CYP11B1

• CYP11NB1タンパク質

関

steroid 11-beta-hydroxylase

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/07/11 11:01:13」(JST)

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Cytochrome P450, family 11, subfamily B, polypeptide 1
Identifiers
Symbols	CYP11B1; CPN1; CYP11B; FHI; P450C11
External IDs	OMIM: 610613 MGI: 88584 HomoloGene: 106947 ChEMBL: 1908 GeneCards: CYP11B1 Gene
EC number	1.14.15.4
Gene Ontology Molecular function • monooxygenase activity • steroid 11-beta-monooxygenase activity • steroid 11-beta-monooxygenase activity • electron carrier activity • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen • heme binding • heme binding • metal ion binding Cellular component • mitochondrion • mitochondrion • mitochondrial inner membrane • mitochondrial inner membrane • membrane Biological process • C21-steroid hormone biosynthetic process • glucocorticoid biosynthetic process • mineralocorticoid biosynthetic process • xenobiotic metabolic process • response to stress • immune response • steroid metabolic process • regulation of blood pressure • aldosterone biosynthetic process • aldosterone biosynthetic process • cellular response to hormone stimulus • cortisol biosynthetic process • cortisol biosynthetic process • cellular response to potassium ion • glucose homeostasis • small molecule metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1584	110115
Ensembl	ENSG00000160882	ENSMUSG00000075604
UniProt	P15538	Q3TG86
RefSeq (mRNA)	NM_000497.3	NM_001033229.3
RefSeq (protein)	NP_000488.3	NP_001028401.2
Location (UCSC)	Chr 8: 143.95 – 143.96 Mb	Chr 15: 74.67 – 74.67 Mb
PubMed search	[1]	[2]

Steroid 11β-hydroxylase is a steroid hydroxylase found in the zona fasciculata. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane and is involved in the conversion of 11-deoxycortisol to cortisol in the adrenal cortex. Mutations in this gene cause congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Transcript variants encoding different isoforms have been noted for this gene.

It is reversibly inhibited by etomidate.

Function

It generates cortisol from 11-deoxycortisol and corticosterone from 11-deoxycorticosterone. Note the extra "–OH" added at the 11 position (near the center, on ring "C"):

• 11-Deoxycortisol

• Cortisol

• 11-deoxycorticosterone

• Corticosterone

Clinical significance

A mutation is associated with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

Additional images

Steroidogenesis, showing steroid 11-beta-hydroxylase vertically at right.

• Corticosteroid biosynthetic pathway in rat

• Steroid numbering

References

Further reading

• Helmberg A (1993). "Twin genes and endocrine disease: CYP21 and CYP11B genes". Acta Endocrinol. 129 (2): 97–108. PMID 8372604. 
• Stowasser M, Gunasekera TG, Gordon RD (2002). "Familial varieties of primary aldosteronism". Clin. Exp. Pharmacol. Physiol. 28 (12): 1087–90. DOI:10.1046/j.1440-1681.2001.03574.x. PMID 11903322. 
• Helmberg A, Ausserer B, Kofler R (1992). "Frame shift by insertion of 2 basepairs in codon 394 of CYP11B1 causes congenital adrenal hyperplasia due to steroid 11 beta-hydroxylase deficiency". J. Clin. Endocrinol. Metab. 75 (5): 1278–81. DOI:10.1210/jc.75.5.1278. PMID 1430088. 
• Pascoe L, Curnow KM, Slutsker L et al. (1992). "Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2". Proc. Natl. Acad. Sci. U.S.A. 89 (17): 8327–31. DOI:10.1073/pnas.89.17.8327. PMC 49911. PMID 1518866. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49911. 
• Kawamoto T, Mitsuuchi Y, Toda K et al. (1992). "Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans". Proc. Natl. Acad. Sci. U.S.A. 89 (4): 1458–62. DOI:10.1073/pnas.89.4.1458. PMC 48470. PMID 1741400. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=48470. 
• White PC, Dupont J, New MI et al. (1991). "A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin". J. Clin. Invest. 87 (5): 1664–7. DOI:10.1172/JCI115182. PMC 295260. PMID 2022736. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=295260. 
• Kawamoto T, Mitsuuchi Y, Toda K et al. (1990). "Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta". FEBS Lett. 269 (2): 345–9. DOI:10.1016/0014-5793(90)81190-Y. PMID 2401360. 
• Mornet E, Dupont J, Vitek A, White PC (1990). "Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta)". J. Biol. Chem. 264 (35): 20961–7. PMID 2592361. 
• Chua SC, Szabo P, Vitek A et al. (1987). "Cloning of cDNA encoding steroid 11 beta-hydroxylase (P450c11)". Proc. Natl. Acad. Sci. U.S.A. 84 (20): 7193–7. DOI:10.1073/pnas.84.20.7193. PMC 299256. PMID 3499608. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=299256. 
• Naiki Y, Kawamoto T, Mitsuuchi Y et al. (1994). "A nonsense mutation (TGG [Trp116]-->TAG [Stop]) in CYP11B1 causes steroid 11 beta-hydroxylase deficiency". J. Clin. Endocrinol. Metab. 77 (6): 1677–82. DOI:10.1210/jc.77.6.1677. PMID 7903314. 
• Joehrer K, Geley S, Strasser-Wozak EM et al. (1998). "CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency". Hum. Mol. Genet. 6 (11): 1829–34. DOI:10.1093/hmg/6.11.1829. PMID 9302260. 
• Cargill M, Altshuler D, Ireland J et al. (1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nat. Genet. 22 (3): 231–8. DOI:10.1038/10290. PMID 10391209. 
• Halushka MK, Fan JB, Bentley K et al. (1999). "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis". Nat. Genet. 22 (3): 239–47. DOI:10.1038/10297. PMID 10391210. 
• Cao PR, Bernhardt R (1999). "Interaction of CYP11B1 (cytochrome P-45011 beta) with CYP11A1 (cytochrome P-450scc) in COS-1 cells". Eur. J. Biochem. 262 (3): 720–6. DOI:10.1046/j.1432-1327.1999.00414.x. PMID 10411633. 
• Loidi L, Quinteiro C, Barros F et al. (2000). "The C494F variant in the CYP11B1 gene is a sequence polymorphism in the Spanish population". J. Clin. Endocrinol. Metab. 84 (12): 4749. DOI:10.1210/jc.84.12.4749. PMID 10599751. 
• Chabre O, Portrat-Doyen S, Chaffanjon P et al. (2000). "Bilateral laparoscopic adrenalectomy for congenital adrenal hyperplasia with severe hypertension, resulting from two novel mutations in splice donor sites of CYP11B1". J. Clin. Endocrinol. Metab. 85 (11): 4060–8. DOI:10.1210/jc.85.11.4060. PMID 11095433. 
• Fisher A, Friel EC, Bernhardt R et al. (2001). "Effects of 18-hydroxylated steroids on corticosteroid production by human aldosterone synthase and 11beta-hydroxylase". J. Clin. Endocrinol. Metab. 86 (9): 4326–9. DOI:10.1210/jc.86.9.4326. PMID 11549669. 
• Hampf M, Dao NT, Hoan NT, Bernhardt R (2001). "Unequal crossing-over between aldosterone synthase and 11beta-hydroxylase genes causes congenital adrenal hyperplasia". J. Clin. Endocrinol. Metab. 86 (9): 4445–52. DOI:10.1210/jc.86.9.4445. PMID 11549691. 

External links

• Steroid+11-beta-hydroxylase at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. Uncommon congenital adrenal hyperplasias
• 2. Genetic factors in the pathogenesis of hypertension
• 3. 副腎ステロイド生合成 adrenal steroid biosynthesis
• 4. 副腎疾患におけるレニン-アンギオテンシン-アルドステロン系の評価 assays of the renin angiotensin aldosterone system in adrenal disease
• 5. 副腎アンドロゲンの測定 measurement of adrenal androgens

English Journal

• Phenotypic, metabolic, and molecular genetic characterization of six patients with congenital adrenal hyperplasia caused by novel mutations in the CYP11B1 gene.

• Nguyen HH1, Eiden-Plach A2, Hannemann F2, Malunowicz EM3, Hartmann MF4, Wudy SA4, Bernhardt R5.
• The Journal of steroid biochemistry and molecular biology.J Steroid Biochem Mol Biol.2016 Jan;155(Pt A):126-34. doi: 10.1016/j.jsbmb.2015.10.011. Epub 2015 Oct 22.
• Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder of steroidogenesis. Steroid 11β-hydroxylase deficiency (11β-OHD) due to mutations in the CYP11B1 gene is the second most common form of CAH. In this study, 6 patients suffering from CAH were diagnosed with 11β-OHD u
• PMID 26476331

• Adrenocortical endocrine disruption.

• Harvey PW1.
• The Journal of steroid biochemistry and molecular biology.J Steroid Biochem Mol Biol.2016 Jan;155(Pt B):199-206. doi: 10.1016/j.jsbmb.2014.10.009. Epub 2014 Oct 18.
• The adrenal has been neglected in endocrine disruption regulatory testing strategy. The adrenal is a vital organ, adrenocortical insufficiency is recognised in life threatening "adrenal crises" and Addison's disease, and the consequences of off-target toxicological inhibition of adrenocortical stero
• PMID 25460300

• A Family-Based Association Study of CYP11A1 and CYP11B1 Gene Polymorphisms With Autism in Chinese Trios.

• Deng HZ1, You C1, Xing Y2, Chen KY2, Zou XB3.
• Journal of child neurology.J Child Neurol.2015 Dec 21. pii: 0883073815620672. [Epub ahead of print]
• Autism spectrum disorder is a group of neurodevelopmental disorders with the higher prevalence in males. Our previous studies have indicated lower progesterone levels in the children with autism spectrum disorder, suggesting involvement of the cytochrome P-450scc gene (CYP11A1) and cytochrome P-4501
• PMID 26690694

Japanese Journal

• The combination of a novel 2 bp deletion mutation and p.D63H in CYP11B1 cause congenital adrenal hyperplasia due to steroid 11β-hydroxylase deficiency

• Endocrine Journal 63(3), 301-310, 2016
• NAID 130005140777

• The combination of a novel 2 bp deletion mutation and p.D63H in <i>CYP11B1</i> cause congenital adrenal hyperplasia due to steroid 11β-hydroxylase deficiency

• Endocrine Journal advpub(0), 2016
• NAID 130005120247

• 原発性アルドステロン症の最近の進歩 : アルドステロン合成の場の同定と遺伝子変異 (内分泌) -- (臨床分野での進歩)

• Annual review. 糖尿病・代謝・内分泌, 177-182, 2015
• NAID 40020368652

Related Pictures

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★リンクテーブル★

リンク元	「副腎皮質ホルモン」「CYP11NB1タンパク質」

「副腎皮質ホルモン」

　　[★]

英

adrenocortical hormone

同

副腎皮質ステロイド adrenocorticoids

関

副腎皮質刺激ホルモン放出ホルモン、副腎皮質刺激ホルモン

ステロイド

関

副腎、副腎皮質、ステロイド、コルチコステロイド、ステロイドホルモン、コルチコイド。副腎皮質ホルモン剤

• 図：SP.891(組織),892(構造式)
• 副腎皮質の球状層、索状層、網状層で合成される

種類(主要なもののみ)

• 電解質コルチコイド

球状層から分泌される。アルドステロン

• 糖質コルチコイド

索状層から分泌される。コルチゾール

• 副腎アンドロジェン

網状層から分泌される。アンドロステンジオン

コレステロール cholesterol
↓CYP11A1
プレグネノロン pregnenolone	－－→ CYP17 17α-hydroxylase	17α-ヒドロキシプレグネノロン 17α-hydroxypregnenolone	－－→ CYP17 17α-hydroxylase	デヒドロエピアンドロステロン dehydroepiandrosterone DHEA
↓3β-HSD 3β-hydroxysteroid dehydrogenase		↓3β-HSD		↓3β-HSD
プロゲステロン progesterone	－－→ CYP17 17α-hydroxylase	17α-ヒドロキシプロゲステロン 17α-hydroxyprogesterone	－－→ CYP17 17α-hydroxylase	アンドロステンジオン androstenedione Δ4androstene-3,17-dion
↓CYP21 21-hydroxylase		↓CYP21 21-hydroxylase
デオキシコルチコステロン deoxycorticosterone		11-デオキシコルチゾール 11-deoxycortisol
↓CYP11B2　11β-hydroxylase		↓CYP11B1　11β-hydroxylase
コルチコステロン corticosterone		コルチゾール cortisol
↓CYP11B2 18-hydroxylase
18-ヒドロキシコルチコステロン 18-hydroxycorticosterone
↓CYP11B2 18-hydroxydehydrogenase
アルドステロン aldosterone
球状増 zona glomerulosa		索状層 zona fasciculata		網状層 zona reticularis

臨床関連

• 副腎皮質ホルモン過多：クッシング症候群
• 副腎皮質ホルモン欠乏：アジソン病
• 副腎皮質ホルモン合成異常：先天性副腎過形成

21-hydroxylaseが正常に機能しないことにより生じる (L.320)

薬理学

• 副腎皮質ホルモン製剤

副腎皮質から分泌されるホルモン (SP.895)

名称		血漿濃度 (ng/ml)	1日分泌量 (mg/day)
糖質コルチコイド	コルチゾール	40～180	15～20
	コルチコステロン	2～6	2～5
鉱質コルチコイド	アルドステロン	0.05～0.20	0.05～0.15
	11-DOC	0.05～0.30	0.10～0.20
副腎アンドロジェン	DHEA	2～8	7～15
	DHEA-S	1～4
	アンドロステンジオン	1～2	2～3

「CYP11NB1タンパク質」

　　[★]

英

CYP11B1

関

ステロイド11β水酸化酵素