CYP2R1

Vitamin D 25-hydroxylase also known as cytochrome P450 2R1 is an enzyme that in humans is encoded by the CYP2R1 gene.[5][6][7]

CYP2R1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCYP2R1, cytochrome P450 family 2 subfamily R member 1
External IDsOMIM: 608713 MGI: 2449771 HomoloGene: 75210 GeneCards: CYP2R1
Gene location (Human)
Chr.Chromosome 11 (human)[1]
Band11p15.2Start14,877,440 bp[1]
End14,892,252 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

120227

244209

Ensembl

ENSG00000186104

ENSMUSG00000030670

UniProt

Q6VVX0

Q6VVW9

RefSeq (mRNA)

NM_177382

RefSeq (protein)

NP_796356

Location (UCSC)Chr 11: 14.88 – 14.89 MbChr 7: 114.55 – 114.56 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 Vitamin D-dependent rickets type IB. Symptoms are low circulating levels of 25-hydroxyvitamin D and classic symptoms of vitamin D deficiency.[6] 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.[6]

Conversion of cholecalciferol to calcidiol as catalyzed by CYP2R1.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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|{{{bSize}}}px|alt=Vitamin D Synthesis Pathway (view / edit)]]
Vitamin D Synthesis Pathway (view / edit)
  1. The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

Model organisms

Model organisms have been used in the study of CYP2R1 function. A conditional knockout mouse line called Cyp2r1tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[8] Male and female animals underwent a standardized phenotypic screen[9] to determine the effects of deletion.[10][11][12][13] Additional screens performed: - In-depth immunological phenotyping[14]

References
  1. GRCh38: Ensembl release 89: ENSG00000186104 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000030670 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Nelson DR (Dec 2002). "Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution". Arch Biochem Biophys. 409 (1): 18–24. doi:10.1016/S0003-9861(02)00553-2. PMID 12464240.
  6. Cheng JB, Levine MA, Bell NH, Mangelsdorf DJ, Russell DW (2004-05-18). "Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase". Proc Natl Acad Sci U S A. 101 (20): 7711–7715. Bibcode:2004PNAS..101.7711C. doi:10.1073/pnas.0402490101. PMC 419671. PMID 15128933.
  7. "Entrez Gene: CYP2R1 cytochrome P450, family 2, subfamily R, polypeptide 1".
  8. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  9. "International Mouse Phenotyping Consortium".
  10. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  11. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  12. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  13. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  14. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading


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