C11B1_RAT
ID C11B1_RAT Reviewed; 499 AA.
AC P15393; Q64655;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Cytochrome P450 11B1, mitochondrial;
DE AltName: Full=CYPXIB1;
DE AltName: Full=Cytochrome P450(11 beta)-DS;
DE AltName: Full=Cytochrome P450C11;
DE AltName: Full=Steroid 11-beta-hydroxylase, CYP11B1 {ECO:0000250|UniProtKB:P15538};
DE EC=1.14.15.4 {ECO:0000250|UniProtKB:P15538};
DE Flags: Precursor;
GN Name=Cyp11b1; Synonyms=Cyp11b-1;
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 STRAIN=Sprague-Dawley;
RX PubMed=2551730; DOI=10.1016/0014-5793(89)81053-1;
RA Nonaka Y., Matsukawa N., Morohashi K., Omura T., Ogihara T., Teraoka H.,
RA Okamoto M.;
RT "Molecular cloning and sequence analysis of cDNA encoding rat adrenal
RT cytochrome P-450(11)beta.";
RL FEBS Lett. 255:21-26(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Dahl salt-resistant; TISSUE=Adrenal gland;
RX PubMed=8473350; DOI=10.1016/s0021-9258(18)52985-9;
RA Matsukawa N., Nonaka Y., Higaki J., Nagano M., Mikami H., Ogihara T.,
RA Okamoto M.;
RT "Dahl's salt-resistant normotensive rat has mutations in cytochrome P450(11
RT beta), but the salt-sensitive hypertensive rat does not.";
RL J. Biol. Chem. 268:9117-9121(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=8473352; DOI=10.1016/s0021-9258(18)52987-2;
RA Mukai K., Imai M., Shimada H., Ishimura Y.;
RT "Isolation and characterization of rat CYP11B genes involved in late steps
RT of mineralo- and glucocorticoid syntheses.";
RL J. Biol. Chem. 268:9130-9137(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE.
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 NUCLEOTIDE SEQUENCE.
RC STRAIN=Dahl salt-resistant;
RX PubMed=7626522; DOI=10.1016/0960-0760(95)00025-u;
RA Okamoto M., Nonaka Y., Ohta M., Takemori H., Halder S.K., Zhi-Nong W.,
RA Sun T., Hatano O., Takakusa A., Murakami T.;
RT "Cytochrome P450(11 beta): structure-function relationship of the enzyme
RT and its involvement in blood pressure regulation.";
RL J. Steroid Biochem. Mol. Biol. 53:89-94(1995).
RN [6]
RP PROTEIN SEQUENCE OF 25-44.
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 involved in the biosynthesis
CC of adrenal corticoids. Catalyzes the hydroxylation of carbon hydrogen
CC bond at 11-beta position of 11-deoxycortisol and 11-
CC deoxycorticosterone/21-hydroxyprogesterone yielding cortisol or
CC corticosterone, respectively. 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). {ECO:0000250|UniProtKB:P15538}.
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:P15538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15630;
CC Evidence={ECO:0000250|UniProtKB:P15538};
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:P15538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46101;
CC Evidence={ECO:0000250|UniProtKB:P15538};
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:P15538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46105;
CC Evidence={ECO:0000250|UniProtKB:P15538};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P19099};
CC -!- PATHWAY: Steroid biosynthesis; glucocorticoid biosynthesis.
CC {ECO:0000250|UniProtKB:P15538}.
CC -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000250|UniProtKB:P15538}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P14137}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P14137}.
CC -!- TISSUE SPECIFICITY: Adrenal zona fasciculata/reticularis.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; D11354; BAA01957.1; -; mRNA.
DR EMBL; D14091; BAA03171.1; -; Genomic_DNA.
DR EMBL; X15431; CAA33472.1; -; mRNA.
DR EMBL; D10107; BAA00988.1; -; mRNA.
DR PIR; A46039; A46039.
DR AlphaFoldDB; P15393; -.
DR SMR; P15393; -.
DR STRING; 10116.ENSRNOP00000035538; -.
DR BindingDB; P15393; -.
DR ChEMBL; CHEMBL4970; -.
DR DrugCentral; P15393; -.
DR UCSC; RGD:2453; rat.
DR RGD; 2453; Cyp11b1.
DR eggNOG; KOG0159; Eukaryota.
DR InParanoid; P15393; -.
DR OrthoDB; 1264614at2759; -.
DR PhylomeDB; P15393; -.
DR Reactome; R-RNO-194002; Glucocorticoid biosynthesis.
DR Reactome; R-RNO-211976; Endogenous sterols.
DR SABIO-RK; P15393; -.
DR UniPathway; UPA00788; -.
DR PRO; PR:P15393; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:RGD.
DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0047783; F:corticosterone 18-monooxygenase activity; IBA:GO_Central.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
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:0005496; F:steroid binding; IDA:RGD.
DR GO; GO:0046085; P:adenosine metabolic process; IEP:RGD.
DR GO; GO:0032342; P:aldosterone biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; IBA:GO_Central.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:RGD.
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:0034651; P:cortisol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0034650; P:cortisol metabolic process; IBA:GO_Central.
DR GO; GO:0018894; P:dibenzo-p-dioxin metabolic process; IEP:RGD.
DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IDA:RGD.
DR GO; GO:0008211; P:glucocorticoid metabolic process; TAS:RGD.
DR GO; GO:0071548; P:response to dexamethasone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0006694; P:steroid biosynthetic process; IDA:RGD.
DR GO; GO:0008202; P:steroid metabolic process; TAS: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..24
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:2738055"
FT CHAIN 25..499
FT /note="Cytochrome P450 11B1, mitochondrial"
FT /id="PRO_0000003603"
FT BINDING 446
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 127
FT /note="R -> C (in strain: Dahl salt-resistant)"
FT VARIANT 351
FT /note="V -> A (in strain: Dahl salt-resistant)"
FT VARIANT 381
FT /note="V -> L (in strain: Dahl salt-resistant)"
FT VARIANT 384
FT /note="I -> L (in strain: Dahl salt-resistant)"
FT VARIANT 443
FT /note="V -> M (in strain: Dahl salt-resistant)"
SQ SEQUENCE 499 AA; 57459 MW; 19C041F96A673C7E CRC64;
MALRVTADVW LARPWQCLHR TRALGTTAKV APKTLKPFEA IPQYSRNKWL KMIQILREQG
QENLHLEMHQ AFQELGPIFR HSAGGAQIVS VMLPEDAEKL HQVESILPHR MPLEPWVAHR
ELRGLRRGVF LLNGADWRFN RLQLNPNMLS PKAIQSFVPF VDVVARDFVE NLKKRMLENV
HGSMSINIQS NMFNYTMEAS HFVISGERLG LTGHDLKPES VTFTHALHSM FKSTTQLMFL
PKSLTRWTST RVWKEHFDSW DIISEYVTKC IKNVYRELAE GRQQSWSVIS EMVAQSTLSM
DAIHANSMEL IAGSVDTTAI SLVMTLFELA RNPDVQQALR QESLAAEASI VANPQKAMSD
LPLLRAALKE TLRLYPVGSF VERIVHSDLV LQNYHVPAGT FVIIYLYSMG RNPAVFPRPE
RYMPQRWLER KRSFQHLAFG FGVRQCLGRR LAEVEMLLLL HHMLKTFQVE TLRQEDMQMV
FRFLLMPSSS PFLTFRPVS
