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P19099 (C11B2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 161. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome P450 11B2, mitochondrial
Alternative name(s):
Aldosterone synthase
Short name=ALDOS
EC=1.14.15.4
EC=1.14.15.5
Aldosterone-synthesizing enzyme
CYPXIB2
Cytochrome P-450Aldo
Cytochrome P-450C18
Steroid 18-hydroxylase
Gene names
Name:CYP11B2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length503 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone. Ref.6

Catalytic activity

A steroid + reduced adrenodoxin + O2 = an 11-beta-hydroxysteroid + oxidized adrenodoxin + H2O. Ref.6

Corticosterone + reduced adrenodoxin + O2 = 18-hydroxycorticosterone + oxidized adrenodoxin + H2O. Ref.6

Cofactor

Heme group. Ref.6

Subcellular location

Mitochondrion membrane.

Involvement in disease

Corticosterone methyloxidase 1 deficiency (CMO-1 deficiency) [MIM:203400]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Corticosterone methyloxidase 2 deficiency (CMO-2 deficiency) [MIM:610600]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Familial hyperaldosteronism 1 (FH1) [MIM:103900]: A disorder characterized by hypertension, variable hyperaldosteronism, and abnormal adrenal steroid production, including 18-oxocortisol and 18-hydroxycortisol. There is significant phenotypic heterogeneity, and some individuals never develop hypertension.
Note: The disease is caused by mutations affecting the gene represented in this entry. The molecular defect causing hyperaldosteronism familial 1 is an anti-Lepore-type fusion of the CYP11B1 and CYP11B2 genes. The hybrid gene has the promoting part of CYP11B1, ACTH-sensitive, and the coding part of CYP11B2. Ref.10

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords
   Biological processLipid metabolism
Steroid metabolism
Steroidogenesis
   Cellular componentMembrane
Mitochondrion
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransit peptide
   LigandHeme
Iron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processC21-steroid hormone biosynthetic process

Inferred from direct assay Ref.2. Source: BHF-UCL

aldosterone biosynthetic process

Inferred from direct assay Ref.6. Source: UniProtKB

cellular response to hormone stimulus

Inferred from expression pattern PubMed 19342457. Source: UniProtKB

cellular response to potassium ion

Inferred from expression pattern PubMed 19342457. Source: UniProtKB

cortisol biosynthetic process

Inferred from mutant phenotype PubMed 19342457. Source: UniProtKB

mineralocorticoid biosynthetic process

Traceable author statement. Source: Reactome

potassium ion homeostasis

Inferred from mutant phenotype PubMed 9838244. Source: BHF-UCL

regulation of blood volume by renal aldosterone

Inferred from mutant phenotype PubMed 14614232. Source: BHF-UCL

renal water homeostasis

Inferred by curator Ref.2. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

sodium ion homeostasis

Inferred from mutant phenotype PubMed 9838244. Source: BHF-UCL

steroid metabolic process

Traceable author statement. Source: Reactome

sterol metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentmitochondrial inner membrane

Inferred by curator Ref.2. Source: BHF-UCL

mitochondrion

Inferred from direct assay PubMed 1741400Ref.2. Source: BHF-UCL

   Molecular_functioncorticosterone 18-monooxygenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

heme binding

Inferred from direct assay Ref.6. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

steroid 11-beta-monooxygenase activity

Inferred from direct assay Ref.6. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2424Mitochondrion
Chain25 – 503479Cytochrome P450 11B2, mitochondrial
PRO_0000003597

Sites

Metal binding4501Iron (heme axial ligand)

Natural variations

Natural variant291A → T. Ref.15
Corresponds to variant rs6438 [ dbSNP | Ensembl ].
VAR_014151
Natural variant301R → Q. Ref.15
Corresponds to variant rs6441 [ dbSNP | Ensembl ].
VAR_014152
Natural variant1401N → NRL in CMO-1 deficiency; the enzyme is inactive.
VAR_018470
Natural variant1731K → R. Ref.14 Ref.15 Ref.17
Corresponds to variant rs4539 [ dbSNP | Ensembl ].
VAR_001266
Natural variant1811R → W in CMO-2 deficiency; reduces 18-hydroxylase and abolishes 18-oxidase activities; leaves 11 beta-hydroxylase activity intact. Ref.7 Ref.8
Corresponds to variant rs28931609 [ dbSNP | Ensembl ].
VAR_001267
Natural variant1851T → I in CMO-2 deficiency. Ref.12 Ref.19
VAR_018471
Natural variant1981E → D in CMO-2 deficiency. Ref.13
VAR_001268
Natural variant2221N → T.
Corresponds to variant rs5308 [ dbSNP | Ensembl ].
VAR_014643
Natural variant2481I → T. Ref.15 Ref.17
Corresponds to variant rs4547 [ dbSNP | Ensembl ].
VAR_014153
Natural variant2811N → S. Ref.15 Ref.17
Corresponds to variant rs4537 [ dbSNP | Ensembl ].
VAR_014154
Natural variant3391I → T. Ref.15 Ref.17
Corresponds to variant rs4544 [ dbSNP | Ensembl ].
VAR_014155
Natural variant3831E → V.
Corresponds to variant rs5312 [ dbSNP | Ensembl ].
VAR_014644
Natural variant3861V → A in CMO-2 deficiency; small but consistent reduction in the production of 18-hydroxycorticosterone. Ref.7 Ref.8 Ref.13 Ref.15 Ref.17
Corresponds to variant rs4541 [ dbSNP | Ensembl ].
VAR_001269
Natural variant4031V → E.
Corresponds to variant rs5315 [ dbSNP | Ensembl ].
VAR_014645
Natural variant4351G → S. Ref.15 Ref.17
Corresponds to variant rs4545 [ dbSNP | Ensembl ].
VAR_014156
Natural variant4611L → P in CMO-1 deficiency; abolishes the 18-hydroxylase activity required for conversion of 11-deoxycorticosterone to aldosterone. Ref.11
VAR_018472
Natural variant4871F → V.
Corresponds to variant rs5317 [ dbSNP | Ensembl ].
VAR_014646
Natural variant4981T → A in CMO-2 deficiency. Ref.19
VAR_018473

Experimental info

Sequence conflict171S → C in AAA35741. Ref.1
Sequence conflict551I → M in AAA35741. Ref.1
Sequence conflict1191Y → I in AAA35741. Ref.1
Sequence conflict2491S → R in CAA38539. Ref.2
Sequence conflict3421Q → K in AAA35741. Ref.1
Sequence conflict4381F → L in AAA35741. Ref.1
Sequence conflict4701H → R in AAA35741. Ref.1

Secondary structure

......................................................................... 503
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P19099 [UniParc].

Last modified July 15, 1998. Version 3.
Checksum: 42BA671704CEE35D

FASTA50357,560
        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 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta)."
Mornet E., Dupont J., Vitek A., White P.C.
J. Biol. Chem. 264:20961-20967(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism."
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.
Biochem. Biophys. Res. Commun. 173:309-316(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Adrenal gland.
[3]Kawamoto T., Miyahara K., Mitsuuchi Y., Ulick S., Shizuta Y.
Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Blood.
[4]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Structural insights into aldosterone synthase substrate specificity and targeted inhibition."
Strushkevich N., Gilep A.A., Shen L., Arrowsmith C.H., Edwards A.M., Usanov S.A., Park H.W.
Mol. Endocrinol. 27:315-324(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 34-503 IN COMPLEXES WITH HEME; DESOXYCORTICOSTERONE AND SYNTHETIC INHIBITOR FADROZOLE, CATALYTIC ACTIVITY, COFACTOR, FUNCTION.
[7]"Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency."
Pascoe L., Curnow K.M., Slutsker L., Roesler A., White P.C.
Proc. Natl. Acad. Sci. U.S.A. 89:4996-5000(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMO-2 DEFICIENCY TRP-181 AND ALA-386.
[8]"Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients."
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. 182:974-979(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMO-2 DEFICIENCY TRP-181 AND ALA-386.
[9]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)
[10]"Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450(C18) gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients."
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.
Biochem. Biophys. Res. Commun. 190:864-869(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[11]"CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450C18)."
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.
Biochem. Biophys. Res. Commun. 234:382-385(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMO-1 DEFICIENCY PRO-461.
[12]"Mutation THR-185 ILE is associated with corticosterone methyl oxidase deficiency type II."
Peter M., Buenger K., Solyom J., Sippell W.G.
Eur. J. Pediatr. 157:378-381(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMO-2 DEFICIENCY ILE-185.
[13]"Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene."
Portrat-Doyen S., Tourniaire J., Richard O., Mulatero P., Aupetit-Faisant B., Curnow K.M., Pascoe L., Morel Y.
J. Clin. Endocrinol. Metab. 83:4156-4161(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMO-2 DEFICIENCY ASP-198 AND ALA-386.
[14]"Genetic polymorphism of CYP11B2 gene and hypertension in Japanese."
Tamaki S., Iwai N., Tsujita Y., Kinoshita M.
Hypertension 33:266-270(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ARG-173.
[15]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
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. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-29; GLN-30; ARG-173; THR-248; SER-281; THR-339; ALA-386 AND SER-435.
[16]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)
[17]"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis."
Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A.
Nat. Genet. 22:239-247(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARG-173; THR-248; SER-281; THR-339; ALA-386 AND SER-435.
[18]"Type 1 aldosterone synthase deficiency presenting in a middle-aged man."
Kayes-Wandover K.M., Schindler R.E.L., Taylor H.C., White P.C.
J. Clin. Endocrinol. Metab. 86:1008-1012(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMO-1 DEFICIENCY ARG-LEU-140 INS.
[19]"A compound heterozygote case of type II aldosterone synthase deficiency."
Dunlop F.M., Crock P.A., Montalto J., Funder J.W., Curnow K.M.
J. Clin. Endocrinol. Metab. 88:2518-2526(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CMO-2 DEFICIENCY ILE-185 AND ALA-498.
+Additional computationally mapped references.

Web resources

Wikipedia

CYP11B2 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M32881, M32864, M32880 Genomic DNA. Translation: AAA35741.1.
X54741 mRNA. Translation: CAA38539.1.
D13752 Genomic DNA. Translation: BAA02899.1.
EU326306 Genomic DNA. Translation: ACA05912.1.
CH471162 Genomic DNA. Translation: EAW82292.1.
CCDSCCDS6393.1.
PIRB34181.
RefSeqNP_000489.3. NM_000498.3.
UniGeneHs.632054.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4DVQX-ray2.49A/B/C/D/E/F/G/H/I/J/K/L34-503[»]
4FDHX-ray2.71A/B/C/D/E/F/G/H/I/J/K/L34-503[»]
ProteinModelPortalP19099.
SMRP19099. Positions 34-502.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107957. 1 interaction.
STRING9606.ENSP00000325822.

Chemistry

BindingDBP19099.
ChEMBLCHEMBL2722.
DrugBankDB00796. Candesartan.
DB01011. Metyrapone.

Polymorphism databases

DMDM3041666.

Proteomic databases

PaxDbP19099.
PRIDEP19099.

Protocols and materials databases

DNASU1585.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000323110; ENSP00000325822; ENSG00000179142.
GeneID1585.
KEGGhsa:1585.
UCSCuc003yxk.1. human.

Organism-specific databases

CTD1585.
GeneCardsGC08M143988.
H-InvDBHIX0034383.
HGNCHGNC:2592. CYP11B2.
HPAHPA049171.
MIM103900. phenotype.
124080. gene.
203400. phenotype.
610600. phenotype.
neXtProtNX_P19099.
Orphanet403. Familial hyperaldosteronism type 1.
99763. Familial hyperreninemic hypoaldosteronism type 1.
PharmGKBPA134.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000013161.
HOVERGENHBG051098.
InParanoidP19099.
KOK07433.
OMAPFEAMPQ.
OrthoDBEOG7ZWD2T.
PhylomeDBP19099.
TreeFamTF105094.

Enzyme and pathway databases

BioCycMetaCyc:HS11355-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.

Gene expression databases

ArrayExpressP19099.
BgeeP19099.
CleanExHS_CYP11B2.
GenevestigatorP19099.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002399. Cyt_P450_mitochondrial.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00408. MITP450.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiAldosterone_synthase.
GenomeRNAi1585.
NextBio6515.
PROP19099.
SOURCESearch...

Entry information

Entry nameC11B2_HUMAN
AccessionPrimary (citable) accession number: P19099
Secondary accession number(s): B0ZBE4, Q16726
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: July 15, 1998
Last modified: July 9, 2014
This is version 161 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM