[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. PubMed=2592361 [NCBI, ExPASy, EBI, Israel, Japan] Mornet E., Dupont J., Vitek A., White P.C.; "Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta)."; J. Biol. Chem. 264:20961-20967(1989).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Adrenal gland; DOI=10.1016/S0006-291X(05)81058-7; PubMed=2256920 [NCBI, ExPASy, EBI, Israel, Japan] Kawamoto T., Mitsuuchi Y., Ohnishi T., Ichikawa Y., Yokoyama Y., Sumimoto H., Toda K., Miyahara K., Kuribayashi I., Nakao K., Hosoda K., Yamamoto Y., Imura H., Shizuta Y.; "Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism."; Biochem. Biophys. Res. Commun. 173:309-316(1990).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. TISSUE=Blood; Kawamoto T., Miyahara K., Mitsuuchi Y., Ulick S., Shizuta Y.; Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
[4]	VARIANTS CMO-2 DEFICIENCY TRP-181 AND ALA-386. PubMed=1594605 [NCBI, ExPASy, EBI, Israel, Japan] Pascoe L., Curnow K.M., Slutsker L., Roesler A., White P.C.; "Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency."; Proc. Natl. Acad. Sci. U.S.A. 89:4996-5000(1992).
[5]	VARIANTS CMO-2 DEFICIENCY TRP-181 AND ALA-386. DOI=10.1016/0006-291X(92)91827-D; PubMed=1346492 [NCBI, ExPASy, EBI, Israel, Japan] Mitsuuchi Y., Kawamoto T., Naiki Y., Miyahara K., Toda K., Kuribayashi I., Orii T., Yasuda K., Miura K., Nakao K., Imura H., Ulick S., Shizuta Y.; "Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients."; Biochem. Biophys. Res. Commun. 182:974-979(1992).
[6]	ERRATUM. Mitsuuchi Y., Kawamoto T., Naiki Y., Miyahara K., Toda K., Kuribayashi I., Orii T., Yasuda K., Miura K., Nakao K., Imura H., Ulick S., Shizuta Y.; Biochem. Biophys. Res. Commun. 184:1529-1530(1992).
[7]	DISEASE. DOI=10.1006/bbrc.1993.1128; PubMed=8439335 [NCBI, ExPASy, EBI, Israel, Japan] Mitsuuchi Y., Kawamoto T., Miyahara K., Ulick S., Morton D.H., Naiki Y., Kuribayashi I., Toda K., Hara T., Orii T., Yasuda K., Miura K., Yamamoto Y., Imura H., Shizuta Y.; "Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450(C18) gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients."; Biochem. Biophys. Res. Commun. 190:864-869(1993).
[8]	VARIANT CMO-1 DEFICIENCY PRO-461. DOI=10.1006/bbrc.1997.6651; PubMed=9177280 [NCBI, ExPASy, EBI, Israel, Japan] Nomoto S., Massa G., Mitani F., Ishimura Y., Miyahara K., Toda K., Nagano I., Yamashiro T., Ogoshi S., Fukata J., Onishi S., Hashimoto K., Doi Y., Imura H., Shizuta Y.; "CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450C18)."; Biochem. Biophys. Res. Commun. 234:382-385(1997).
[9]	VARIANT CMO-2 DEFICIENCY ILE-185. DOI=10.1007/s004310050833; PubMed=9625333 [NCBI, ExPASy, EBI, Israel, Japan] Peter M., Buenger K., Solyom J., Sippell W.G.; "Mutation THR-185 ILE is associated with corticosterone methyl oxidase deficiency type II."; Eur. J. Pediatr. 157:378-381(1998).
[10]	VARIANTS CMO-2 DEFICIENCY ASP-198 AND ALA-386. DOI=10.1210/jc.83.11.4156; PubMed=9814506 [NCBI, ExPASy, EBI, Israel, Japan] Portrat-Doyen S., Tourniaire J., Richard O., Mulatero P., Aupetit-Faisant B., Curnow K.M., Pascoe L., Morel Y.; "Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene."; J. Clin. Endocrinol. Metab. 83:4156-4161(1998).
[11]	VARIANT ARG-173. PubMed=9931115 [NCBI, ExPASy, EBI, Israel, Japan] Tamaki S., Iwai N., Tsujita Y., Kinoshita M.; "Genetic polymorphism of CYP11B2 gene and hypertension in Japanese."; Hypertension 33:266-270(1999).
[12]	VARIANTS THR-29; GLN-30; ARG-173; THR-248; SER-281; THR-339; ALA-386 AND SER-435. DOI=10.1038/10290; PubMed=10391209 [NCBI, ExPASy, EBI, Israel, Japan] Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.; "Characterization of single-nucleotide polymorphisms in coding regions of human genes."; Nat. Genet. 22:231-238(1999).
[13]	ERRATUM. Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.; Nat. Genet. 23:373-373(1999).
[14]	VARIANTS ARG-173; THR-248; SER-281; THR-339; ALA-386 AND SER-435. DOI=10.1038/10297; PubMed=10391210 [NCBI, ExPASy, EBI, Israel, Japan] Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A.; "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis."; Nat. Genet. 22:239-247(1999).
[15]	VARIANT CMO-1 DEFICIENCY ARG-LEU-140 INS. DOI=10.1210/jc.86.3.1008; PubMed=11238478 [NCBI, ExPASy, EBI, Israel, Japan] Kayes-Wandover K.M., Schindler R.E.L., Taylor H.C., White P.C.; "Type 1 aldosterone synthase deficiency presenting in a middle-aged man."; J. Clin. Endocrinol. Metab. 86:1008-1012(2001).
[16]	VARIANTS CMO-2 DEFICIENCY ILE-185 AND ALA-498. DOI=10.1210/jc.2003-030353; PubMed=12788848 [NCBI, ExPASy, EBI, Israel, Japan] Dunlop F.M., Crock P.A., Montalto J., Funder J.W., Curnow K.M.; "A compound heterozygote case of type II aldosterone synthase deficiency."; J. Clin. Endocrinol. Metab. 88:2518-2526(2003).

Comments

FUNCTION: Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
CATALYTIC ACTIVITY: A steroid + reduced adrenal ferredoxin + O₂ = an 11-beta-hydroxysteroid + oxidized adrenal ferredoxin + H₂O.
CATALYTIC ACTIVITY: Corticosterone + reduced adrenal ferredoxin + O₂ = 18-hydroxycorticosterone + oxidized adrenal ferredoxin + H₂O.
COFACTOR: Heme group (By similarity).
SUBCELLULAR LOCATION: Mitochondrion membrane.
DISEASE: Defects in CYP11B2 are the cause of corticosterone methyloxidase type 1 deficiency (CMO-1 deficiency) [MIM:203400]; also called aldosterone deficiency due to defect in 18-hydroxylase or aldosterone deficiency I. CMO-1 deficiency is an autosomal recessive disorder of aldosterone biosynthesis. There are two biochemically different forms of selective aldosterone deficiency be termed corticosterone methyloxidase (CMO) deficiency type 1 and type 2. In CMO-1 deficiency, aldosterone is undetectable in plasma, while its immediate precursor, 18-hydroxycorticosterone, is low or normal.
DISEASE: Defects in CYP11B2 are the cause of corticosterone methyloxidase type 2 deficiency (CMO-2 deficiency) [MIM:610600]. CMO-2 is an autosomal recessive disorder of aldosterone biosynthesis. In CMO-2 deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18-hydroxycorticosterone. Consequently, patients have a greatly increased ratio of 18-hydroxycorticosterone to aldosterone and a low ratio of corticosterone to 18-hydroxycorticosterone in serum.
DISEASE: An anti-Lepore-type fusion of the CYP11B2 and CYP11B1 genes is a cause of glucocorticoid-remediable aldosteronism (GRA) [MIM:103900].
SIMILARITY: Belongs to the cytochrome P450 family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=CYP11B2";.
WEB RESOURCE: Name=Wikipedia; Note=CYP11B2 entry; URL="http://en.wikipedia.org/wiki/CYP11B2";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M32881; AAA35741.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M32864; AAA35741.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M32880; AAA35741.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X54741; CAA38539.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
D13752; BAA02899.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

B34181; B34181.

NP_000489.3; -.

3D structure databases

HSSP

P00189; 1SCC. [HSSP ENTRY / PDB]

ModBase

P19099.

Enzyme and pathway databases

Reactome

REACT_602; Lipid and lipoprotein metabolism.

Organism-specific databases

HGNC:2592; CYP11B2.

103900; phenotype. [NCBI / EBI]
124080; gene. [NCBI / EBI]
203400; phenotype. [NCBI / EBI]
610600; phenotype. [NCBI / EBI]

Orphanet

34145; Berger disease.
85142; Conn's syndrome.
403; Hyperaldosteronism, familial, type 1.
427; Hypoaldosteronism, familial.

PharmGKB

PA134; -.

GeneCards

P19099.

Gene expression databases

ArrayExpress

P19099; -.

CleanEx

HS_CYP11B2; -.

GermOnline

ENSG00000179142; Homo sapiens.

Ontologies

GO:0004507;	Molecular function: steroid 11-beta-monooxygenase activity (traceable author statement from ProtInc).
GO:0006704;	Biological process: glucocorticoid biosynthetic process (traceable author statement from ProtInc).
GO:0008217;	Biological process: regulation of blood pressure (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR001128; Cyt_P450.
IPR002399; Cyt_P450_mit.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.630.10; Cyt_P450; 1.

PANTHER

PTHR19383; Cyt_P450; 1.

Pfam

PF00067; p450; 1.
Pfam graphical view of domain structure.

PRINTS

PR00408; MITP450.
PR00385; P450.

PROSITE

PS00086; CYTOCHROME_P450; 1.

BLOCKS

P19099.

Genome annotation databases

Ensembl

ENSG00000179142; Homo sapiens. [Contig view]

GeneID

1585; -.

KEGG

hsa:1585; -.

Phylogenomic databases

HOGENOM

P19099; -.

HOVERGEN

P19099; -.

Other

DrugBank

DB00796; Candesartan.
DB01011; Metyrapone.

SOURCE

CYP11B2; Homo sapiens.

ProtoNet

P19099.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Disease mutation; Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Mitochondrion; Monooxygenase; Oxidoreductase; Polymorphism; Steroid metabolism; Steroidogenesis; Transit peptide.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`TRANSIT`	`1 24`	`24`	`Mitochondrion.`
`CHAIN`	`25 503`	`479`	`Cytochrome P450 11B2, mitochondrial.`	`PRO_0000003597`
`METAL`	`450 450`		`Iron (heme axial ligand) (By similarity).`
`VARIANT`	`29 29`	`1`	`A -> T (in dbSNP:rs6438 [NCBI]).`	`VAR_014151`
`VARIANT`	`30 30`	`1`	`R -> Q (in dbSNP:rs6441 [NCBI]).`	`VAR_014152`
`VARIANT`	`140 140`	`1`	`N -> NRL (in CMO-1 deficiency; the enzyme is inactive).`	`VAR_018470`
`VARIANT`	`173 173`	`1`	`K -> R (in dbSNP:rs4539 [NCBI]).`	`VAR_001266`
`VARIANT`	`181 181`	`1`	`R -> W (in CMO-2 deficiency; reduces 18-hydroxylase and abolishes 18-oxidase activities; leaves 11 beta-hydroxylase activity intact).`	`VAR_001267`
`VARIANT`	`185 185`	`1`	`T -> I (in CMO-2 deficiency).`	`VAR_018471`
`VARIANT`	`198 198`	`1`	`E -> D (in CMO-2 deficiency).`	`VAR_001268`
`VARIANT`	`222 222`	`1`	`N -> T (in dbSNP:rs5308 [NCBI]).`	`VAR_014643`
`VARIANT`	`248 248`	`1`	`I -> T (in dbSNP:rs4547 [NCBI]).`	`VAR_014153`
`VARIANT`	`281 281`	`1`	`N -> S (in dbSNP:rs4537 [NCBI]).`	`VAR_014154`
`VARIANT`	`339 339`	`1`	`I -> T (in dbSNP:rs4544 [NCBI]).`	`VAR_014155`
`VARIANT`	`383 383`	`1`	`E -> V (in dbSNP:rs5312 [NCBI]).`	`VAR_014644`
`VARIANT`	`386 386`	`1`	`V -> A (in CMO-2 deficiency; small but consistent reduction in the production of 18-hydroxycorticosterone; dbSNP:rs4541 [NCBI]).`	`VAR_001269`
`VARIANT`	`403 403`	`1`	`V -> E (in dbSNP:rs5315 [NCBI]).`	`VAR_014645`
`VARIANT`	`435 435`	`1`	`G -> S (in dbSNP:rs4545 [NCBI]).`	`VAR_014156`
`VARIANT`	`461 461`	`1`	`L -> P (in CMO-1 deficiency; abolishes the 18-hydroxylase activity required for conversion of 11-deoxycorticosterone to aldosterone).`	`VAR_018472`
`VARIANT`	`487 487`	`1`	`F -> V (in dbSNP:rs5317 [NCBI]).`	`VAR_014646`
`VARIANT`	`498 498`	`1`	`T -> A (in CMO-2 deficiency).`	`VAR_018473`
`CONFLICT`	`17 17`		`S -> C (in Ref. 1; AAA35741).`
`CONFLICT`	`55 55`		`I -> M (in Ref. 1; AAA35741).`
`CONFLICT`	`119 119`		`Y -> I (in Ref. 1; AAA35741).`
`CONFLICT`	`249 249`		`S -> R (in Ref. 2; CAA38539).`
`CONFLICT`	`342 342`		`Q -> K (in Ref. 1; AAA35741).`
`CONFLICT`	`438 438`		`F -> L (in Ref. 1; AAA35741).`
`CONFLICT`	`470 470`		`H -> R (in Ref. 1; AAA35741).`

Sequence information

Length: 503 AA [This is the length of the unprocessed precursor]

Molecular weight: 57560 Da [This is the MW of the unprocessed precursor]

CRC64: 42BA671704CEE35D [This is a checksum on the sequence]

        10         20         30         40         50         60 
MALRAKAEVC VAAPWLSLQR ARALGTRAAR APRTVLPFEA MPQHPGNRWL RLLQIWREQG 

        70         80         90        100        110        120 
YEHLHLEMHQ TFQELGPIFR YNLGGPRMVC VMLPEDVEKL QQVDSLHPCR MILEPWVAYR 

       130        140        150        160        170        180 
QHRGHKCGVF LLNGPEWRFN RLRLNPDVLS PKAVQRFLPM VDAVARDFSQ ALKKKVLQNA 

       190        200        210        220        230        240 
RGSLTLDVQP SIFHYTIEAS NLALFGERLG LVGHSPSSAS LNFLHALEVM FKSTVQLMFM 

       250        260        270        280        290        300 
PRSLSRWISP KVWKEHFEAW DCIFQYGDNC IQKIYQELAF NRPQHYTGIV AELLLKAELS 

       310        320        330        340        350        360 
LEAIKANSME LTAGSVDTTA FPLLMTLFEL ARNPDVQQIL RQESLAAAAS ISEHPQKATT 

       370        380        390        400        410        420 
ELPLLRAALK ETLRLYPVGL FLERVVSSDL VLQNYHIPAG TLVQVFLYSL GRNAALFPRP 

       430        440        450        460        470        480 
ERYNPQRWLD IRGSGRNFHH VPFGFGMRQC LGRRLAEAEM LLLLHHVLKH FLVETLTQED 

       490        500 
IKMVYSFILR PGTSPLLTFR AIN

P19099 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools