ID C11B1_BOVIN Reviewed; 503 AA. AC P15150; Q29457; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1990, sequence version 2. DT 24-JAN-2024, entry version 150. DE RecName: Full=Cytochrome P450 11B1, mitochondrial; DE AltName: Full=CYPXIB1; DE AltName: Full=Cytochrome P450C11; DE AltName: Full=Steroid 11-beta-hydroxylase, CYP11B1 {ECO:0000303|PubMed:3499608}; DE EC=1.14.15.4 {ECO:0000305|PubMed:3821110}; DE EC=1.14.15.5 {ECO:0000305|PubMed:10491169}; DE Flags: Precursor; GN Name=CYP11B1; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOZYME-2), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=3429448; DOI=10.1093/oxfordjournals.jbchem.a122089; RA Morohashi K., Yoshioka H., Gotoh O., Okada Y., Yamamoto K., Miyata T., RA Sogawa K., Fujii-Kuriyama Y., Omura T.; RT "Molecular cloning and nucleotide sequence of DNA of mitochondrial RT cytochrome P-450(11 beta) of bovine adrenal cortex."; RL J. Biochem. 102:559-568(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOZYME-3). RC TISSUE=Adrenal cortex; RX PubMed=3266212; DOI=10.1093/oxfordjournals.jbchem.a122533; RA Kirita S., Morohashi K., Hashimoto T., Yoshioka H., Fujii-Kuriyama Y., RA Omura T.; RT "Expression of two kinds of cytochrome P-450(11 beta) mRNA in bovine RT adrenal cortex."; RL J. Biochem. 104:683-686(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3499608; DOI=10.1073/pnas.84.20.7193; RA Chua S.C., Szabo P., Vitek A., Grzeschik K.H., John M., White P.C.; RT "Cloning of cDNA encoding steroid 11 beta-hydroxylase (P450c11)."; RL Proc. Natl. Acad. Sci. U.S.A. 84:7193-7197(1987). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2753866; DOI=10.1093/oxfordjournals.jbchem.a122725; RA Hashimoto T., Morohashi K., Omura T.; RT "Cloning and characterization of bovine cytochrome P-450(11 beta) genes."; RL J. Biochem. 105:676-679(1989). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1965187; DOI=10.1093/oxfordjournals.jbchem.a123302; RA Kirita S., Hashimoto T., Kitajima M., Honda S., Morohashi K., Omura T.; RT "Structural analysis of multiple bovine P-450(11 beta) genes and their RT promoter activities."; RL J. Biochem. 108:1030-1041(1990). RN [6] RP FUNCTION. RX PubMed=708075; DOI=10.1016/0003-9861(78)90280-1; RA Sato H., Ashida N., Suhara K., Itagaki E., Takemori S., Katagiri M.; RT "Properties of an adrenal cytochrome P-450 (P-45011beta) for the RT hydroxylations of corticosteroids."; RL Arch. Biochem. Biophys. 190:307-314(1978). RN [7] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=4044554; DOI=10.1093/oxfordjournals.jbchem.a135264; RA Wada A., Ohnishi T., Nonaka Y., Okamoto M., Yamano T.; RT "Synthesis of aldosterone by a reconstituted system of cytochrome P-45011 RT beta from bovine adrenocortical mitochondria."; RL J. Biochem. 98:245-256(1985). RN [8] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=3821110; DOI=10.1016/0022-4731(87)90033-1; RA Ohta M., Fujii S., Wada A., Ohnishi T., Yamano T., Okamoto M.; RT "Production of 19-hydroxy-11-deoxycorticosterone and 19-oxo-11- RT deoxycorticosterone from 11-deoxycorticosterone by cytochrome P- RT 450(11)beta."; RL J. Steroid Biochem. 26:73-81(1987). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=10491169; DOI=10.1046/j.1432-1327.1999.00704.x; RA Cao P.R., Bernhardt R.; RT "Modulation of aldosterone biosynthesis by adrenodoxin mutants with RT different electron transport efficiencies."; RL Eur. J. Biochem. 265:152-159(1999). CC -!- FUNCTION: A cytochrome P450 monooxygenase that catalyzes the CC biosynthesis of aldosterone and other adrenal corticoids. Differing CC from other species (such as human, rat and mice), it is able to CC catalyze three sequential oxidative reactions of 11-deoxycorticosterone CC (21-hydroxyprogesterone), namely 11-beta hydroxylation, followed by two CC successive oxidations at C18 yielding 18-hydroxy and then 18-oxo CC intermediates, and ending with the formation of aldosterone (Probable). CC Steroid 11beta, 18- and 19-hydroxylase (Probable). Mechanistically, CC uses molecular oxygen inserting one oxygen atom into a substrate and CC reducing the second into a water molecule. Two electrons are provided CC by NADPH via a two-protein mitochondrial transfer system comprising CC flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron- CC sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (Probable). CC {ECO:0000305|PubMed:10491169, ECO:0000305|PubMed:3821110, CC ECO:0000305|PubMed:4044554, ECO:0000305|PubMed:708075}. 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:0000305|PubMed:3821110}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15630; CC Evidence={ECO:0000305|PubMed:3821110}; 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:0000305|PubMed:3821110}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46105; CC Evidence={ECO:0000305|PubMed:3821110}; 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:0000305|PubMed:10491169}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11873; CC Evidence={ECO:0000305|PubMed:10491169}; 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:0000305|PubMed:10491169}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50793; CC Evidence={ECO:0000305|PubMed:10491169}; 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:0000305|PubMed:3821110}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76156; CC Evidence={ECO:0000305|PubMed:3821110}; CC -!- CATALYTIC ACTIVITY: CC Reaction=19-hydroxy-11-deoxycorticosterone + 2 H(+) + O2 + 2 reduced CC [adrenodoxin] = 19-oxo-11-deoxycorticosterone + 2 H2O + 2 oxidized CC [adrenodoxin]; Xref=Rhea:RHEA:76439, Rhea:RHEA-COMP:9998, Rhea:RHEA- CC COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:174650, CC ChEBI:CHEBI:195167; Evidence={ECO:0000269|PubMed:3821110}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76440; CC Evidence={ECO:0000305|PubMed:3821110}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC Evidence={ECO:0000250|UniProtKB:P19099}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=4.8 uM for 21-hydroxyprogesterone {ECO:0000305|PubMed:10491169}; 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 -!- MISCELLANEOUS: The sequence shown is that of isozyme 11-beta-2. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA00127.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D00185; BAA00127.1; ALT_FRAME; mRNA. DR EMBL; D00361; BAA00268.1; -; mRNA. DR EMBL; M17843; AAA83383.1; -; mRNA. DR EMBL; D00455; BAA00347.1; -; Genomic_DNA. DR PIR; A28415; A28415. DR PIR; JX0071; JX0071. DR PIR; JX0151; JX0151. DR RefSeq; NP_777063.2; NM_174638.3. DR AlphaFoldDB; P15150; -. DR SMR; P15150; -. DR STRING; 9913.ENSBTAP00000047946; -. DR BindingDB; P15150; -. DR ChEMBL; CHEMBL2927; -. DR DrugCentral; P15150; -. DR PaxDb; 9913-ENSBTAP00000048098; -. DR GeneID; 282422; -. DR KEGG; bta:282422; -. DR CTD; 1584; -. DR eggNOG; KOG0159; Eukaryota. DR InParanoid; P15150; -. DR OrthoDB; 2658719at2759; -. DR UniPathway; UPA00788; -. DR PRO; PR:P15150; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central. 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; IBA:GO_Central. DR GO; GO:0032342; P:aldosterone biosynthetic process; IBA:GO_Central. 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:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central. 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 1: Evidence at protein level; KW Direct protein sequencing; Heme; Iron; Lipid metabolism; Membrane; KW Metal-binding; Mitochondrion; Mitochondrion inner membrane; Monooxygenase; KW Oxidoreductase; Reference proteome; Steroid metabolism; Steroidogenesis; KW Transit peptide. FT TRANSIT 1..24 FT /note="Mitochondrion" FT CHAIN 25..503 FT /note="Cytochrome P450 11B1, mitochondrial" FT /id="PRO_0000003594" FT BINDING 450 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 30 FT /note="A -> V (in 11-beta-3)" FT VARIANT 60 FT /note="S -> G (in 11-beta-3)" FT VARIANT 106 FT /note="H -> R (in 11-beta-3)" FT CONFLICT 191..192 FT /note="SV -> RL (in Ref. 3; AAA83383)" FT /evidence="ECO:0000305" FT CONFLICT 337 FT /note="Q -> T (in Ref. 4; BAA00347 and 5; no nucleotide FT entry)" FT /evidence="ECO:0000305" FT CONFLICT 347 FT /note="A -> P (in Ref. 3; AAA83383)" FT /evidence="ECO:0000305" FT CONFLICT 502 FT /note="I -> Y (in Ref. 4; BAA00347)" FT /evidence="ECO:0000305" SQ SEQUENCE 503 AA; 57847 MW; 9FBEEC132975FD72 CRC64; MALWAKARVR MAGPWLSLHE ARLLGTRGAA APKAVLPFEA MPRCPGNKWM RMLQIWKEQS SENMHLDMHQ TFQELGPIFR YDVGGRHMVF VMLPEDVERL QQADSHHPQR MILEPWLAYR QARGHKCGVF LLNGPQWRLD RLRLNPDVLS LPALQKYTPL VDGVARDFSQ TLKARVLQNA RGSLTLDIAP SVFRYTIEAS TLVLYGERLG LLTQQPNPDS LNFIHALEAM LKSTVQLMFV PRRLSRWMST NMWREHFEAW DYIFQYANRA IQRIYQELAL GHPWHYSGIV AELLMRADMT LDTIKANTID LTAGSVDTTA FPLLMTLFEL ARNPEVQQAV RQESLVAEAR ISENPQRAIT ELPLLRAALK ETLRLYPVGI TLEREVSSDL VLQNYHIPAG TLVKVLLYSL GRNPAVFARP ESYHPQRWLD RQGSGSRFPH LAFGFGVRQC LGRRVAEVEM LLLLHHVLKN FLVETLEQED IKMVYRFILM PSTLPLFTFR AIQ //