CYP2R1

Cytochrome P450, family 2, subfamily R, polypeptide 1
PDB rendering based on 2ojd.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3C6G, 3CZH, 3DL9
Identifiers
Symbols	CYP2R1 ; MGC4663
External IDs	OMIM: 608713 MGI: 2449771 HomoloGene: 75210 GeneCards: CYP2R1 Gene
EC number	1.14.13.159
Gene ontology Molecular function • iron ion binding • steroid hydroxylase activity • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen • oxygen binding • heme binding • vitamin D3 25-hydroxylase activity Cellular component • cytoplasm • endoplasmic reticulum membrane • intracellular membrane-bounded organelle Biological process • organic acid metabolic process • vitamin metabolic process • xenobiotic metabolic process • steroid metabolic process • response to cesium ion • response to ionizing radiation • calcitriol biosynthetic process from calciol • vitamin D metabolic process • exogenous drug catabolic process • small molecule metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	120227	244209
Ensembl	ENSG00000186104	ENSMUSG00000030670
UniProt	Q6VVX0	Q6VVW9
RefSeq (mRNA)	NM_024514	NM_177382
RefSeq (protein)	NP_078790	NP_796356
Location (UCSC)	Chr 11: 14.88 – 14.89 Mb	Chr 7: 114.55 – 114.56 Mb
PubMed search	[1]	[2]

Vitamin D 25-hydroxylase also known as cytochrome P450 2R1 is an enzyme that in humans is encoded by the CYP2R1 gene.

Function

Vitamin D 25-hydroxylase is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. Found in the liver, this enzyme is a microsomal vitamin D hydroxylase that converts vitamin D into 25-hydroxyvitamin D (calcidiol), which is the major circulatory form of the vitamin.

Clinical significance

An inherited mutation in the CYP2R1 gene which results in the substitution of a proline for a leucine residue at codon 99 eliminates the enzyme activity and is associated with low circulating levels of 25-hydroxyvitamin D and classic symptoms of vitamin D deficiency. The gene product which it encodes, vitamin D 25-hydroxylase, has therefore been proposed as the key enzyme in the conversion of cholecalciferol (vitamin D₃) to calcidiol. Calcidiol is subsequently converted by the action of 25-hydroxyvitamin D3 1-alpha-hydroxylase to calcitriol, the active form of vitamin D₃ that binds to the vitamin D receptor (VDR) which mediates most of the physiological actions of the vitamin.

Conversion of cholecalciferol to calcidiol as catalyzed by CYP2R1.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.

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|{{{bSize}}}px|alt=Vitamin D Synthesis Pathway edit]]

File:VitaminDSynthesis WP1531.png

Vitamin D Synthesis Pathway edit

Model organisms

Model organisms have been used in the study of CYP2R1 function. A conditional knockout mouse line called Cyp2r1^{tm1b(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping

Cyp2r1 knockout mouse phenotype

Characteristic	Phenotype
All data available at.
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal