ID   C11B2_MESAU             Reviewed;         500 AA.
AC   Q64658;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   24-JAN-2024, entry version 94.
DE   RecName: Full=Cytochrome P450 11B2, mitochondrial;
DE   AltName: Full=Aldosterone synthase {ECO:0000303|PubMed:9303441};
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:0000250|UniProtKB:P19099};
DE   AltName: Full=Cytochrome P-450Aldo;
DE   AltName: Full=Cytochrome P-450C18;
DE   AltName: Full=Steroid 11-beta-hydroxylase, CYP11B2;
DE            EC=1.14.15.4 {ECO:0000250|UniProtKB:P19099};
DE   AltName: Full=Steroid 18-hydroxylase;
DE   Flags: Precursor;
GN   Name=CYP11B2;
OS   Mesocricetus auratus (Golden hamster).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Cricetinae; Mesocricetus.
OX   NCBI_TaxID=10036;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Adrenal glomerulosa;
RX   PubMed=8031709; DOI=10.1016/0960-0760(94)90003-5;
RA   Lehoux J.-G., Mason J.I., Bernard H., Ducharme L., Lehoux J., Veronneau S.,
RA   Lefebvre A.;
RT   "The presence of two cytochrome P450 aldosterone synthase mRNAs in the
RT   hamster adrenal.";
RL   J. Steroid Biochem. Mol. Biol. 49:131-137(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9303441; DOI=10.1089/dna.1997.16.993;
RA   Coulombe N., Lefebvre A., Lehoux J.-G.;
RT   "Characterization of the hamster CYP11B2 gene encoding adrenal cytochrome
RT   P450 aldosterone synthase.";
RL   DNA Cell Biol. 16:993-1002(1997).
CC   -!- FUNCTION: A cytochrome P450 monooxygenase that catalyzes the
CC       biosynthesis of aldosterone, the main mineralocorticoid in the human
CC       body responsible for salt and water homeostasis, thus involved in blood
CC       pressure regulation, arterial hypertension, and the development of
CC       heart failure. Catalyzes three sequential oxidative reactions of 11-
CC       deoxycorticosterone (21-hydroxyprogesterone), namely 11-beta
CC       hydroxylation, followed by two successive oxidations at C18 yielding
CC       18-hydroxy and then 18-oxo intermediates (that would not leave the
CC       enzyme active site during the consecutive hydroxylation reactions),
CC       ending with the formation of aldosterone. Can also produce 18-
CC       hydroxycortisol and 18-oxocortisol, derived from successive oxidations
CC       of cortisol at C18, normally found at very low levels, but
CC       significantly increased in primary aldosteronism, the most common form
CC       of secondary hypertension. Mechanistically, uses molecular oxygen
CC       inserting one oxygen atom into a substrate and reducing the second into
CC       a water molecule. Two electrons are provided by NADPH via a two-protein
CC       mitochondrial transfer system comprising flavoprotein FDXR
CC       (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1
CC       or FDX2 (adrenodoxin/ferredoxin). Could also be involved in the
CC       androgen metabolic pathway. {ECO:0000250|UniProtKB:P19099}.
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:0000250|UniProtKB:P19099};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15630;
CC         Evidence={ECO:0000250|UniProtKB:P19099};
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:0000250|UniProtKB:P19099};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46105;
CC         Evidence={ECO:0000250|UniProtKB:P19099};
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:0000250|UniProtKB:P19099};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11873;
CC         Evidence={ECO:0000250|UniProtKB:P19099};
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:0000250|UniProtKB:P19099};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50793;
CC         Evidence={ECO:0000250|UniProtKB:P19099};
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:0000250|UniProtKB:P19099};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46101;
CC         Evidence={ECO:0000250|UniProtKB:P19099};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=21-hydroxyprogesterone + 2 H(+) + O2 + 2 reduced [adrenodoxin]
CC         = 18-hydroxy-11-deoxycorticosterone + H2O + 2 oxidized [adrenodoxin];
CC         Xref=Rhea:RHEA:76151, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:16973, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC         ChEBI:CHEBI:195166; Evidence={ECO:0000250|UniProtKB:P30099};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76152;
CC         Evidence={ECO:0000250|UniProtKB:P30099};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=cortisol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 18-
CC         hydroxycortisol + H2O + 2 oxidized [adrenodoxin];
CC         Xref=Rhea:RHEA:76019, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:17650, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC         ChEBI:CHEBI:89455; Evidence={ECO:0000250|UniProtKB:P19099};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76020;
CC         Evidence={ECO:0000250|UniProtKB:P19099};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=18-hydroxycortisol + 2 H(+) + O2 + 2 reduced [adrenodoxin] =
CC         18-oxocortisol + 2 H2O + 2 oxidized [adrenodoxin];
CC         Xref=Rhea:RHEA:76023, 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:89213,
CC         ChEBI:CHEBI:89455; Evidence={ECO:0000250|UniProtKB:P19099};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76024;
CC         Evidence={ECO:0000250|UniProtKB:P19099};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:P19099};
CC   -!- PATHWAY: Steroid biosynthesis. {ECO:0000250|UniProtKB:P19099}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000250|UniProtKB:P14137}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P14137}.
CC   -!- TISSUE SPECIFICITY: Adrenal gland.
CC   -!- INDUCTION: By low sodium intake.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; S73810; AAB31349.1; -; mRNA.
DR   EMBL; U71280; AAB16805.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q64658; -.
DR   SMR; Q64658; -.
DR   eggNOG; KOG0159; Eukaryota.
DR   Proteomes; UP000189706; Unplaced.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0047783; F:corticosterone 18-monooxygenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004507; F:steroid 11-beta-monooxygenase activity; ISS:UniProtKB.
DR   GO; GO:0032342; P:aldosterone biosynthetic process; ISS:UniProtKB.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 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   PANTHER; PTHR24279; -; 1.
DR   PANTHER; PTHR24279:SF1; CYTOCHROME P450 11B2, MITOCHONDRIAL; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00408; MITP450.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   2: Evidence at transcript level;
KW   Heme; Iron; Membrane; Metal-binding; Mitochondrion;
KW   Mitochondrion inner membrane; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Steroidogenesis; Transit peptide.
FT   TRANSIT         1..24
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250"
FT   CHAIN           25..500
FT                   /note="Cytochrome P450 11B2, mitochondrial"
FT                   /id="PRO_0000003599"
FT   BINDING         381
FT                   /ligand="21-hydroxyprogesterone"
FT                   /ligand_id="ChEBI:CHEBI:16973"
FT                   /evidence="ECO:0000250|UniProtKB:P19099"
FT   BINDING         447
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:0000250|UniProtKB:P19099"
SQ   SEQUENCE   500 AA;  57332 MW;  38251EDAD2085DE8 CRC64;
     MALRAKADVW LARPWQCLPR TRALGTTAAL APNTLRPFEA IPQYSRNRWL KMLQILREEG
     QEGLHLEMHE AFRELGPIFR YSMGRTQVVS VMLPEDAEKL HQVESMHPRR MHLEPWVAHR
     EHRGLSRGVF LLNGPEWRFN RLRLNPHVLS PKAVQKFVPM VDMVARDFLE SLKKKVFQNA
     RGSLTMDVQQ SLFNYSIEAS NFVLFGERLG LLGHDLSPAS LTFIHALHSV FKTTPQLMFL
     PRSLTRWTST RVWKEHFEAW DVISEYVNRC IRKVHQELRL GSPHTYSGIV AELMSQGALP
     LDAIRANSIE LTAGSVDTTT FPLVMALFEL ARNPDVQQAV RQESLAAEAS VAANPQRAMS
     DLPLLRAVLK ETLRLYPVGG FLERILSSDL VLQNYHVPAG TLVLLYLYSM GRNPAVFPRP
     EHYLPQRWLE RNGSFQHLTF GFGVRQCLGK RLAQVEMLLL LHHVLKSFRV ETQEREDVRM
     VYRFVLAPSS SPLLTFRPVS
//