CYP27B1
Function
A cytochrome P450 monooxygenase involved in vitamin D metabolism and in calcium and phosphorus homeostasis. Catalyzes the rate-limiting step in the activation of vitamin D in the kidney, namely the hydroxylation of 25-hydroxyvitamin D3/calcidiol at the C1alpha-position to form the hormonally active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3/calcitriol that acts via the vitamin D receptor (VDR) (PubMed:10518789, PubMed:10566658, PubMed:12050193, PubMed:22862690, PubMed:9486994). Has 1alpha-hydroxylase activity on vitamin D intermediates of the CYP24A1-mediated inactivation pathway (PubMed:10518789, PubMed:22862690). Converts 24R,25-dihydroxyvitamin D3/secalciferol to 1-alpha,24,25-trihydroxyvitamin D3, an active ligand of VDR. Also active on 25-hydroxyvitamin D2 (PubMed:10518789). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:22862690).
Involvement in disease
Rickets vitamin D-dependent 1A
VDDR1A
A disorder caused by a selective deficiency of the active form of vitamin D (1,25-dihydroxyvitamin D3) and resulting in defective bone mineralization and clinical features of rickets.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Hormone biosynthesis; vitamin D biosynthesis.
Sequence Similarities
Belongs to the cytochrome P450 family.
Tissue Specificity
Kidney.
Cellular localization
- Mitochondrion membrane
Alternative names
CYP1ALPHA, CYP27B, CYP27B1, 25-OHD-1 alpha-hydroxylase, 25-hydroxyvitamin D(3) 1-alpha-hydroxylase, Calcidiol 1-monooxygenase, Cytochrome P450 subfamily XXVIIB polypeptide 1, Cytochrome P450C1 alpha, Cytochrome P450VD1-alpha, Cytochrome p450 27B1, VD3 1A hydroxylase