ID   C11B1_CAVPO             Reviewed;         500 AA.
AC   Q64408;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   13-SEP-2023, entry version 116.
DE   RecName: Full=Cytochrome P450 11B1, mitochondrial;
DE   AltName: Full=Aldosterone synthase;
DE   AltName: Full=CYPXIB1;
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;
OS   Cavia porcellus (Guinea pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC   Cavia.
OX   NCBI_TaxID=10141;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Dunkin-Hartley; TISSUE=Adrenal gland;
RX   PubMed=8619851; DOI=10.1006/bbrc.1996.0591;
RA   Buelow H.E., Mobius K., Bahr V., Bernhardt R.;
RT   "Molecular cloning and functional expression of the cytochrome P450 11B-
RT   hydroxylase of the guinea pig.";
RL   Biochem. Biophys. Res. Commun. 221:304-312(1996).
CC   -!- FUNCTION: A cytochrome P450 monooxygenase involved in the biosynthesis
CC       of adrenal corticoids (By similarity). Catalyzes a variety of reactions
CC       that are essential for many species, including detoxification, defense,
CC       and the formation of endogenous chemicals like steroid hormones (By
CC       similarity). Steroid 11beta, 18- and 19-hydroxylase with preferred
CC       regioselectivity at 11beta, then 18, and lastly 19. Catalyzes the
CC       hydroxylation of 11-deoxycortisol and 11-deoxycorticosterone (21-
CC       hydroxyprogesterone) at 11beta position, yielding cortisol or
CC       corticosterone, respectively, but cannot produce aldosterone (By
CC       similarity). Mechanistically, uses molecular oxygen inserting one
CC       oxygen atom into a substrate for hydroxylation and reducing the second
CC       into a water molecule. Two electrons are provided by NADPH via a two-
CC       protein mitochondrial transfer system comprising flavoprotein FDXR
CC       (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1
CC       or FDX2 (adrenodoxin/ferredoxin). Due to its lack of 18-oxidation
CC       activity, it is incapable of generating aldosterone. Could also be
CC       involved in the androgen metabolic pathway (By similarity).
CC       {ECO:0000250|UniProtKB:P15393, 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   -!- 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:P15393};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76152;
CC         Evidence={ECO:0000250|UniProtKB:P15393};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=21-hydroxyprogesterone + 2 H(+) + O2 + 2 reduced [adrenodoxin]
CC         = 19-hydroxy-11-deoxycorticosterone + H2O + 2 oxidized [adrenodoxin];
CC         Xref=Rhea:RHEA:76155, 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:195167; Evidence={ECO:0000250|UniProtKB:P15393};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76156;
CC         Evidence={ECO:0000250|UniProtKB:P15393};
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:P15393};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76020;
CC         Evidence={ECO:0000250|UniProtKB:P15393};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=11-deoxycortisol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 18-
CC         hydroxy-11-deoxycortisol + H2O + 2 oxidized [adrenodoxin];
CC         Xref=Rhea:RHEA:76163, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:28324, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC         ChEBI:CHEBI:195179; Evidence={ECO:0000250|UniProtKB:P15393};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76164;
CC         Evidence={ECO:0000250|UniProtKB:P15393};
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   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; Z69785; CAA93633.1; -; mRNA.
DR   PIR; JC4709; JC4709.
DR   RefSeq; NP_001166410.1; NM_001172939.1.
DR   AlphaFoldDB; Q64408; -.
DR   SMR; Q64408; -.
DR   STRING; 10141.ENSCPOP00000012206; -.
DR   GeneID; 111755182; -.
DR   CTD; 1584; -.
DR   eggNOG; KOG0159; Eukaryota.
DR   HOGENOM; CLU_001570_28_4_1; -.
DR   InParanoid; Q64408; -.
DR   OrthoDB; 2658719at2759; -.
DR   UniPathway; UPA00788; -.
DR   Proteomes; UP000005447; Unassembled WGS sequence.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
DR   GO; GO:0006704; P:glucocorticoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
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; PR00463; EP450I.
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; Lipid metabolism; Membrane; Metal-binding; Mitochondrion;
KW   Mitochondrion inner membrane; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Steroid metabolism; Steroidogenesis; Transit peptide.
FT   TRANSIT         1..24
FT                   /note="Mitochondrion"
FT   CHAIN           25..500
FT                   /note="Cytochrome P450 11B1, mitochondrial"
FT                   /id="PRO_0000003595"
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;  57820 MW;  C4B5AB6041CD4AF2 CRC64;
     MAFRLKSDVR LAGSWLCLRG ARALGTRAVT ASKASVLPFE VIPQHQGNKR QRVLQFWKEQ
     NHDDLHLEMH QTFQELGPIF RCDVGSTRIV AVMLPEDCAR LHQAESPYPH RMHLEPWMAY
     REHRRQNLGV FLLNGPEWLS NRRWLNPNVL SPKAVQNLLP MVDTVARDFS EALKQKVLQS
     AQGSLTMDMQ PDIHKYTVEV SNFALFGERL GLFGCNPSSQ SLKFIHALEA VFKTTTQLMF
     LPRSLSRWMR SQAWKEHFEA WDYISEYAEN RIQKKYEELA RGCSQYNSIV ANLMLQGNLP
     LRAMKANIMD LVAGSVDTTA LPLMMTLFEL ARNPTVQQAL RQESMATEPN IYENPQRLRM
     ELPLLWAAIK ETLRMYPVGL FLERFLTSPL VLQNYHIPAG TLVHLNLYSM GRNPEVFLSP
     EHYNPQRWLE NKETYKHLAF GFGVRQCIGR RLAEVEMLLF LHHVLKSFCV ETAFQEDVKF
     AYRFVMMPTS APLLTFRPVS
//