UniProt functional annotation for P19099



	UniProt functional annotation for P19099

UniProt code: P19099.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: A cytochrome P450 monooxygenase that catalyzes the biosynthesis of adrenal mineralocorticoid aldosterone (PubMed:11856349, PubMed:23322723, PubMed:1594605, PubMed:9814506). Catalyzes three sequential oxidative reactions of 11-deoxycorticosterone/21- hydroxyprogesterone, namely 11-beta hydroxylation followed with two successive oxidations at C18 to yield 18-hydroxy and then 18-aldehyde derivatives, resulting in the formation of aldosterone (PubMed:11856349, PubMed:23322723, PubMed:1594605, PubMed:9814506). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:11856349, PubMed:23322723, PubMed:1594605, PubMed:9814506). {ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:23322723, ECO:0000269|PubMed:9814506}.

Catalytic activity: Reaction=a steroid + 2 H(+) + O2 + 2 reduced [adrenodoxin] = an 11beta- hydroxysteroid + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:15629, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:35341, ChEBI:CHEBI:35346; EC=1.14.15.4; Evidence={ECO:0000269|PubMed:23322723}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15630; Evidence={ECO:0000305|PubMed:23322723};

Catalytic activity: Reaction=21-hydroxyprogesterone + 2 H(+) + O2 + 2 reduced [adrenodoxin] = corticosterone + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46104, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16827, ChEBI:CHEBI:16973, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; Evidence={ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:9814506}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46105; Evidence={ECO:0000305|PubMed:11856349};

Catalytic activity: Reaction=corticosterone + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 18- hydroxycorticosterone + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:11872, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16485, ChEBI:CHEBI:16827, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; EC=1.14.15.5; Evidence={ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:23322723, ECO:0000269|PubMed:9814506}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11873; Evidence={ECO:0000305|PubMed:11856349};

Catalytic activity: Reaction=18-hydroxycorticosterone + 2 H(+) + O2 + 2 reduced [adrenodoxin] = aldosterone + 2 H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:50792, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16485, ChEBI:CHEBI:27584, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; Evidence={ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:9814506}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50793; Evidence={ECO:0000305|PubMed:11856349};

Catalytic activity: Reaction=11-deoxycortisol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = cortisol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46100, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17650, ChEBI:CHEBI:28324, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; Evidence={ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:23322723}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46101; Evidence={ECO:0000305|PubMed:23322723};

Cofactor: Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269|PubMed:23322723};

Pathway: Steroid biosynthesis. {ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:23322723, ECO:0000269|PubMed:9814506}.

Subcellular location: Mitochondrion inner membrane {ECO:0000250|UniProtKB:P14137}; Peripheral membrane protein {ECO:0000250|UniProtKB:P14137}.

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. {ECO:0000269|PubMed:11238478, ECO:0000269|PubMed:9177280}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: 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. {ECO:0000269|PubMed:12788848, ECO:0000269|PubMed:1346492, ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:9625333, ECO:0000269|PubMed:9814506}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Hyperaldosteronism, familial, 1 (HALD1) [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 variants 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.

Similarity: Belongs to the cytochrome P450 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		A cytochrome P450 monooxygenase that catalyzes the biosynthesis of adrenal mineralocorticoid aldosterone (PubMed:11856349, PubMed:23322723, PubMed:1594605, PubMed:9814506). Catalyzes three sequential oxidative reactions of 11-deoxycorticosterone/21- hydroxyprogesterone, namely 11-beta hydroxylation followed with two successive oxidations at C18 to yield 18-hydroxy and then 18-aldehyde derivatives, resulting in the formation of aldosterone (PubMed:11856349, PubMed:23322723, PubMed:1594605, PubMed:9814506). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:11856349, PubMed:23322723, PubMed:1594605, PubMed:9814506). {ECO:0000269\|PubMed:11856349, ECO:0000269\|PubMed:1594605, ECO:0000269\|PubMed:23322723, ECO:0000269\|PubMed:9814506}.


Catalytic activity:		Reaction=a steroid + 2 H(+) + O2 + 2 reduced [adrenodoxin] = an 11beta- hydroxysteroid + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:15629, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:35341, ChEBI:CHEBI:35346; EC=1.14.15.4; Evidence={ECO:0000269\|PubMed:23322723}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15630; Evidence={ECO:0000305\|PubMed:23322723};
Catalytic activity:		Reaction=21-hydroxyprogesterone + 2 H(+) + O2 + 2 reduced [adrenodoxin] = corticosterone + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46104, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16827, ChEBI:CHEBI:16973, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; Evidence={ECO:0000269\|PubMed:11856349, ECO:0000269\|PubMed:1594605, ECO:0000269\|PubMed:9814506}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46105; Evidence={ECO:0000305\|PubMed:11856349};
Catalytic activity:		Reaction=corticosterone + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 18- hydroxycorticosterone + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:11872, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16485, ChEBI:CHEBI:16827, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; EC=1.14.15.5; Evidence={ECO:0000269\|PubMed:11856349, ECO:0000269\|PubMed:1594605, ECO:0000269\|PubMed:23322723, ECO:0000269\|PubMed:9814506}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11873; Evidence={ECO:0000305\|PubMed:11856349};
Catalytic activity:		Reaction=18-hydroxycorticosterone + 2 H(+) + O2 + 2 reduced [adrenodoxin] = aldosterone + 2 H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:50792, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16485, ChEBI:CHEBI:27584, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; Evidence={ECO:0000269\|PubMed:11856349, ECO:0000269\|PubMed:1594605, ECO:0000269\|PubMed:9814506}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50793; Evidence={ECO:0000305\|PubMed:11856349};
Catalytic activity:		Reaction=11-deoxycortisol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = cortisol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46100, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17650, ChEBI:CHEBI:28324, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; Evidence={ECO:0000269\|PubMed:11856349, ECO:0000269\|PubMed:23322723}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46101; Evidence={ECO:0000305\|PubMed:23322723};
Cofactor:		Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000269\|PubMed:23322723};
Pathway:		Steroid biosynthesis. {ECO:0000269\|PubMed:11856349, ECO:0000269\|PubMed:1594605, ECO:0000269\|PubMed:23322723, ECO:0000269\|PubMed:9814506}.
Subcellular location:		Mitochondrion inner membrane {ECO:0000250\|UniProtKB:P14137}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P14137}.
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. {ECO:0000269\|PubMed:11238478, ECO:0000269\|PubMed:9177280}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		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. {ECO:0000269\|PubMed:12788848, ECO:0000269\|PubMed:1346492, ECO:0000269\|PubMed:1594605, ECO:0000269\|PubMed:9625333, ECO:0000269\|PubMed:9814506}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Hyperaldosteronism, familial, 1 (HALD1) [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 variants 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.
Similarity:		Belongs to the cytochrome P450 family. {ECO:0000305}.