C11B2_MESAU
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 03-AUG-2022, entry version 90.
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 adrenal mineralocorticoid aldosterone. 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 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 {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 -!- 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 STRING; 10036.XP_005086076.1; -.
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; -; 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 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
