C11B2_RAT
ID C11B2_RAT Reviewed; 510 AA.
AC P30099; Q64540;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 152.
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 P450-Aldo-1;
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=2350348; DOI=10.1016/0006-291x(90)91460-a;
RA Matsukawa N., Nonaka Y., Ying Z., Higaki J., Ogihara T., Okamoto M.;
RT "Molecular cloning and expression of cDNAS encoding rat aldosterone
RT synthase: variants of cytochrome P-450(11 beta).";
RL Biochem. Biophys. Res. Commun. 169:245-252(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1562515; DOI=10.1016/0960-0760(92)90367-r;
RA Okamoto M., Nonaka Y.;
RT "Molecular biology of rat steroid 11 beta-hydroxylase [P450(11 beta)] and
RT aldosterone synthase [P450(11 beta, aldo)].";
RL J. Steroid Biochem. Mol. Biol. 41:415-419(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Adrenal gland;
RX PubMed=8333830; DOI=10.1006/bbrc.1993.1792;
RA Zhou M., Gomez-Sanchez C.E.;
RT "Cloning and expression of a rat cytochrome P-450 11 beta-
RT hydroxylase/aldosterone synthase (CYP11B2) cDNA variant.";
RL Biochem. Biophys. Res. Commun. 194:112-117(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, AND VARIANT GLY-84.
RX PubMed=8468320; DOI=10.1093/oxfordjournals.jbchem.a124018;
RA Nomura M., Morohashi K., Kirita S., Nonaka Y., Okamoto M., Nawata H.,
RA Omura T.;
RT "Three forms of rat CYP11B genes: 11 beta-hydroxylase gene, aldosterone
RT synthase gene, and a novel gene.";
RL J. Biochem. 113:144-152(1993).
RN [5]
RP PROTEIN SEQUENCE OF 35-54.
RC TISSUE=Adrenal cortex;
RX PubMed=2738055; DOI=10.1016/s0021-9258(18)60408-9;
RA Ogishima T., Mitani F., Ishimura Y.;
RT "Isolation of aldosterone synthase cytochrome P-450 from zona glomerulosa
RT mitochondria of rat adrenal cortex.";
RL J. Biol. Chem. 264:10935-10938(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 -!- TISSUE SPECIFICITY: Adrenal cortex. {ECO:0000269|PubMed:2738055}.
CC -!- INDUCTION: A 12-fold increase was seen in the presence of a low sodium-
CC high potassium diet. {ECO:0000269|PubMed:8468320}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; D00567; BAA00444.1; -; mRNA.
DR EMBL; U14908; AAB60457.1; -; mRNA.
DR PIR; A35342; A35342.
DR PIR; JN0615; JN0615.
DR AlphaFoldDB; P30099; -.
DR SMR; P30099; -.
DR BindingDB; P30099; -.
DR ChEMBL; CHEMBL3237; -.
DR iPTMnet; P30099; -.
DR PhosphoSitePlus; P30099; -.
DR UCSC; RGD:2454; rat.
DR RGD; 2454; Cyp11b2.
DR InParanoid; P30099; -.
DR PhylomeDB; P30099; -.
DR Reactome; R-RNO-194002; Glucocorticoid biosynthesis.
DR Reactome; R-RNO-211976; Endogenous sterols.
DR PRO; PR:P30099; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0047783; F:corticosterone 18-monooxygenase activity; IDA:RGD.
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:RGD.
DR GO; GO:0032342; P:aldosterone biosynthetic process; IDA:RGD.
DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; IDA:RGD.
DR GO; GO:0032870; P:cellular response to hormone stimulus; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0031670; P:cellular response to nutrient; IEP:RGD.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEP:RGD.
DR GO; GO:0035865; P:cellular response to potassium ion; ISO:RGD.
DR GO; GO:0051365; P:cellular response to potassium ion starvation; IEP:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; IBA:GO_Central.
DR GO; GO:0034651; P:cortisol biosynthetic process; ISO:RGD.
DR GO; GO:0034650; P:cortisol metabolic process; IBA:GO_Central.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IDA:RGD.
DR GO; GO:0045777; P:positive regulation of blood pressure; IMP:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0009651; P:response to salt stress; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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 1: Evidence at protein level;
KW Direct protein sequencing; Heme; Iron; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion inner membrane; Monooxygenase; Oxidoreductase;
KW Reference proteome; Steroidogenesis; Transit peptide.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:2738055"
FT CHAIN 35..510
FT /note="Cytochrome P450 11B2, mitochondrial"
FT /id="PRO_0000003604"
FT BINDING 391
FT /ligand="21-hydroxyprogesterone"
FT /ligand_id="ChEBI:CHEBI:16973"
FT /evidence="ECO:0000250|UniProtKB:P19099"
FT BINDING 457
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 VARIANT 84
FT /note="E -> G"
FT /evidence="ECO:0000269|PubMed:8468320"
FT VARIANT 146
FT /note="E -> D"
FT VARIANT 261
FT /note="Q -> R"
FT VARIANT 509
FT /note="I -> V"
FT CONFLICT 1..13
FT /note="MGACDNDFIELHS -> MNKAPAKAL (in Ref. 3; AAB60457)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 510 AA; 58241 MW; 2E5129EE513DEA9E CRC64;
MGACDNDFIE LHSRVTADVW LARPWQCLHR TRALGTTATL APKTLKPFEA IPQYSRNKWL
KMIQILREQG QENLHLEMHQ AFQELGPIFR HSAGGAQIVS VMLPEDAEKL HQVESILPRR
MHLEPWVAHR ELRGLRRGVF LLNGAEWRFN RLKLNPNVLS PKAVQNFVPM VDEVARDFLE
ALKKKVRQNA RGSLTMDVQQ SLFNYTIEAS NFALFGERLG LLGHDLNPGS LKFIHALHSM
FKSTTQLLFL PRSLTRWTST QVWKEHFDAW DVISEYANRC IWKVHQELRL GSSQTYSGIV
AALITQGALP LDAIKANSME LTAGSVDTTA IPLVMTLFEL ARNPDVQQAL RQETLAAEAS
IAANPQKAMS DLPLLRAALK ETLRLYPVGG FLERILNSDL VLQNYHVPAG TLVLLYLYSM
GRNPAVFPRP ERYMPQRWLE RKRSFQHLAF GFGVRQCLGR RLAEVEMLLL LHHMLKTFQV
ETLRQEDVQM AYRFVLMPSS SPVLTFRPIS
