CYP2R1

Cytochrome P450, family 2, subfamily R, polypeptide 1
PDB rendering based on 2ojd.
Available structures PDB 3C6G, 3CZH, 3DL9
Identifiers
Symbols	CYP2R1; MGC4663
External IDs	OMIM: 608713 MGI: 2449771 HomoloGene: 75210 GeneCards: CYP2R1 Gene
EC number	1.14.13.15
Gene Ontology Molecular function • monooxygenase activity • electron carrier activity • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen • heme binding • vitamin D3 25-hydroxylase activity • metal ion binding • cholestanetriol 26-monooxygenase activity Cellular component • endoplasmic reticulum • endoplasmic reticulum membrane • microsome • membrane Biological process • vitamin metabolic process • xenobiotic metabolic process • steroid metabolic process • vitamin D metabolic process • hormone biosynthetic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	120227	244209
Ensembl	ENSG00000186104	ENSMUSG00000030670
UniProt	Q6VVX0	Q32MW0
RefSeq (mRNA)	NM_024514	NM_177382.3
RefSeq (protein)	NP_078790	NP_796356.2
Location (UCSC)	Chr 11: 14.9 – 14.91 Mb	Chr 7: 121.69 – 121.71 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.^[1][2][3]

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. 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.^[2] 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.^[2]

Conversion of cholecalciferol to calcidiol as catalyzed by CYP2R1.

References

1. ^ 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. 
2. ^ ^{a b c} 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=419671. 
3. ^ "Entrez Gene: CYP2R1 cytochrome P450, family 2, subfamily R, polypeptide 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=120227. 

Further reading

• Ramos-Lopez E, Brück P, Jansen T, et al. (2008). "CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans.". Diabetes Metab. Res. Rev. 23 (8): 631–6. doi:10.1002/dmrr.719. PMID 17607662. 
• Ramos-Lopez E, Brück P, Jansen T, et al. (2007). "CYP2R1-, CYP27B1- and CYP24-mRNA expression in German type 1 diabetes patients.". J. Steroid Biochem. Mol. Biol. 103 (3–5): 807–10. doi:10.1016/j.jsbmb.2006.12.056. PMID 17223345. 
• Wjst M, Altmüller J, Faus-Kessler T, et al. (2006). "Asthma families show transmission disequilibrium of gene variants in the vitamin D metabolism and signalling pathway". Respir. Res. 7: 60. doi:10.1186/1465-9921-7-60. PMC 1508148. PMID 16600026. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1508148. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Shinkyo R, Sakaki T, Kamakura M, et al. (2004). "Metabolism of vitamin D by human microsomal CYP2R1". Biochem. Biophys. Res. Commun. 324 (1): 451–7. doi:10.1016/j.bbrc.2004.09.073. PMID 15465040. 
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode 2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.