ID   CP51_UNCNE              Reviewed;         524 AA.
AC   O14442; O14422;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   11-JUL-2001, sequence version 2.
DT   03-AUG-2022, entry version 96.
DE   RecName: Full=Eburicol 14-alpha-demethylase;
DE            EC=1.14.14.154;
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;
OS   Uncinula necator (Grape powdery mildew).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Leotiomycetes;
OC   Erysiphales; Erysiphaceae; Erysiphe.
OX   NCBI_TaxID=52586;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT PHE-136.
RC   STRAIN=FPE11;
RX   PubMed=9300816; DOI=10.1016/s0378-1119(97)00141-8;
RA   Delye C., Laigret F., Corio-Costet M.-F.;
RT   "Cloning and sequence analysis of the eburicol 14alpha-demethylase gene of
RT   the obligate biotrophic grape powdery mildew fungus.";
RL   Gene 195:29-33(1997).
RN   [2]
RP   SEQUENCE REVISION TO 515-517.
RA   Delye C., Laigret F., Corio-Costet M.-F.;
RL   Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   MOLECULAR BASIS OF FUNGICIDE RESISTANCE.
RC   STRAIN=PAZ11;
RX   PubMed=9251183; DOI=10.1128/aem.63.8.2966-2970.1997;
RA   Delye C., Laigret F., Corio-Costet M.-F.;
RT   "A mutation in the 14 alpha-demethylase gene of Uncinula necator that
RT   correlates with resistance to a sterol biosynthesis inhibitor.";
RL   Appl. Environ. Microbiol. 63:2966-2970(1997).
CC   -!- FUNCTION: Catalyzes C14-demethylation of lanosterol which is critical
CC       for ergosterol biosynthesis. It transforms lanosterol into 4,4'-
CC       dimethyl cholesta-8,14,24-triene-3-beta-ol (By similarity).
CC       {ECO:0000250}.
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   -!- 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   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {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; U72657; AAC49811.2; -; Genomic_DNA.
DR   EMBL; U72658; AAC49812.2; -; mRNA.
DR   EMBL; U83840; AAC49801.2; -; Genomic_DNA.
DR   AlphaFoldDB; O14442; -.
DR   SMR; O14442; -.
DR   UniPathway; UPA00770; UER00754.
DR   GO; GO:0016020; C: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: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   2: Evidence at transcript level;
KW   Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding;
KW   Monooxygenase; Oxidoreductase; Steroid biosynthesis; Steroid metabolism;
KW   Sterol biosynthesis; Sterol metabolism.
FT   CHAIN           1..524
FT                   /note="Eburicol 14-alpha-demethylase"
FT                   /id="PRO_0000052010"
FT   BINDING         469
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"
FT   VARIANT         136
FT                   /note="Y -> F (in strain: PAZ11; resistant to triadimenol;
FT                   a sterol demethylation-inhibiting fungicide)"
FT                   /evidence="ECO:0000269|PubMed:9300816"
SQ   SEQUENCE   524 AA;  59840 MW;  24BE154B176CE09A CRC64;
     MYIADILSDL LTQQTTRYGW IFMVTSIAFS IILLAVGLNV LSQLLFRRPY EPPVVFHWFP
     IIGSTISYGI DPYKFYFDCR AKYGDIFTFI LLGKKVTVYL GLQGNNFILN GKLKDVNAEE
     IYTNLTTPVF GRDVVYDCPN SKLMEQKKFM KTALTIEAFH SYVTIIQNEV EAYINNCVSF
     QGESGTVNIS KVMAEITIYT ASHALQGEEV RENFDSSFAA LYHDLDMGFT PINFTFYWAP
     LPWNRARDHA QRTVARTYMN IIQARREEKR SGENKHDIMW ELMRSTYKDG TPVPDREIAH
     MMIALLMAGQ HSSSSTSSWI MLWLAARPDI MEELYEEQLR IFGSEKPFPP LQYEDLSKLQ
     LHQNVLKEVL RLHAPIHSIM RKVKNPMIVP GTKYVIPTSH VLISSPGCTS QDATFFPDPL
     KWDPHRWDIG SGKVLGNDAV DEKYDYGYGL TSTGASSPYL PFGAGRHRCI GEQFATLQLV
     TIMATMVRFF RFRNIDGKQG VVKTDYSSLF SMPLAPALIG WEKR