C11B2_HUMAN
ID C11B2_HUMAN Reviewed; 503 AA.
AC P19099; B0ZBE4; Q16726;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 3.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Cytochrome P450 11B2, mitochondrial;
DE AltName: Full=Aldosterone synthase {ECO:0000303|PubMed:9814506};
DE Short=ALDOS;
DE AltName: Full=Aldosterone-synthesizing enzyme;
DE AltName: Full=CYPXIB2;
DE AltName: Full=Corticosterone 18-monooxygenase, CYP11B2;
DE EC=1.14.15.5 {ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:23322723, ECO:0000269|PubMed:9814506};
DE AltName: Full=Cytochrome P-450Aldo;
DE AltName: Full=Cytochrome P-450C18;
DE AltName: Full=Steroid 11-beta-hydroxylase, CYP11B2 {ECO:0000303|PubMed:2592361};
DE EC=1.14.15.4 {ECO:0000269|PubMed:23322723};
DE AltName: Full=Steroid 18-hydroxylase {ECO:0000303|PubMed:9177280};
DE Flags: Precursor;
GN Name=CYP11B2 {ECO:0000303|PubMed:1346492, ECO:0000312|HGNC:HGNC:2592};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2592361; DOI=10.1016/s0021-9258(19)30030-4;
RA Mornet E., Dupont J., Vitek A., White P.C.;
RT "Characterization of two genes encoding human steroid 11 beta-hydroxylase
RT (P-450(11) beta).";
RL J. Biol. Chem. 264:20961-20967(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=2256920; DOI=10.1016/s0006-291x(05)81058-7;
RA Kawamoto T., Mitsuuchi Y., Ohnishi T., Ichikawa Y., Yokoyama Y.,
RA Sumimoto H., Toda K., Miyahara K., Kuribayashi I., Nakao K., Hosoda K.,
RA Yamamoto Y., Imura H., Shizuta Y.;
RT "Cloning and expression of a cDNA for human cytochrome P-450aldo as related
RT to primary aldosteronism.";
RL Biochem. Biophys. Res. Commun. 173:309-316(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RA Kawamoto T., Miyahara K., Mitsuuchi Y., Ulick S., Shizuta Y.;
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF ILE-112; ASP-147
RP AND LYS-152.
RX PubMed=11856349; DOI=10.1046/j.1432-1033.2002.02729.x;
RA Bechtel S., Belkina N., Bernhardt R.;
RT "The effect of amino-acid substitutions I112P, D147E and K152N in CYP11B2
RT on the catalytic activities of the enzyme.";
RL Eur. J. Biochem. 269:1118-1127(2002).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 34-503 IN COMPLEXES WITH HEME;
RP DESOXYCORTICOSTERONE AND SYNTHETIC INHIBITOR FADROZOLE, CATALYTIC ACTIVITY,
RP COFACTOR, FUNCTION, AND PATHWAY.
RX PubMed=23322723; DOI=10.1210/me.2012-1287;
RA Strushkevich N., Gilep A.A., Shen L., Arrowsmith C.H., Edwards A.M.,
RA Usanov S.A., Park H.W.;
RT "Structural insights into aldosterone synthase substrate specificity and
RT targeted inhibition.";
RL Mol. Endocrinol. 27:315-324(2013).
RN [8]
RP VARIANTS CMO-2 DEFICIENCY TRP-181 AND ALA-386, CATALYTIC ACTIVITY,
RP FUNCTION, AND PATHWAY.
RX PubMed=1594605; DOI=10.1073/pnas.89.11.4996;
RA Pascoe L., Curnow K.M., Slutsker L., Roesler A., White P.C.;
RT "Mutations in the human CYP11B2 (aldosterone synthase) gene causing
RT corticosterone methyloxidase II deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:4996-5000(1992).
RN [9]
RP VARIANTS CMO-2 DEFICIENCY TRP-181 AND ALA-386.
RX PubMed=1346492; DOI=10.1016/0006-291x(92)91827-d;
RA Mitsuuchi Y., Kawamoto T., Naiki Y., Miyahara K., Toda K., Kuribayashi I.,
RA Orii T., Yasuda K., Miura K., Nakao K., Imura H., Ulick S., Shizuta Y.;
RT "Congenitally defective aldosterone biosynthesis in humans: the involvement
RT of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient
RT patients.";
RL Biochem. Biophys. Res. Commun. 182:974-979(1992).
RN [10]
RP ERRATUM OF PUBMED:1346492.
RA Mitsuuchi Y., Kawamoto T., Naiki Y., Miyahara K., Toda K., Kuribayashi I.,
RA Orii T., Yasuda K., Miura K., Nakao K., Imura H., Ulick S., Shizuta Y.;
RL Biochem. Biophys. Res. Commun. 184:1529-1530(1992).
RN [11]
RP DISEASE.
RX PubMed=8439335; DOI=10.1006/bbrc.1993.1128;
RA Mitsuuchi Y., Kawamoto T., Miyahara K., Ulick S., Morton D.H., Naiki Y.,
RA Kuribayashi I., Toda K., Hara T., Orii T., Yasuda K., Miura K.,
RA Yamamoto Y., Imura H., Shizuta Y.;
RT "Congenitally defective aldosterone biosynthesis in humans: inactivation of
RT the P-450(C18) gene (CYP11B2) due to nucleotide deletion in CMO I deficient
RT patients.";
RL Biochem. Biophys. Res. Commun. 190:864-869(1993).
RN [12]
RP VARIANT CMO-1 DEFICIENCY PRO-461.
RX PubMed=9177280; DOI=10.1006/bbrc.1997.6651;
RA Nomoto S., Massa G., Mitani F., Ishimura Y., Miyahara K., Toda K.,
RA Nagano I., Yamashiro T., Ogoshi S., Fukata J., Onishi S., Hashimoto K.,
RA Doi Y., Imura H., Shizuta Y.;
RT "CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2
RT gene encoding steroid 18-hydroxylase (P450C18).";
RL Biochem. Biophys. Res. Commun. 234:382-385(1997).
RN [13]
RP VARIANT CMO-2 DEFICIENCY ILE-185.
RX PubMed=9625333; DOI=10.1007/s004310050833;
RA Peter M., Buenger K., Solyom J., Sippell W.G.;
RT "Mutation THR-185 ILE is associated with corticosterone methyl oxidase
RT deficiency type II.";
RL Eur. J. Pediatr. 157:378-381(1998).
RN [14]
RP VARIANTS CMO-2 DEFICIENCY ASP-198 AND ALA-386, FUNCTION, CATALYTIC
RP ACTIVITY, AND PATHWAY.
RX PubMed=9814506; DOI=10.1210/jcem.83.11.5258;
RA Portrat-Doyen S., Tourniaire J., Richard O., Mulatero P.,
RA Aupetit-Faisant B., Curnow K.M., Pascoe L., Morel Y.;
RT "Isolated aldosterone synthase deficiency caused by simultaneous E198D and
RT V386A mutations in the CYP11B2 gene.";
RL J. Clin. Endocrinol. Metab. 83:4156-4161(1998).
RN [15]
RP VARIANT ARG-173.
RX PubMed=9931115; DOI=10.1161/01.hyp.33.1.266;
RA Tamaki S., Iwai N., Tsujita Y., Kinoshita M.;
RT "Genetic polymorphism of CYP11B2 gene and hypertension in Japanese.";
RL Hypertension 33:266-270(1999).
RN [16]
RP VARIANTS THR-29; GLN-30; ARG-173; THR-248; SER-281; THR-339; ALA-386 AND
RP SER-435.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [17]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [18]
RP VARIANTS ARG-173; THR-248; SER-281; THR-339; ALA-386 AND SER-435.
RX PubMed=10391210; DOI=10.1038/10297;
RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A.,
RA Cooper R., Lipshutz R., Chakravarti A.;
RT "Patterns of single-nucleotide polymorphisms in candidate genes for blood-
RT pressure homeostasis.";
RL Nat. Genet. 22:239-247(1999).
RN [19]
RP VARIANT CMO-1 DEFICIENCY ARG-LEU-140 INS.
RX PubMed=11238478; DOI=10.1210/jcem.86.3.7326;
RA Kayes-Wandover K.M., Schindler R.E.L., Taylor H.C., White P.C.;
RT "Type 1 aldosterone synthase deficiency presenting in a middle-aged man.";
RL J. Clin. Endocrinol. Metab. 86:1008-1012(2001).
RN [20]
RP VARIANTS CMO-2 DEFICIENCY ILE-185 AND ALA-498.
RX PubMed=12788848; DOI=10.1210/jc.2003-030353;
RA Dunlop F.M., Crock P.A., Montalto J., Funder J.W., Curnow K.M.;
RT "A compound heterozygote case of type II aldosterone synthase deficiency.";
RL J. Clin. Endocrinol. Metab. 88:2518-2526(2003).
CC -!- FUNCTION: A cytochrome P450 monooxygenase that catalyzes the
CC biosynthesis of adrenal mineralocorticoid aldosterone (PubMed:11856349,
CC PubMed:23322723, PubMed:1594605, PubMed:9814506). Catalyzes three
CC sequential oxidative reactions of 11-deoxycorticosterone/21-
CC hydroxyprogesterone, namely 11-beta hydroxylation followed with two
CC successive oxidations at C18 to yield 18-hydroxy and then 18-aldehyde
CC derivatives, resulting in the formation of aldosterone
CC (PubMed:11856349, PubMed:23322723, PubMed:1594605, PubMed:9814506).
CC Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC substrate and reducing the second into a water molecule. Two electrons
CC are provided by NADPH via a two-protein mitochondrial transfer system
CC comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and
CC nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin)
CC (PubMed:11856349, PubMed:23322723, PubMed:1594605, PubMed:9814506).
CC {ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:1594605,
CC ECO:0000269|PubMed:23322723, ECO:0000269|PubMed:9814506}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a steroid + 2 H(+) + O2 + 2 reduced [adrenodoxin] = an 11beta-
CC hydroxysteroid + H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:15629, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:35341,
CC ChEBI:CHEBI:35346; EC=1.14.15.4;
CC Evidence={ECO:0000269|PubMed:23322723};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15630;
CC Evidence={ECO:0000305|PubMed:23322723};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=21-hydroxyprogesterone + 2 H(+) + O2 + 2 reduced [adrenodoxin]
CC = corticosterone + H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:46104, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16827, ChEBI:CHEBI:16973, ChEBI:CHEBI:33737,
CC ChEBI:CHEBI:33738; Evidence={ECO:0000269|PubMed:11856349,
CC ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:9814506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46105;
CC Evidence={ECO:0000305|PubMed:11856349};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=corticosterone + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 18-
CC hydroxycorticosterone + H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:11872, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16485, ChEBI:CHEBI:16827, ChEBI:CHEBI:33737,
CC ChEBI:CHEBI:33738; EC=1.14.15.5;
CC Evidence={ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:1594605,
CC ECO:0000269|PubMed:23322723, ECO:0000269|PubMed:9814506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11873;
CC Evidence={ECO:0000305|PubMed:11856349};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=18-hydroxycorticosterone + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = aldosterone + 2 H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:50792, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16485, ChEBI:CHEBI:27584, ChEBI:CHEBI:33737,
CC ChEBI:CHEBI:33738; Evidence={ECO:0000269|PubMed:11856349,
CC ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:9814506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50793;
CC Evidence={ECO:0000305|PubMed:11856349};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-deoxycortisol + 2 H(+) + O2 + 2 reduced [adrenodoxin] =
CC cortisol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46100,
CC Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17650,
CC ChEBI:CHEBI:28324, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738;
CC Evidence={ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:23322723};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46101;
CC Evidence={ECO:0000305|PubMed:23322723};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:23322723};
CC -!- PATHWAY: Steroid biosynthesis. {ECO:0000269|PubMed:11856349,
CC ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:23322723,
CC ECO:0000269|PubMed:9814506}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P14137}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P14137}.
CC -!- DISEASE: Corticosterone methyloxidase 1 deficiency (CMO-1 deficiency)
CC [MIM:203400]: Autosomal recessive disorder of aldosterone biosynthesis.
CC There are two biochemically different forms of selective aldosterone
CC deficiency be termed corticosterone methyloxidase (CMO) deficiency type
CC 1 and type 2. In CMO-1 deficiency, aldosterone is undetectable in
CC plasma, while its immediate precursor, 18-hydroxycorticosterone, is low
CC or normal. {ECO:0000269|PubMed:11238478, ECO:0000269|PubMed:9177280}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Corticosterone methyloxidase 2 deficiency (CMO-2 deficiency)
CC [MIM:610600]: Autosomal recessive disorder of aldosterone biosynthesis.
CC In CMO-2 deficiency, aldosterone can be low or normal, but at the
CC expense of increased secretion of 18-hydroxycorticosterone.
CC Consequently, patients have a greatly increased ratio of 18-
CC hydroxycorticosterone to aldosterone and a low ratio of corticosterone
CC to 18-hydroxycorticosterone in serum. {ECO:0000269|PubMed:12788848,
CC ECO:0000269|PubMed:1346492, ECO:0000269|PubMed:1594605,
CC ECO:0000269|PubMed:9625333, ECO:0000269|PubMed:9814506}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Hyperaldosteronism, familial, 1 (HALD1) [MIM:103900]: A
CC disorder characterized by hypertension, variable hyperaldosteronism,
CC and abnormal adrenal steroid production, including 18-oxocortisol and
CC 18-hydroxycortisol. There is significant phenotypic heterogeneity, and
CC some individuals never develop hypertension. Note=The disease is caused
CC by variants affecting the gene represented in this entry. The molecular
CC defect causing hyperaldosteronism familial 1 is an anti-Lepore-type
CC fusion of the CYP11B1 and CYP11B2 genes. The hybrid gene has the
CC promoting part of CYP11B1, ACTH-sensitive, and the coding part of
CC CYP11B2.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CYP11B2 entry;
CC URL="https://en.wikipedia.org/wiki/CYP11B2";
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DR EMBL; M32881; AAA35741.1; -; Genomic_DNA.
DR EMBL; M32864; AAA35741.1; JOINED; Genomic_DNA.
DR EMBL; M32880; AAA35741.1; JOINED; Genomic_DNA.
DR EMBL; X54741; CAA38539.1; -; mRNA.
DR EMBL; D13752; BAA02899.1; -; Genomic_DNA.
DR EMBL; EU326306; ACA05912.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82292.1; -; Genomic_DNA.
DR CCDS; CCDS6393.1; -.
DR PIR; B34181; B34181.
DR RefSeq; NP_000489.3; NM_000498.3.
DR PDB; 4DVQ; X-ray; 2.49 A; A/B/C/D/E/F/G/H/I/J/K/L=34-503.
DR PDB; 4FDH; X-ray; 2.71 A; A/B/C/D/E/F/G/H/I/J/K/L=34-503.
DR PDB; 4ZGX; X-ray; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L=28-503.
DR PDB; 6XZ8; X-ray; 3.00 A; A/B/C=28-503.
DR PDB; 6XZ9; X-ray; 2.77 A; A/B/C=28-503.
DR PDB; 7M8I; X-ray; 2.94 A; A/B/C=31-503.
DR PDB; 7M8V; X-ray; 3.08 A; A/B/C/D/E/F/G/H/I/J/K/L=31-503.
DR PDBsum; 4DVQ; -.
DR PDBsum; 4FDH; -.
DR PDBsum; 4ZGX; -.
DR PDBsum; 6XZ8; -.
DR PDBsum; 6XZ9; -.
DR PDBsum; 7M8I; -.
DR PDBsum; 7M8V; -.
DR AlphaFoldDB; P19099; -.
DR SMR; P19099; -.
DR BioGRID; 107957; 7.
DR STRING; 9606.ENSP00000325822; -.
DR BindingDB; P19099; -.
DR ChEMBL; CHEMBL2722; -.
DR DrugBank; DB04630; Aldosterone.
DR DrugBank; DB00700; Eplerenone.
DR DrugBank; DB00292; Etomidate.
DR DrugBank; DB00741; Hydrocortisone.
DR DrugBank; DB14539; Hydrocortisone acetate.
DR DrugBank; DB14540; Hydrocortisone butyrate.
DR DrugBank; DB14543; Hydrocortisone probutate.
DR DrugBank; DB14545; Hydrocortisone succinate.
DR DrugBank; DB14544; Hydrocortisone valerate.
DR DrugBank; DB01011; Metyrapone.
DR DrugBank; DB01388; Mibefradil.
DR DrugBank; DB11837; Osilodrostat.
DR DrugBank; DB00421; Spironolactone.
DR DrugBank; DB06281; Torcetrapib.
DR DrugCentral; P19099; -.
DR GuidetoPHARMACOLOGY; 1360; -.
DR SwissLipids; SLP:000001198; -.
DR iPTMnet; P19099; -.
DR PhosphoSitePlus; P19099; -.
DR BioMuta; CYP11B2; -.
DR DMDM; 3041666; -.
DR MassIVE; P19099; -.
DR PaxDb; P19099; -.
DR PeptideAtlas; P19099; -.
DR PRIDE; P19099; -.
DR ProteomicsDB; 53632; -.
DR Antibodypedia; 14554; 246 antibodies from 33 providers.
DR DNASU; 1585; -.
DR Ensembl; ENST00000323110.2; ENSP00000325822.2; ENSG00000179142.2.
DR GeneID; 1585; -.
DR KEGG; hsa:1585; -.
DR MANE-Select; ENST00000323110.2; ENSP00000325822.2; NM_000498.3; NP_000489.3.
DR UCSC; uc003yxk.1; human.
DR CTD; 1585; -.
DR DisGeNET; 1585; -.
DR GeneCards; CYP11B2; -.
DR HGNC; HGNC:2592; CYP11B2.
DR HPA; ENSG00000179142; Tissue enriched (adrenal).
DR MalaCards; CYP11B2; -.
DR MIM; 103900; phenotype.
DR MIM; 124080; gene.
DR MIM; 203400; phenotype.
DR MIM; 610600; phenotype.
DR neXtProt; NX_P19099; -.
DR OpenTargets; ENSG00000179142; -.
DR Orphanet; 556030; Early-onset familial hypoaldosteronism.
DR Orphanet; 403; Familial hyperaldosteronism type I.
DR PharmGKB; PA134; -.
DR VEuPathDB; HostDB:ENSG00000179142; -.
DR eggNOG; KOG0159; Eukaryota.
DR GeneTree; ENSGT00940000163354; -.
DR HOGENOM; CLU_001570_28_4_1; -.
DR InParanoid; P19099; -.
DR OMA; FHNVPFG; -.
DR OrthoDB; 481145at2759; -.
DR PhylomeDB; P19099; -.
DR TreeFam; TF105094; -.
DR BioCyc; MetaCyc:HS11355-MON; -.
DR BRENDA; 1.14.15.4; 2681.
DR BRENDA; 1.14.15.5; 2681.
DR PathwayCommons; P19099; -.
DR Reactome; R-HSA-193993; Mineralocorticoid biosynthesis.
DR Reactome; R-HSA-194002; Glucocorticoid biosynthesis.
DR Reactome; R-HSA-211976; Endogenous sterols.
DR Reactome; R-HSA-5579009; Defective CYP11B2 causes CMO-1 deficiency.
DR SignaLink; P19099; -.
DR SIGNOR; P19099; -.
DR BioGRID-ORCS; 1585; 11 hits in 1065 CRISPR screens.
DR GeneWiki; Aldosterone_synthase; -.
DR GenomeRNAi; 1585; -.
DR Pharos; P19099; Tchem.
DR PRO; PR:P19099; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P19099; protein.
DR Bgee; ENSG00000179142; Expressed in right adrenal gland cortex and 25 other tissues.
DR Genevisible; P19099; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0047783; F:corticosterone 18-monooxygenase activity; IBA:GO_Central.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004507; F:steroid 11-beta-monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0008395; F:steroid hydroxylase activity; TAS:Reactome.
DR GO; GO:0032342; P:aldosterone biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:UniProtKB.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IBA:GO_Central.
DR GO; GO:0035865; P:cellular response to potassium ion; IEP:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IBA:GO_Central.
DR GO; GO:0034651; P:cortisol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0034650; P:cortisol metabolic process; IBA:GO_Central.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006705; P:mineralocorticoid biosynthetic process; TAS:Reactome.
DR GO; GO:0055075; P:potassium ion homeostasis; IMP:BHF-UCL.
DR GO; GO:0002017; P:regulation of blood volume by renal aldosterone; IMP:BHF-UCL.
DR GO; GO:0003091; P:renal water homeostasis; IC:BHF-UCL.
DR GO; GO:0055078; P:sodium ion homeostasis; IMP:BHF-UCL.
DR GO; GO:0016125; P:sterol metabolic process; TAS:Reactome.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002399; Cyt_P450_mitochondrial.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00408; MITP450.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion inner membrane; Monooxygenase;
KW Oxidoreductase; Reference proteome; Steroid metabolism; Steroidogenesis;
KW Transit peptide.
FT TRANSIT 1..24
FT /note="Mitochondrion"
FT CHAIN 25..503
FT /note="Cytochrome P450 11B2, mitochondrial"
FT /id="PRO_0000003597"
FT BINDING 381
FT /ligand="21-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:16973"
FT /evidence="ECO:0000269|PubMed:23322723,
FT ECO:0007744|PDB:4DVQ"
FT BINDING 450
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:23322723,
FT ECO:0007744|PDB:4DVQ, ECO:0007744|PDB:4FDH"
FT VARIANT 29
FT /note="A -> T (in dbSNP:rs6438)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_014151"
FT VARIANT 30
FT /note="R -> Q (in dbSNP:rs6441)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_014152"
FT VARIANT 140
FT /note="N -> NRL (in CMO-1 deficiency; the enzyme is
FT inactive)"
FT /id="VAR_018470"
FT VARIANT 173
FT /note="K -> R (in dbSNP:rs4539)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210, ECO:0000269|PubMed:9931115"
FT /id="VAR_001266"
FT VARIANT 181
FT /note="R -> W (in CMO-2 deficiency; reduces 18-hydroxylase
FT and abolishes 18-oxidase activities; leaves 11 beta-
FT hydroxylase activity intact; dbSNP:rs28931609)"
FT /evidence="ECO:0000269|PubMed:1346492,
FT ECO:0000269|PubMed:1594605"
FT /id="VAR_001267"
FT VARIANT 185
FT /note="T -> I (in CMO-2 deficiency; dbSNP:rs121912978)"
FT /evidence="ECO:0000269|PubMed:12788848,
FT ECO:0000269|PubMed:9625333"
FT /id="VAR_018471"
FT VARIANT 198
FT /note="E -> D (in CMO-2 deficiency; slightly reduced 11-
FT beta-hydroxylase activity, greatly decreased 18-hydroxylase
FT activity and absent 18-oxidase activity when associated
FT with A-386.; dbSNP:rs104894072)"
FT /evidence="ECO:0000269|PubMed:9814506"
FT /id="VAR_001268"
FT VARIANT 222
FT /note="N -> T (in dbSNP:rs5308)"
FT /id="VAR_014643"
FT VARIANT 248
FT /note="I -> T (in dbSNP:rs4547)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210"
FT /id="VAR_014153"
FT VARIANT 281
FT /note="N -> S (in dbSNP:rs4537)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210"
FT /id="VAR_014154"
FT VARIANT 339
FT /note="I -> T (in dbSNP:rs4544)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210"
FT /id="VAR_014155"
FT VARIANT 383
FT /note="E -> V (in dbSNP:rs5312)"
FT /id="VAR_014644"
FT VARIANT 386
FT /note="V -> A (in CMO-2 deficiency; small but consistent
FT reduction in the production of 18-hydroxycorticosterone;
FT slightly reduced 11-beta-hydroxylase activity, greatly
FT decreased 18-hydroxylase activity and absent 18-oxidase
FT activity when associated with D-198.; dbSNP:rs61757294)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210, ECO:0000269|PubMed:1346492,
FT ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:9814506"
FT /id="VAR_001269"
FT VARIANT 403
FT /note="V -> E (in dbSNP:rs5315)"
FT /id="VAR_014645"
FT VARIANT 435
FT /note="G -> S (in dbSNP:rs4545)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210"
FT /id="VAR_014156"
FT VARIANT 461
FT /note="L -> P (in CMO-1 deficiency; abolishes the 18-
FT hydroxylase activity required for conversion of 11-
FT deoxycorticosterone to aldosterone; dbSNP:rs72554627)"
FT /evidence="ECO:0000269|PubMed:9177280"
FT /id="VAR_018472"
FT VARIANT 487
FT /note="F -> V (in dbSNP:rs5317)"
FT /id="VAR_014646"
FT VARIANT 498
FT /note="T -> A (in CMO-2 deficiency; dbSNP:rs72554626)"
FT /evidence="ECO:0000269|PubMed:12788848"
FT /id="VAR_018473"
FT MUTAGEN 112
FT /note="I->P: Increases 11-beta- and 18-hydroxylase
FT activities toward 11-deoxycorticosterone; increases 11-
FT beta-hydroxylase activity toward 11-deoxycortisol."
FT /evidence="ECO:0000269|PubMed:11856349"
FT MUTAGEN 147
FT /note="D->E: Increases 11-beta-hydroxylase activity toward
FT 11-deoxycorticosterone and 11-deoxycortisol."
FT /evidence="ECO:0000269|PubMed:11856349"
FT MUTAGEN 152
FT /note="K->N: No significant effect on hydroxylase
FT activities toward 11-deoxycorticosterone and 11-
FT deoxycortisol."
FT /evidence="ECO:0000269|PubMed:11856349"
FT CONFLICT 17
FT /note="S -> C (in Ref. 1; AAA35741)"
FT /evidence="ECO:0000305"
FT CONFLICT 55
FT /note="I -> M (in Ref. 1; AAA35741)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="Y -> I (in Ref. 1; AAA35741)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="S -> R (in Ref. 2; CAA38539)"
FT /evidence="ECO:0000305"
FT CONFLICT 342
FT /note="Q -> K (in Ref. 1; AAA35741)"
FT /evidence="ECO:0000305"
FT CONFLICT 438
FT /note="F -> L (in Ref. 1; AAA35741)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="H -> R (in Ref. 1; AAA35741)"
FT /evidence="ECO:0000305"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 48..58
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 64..75
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 94..103
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 114..123
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 134..142
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 145..148
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 151..178
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 182..186
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 189..205
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 218..238
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 242..248
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 250..280
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 289..296
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 301..313
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 317..332
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 334..353
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 355..357
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 358..361
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 363..375
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 381..385
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 402..406
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 407..410
FT /evidence="ECO:0007829|PDB:4DVQ"
FT TURN 414..416
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 427..430
FT /evidence="ECO:0007829|PDB:4DVQ"
FT HELIX 446..448
FT /evidence="ECO:0007829|PDB:4FDH"
FT HELIX 453..470
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 471..474
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 483..493
FT /evidence="ECO:0007829|PDB:4DVQ"
FT STRAND 497..501
FT /evidence="ECO:0007829|PDB:4DVQ"
SQ SEQUENCE 503 AA; 57560 MW; 42BA671704CEE35D CRC64;
MALRAKAEVC VAAPWLSLQR ARALGTRAAR APRTVLPFEA MPQHPGNRWL RLLQIWREQG
YEHLHLEMHQ TFQELGPIFR YNLGGPRMVC VMLPEDVEKL QQVDSLHPCR MILEPWVAYR
QHRGHKCGVF LLNGPEWRFN RLRLNPDVLS PKAVQRFLPM VDAVARDFSQ ALKKKVLQNA
RGSLTLDVQP SIFHYTIEAS NLALFGERLG LVGHSPSSAS LNFLHALEVM FKSTVQLMFM
PRSLSRWISP KVWKEHFEAW DCIFQYGDNC IQKIYQELAF NRPQHYTGIV AELLLKAELS
LEAIKANSME LTAGSVDTTA FPLLMTLFEL ARNPDVQQIL RQESLAAAAS ISEHPQKATT
ELPLLRAALK ETLRLYPVGL FLERVVSSDL VLQNYHIPAG TLVQVFLYSL GRNAALFPRP
ERYNPQRWLD IRGSGRNFHH VPFGFGMRQC LGRRLAEAEM LLLLHHVLKH FLVETLTQED
IKMVYSFILR PGTSPLLTFR AIN
