P19099 · C11B2_HUMAN

  • Protein
    Cytochrome P450 11B2, mitochondrial
  • Gene
    CYP11B2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

A cytochrome P450 monooxygenase that catalyzes the biosynthesis of aldosterone, the main mineralocorticoid in the human body responsible for salt and water homeostasis, thus involved in blood pressure regulation, arterial hypertension, and the development of heart failure (PubMed:11856349, PubMed:12530636, PubMed:1518866, PubMed:15356073, PubMed:1594605, PubMed:1775135, PubMed:22446688, PubMed:23322723, PubMed:9814482, PubMed:9814506).
Catalyzes three sequential oxidative reactions of 11-deoxycorticosterone (21-hydroxyprogesterone), namely 11-beta hydroxylation, followed by two successive oxidations at C18 yielding 18-hydroxy and then 18-oxo intermediates (that would not leave the enzyme active site during the consecutive hydroxylation reactions), ending with the formation of aldosterone (PubMed:11856349, PubMed:12530636, PubMed:1518866, PubMed:1594605, PubMed:1775135, PubMed:22446688, PubMed:23322723, PubMed:9814506).
Can also produce 18-hydroxycortisol and 18-oxocortisol, derived from successive oxidations of cortisol at C18, normally found at very low levels, but significantly increased in primary aldosteronism, the most common form of secondary hypertension (PubMed:15356073, PubMed:9814482).
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:1594605, PubMed:23322723, PubMed:9814506).
Could also be involved in the androgen metabolic pathway (Probable)

Miscellaneous

Expressed in aldosterone-secreting tumors and in adrenal glands of patients with idiopathic hyperaldosteronism.

Catalytic activity

  • a steroid + 2 H+ + O2 + 2 reduced [adrenodoxin] = an 11beta-hydroxysteroid + H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
    EC:1.14.15.4 (UniProtKB | ENZYME | Rhea)
  • 21-hydroxyprogesterone + 2 H+ + O2 + 2 reduced [adrenodoxin] = corticosterone + H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
  • corticosterone + 2 H+ + O2 + 2 reduced [adrenodoxin] = 18-hydroxycorticosterone + H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
    EC:1.14.15.5 (UniProtKB | ENZYME | Rhea)
  • 18-hydroxycorticosterone + 2 H+ + O2 + 2 reduced [adrenodoxin] = aldosterone + 2 H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
  • 11-deoxycortisol + 2 H+ + O2 + 2 reduced [adrenodoxin] = cortisol + H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
  • 21-hydroxyprogesterone + 2 H+ + O2 + 2 reduced [adrenodoxin] = 18-hydroxy-11-deoxycorticosterone + H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
  • cortisol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 18-hydroxycortisol + H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
  • 18-hydroxycortisol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 18-oxocortisol + 2 H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.

Cofactor

heme (UniProtKB | Rhea| CHEBI:30413 )

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
2.6 μMcortisol
106 μM11-deoxycorticosterone
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
238 nmol/min/nmolwith 11-deoxycorticosterone

Pathway

Steroid biosynthesis.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site38121-hydroxyprogesterone (UniProtKB | ChEBI)
Binding site450Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue

GO annotations

AspectTerm
Cellular Componentmitochondrial inner membrane
Cellular Componentmitochondrion
Molecular Functioncorticosterone 18-monooxygenase activity
Molecular Functionheme binding
Molecular Functioniron ion binding
Molecular Functionsteroid 11-beta-monooxygenase activity
Molecular Functionsteroid hydroxylase activity
Biological Processaldosterone biosynthetic process
Biological ProcessC21-steroid hormone biosynthetic process
Biological Processcellular response to hormone stimulus
Biological Processcellular response to peptide hormone stimulus
Biological Processcellular response to potassium ion
Biological Processcholesterol metabolic process
Biological Processcortisol biosynthetic process
Biological Processcortisol metabolic process
Biological Processglucocorticoid biosynthetic process
Biological Processmineralocorticoid biosynthetic process
Biological Processpotassium ion homeostasis
Biological Processregulation of blood volume by renal aldosterone
Biological Processrenal water homeostasis
Biological Processsodium ion homeostasis
Biological Processsterol metabolic process

Keywords

Enzyme and pathway databases

Chemistry

Names & Taxonomy

Protein names

  • Recommended name
    Cytochrome P450 11B2, mitochondrial
  • Alternative names
    • Aldosterone synthase
      (ALDOS)
    • Aldosterone-synthesizing enzyme
    • CYPXIB2
    • Corticosterone 18-monooxygenase, CYP11B2 (EC:1.14.15.5
      ) . EC:1.14.15.5 (UniProtKB | ENZYME | Rhea)
    • Cytochrome P-450Aldo

Gene names

    • Name
      CYP11B2

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P19099
  • Secondary accessions
    • B0ZBE4
    • Q16726

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Disease & Variants

Involvement in disease

Corticosterone methyloxidase 1 deficiency (CMO-1 deficiency)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    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.
  • See also
    MIM:203400
Natural variants in CMO-1 deficiency
Variant IDPosition(s)ChangeDescription
VAR_018470140N>NRLin CMO-1 deficiency; the enzyme is inactive
VAR_018472461L>Pin CMO-1 deficiency; abolishes the 18-hydroxylase activity required for conversion of 11-deoxycorticosterone to aldosterone; dbSNP:rs72554627

Corticosterone methyloxidase 2 deficiency (CMO-2 deficiency)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    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.
  • See also
    MIM:610600
Natural variants in CMO-2 deficiency
Variant IDPosition(s)ChangeDescription
VAR_001267181R>Win CMO-2 deficiency; reduces 18-hydroxylase and abolishes 18-oxidase activities; leaves 11 beta-hydroxylase activity intact; dbSNP:rs28931609
VAR_018471185T>Iin CMO-2 deficiency; dbSNP:rs121912978
VAR_001268198E>Din CMO-2 deficiency; associated in cis with A-386; slightly reduced 11-beta-hydroxylase activity, greatly decreased 18-hydroxylase activity and absent 18-oxidase activity when associated with A-386; dbSNP:rs104894072
VAR_001269386V>Ain CMO-2 deficiency; associated in cis with D-198; small but consistent reduction in the production of 18-hydroxycorticosterone; slightly reduced 11-beta-hydroxylase activity, greatly decreased 18-hydroxylase activity and absent 18-oxidase activity when associated with D-198; dbSNP:rs61757294
VAR_018473498T>Ain CMO-2 deficiency; dbSNP:rs72554626

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_01415129in dbSNP:rs6438
Natural variantVAR_01415230in dbSNP:rs6441
Mutagenesis112Increases 11-beta- and 18-hydroxylase activities toward 11-deoxycorticosterone; increases 11-beta-hydroxylase activity toward 11-deoxycortisol.
Natural variantVAR_018470140in CMO-1 deficiency; the enzyme is inactive
Mutagenesis147Increases 11-beta-hydroxylase activity toward 11-deoxycorticosterone and 11-deoxycortisol.
Mutagenesis152No significant effect on hydroxylase activities toward 11-deoxycorticosterone and 11-deoxycortisol.
Natural variantVAR_001266173in dbSNP:rs4539
Natural variantVAR_001267181in CMO-2 deficiency; reduces 18-hydroxylase and abolishes 18-oxidase activities; leaves 11 beta-hydroxylase activity intact; dbSNP:rs28931609
Natural variantVAR_018471185in CMO-2 deficiency; dbSNP:rs121912978
Natural variantVAR_001268198in CMO-2 deficiency; associated in cis with A-386; slightly reduced 11-beta-hydroxylase activity, greatly decreased 18-hydroxylase activity and absent 18-oxidase activity when associated with A-386; dbSNP:rs104894072
Natural variantVAR_014643222in dbSNP:rs5308
Natural variantVAR_014153248in dbSNP:rs4547
Natural variantVAR_014154281in dbSNP:rs4537
Natural variantVAR_014155339in dbSNP:rs4544
Natural variantVAR_014644383in dbSNP:rs5312
Natural variantVAR_001269386in CMO-2 deficiency; associated in cis with D-198; small but consistent reduction in the production of 18-hydroxycorticosterone; slightly reduced 11-beta-hydroxylase activity, greatly decreased 18-hydroxylase activity and absent 18-oxidase activity when associated with D-198; dbSNP:rs61757294
Natural variantVAR_014645403in dbSNP:rs5315
Natural variantVAR_014156435in dbSNP:rs4545
Natural variantVAR_018472461in CMO-1 deficiency; abolishes the 18-hydroxylase activity required for conversion of 11-deoxycorticosterone to aldosterone; dbSNP:rs72554627
Natural variantVAR_014646487in dbSNP:rs5317
Natural variantVAR_018473498in CMO-2 deficiency; dbSNP:rs72554626

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 751 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for transit peptide, chain.

TypeIDPosition(s)Description
Transit peptide1-24Mitochondrion
ChainPRO_000000359725-503Cytochrome P450 11B2, mitochondrial

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed sporadically in the zona glomerulosa (zG) of the adrenal cortex (conventional zonation), as well as in aldosterone-producing cell clusters (APCCs) composed of morphological zG cells in contact with the capsule (variegated zonation).

Induction

Expression is induced by angiotensin II, potassium (K+), and also by cAMP.

Gene expression databases

Organism-specific databases

Interaction

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Sequence similarities

Belongs to the cytochrome P450 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    503
  • Mass (Da)
    57,560
  • Last updated
    1998-07-15 v3
  • Checksum
    42BA671704CEE35D
MALRAKAEVCVAAPWLSLQRARALGTRAARAPRTVLPFEAMPQHPGNRWLRLLQIWREQGYEHLHLEMHQTFQELGPIFRYNLGGPRMVCVMLPEDVEKLQQVDSLHPCRMILEPWVAYRQHRGHKCGVFLLNGPEWRFNRLRLNPDVLSPKAVQRFLPMVDAVARDFSQALKKKVLQNARGSLTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQLMFMPRSLSRWISPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFNRPQHYTGIVAELLLKAELSLEAIKANSMELTAGSVDTTAFPLLMTLFELARNPDVQQILRQESLAAAASISEHPQKATTELPLLRAALKETLRLYPVGLFLERVVSSDLVLQNYHIPAGTLVQVFLYSLGRNAALFPRPERYNPQRWLDIRGSGRNFHHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHFLVETLTQEDIKMVYSFILRPGTSPLLTFRAIN

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict17in Ref. 1; AAA35741
Sequence conflict55in Ref. 1; AAA35741
Sequence conflict119in Ref. 1; AAA35741
Sequence conflict249in Ref. 2; CAA38539
Sequence conflict342in Ref. 1; AAA35741
Sequence conflict438in Ref. 1; AAA35741
Sequence conflict470in Ref. 1; AAA35741

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M32881
EMBL· GenBank· DDBJ
AAA35741.1
EMBL· GenBank· DDBJ
Genomic DNA
M32864
EMBL· GenBank· DDBJ
AAA35741.1
EMBL· GenBank· DDBJ
Genomic DNA
M32880
EMBL· GenBank· DDBJ
AAA35741.1
EMBL· GenBank· DDBJ
Genomic DNA
X54741
EMBL· GenBank· DDBJ
CAA38539.1
EMBL· GenBank· DDBJ
mRNA
D13752
EMBL· GenBank· DDBJ
BAA02899.1
EMBL· GenBank· DDBJ
Genomic DNA
EU326306
EMBL· GenBank· DDBJ
ACA05912.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471162
EMBL· GenBank· DDBJ
EAW82292.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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