzyme. MA-10 cell stimulation with either human chorionic gonadotropin or uncarboxylated-osteocalcin increases CYP2R1 protein expression in a dose-dependent manner and, in turn, increases the release of 25-hydroxy-vitamin D in culture medium. Osteocalcin, in particular uncarboxylated osteocalcin, stimulates 25-hydroxylation of vitamin D in Leydig cells through a direct effect on the expression of the main actor in the 25-hydroxylase activity of vitamin D, the CYP2R1 protein
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
experimental autoimmune encephalomyelitis development is markedly suppressed in mice lacking the vitamin D receptor and partially suppressed in vitamin D-insufficient mice. The absence of either of the two key hydroxylases, i.e., 25-hydroxylase and 1alpha-hydroxylase, neither inhibits nor enhances the development of experimental autoimmune encephalomyelitis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Cheng, J.B.; Motola, D.L.; Mangelsdorf, D.J.; Russell, D.W.
De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase
J. Biol. Chem.
278
38084-38093
2003
Mus musculus (Q6VVW9)
Manually annotated by BRENDA team
Wang, Y.; Marling, S.J.; Zhu, J.G.; Severson, K.S.; DeLuca, H.F.
Development of experimental autoimmune encephalomyelitis (EAE) in mice requires vitamin D and the vitamin D receptor
Proc. Natl. Acad. Sci. USA
109
8501-8504
2012
Mus musculus
Manually annotated by BRENDA team
De Toni, L.; De Filippis, V.; Tescari, S.; Ferigo, M.; Ferlin, A.; Scattolini, V.; Avogaro, A.; Vettor, R.; Foresta, C.
Uncarboxylated osteocalcin stimulates 25-hydroxy vitamin D production in Leydig cell line through a GPRC6a-dependent pathway
Endocrinology
155
4266-4274
2014
Mus musculus (Q6VVW9), Mus musculus
Manually annotated by BRENDA team
Zhu, J.G.; Ochalek, J.T.; Kaufmann, M.; Jones, G.; Deluca, H.F.
CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo
Proc. Natl. Acad. Sci. USA
110
15650-15655
2013
Mus musculus (Q6VVW9), Mus musculus C57BL/6 (Q6VVW9)
Manually annotated by BRENDA team