Steroid 21-hydroxylase
Also known as: CYP21, CYP21A2, CYP21B
Function
A cytochrome P450 monooxygenase that plays a major role in adrenal steroidogenesis. Catalyzes the hydroxylation at C-21 of progesterone and 17alpha-hydroxyprogesterone to respectively form 11-deoxycorticosterone and 11-deoxycortisol, intermediate metabolites in the biosynthetic pathway of mineralocorticoids and glucocorticoids. 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 cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase).
Classification
- Family (Pfam)
- PF00067 p450
- InterPro
- Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_sf
- Functional cluster
- Secreted Growth Factors & Cytokines
Experimental structures · PDB · 2
A predicted model is available from AlphaFold.
Gene Ontology · 14
- GO:0005789 endoplasmic reticulum membrane
- GO:0103069 17-hydroxyprogesterone 21-hydroxylase activity
- GO:0020037 heme binding
- GO:0005506 iron ion binding
- GO:0106309 progesterone 21-hydroxylase activity
- GO:0004509 steroid 21-monooxygenase activity
- GO:0005496 steroid binding
- GO:0008395 steroid hydroxylase activity
- GO:0034651 cortisol biosynthetic process
- GO:0006704 glucocorticoid biosynthetic process
- GO:0006705 mineralocorticoid biosynthetic process
- GO:0006694 steroid biosynthetic process
- GO:0008202 steroid metabolic process
- GO:0016125 sterol metabolic process
Disease associations
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Steroid 21-hydroxylase 0.99
- Steroid 21-hydroxylase 0.99
- Steroid 21-hydroxylase 0.98
- Steroid 21-hydroxylase 0.98
- Steroid 21-hydroxylase 0.98
- Steroid 21-hydroxylase 0.98
- Steroid 21-hydroxylase 0.97
- Steroid 21-hydroxylase 0.97
- Steroid 17-alpha-hydroxylase/17,20 lyase 0.96
- Steroid 17-alpha-hydroxylase/17,20 lyase 0.88
- Steroid 17-alpha-hydroxylase/17,20 lyase 0.88
- Cytochrome P450 2D15 0.88
Co-cited proteins · studied together in the literature
- Steroid 21-hydroxylase 1 shared papers
- Cytochrome P450 11B1, mitochondrial 1 shared papers
Literature · 69 cited papers
- Identification of a novel compound heterozygous mutation of the CYP21A2 gene causing 21-hydroxylase deficiency in a Chinese pedigree. Mol. Med. Report. · 2018
- A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics. Eur. J. Hum. Genet. · 2017
- Functional and structural consequences of nine CYP21A2 mutations ranging from very mild to severe effects. Int. J. Endocrinol. · 2016
- Human Cytochrome P450 21A2, the major steroid 21-hydroxylase: structure of the enzyme-progesterone substrate complex and rate-limiting c-h bond cleavage. J. Biol. Chem. · 2015
- Both positive and negative selection pressures contribute to the polymorphism pattern of the duplicated human CYP21A2 gene. PLoS ONE · 2013
- Intraspecific evolution of human RCCX copy number variation traced by haplotypes of the CYP21A2 gene. Genome Biol. Evol. · 2013
- p.H282N and p.Y191H: 2 novel CYP21A2 mutations in Italian congenital adrenal hyperplasia patients. Metabolism · 2012
- A large view of CYP21 locus among Sicilians and other populations: identification of a novel CYP21A2 variant in Sicily. J. Endocrinol. Invest. · 2011
- Phenotype-genotype correlations of 13 rare CYP21A2 mutations detected in 46 patients affected with 21-hydroxylase deficiency and in one carrier. J. Clin. Endocrinol. Metab. · 2010
- Linkage analysis of the C4A/C4B copy number variation and polymorphisms of the adjacent steroid 21-hydroxylase gene in a healthy population. Mol. Immunol. · 2009
- Functional and structural consequences of a novel point mutation in the CYP21A2 gene causing congenital adrenal hyperplasia: potential relevance of helix C for P450 oxidoreductase-21-hydroxylase interaction. J. Clin. Endocrinol. Metab. · 2008
- Inhibition of CYP21A2 enzyme activity caused by novel missense mutations identified in Brazilian and Scandinavian patients. J. Clin. Endocrinol. Metab. · 2008
- … and 57 more in the literature graph
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