21-Hydroxylase

Steroid 21-monooxygenase
Identifiers
EC number	1.14.99.10
CAS number	9029-68-9
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles

Cytochrome P450, family 21, subfamily A, polypeptide 2
Identifiers
Symbols	CYP21A2; CA21H; CAH1; CPS1; CYP21; CYP21B; MGC150536; MGC150537; P450c21B
External IDs	OMIM: 613815 MGI: 88591 HomoloGene: 68063 GeneCards: CYP21A2 Gene
EC number	1.14.99.10
Gene Ontology Molecular function • steroid 21-monooxygenase activity • steroid binding • steroid hydroxylase activity • electron carrier activity • heme binding • metal ion binding Cellular component • endoplasmic reticulum • endoplasmic reticulum membrane • microsome • membrane Biological process • steroid biosynthetic process • glucocorticoid biosynthetic process • mineralocorticoid biosynthetic process • xenobiotic metabolic process • steroid metabolic process • hormone biosynthetic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1589	13079
Ensembl	ENSG00000168482	ENSMUSG00000024365
UniProt	P08686	A0JP50
RefSeq (mRNA)	NM_000500.7	NM_009995.2
RefSeq (protein)	NP_000491.4	NP_034125.2
Location (UCSC)	Chr c6_COX: 32.1 – 32.1 Mb	Chr 17: 34.94 – 34.94 Mb
PubMed search	[1]	[2]

Steroid 21-hydroxylase is a cytochrome P450 enzyme that is involved with the biosynthesis of the steroid hormones aldosterone and cortisol.^[1]

In humans, 21-Hydroxylase is encoded by the gene CYP21A2.^[2]

Names and classification

21-Hydroxylase is also called steroid 21-monooxygenase, 21α-Hydroxylase, and, less commonly 21β-Hydroxylase.

Function

This gene encodes 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 protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone.^[3]

Reaction

21-Hydroxylase catalyses the hydroxylation of the carbon atom 21 in steroids (adding an "–OH"), which is necessary with the formation of these hormones.

Progesterone   11-deoxycorticosterone   Steroid numbering - #21 is near center top

Pathway

Human steroidogenesis, showing both reactions of 21-Hydroxylase at center top.

Corticosteroid biosynthetic pathway in the rat.

Clinical significance

A defect within the CYP21A2 gene causes a disturbance of the development of the enzyme, which leads to congenital adrenal hyperplasia due to 21-hydroxylase deficiency. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought account for many cases of steroid 21-hydroxylase deficiency.^[3]

References

1. ^ Ryan KJ, Engel LL (March 1957). "Hydroxylation of steroids at carbon 21". J. Biol. Chem. 225 (1): 103–14. PMID 13416221. http://www.jbc.org/content/225/1/103.full.pdf. 
2. ^ Higashi Y, Yoshioka H, Yamane M, Gotoh O, Fujii-Kuriyama Y (May 1986). "Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene". Proc. Natl. Acad. Sci. U.S.A. 83 (9): 2841–5. doi:10.1073/pnas.83.9.2841. PMC 323402. PMID 3486422. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=323402. 
3. ^ ^{a b} "Entrez Gene: CYP21A2 cytochrome P450, family 21, subfamily A, polypeptide 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1589. 

Further reading

• White PC, Tusie-Luna MT, New MI, Speiser PW (1994). "Mutations in steroid 21-hydroxylase (CYP21).". Hum. Mutat. 3 (4): 373–8. doi:10.1002/humu.1380030408. PMID 8081391. 
• Helmberg A (1993). "Twin genes and endocrine disease: CYP21 and CYP11B genes.". Acta Endocrinol. 129 (2): 97–108. PMID 8372604. 
• de-Araujo M, Sanches MR, Suzuki LA, et al. (1996). "Molecular analysis of CYP21 and C4 genes in Brazilian families with the classical form of steroid 21-hydroxylase deficiency.". Braz. J. Med. Biol. Res. 29 (1): 1–13. PMID 8731325. 
• Yu CY (1999). "Molecular genetics of the human MHC complement gene cluster.". Exp. Clin. Immunogenet. 15 (4): 213–30. doi:10.1159/000019075. PMID 10072631. 
• Forest MG, Tardy V, Nicolino M, et al. (2005). "21-Hydroxylase deficiency: an exemplary model of the contribution of molecular biology in the understanding and management of the disease.". Ann. Endocrinol. (Paris) 66 (3): 225–32. PMID 15988383. 

External links

• GeneReviews/NCBI/NIH/UW entry on 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia
• OMIM entry on 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia
• Synthesis of Desoxycorticosterone from Progesterone through 21-Hydroxylase (Image)
• MeSH Steroid+21-Hydroxylase

This article incorporates text from the United States National Library of Medicine, which is in the public domain.