IUBMB Enzyme Nomenclature


Accepted name: vitamin D 25-hydroxylase

Reaction: calciol + O2 + [reduced NADPH—hemoprotein reductase] = calcidiol + [oxidized NADPH—hemoprotein reductase] + H2O

For diagram of reaction click here.

Glossary: calciol = cholecalciferol = vitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3-ol
calcidiol = 25-hydroxyvitamin D3 = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol

Other name(s): vitamin D2 25-hydroxylase; vitamin D3 25-hydroxylase; CYP2R1

Systematic name: calciol,NADPH—hemoprotein reductase:oxygen oxidoreductase (25-hydroxylating)

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 [4]. The direct electron donor to the enzyme is EC, NADPH—hemoprotein reductase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:


1. Cheng, J.B., Motola, D.L., Mangelsdorf, D.J. and Russell, D.W. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J. Biol. Chem. 278 (2003) 38084-38093. [PMID: 12867411]

2. Shinkyo, R., Sakaki, T., Kamakura, M., Ohta, M. and Inouye, K. Metabolism of vitamin D by human microsomal CYP2R1. Biochem. Biophys. Res. Commun. 324 (2004) 451-457. [PMID: 15465040]

3. Strushkevich, N., Usanov, S.A., Plotnikov, A.N., Jones, G. and Park, H.W. Structural analysis of CYP2R1 in complex with vitamin D3. J. Mol. Biol. 380 (2008) 95-106. [PMID: 18511070]

4. Zhu, J. and Deluca, H.F. Vitamin D 25-hydroxylase - Four decades of searching, are we there yet ? Arch. Biochem. Biophys. 523 (2012) 30-36. [PMID: 22310641]

[EC created 2012 as EC, transferred 2016 to EC]

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