ID   CP51_CANTR              Reviewed;         528 AA.
AC   P14263;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1990, sequence version 2.
DT   02-SEP-2026, entry version 126.
DE   RecName: Full=Lanosterol 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=ERG11; Synonyms=CYP51;
OS   Candida tropicalis (Yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Pichiomycetes;
OC   Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX   NCBI_TaxID=5482;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 750 / CBS 94 / DSM 11953 / JCM 1541 / NBRC 1400;
RX   PubMed=3068024; DOI=10.1089/dna.1988.7.617;
RA   Chen C., Kalb V.F., Turi T.G., Loper J.C.;
RT   "Primary structure of the cytochrome P450 lanosterol 14 alpha-demethylase
RT   gene from Candida tropicalis.";
RL   DNA 7:617-626(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 434-528.
RC   STRAIN=ATCC 750 / CBS 94 / DSM 11953 / JCM 1541 / NBRC 1400;
RX   PubMed=3304292; DOI=10.1016/0006-291x(87)90792-3;
RA   Chen C., Turi T.G., Sanglard D., Loper J.C.;
RT   "Isolation of the Candida tropicalis gene for P450 lanosterol demethylase
RT   and its expression in Saccharomyces cerevisiae.";
RL   Biochem. Biophys. Res. Commun. 146:1311-1317(1987).
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 reduced [NADPH--hemoprotein
CC         reductase] + 3 O2 = a Delta(14) steroid + formate + 3 oxidized
CC         [NADPH--hemoprotein reductase] + 4 H2O + 4 H(+);
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 + reduced [NADPH--hemoprotein
CC         reductase] + O2 = a 14alpha-hydroxymethyl steroid + oxidized
CC         [NADPH--hemoprotein reductase] + H2O + H(+); Xref=Rhea:RHEA:68060,
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: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 + reduced [NADPH--hemoprotein
CC         reductase] + O2 = a 14alpha-formyl steroid + oxidized
CC         [NADPH--hemoprotein reductase] + 2 H2O + H(+); 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 + reduced [NADPH--hemoprotein
CC         reductase] + O2 = a Delta(14) steroid + formate + oxidized
CC         [NADPH--hemoprotein reductase] + H2O + 2 H(+); Xref=Rhea:RHEA:68068,
CC         Rhea:RHEA-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 reduced [NADPH--hemoprotein reductase] + 3 O2 =
CC         4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 3
CC         oxidized [NADPH--hemoprotein reductase] + 4 H2O + 4 H(+);
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 + reduced [NADPH--hemoprotein reductase] + O2 = 32-
CC         hydroxylanosterol + oxidized [NADPH--hemoprotein reductase] + H2O +
CC         H(+); 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 + reduced [NADPH--hemoprotein reductase]
CC         + O2 = 32-oxolanosterol + oxidized [NADPH--hemoprotein reductase] + 2
CC         H2O + H(+); Xref=Rhea:RHEA:75107, 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:166681,
CC         ChEBI:CHEBI:166806; 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 + reduced [NADPH--hemoprotein reductase] + O2
CC         = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate +
CC         oxidized [NADPH--hemoprotein reductase] + H2O + 2 H(+);
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 reduced [NADPH--hemoprotein reductase] + 3 O2 =
CC         14-demethyleburicol + formate + 3 oxidized [NADPH--hemoprotein
CC         reductase] + 4 H2O + 4 H(+); Xref=Rhea:RHEA:75439, 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:70315,
CC         ChEBI:CHEBI:194330; 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 + reduced [NADPH--hemoprotein reductase] + O2 = 32-
CC         hydroxyeburicol + oxidized [NADPH--hemoprotein reductase] + H2O +
CC         H(+); 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 + reduced [NADPH--hemoprotein reductase] +
CC         O2 = 32-oxoeburicol + oxidized [NADPH--hemoprotein reductase] + 2 H2O
CC         + H(+); Xref=Rhea:RHEA:75431, 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:194328,
CC         ChEBI:CHEBI:194329; 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 + reduced [NADPH--hemoprotein reductase] + O2 =
CC         14-demethyleburicol + formate + oxidized [NADPH--hemoprotein
CC         reductase] + H2O + 2 H(+); Xref=Rhea:RHEA:75435, 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:194329,
CC         ChEBI:CHEBI:194330; 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; M23673; AAA53284.1; -; Genomic_DNA.
DR   EMBL; M17595; AAA34316.1; -; Genomic_DNA.
DR   PIR; A31854; A31854.
DR   AlphaFoldDB; P14263; -.
DR   SMR; P14263; -.
DR   DrugBank; DB01167; Itraconazole.
DR   EnsemblFungi; CTRG_05283-t43_1; CTRG_05283-t43_1-p1; CTRG_05283.
DR   VEuPathDB; FungiDB:CTMYA2_056970; -.
DR   VEuPathDB; FungiDB:CTRG_05283; -.
DR   BRENDA; 1.14.14.154; 1146.
DR   UniPathway; UPA00770; UER00754.
DR   GO; GO:0032541; C:cortical endoplasmic reticulum; IEA:EnsemblFungi.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0097038; C:perinuclear endoplasmic reticulum; IEA:EnsemblFungi.
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:0006696; P:ergosterol biosynthetic process; IEA:UniProtKB-ARBA.
DR   CDD; cd11042; CYP51-like; 1.
DR   FunFam; 1.10.630.10:FF:000033; 14-alpha sterol demethylase; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   InterPro; IPR050529; CYP51A1-like.
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   3: Inferred from homology;
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..528
FT                   /note="Lanosterol 14-alpha demethylase"
FT                   /id="PRO_0000052005"
FT   BINDING         470
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   CONFLICT        448
FT                   /note="G -> V (in Ref. 2; AAA34316)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        500
FT                   /note="V -> G (in Ref. 2; AAA34316)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   528 AA;  60928 MW;  83F8E3C1C1E826B9 CRC64;
     MAIVDTAIDG INYFLSLSLT QQITILVVFP FIYNIAWQLL YSLRKDRVPM VFYWIPWFGS
     AASYGMQPYE FFEKCRLKYG DVFSFMLLGK VMTVYLGPKG HEFIYNAKLS DVSAEEAYTH
     LTTPVFGKGV IYDCPNSRLM EQKKFAKFAL TTDSFKTYVP KIREEVLNYF VNDVSFKTKE
     RDHGVASVMK TQPEITIFTA SRCLFGDEMR KSFDRSFAQL YADLDKGFTP INFVFPNLPL
     PHYWRRDAAQ RKISAHYMKE IKRRRESGDI DPKRDLIDSL LVNSTYKDGV KMTDQEIANL
     LIGVLMGGQH TSASTSAWFL LHLAEQPQLQ DDLYEELTNL LKEKGGDLND LTYEDLQKLP
     LVNNTIKETL RMHMPLHSIF RKVMNPLRVP NTKYVIPKGH YVLVSAGYAH TSDRWFEHPE
     HFNPRRWESD DTKASAVSFN SEDTVDYGFG KISKGVSSPY LPFGGGRHRC IGEQFAYVQL
     GTILTTYIYN FKWRLNGDKV PDVDYQSMVT LPLEPAEIVW EKRDTCMV
//