ID   CP51_CANAL              Reviewed;         528 AA.
AC   P10613; Q5A524; Q92208;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 2.
DT   16-JUN-2009, entry version 74.
DE   RecName: Full=Lanosterol 14-alpha demethylase;
DE            EC=1.14.13.70;
DE   AltName: Full=Cytochrome P450 51;
DE   AltName: Full=CYPLI;
DE   AltName: Full=P450-LIA1;
DE   AltName: Full=Sterol 14-alpha demethylase;
DE   AltName: Full=P450-14DM;
GN   Name=ERG11; Synonyms=CYP51, ERG16; ORFNames=CaO19.922;
OS   Candida albicans (Yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina;
OC   Saccharomycetes; Saccharomycetales; mitosporic Saccharomycetales;
OC   Candida.
OX   NCBI_TaxID=5476;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=SC5314;
RX   MEDLINE=89128456; PubMed=2644625; DOI=10.1093/nar/17.2.804;
RA   Lai M.H., Kirsch D.R.;
RT   "Nucleotide sequence of cytochrome P450 L1A1 (lanosterol 14 alpha-
RT   demethylase) from Candida albicans.";
RL   Nucleic Acids Res. 17:804-804(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=CA100, CA11, CA36, and CA95;
RA   Orru G., Ciusa M.L., Pilia F., Taccori F., Cosentino S., Pisano M.B.,
RA   Meloni M., Fadda M.E.;
RT   "ERG11 mutations in oral strains of Candida albicans isolated in
RT   Sardinia.";
RL   Submitted (JUN-2008) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=SC5314;
RX   PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA   Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S.,
RA   Magee B.B., Newport G., Thorstenson Y.R., Agabian N., Magee P.T.,
RA   Davis R.W., Scherer S.;
RT   "The diploid genome sequence of Candida albicans.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-48 AND 467-528, AND VARIANT
RP   LYS-467.
RC   STRAIN=SS;
RX   MEDLINE=97354377; PubMed=9210671;
RA   White T.C.;
RT   "The presence of an R467K amino acid substitution and loss of allelic
RT   variation correlate with an azole-resistant lanosterol 14-alpha
RT   demethylase in Candida albicans.";
RL   Antimicrob. Agents Chemother. 41:1488-1494(1997).
RN   [5]
RP   3D-STRUCTURE MODELING.
RX   MEDLINE=95118948; PubMed=7819160; DOI=10.1016/0263-7855(94)80086-3;
RA   Boscott P.E., Grant G.H.;
RT   "Modeling cytochrome P450 14-alpha demethylase (Candida albicans) from
RT   P450cam.";
RL   J. Mol. Graph. 12:185-192(1994).
RN   [6]
RP   VARIANTS FLUCONAZOLE-RESISTANT.
RX   MEDLINE=97372542; PubMed=9228762; DOI=10.1016/S0378-1097(97)00172-9;
RA   Loffler J., Kelly S.L., Hebart H., Schumacher U., Lass-Florl C.,
RA   Einsele H.;
RT   "Molecular analysis of cyp51 from fluconazole-resistant Candida
RT   albicans strains.";
RL   FEMS Microbiol. Lett. 151:263-268(1997).
CC   -!- FUNCTION: Catalyzes C14-demethylation of lanosterol which is
CC       critical for ergosterol biosynthesis. It transforms lanosterol
CC       into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
CC   -!- CATALYTIC ACTIVITY: Obtusifoliol + 3 O(2) + 3 NADPH = 4-alpha-
CC       methyl-5-alpha-ergosta-8,14,24(28)-trien-3-beta-ol + formate + 3
CC       NADP(+) + 4 H(2)O.
CC   -!- COFACTOR: Heme group (By similarity).
CC   -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol
CC       from lanosterol: step 1/6.
CC   -!- SUBCELLULAR LOCATION: Membrane (Potential). Membrane; Single-pass
CC       membrane protein.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family.
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DR   EMBL; X13296; CAA31658.1; -; Genomic_DNA.
DR   EMBL; EU819548; ACF34636.1; -; Genomic_DNA.
DR   EMBL; EU819551; ACF34639.1; -; Genomic_DNA.
DR   EMBL; FJ002303; ACH91036.1; -; Genomic_DNA.
DR   EMBL; FJ403378; ACJ23064.1; -; Genomic_DNA.
DR   EMBL; AACQ01000063; EAK97774.1; -; Genomic_DNA.
DR   EMBL; U67192; AAB08099.1; -; Genomic_DNA.
DR   EMBL; U67193; AAB08100.1; -; Genomic_DNA.
DR   PIR; S02713; O4CK51.
DR   RefSeq; XP_716761.1; -.
DR   GeneID; 3641571; -.
DR   CGD; CAL0003627; ERG11.
DR   OMA; P10613; NFVFPNL.
DR   BRENDA; 1.14.13.70; 1124.
DR   DrugBank; DB00646; Nystatin.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0009055; F:electron carrier activity; IEA:InterPro.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0008398; F:sterol 14-demethylase activity; IEA:EC.
DR   GO; GO:0055114; P:oxidation reduction; IEA:UniProtKB-KW.
DR   GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017973; Cyt_P450_C.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR   Gene3D; G3DSA:1.10.630.10; Cyt_P450; 1.
DR   PANTHER; PTHR19383; Cyt_P450; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   PRINTS; PR00385; P450.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   3: Inferred from homology;
KW   Heme; Iron; Lipid synthesis; Membrane; Metal-binding; Monooxygenase;
KW   NADP; Oxidoreductase; Steroid biosynthesis; Sterol biosynthesis.
FT   CHAIN         1    528       Lanosterol 14-alpha demethylase.
FT                                /FTId=PRO_0000052003.
FT   METAL       470    470       Iron (heme axial ligand) (By similarity).
FT   VARIANT     105    105       F -> L (in fluconazole-resistant
FT                                isolates).
FT   VARIANT     266    266       E -> D (in strain: fluconazole-resistant
FT                                isolates).
FT   VARIANT     287    287       K -> R (in strain: fluconazole-resistant
FT                                isolates).
FT   VARIANT     450    450       G -> E (in strain: fluconazole-resistant
FT                                isolates).
FT   VARIANT     464    464       G -> S (in strain: fluconazole-resistant
FT                                isolates).
FT   VARIANT     467    467       R -> K (in strain: Isolate 13; azole-
FT                                resistant).
FT   VARIANT     488    488       V -> I (in strain: fluconazole-resistant
FT                                isolates).
FT   CONFLICT     19     19       V -> D (in Ref. 4; AAB08099).
SQ   SEQUENCE   528 AA;  60675 MW;  026948CEE4AF1B88 CRC64;
     MAIVETVIDG INYFLSLSVT QQISILLGVP FVYNLVWQYL YSLRKDRAPL VFYWIPWFGS
     AASYGQQPYE FFESCRQKYG DVFSFMLLGK IMTVYLGPKG HEFVFNAKLS DVSAEDAYKH
     LTTPVFGKGV IYDCPNSRLM EQKKFAKFAL TTDSFKRYVP KIREEILNYF VTDESFKLKE
     KTHGVANVMK TQPEITIFTA SRSLFGDEMR RIFDRSFAQL YSDLDKGFTP INFVFPNLPL
     PHYWRRDAAQ KKISATYMKE IKSRRERGDI DPNRDLIDSL LIHSTYKDGV KMTDQEIANL
     LIGILMGGQH TSASTSAWFL LHLGEKPHLQ DVIYQEVVEL LKEKGGDLND LTYEDLQKLP
     SVNNTIKETL RMHMPLHSIF RKVTNPLRIP ETNYIVPKGH YVLVSPGYAH TSERYFDNPE
     DFDPTRWDTA AAKANSVSFN SSDEVDYGFG KVSKGVSSPY LPFGGGRHRC IGEQFAYVQL
     GTILTTFVYN LRWTIDGYKV PDPDYSSMVV LPTEPAEIIW EKRETCMF
//