C11B2_MOUSE
ID C11B2_MOUSE Reviewed; 500 AA.
AC P15539; Q14AB5; Q64661;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Cytochrome P450 11B2, mitochondrial;
DE AltName: Full=Aldosterone synthase {ECO:0000250|UniProtKB:P19099};
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=Cytochrome P450C11;
DE AltName: Full=Steroid 11-beta-hydroxylase, CYP11B2 {ECO:0000250|UniProtKB:P19099};
DE EC=1.14.15.4 {ECO:0000250|UniProtKB:P19099};
DE AltName: Full=Steroid 18-hydroxylase;
DE Flags: Precursor;
GN Name=Cyp11b2; Synonyms=Cyp11b-2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1686470; DOI=10.1210/mend-5-12-1853;
RA Domalik L.J., Chaplin D.D., Kirkman M.S., Wu R.C., Liu W., Howard T.A.,
RA Seldin M.F., Parker K.L.;
RT "Different isozymes of mouse 11 beta-hydroxylase produce mineralocorticoids
RT and glucocorticoids.";
RL Mol. Endocrinol. 5:1853-1861(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-42.
RX PubMed=2783417; DOI=10.1016/s0021-9258(19)85086-x;
RA Mouw A.R., Rice D.A., Meade J.C., Chua S.C., White P.C., Schimmer B.P.,
RA Parker K.L.;
RT "Structural and functional analysis of the promoter region of the gene
RT encoding mouse steroid 11 beta-hydroxylase.";
RL J. Biol. Chem. 264:1305-1309(1989).
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 -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; S85260; AAB21517.2; -; Genomic_DNA.
DR EMBL; BC116908; AAI16909.1; -; mRNA.
DR EMBL; BC119321; AAI19322.1; -; mRNA.
DR EMBL; J04451; AAA50299.1; -; Genomic_DNA.
DR CCDS; CCDS27536.3; -.
DR PIR; A41552; A41552.
DR RefSeq; NP_034121.3; NM_009991.3.
DR AlphaFoldDB; P15539; -.
DR SMR; P15539; -.
DR STRING; 10090.ENSMUSP00000131503; -.
DR BindingDB; P15539; -.
DR ChEMBL; CHEMBL3621020; -.
DR DrugCentral; P15539; -.
DR PhosphoSitePlus; P15539; -.
DR MaxQB; P15539; -.
DR PaxDb; P15539; -.
DR PRIDE; P15539; -.
DR ProteomicsDB; 273851; -.
DR DNASU; 13072; -.
DR Ensembl; ENSMUST00000238900; ENSMUSP00000158954; ENSMUSG00000022589.
DR GeneID; 13072; -.
DR KEGG; mmu:13072; -.
DR CTD; 1585; -.
DR MGI; MGI:88584; Cyp11b2.
DR VEuPathDB; HostDB:ENSMUSG00000022589; -.
DR eggNOG; KOG0159; Eukaryota.
DR GeneTree; ENSGT00940000161506; -.
DR InParanoid; P15539; -.
DR OMA; EDIHLEM; -.
DR OrthoDB; 481145at2759; -.
DR PhylomeDB; P15539; -.
DR Reactome; R-MMU-193993; Mineralocorticoid biosynthesis.
DR Reactome; R-MMU-194002; Glucocorticoid biosynthesis.
DR Reactome; R-MMU-211976; Endogenous sterols.
DR BioGRID-ORCS; 13072; 9 hits in 74 CRISPR screens.
DR PRO; PR:P15539; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P15539; protein.
DR Bgee; ENSMUSG00000022589; Expressed in adrenal gland and 20 other tissues.
DR ExpressionAtlas; P15539; baseline and differential.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0047783; F:corticosterone 18-monooxygenase activity; ISO:MGI.
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; IDA:MGI.
DR GO; GO:0032342; P:aldosterone biosynthetic process; IDA:MGI.
DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; ISO:MGI.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IBA:GO_Central.
DR GO; GO:0034650; P:cortisol metabolic process; IBA:GO_Central.
DR GO; GO:0042756; P:drinking behavior; IMP:MGI.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; ISO:MGI.
DR GO; GO:0050801; P:ion homeostasis; IMP:MGI.
DR GO; GO:0045777; P:positive regulation of blood pressure; ISO:MGI.
DR GO; GO:0002017; P:regulation of blood volume by renal aldosterone; IMP:MGI.
DR GO; GO:0001991; P:regulation of systemic arterial blood pressure by circulatory renin-angiotensin; IMP:MGI.
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 CHAIN 25..500
FT /note="Cytochrome P450 11B2, mitochondrial"
FT /id="PRO_0000003600"
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"
FT CONFLICT 491
FT /note="S -> E (in Ref. 1; AAB21517)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 57373 MW; DCAFFF3EF2663195 CRC64;
MALRVTADVW LARPWQCLHR TRALGTTATL APKTLQPFEA IPQYSRNKWL KMIQILREQG
QENLHLEMHQ VFRELGPIFR HSVGKTQIVS VMLPEDAEKL HQVESMLPRR MHLEPWVAHR
ELRGLRRGVF LLNGPEWRLN RLRLNRNVLS PKAVQKFVPM VDMVARDFLE TLKEKVLQNA
RGSLTMDVQQ SLFNYTIEAS NFALFGERLG LLGHDLSPGS LKFIHALHSM FKSTSQLLFL
PKSLTRWTST RVWKEHFDAW DVISEYANRC IWKVHQELRL GSSQTYSGIV AELISQGSLP
LDAIKANSME LTAGSVDTTA IPLVMTLFEL ARNPDVQKAL RQESLAAEAS IAANPQKAMS
DLPLLRAALK ETLRLYPVGG FLERILSSDL VLQNYHVPAG TLVLLYLYSM GRNPAVFPRP
ERYMPQRWLE RKRSFQHLAF GFGVRQCLGR RLAEVEMMLL LHHILKTFQV ETLRQEDVQM
AYRFVLMPSS SPVLTFRPVS
