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 27-MAR-2024, entry version 101.
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: Sterol 14alpha-demethylase that plays a critical role in the
CC third module of ergosterol biosynthesis pathway, being ergosterol the
CC major sterol component in fungal membranes that participates in a
CC variety of functions (By similarity). The third module or late pathway
CC involves the ergosterol synthesis itself through consecutive reactions
CC that mainly occur in the endoplasmic reticulum (ER) membrane (By
CC similarity). In filamentous fungi, during the initial step of this
CC module, lanosterol (lanosta-8,24-dien-3beta-ol) can be metabolized to
CC eburicol (By similarity). Sterol 14alpha-demethylase catalyzes the
CC three-step oxidative removal of the 14alpha-methyl group (C-32) of both
CC these sterols in the form of formate, and converts eburicol and
CC lanosterol to 14-demethyleburicol (4,4,24-trimethylergosta-8,14,24(28)-
CC trienol) and 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol,
CC respectively, which are further metabolized by other enzymes in the
CC pathway to ergosterol (By similarity). Can also use substrates not
CC intrinsic to fungi, such as 24,25-dihydrolanosterol (DHL), producing
CC 4,4-dimethyl-8,14-cholestadien-3-beta-ol, but at lower rates than the
CC endogenous substrates (By similarity). {ECO:0000250|UniProtKB:P10613,
CC ECO:0000250|UniProtKB:P10614, ECO:0000250|UniProtKB:Q4WNT5}.
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:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-methyl steroid + O2 + reduced [NADPH--hemoprotein
CC reductase] = a 14alpha-hydroxymethyl steroid + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68060, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:138029, ChEBI:CHEBI:176901;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68061;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-hydroxymethyl steroid + O2 + reduced [NADPH--
CC hemoprotein reductase] = a 14alpha-formyl steroid + H(+) + 2 H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68064,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:176901, ChEBI:CHEBI:176902;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68065;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-formyl steroid + O2 + reduced [NADPH--hemoprotein
CC reductase] = a Delta(14) steroid + formate + 2 H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68068, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:138031,
CC ChEBI:CHEBI:176902; Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68069;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lanosterol + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] =
CC 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 4
CC H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:25286, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:16521, ChEBI:CHEBI:17813,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.154;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25287;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 32-
CC hydroxylanosterol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:75103, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16521, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:166806; Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75104;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-hydroxylanosterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 32-oxolanosterol + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:75107, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:166681, ChEBI:CHEBI:166806;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75108;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-oxolanosterol + O2 + reduced [NADPH--hemoprotein reductase]
CC = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 2
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:75111, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:17813, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:166681;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75112;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eburicol + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] =
CC 14-demethyleburicol + formate + 4 H(+) + 4 H2O + 3 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:75439, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:70315, ChEBI:CHEBI:194330;
CC Evidence={ECO:0000250|UniProtKB:P10613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75440;
CC Evidence={ECO:0000250|UniProtKB:P10613};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eburicol + O2 + reduced [NADPH--hemoprotein reductase] = 32-
CC hydroxyeburicol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:75427, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:70315,
CC ChEBI:CHEBI:194328; Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75428;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-hydroxyeburicol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 32-oxoeburicol + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:75431, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:194328, ChEBI:CHEBI:194329;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75432;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=32-oxoeburicol + O2 + reduced [NADPH--hemoprotein reductase] =
CC 14-demethyleburicol + formate + 2 H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:75435, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:194329, ChEBI:CHEBI:194330;
CC Evidence={ECO:0000250|UniProtKB:P10614};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75436;
CC Evidence={ECO:0000250|UniProtKB:P10614};
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}.
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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 CDD; cd11042; CYP51-like; 1.
DR Gene3D; 1.10.630.10; Cytochrome P450; 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 PANTHER; PTHR24304:SF2; 24-HYDROXYCHOLESTEROL 7-ALPHA-HYDROXYLASE; 1.
DR PANTHER; PTHR24304; CYTOCHROME P450 FAMILY 7; 1.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
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 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
//
