P19099 · C11B2_HUMAN
- ProteinCytochrome P450 11B2, mitochondrial
- GeneCYP11B2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids503 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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)
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.
- 21-hydroxyprogesterone + 2 H+ + O2 + 2 reduced [adrenodoxin] = corticosterone + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 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
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
2.6 μM | cortisol | |||||
106 μM | 11-deoxycorticosterone |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
238 nmol/min/nmol | with 11-deoxycorticosterone |
Pathway
Steroid biosynthesis.
Features
Showing features for binding site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameCytochrome P450 11B2, mitochondrial
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP19099
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Peripheral membrane protein
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Corticosterone methyloxidase 1 deficiency (CMO-1 deficiency)
- Note
- DescriptionAutosomal 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 alsoMIM:203400
Natural variants in CMO-1 deficiency
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_018470 | 140 | N>NRL | in CMO-1 deficiency; the enzyme is inactive | |
VAR_018472 | 461 | L>P | in 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
- DescriptionAutosomal 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 alsoMIM:610600
Natural variants in CMO-2 deficiency
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_001267 | 181 | R>W | in CMO-2 deficiency; reduces 18-hydroxylase and abolishes 18-oxidase activities; leaves 11 beta-hydroxylase activity intact; dbSNP:rs28931609 | |
VAR_018471 | 185 | T>I | in CMO-2 deficiency; dbSNP:rs121912978 | |
VAR_001268 | 198 | E>D | in 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_001269 | 386 | V>A | in 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_018473 | 498 | T>A | in CMO-2 deficiency; dbSNP:rs72554626 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_014151 | 29 | in dbSNP:rs6438 | |||
Sequence: A → T | ||||||
Natural variant | VAR_014152 | 30 | in dbSNP:rs6441 | |||
Sequence: R → Q | ||||||
Mutagenesis | 112 | Increases 11-beta- and 18-hydroxylase activities toward 11-deoxycorticosterone; increases 11-beta-hydroxylase activity toward 11-deoxycortisol. | ||||
Sequence: I → P | ||||||
Natural variant | VAR_018470 | 140 | in CMO-1 deficiency; the enzyme is inactive | |||
Sequence: N → NRL | ||||||
Mutagenesis | 147 | Increases 11-beta-hydroxylase activity toward 11-deoxycorticosterone and 11-deoxycortisol. | ||||
Sequence: D → E | ||||||
Mutagenesis | 152 | No significant effect on hydroxylase activities toward 11-deoxycorticosterone and 11-deoxycortisol. | ||||
Sequence: K → N | ||||||
Natural variant | VAR_001266 | 173 | in dbSNP:rs4539 | |||
Sequence: K → R | ||||||
Natural variant | VAR_001267 | 181 | in CMO-2 deficiency; reduces 18-hydroxylase and abolishes 18-oxidase activities; leaves 11 beta-hydroxylase activity intact; dbSNP:rs28931609 | |||
Sequence: R → W | ||||||
Natural variant | VAR_018471 | 185 | in CMO-2 deficiency; dbSNP:rs121912978 | |||
Sequence: T → I | ||||||
Natural variant | VAR_001268 | 198 | in 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 | |||
Sequence: E → D | ||||||
Natural variant | VAR_014643 | 222 | in dbSNP:rs5308 | |||
Sequence: N → T | ||||||
Natural variant | VAR_014153 | 248 | in dbSNP:rs4547 | |||
Sequence: I → T | ||||||
Natural variant | VAR_014154 | 281 | in dbSNP:rs4537 | |||
Sequence: N → S | ||||||
Natural variant | VAR_014155 | 339 | in dbSNP:rs4544 | |||
Sequence: I → T | ||||||
Natural variant | VAR_014644 | 383 | in dbSNP:rs5312 | |||
Sequence: E → V | ||||||
Natural variant | VAR_001269 | 386 | in 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 | |||
Sequence: V → A | ||||||
Natural variant | VAR_014645 | 403 | in dbSNP:rs5315 | |||
Sequence: V → E | ||||||
Natural variant | VAR_014156 | 435 | in dbSNP:rs4545 | |||
Sequence: G → S | ||||||
Natural variant | VAR_018472 | 461 | in CMO-1 deficiency; abolishes the 18-hydroxylase activity required for conversion of 11-deoxycorticosterone to aldosterone; dbSNP:rs72554627 | |||
Sequence: L → P | ||||||
Natural variant | VAR_014646 | 487 | in dbSNP:rs5317 | |||
Sequence: F → V | ||||||
Natural variant | VAR_018473 | 498 | in CMO-2 deficiency; dbSNP:rs72554626 | |||
Sequence: T → A |
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.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-24 | Mitochondrion | ||||
Sequence: MALRAKAEVCVAAPWLSLQRARAL | ||||||
Chain | PRO_0000003597 | 25-503 | Cytochrome P450 11B2, mitochondrial | |||
Sequence: GTRAARAPRTVLPFEAMPQHPGNRWLRLLQIWREQGYEHLHLEMHQTFQELGPIFRYNLGGPRMVCVMLPEDVEKLQQVDSLHPCRMILEPWVAYRQHRGHKCGVFLLNGPEWRFNRLRLNPDVLSPKAVQRFLPMVDAVARDFSQALKKKVLQNARGSLTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQLMFMPRSLSRWISPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFNRPQHYTGIVAELLLKAELSLEAIKANSMELTAGSVDTTAFPLLMTLFELARNPDVQQILRQESLAAAASISEHPQKATTELPLLRAALKETLRLYPVGLFLERVVSSDLVLQNYHIPAGTLVQVFLYSLGRNAALFPRPERYNPQRWLDIRGSGRNFHHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHFLVETLTQEDIKMVYSFILRPGTSPLLTFRAIN |
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
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length503
- Mass (Da)57,560
- Last updated1998-07-15 v3
- Checksum42BA671704CEE35D
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 17 | in Ref. 1; AAA35741 | ||||
Sequence: S → C | ||||||
Sequence conflict | 55 | in Ref. 1; AAA35741 | ||||
Sequence: I → M | ||||||
Sequence conflict | 119 | in Ref. 1; AAA35741 | ||||
Sequence: Y → I | ||||||
Sequence conflict | 249 | in Ref. 2; CAA38539 | ||||
Sequence: S → R | ||||||
Sequence conflict | 342 | in Ref. 1; AAA35741 | ||||
Sequence: Q → K | ||||||
Sequence conflict | 438 | in Ref. 1; AAA35741 | ||||
Sequence: F → L | ||||||
Sequence conflict | 470 | in Ref. 1; AAA35741 | ||||
Sequence: H → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |