ID   CP51_MYCBO              Reviewed;         451 AA.
AC   P0A513; A0A1R3XWC0; P77901; X2BFW1;
DT   15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2005, sequence version 1.
DT   03-AUG-2022, entry version 109.
DE   RecName: Full=Lanosterol 14-alpha demethylase;
DE            EC=1.14.14.154 {ECO:0000250|UniProtKB:P9WPP9};
DE   AltName: Full=CYPLI;
DE   AltName: Full=Cytochrome P450 51;
DE   AltName: Full=Cytochrome P450-14DM;
DE   AltName: Full=Cytochrome P450-LIA1;
DE   AltName: Full=Sterol 14-alpha demethylase;
GN   Name=cyp51; OrderedLocusNames=BQ2027_MB0787C;
OS   Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=233413;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-935 / AF2122/97;
RX   PubMed=12788972; DOI=10.1073/pnas.1130426100;
RA   Garnier T., Eiglmeier K., Camus J.-C., Medina N., Mansoor H., Pryor M.,
RA   Duthoy S., Grondin S., Lacroix C., Monsempe C., Simon S., Harris B.,
RA   Atkin R., Doggett J., Mayes R., Keating L., Wheeler P.R., Parkhill J.,
RA   Barrell B.G., Cole S.T., Gordon S.V., Hewinson R.G.;
RT   "The complete genome sequence of Mycobacterium bovis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:7877-7882(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC   STRAIN=ATCC BAA-935 / AF2122/97;
RX   PubMed=28385856; DOI=10.1128/genomea.00157-17;
RA   Malone K.M., Farrell D., Stuber T.P., Schubert O.T., Aebersold R.,
RA   Robbe-Austerman S., Gordon S.V.;
RT   "Updated reference genome sequence and annotation of Mycobacterium bovis
RT   AF2122/97.";
RL   Genome Announc. 5:E00157-E00157(2017).
CC   -!- FUNCTION: Its precise biological substrate is not known. Catalyzes C14-
CC       demethylation of lanosterol, 24,25-dihydrolanosterol and obtusifoliol
CC       which is critical for ergosterol biosynthesis. It transforms lanosterol
CC       into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
CC       {ECO:0000250|UniProtKB:P9WPP9}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 14alpha-methyl steroid + 3 O2 + 3 reduced [NADPH--
CC         hemoprotein reductase] = a Delta(14) steroid + formate + 4 H(+) + 4
CC         H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC         Xref=Rhea:RHEA:54028, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC         ChEBI:CHEBI:138029, ChEBI:CHEBI:138031; EC=1.14.14.154;
CC         Evidence={ECO:0000250|UniProtKB:P9WPP9};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC   -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC       lanosterol: step 1/6.
CC   -!- SUBUNIT: Monomer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; LT708304; SIT99386.1; -; Genomic_DNA.
DR   RefSeq; NP_854445.1; NC_002945.3.
DR   RefSeq; WP_003898577.1; NC_002945.4.
DR   AlphaFoldDB; P0A513; -.
DR   SMR; P0A513; -.
DR   EnsemblBacteria; SIT99386; SIT99386; BQ2027_MB0787C.
DR   PATRIC; fig|233413.5.peg.857; -.
DR   OMA; AWTLIEL; -.
DR   UniPathway; UPA00770; UER00754.
DR   Proteomes; UP000001419; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; 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:0008398; F:sterol 14-demethylase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   3: Inferred from homology;
KW   Cytoplasm; Heme; Iron; Lipid biosynthesis; Lipid metabolism; Metal-binding;
KW   Monooxygenase; Oxidoreductase; Steroid biosynthesis; Steroid metabolism;
KW   Sterol biosynthesis; Sterol metabolism.
FT   CHAIN           1..451
FT                   /note="Lanosterol 14-alpha demethylase"
FT                   /id="PRO_0000052016"
FT   BINDING         394
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"
SQ   SEQUENCE   451 AA;  50878 MW;  B3D671EA9542A57B CRC64;
     MSAVALPRVS GGHDEHGHLE EFRTDPIGLM QRVRDECGDV GTFQLAGKQV VLLSGSHANE
     FFFRAGDDDL DQAKAYPFMT PIFGEGVVFD ASPERRKEML HNAALRGEQM KGHAATIEDQ
     VRRMIADWGE AGEIDLLDFF AELTIYTSSA CLIGKKFRDQ LDGRFAKLYH ELERGTDPLA
     YVDPYLPIES FRRRDEARNG LVALVADIMN GRIANPPTDK SDRDMLDVLI AVKAETGTPR
     FSADEITGMF ISMMFAGHHT SSGTASWTLI ELMRHRDAYA AVIDELDELY GDGRSVSFHA
     LRQIPQLENV LKETLRLHPP LIILMRVAKG EFEVQGHRIH EGDLVAASPA ISNRIPEDFP
     DPHDFVPARY EQPRQEDLLN RWTWIPFGAG RHRCVGAAFA IMQIKAIFSV LLREYEFEMA
     QPPESYRNDH SKMVVQLAQP ACVRYRRRTG V