CP51_CANGA
ID CP51_CANGA Reviewed; 533 AA.
AC P50859; Q02312;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 145.
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; OrderedLocusNames=CAGL0E04334g;
OS Candida glabrata (strain ATCC 2001 / CBS 138 / JCM 3761 / NBRC 0622 / NRRL
OS Y-65) (Yeast) (Torulopsis glabrata).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Nakaseomyces;
OC Nakaseomyces/Candida clade.
OX NCBI_TaxID=284593;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=2001-L5;
RX PubMed=8593007; DOI=10.1128/aac.39.12.2708;
RA Geber A., Hitchcock C.A., Swartz J.E., Pullen F.S., Marsden K.E.,
RA Kwon-Chung K.J., Bennett J.E.;
RT "Deletion of the Candida glabrata ERG3 and ERG11 genes: effect on cell
RT viability, cell growth, sterol composition, and antifungal
RT susceptibility.";
RL Antimicrob. Agents Chemother. 39:2708-2717(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 2001 / CBS 138 / JCM 3761 / NBRC 0622 / NRRL Y-65;
RX PubMed=15229592; DOI=10.1038/nature02579;
RA Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I.,
RA de Montigny J., Marck C., Neuveglise C., Talla E., Goffard N., Frangeul L.,
RA Aigle M., Anthouard V., Babour A., Barbe V., Barnay S., Blanchin S.,
RA Beckerich J.-M., Beyne E., Bleykasten C., Boisrame A., Boyer J.,
RA Cattolico L., Confanioleri F., de Daruvar A., Despons L., Fabre E.,
RA Fairhead C., Ferry-Dumazet H., Groppi A., Hantraye F., Hennequin C.,
RA Jauniaux N., Joyet P., Kachouri R., Kerrest A., Koszul R., Lemaire M.,
RA Lesur I., Ma L., Muller H., Nicaud J.-M., Nikolski M., Oztas S.,
RA Ozier-Kalogeropoulos O., Pellenz S., Potier S., Richard G.-F.,
RA Straub M.-L., Suleau A., Swennen D., Tekaia F., Wesolowski-Louvel M.,
RA Westhof E., Wirth B., Zeniou-Meyer M., Zivanovic Y., Bolotin-Fukuhara M.,
RA Thierry A., Bouchier C., Caudron B., Scarpelli C., Gaillardin C.,
RA Weissenbach J., Wincker P., Souciet J.-L.;
RT "Genome evolution in yeasts.";
RL Nature 430:35-44(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 60-473.
RC STRAIN=ATCC 2001 / CBS 138 / JCM 3761 / NBRC 0622 / NRRL Y-65;
RX PubMed=7989540; DOI=10.1128/jcm.32.8.1902-1907.1994;
RA Burgener-Kairuz P., Zuber J.P., Jaunin P., Buchman T.G., Bille J.,
RA Rossier M.;
RT "Rapid detection and identification of Candida albicans and Torulopsis
RT (Candida) glabrata in clinical specimens by species-specific nested PCR
RT amplification of a cytochrome P-450 lanosterol-alpha-demethylase (L1A1)
RT gene fragment.";
RL J. Clin. Microbiol. 32:1902-1907(1994).
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}.
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DR EMBL; L40389; AAB02329.1; -; Genomic_DNA.
DR EMBL; CR380951; CAG58795.1; -; Genomic_DNA.
DR EMBL; S75389; AAB32679.1; -; Genomic_DNA.
DR RefSeq; XP_445876.1; XM_445876.1.
DR PDB; 5JLC; X-ray; 2.40 A; A=20-533.
DR PDBsum; 5JLC; -.
DR AlphaFoldDB; P50859; -.
DR SMR; P50859; -.
DR STRING; 5478.XP_445876.1; -.
DR DrugBank; DB09040; Efinaconazole.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB01167; Itraconazole.
DR DrugBank; DB01026; Ketoconazole.
DR PRIDE; P50859; -.
DR EnsemblFungi; CAG58795; CAG58795; CAGL0E04334g.
DR GeneID; 2887532; -.
DR KEGG; cgr:CAGL0E04334g; -.
DR CGD; CAL0128884; ERG11.
DR VEuPathDB; FungiDB:CAGL0E04334g; -.
DR eggNOG; KOG0684; Eukaryota.
DR HOGENOM; CLU_001570_15_0_1; -.
DR InParanoid; P50859; -.
DR OMA; AWTLIEL; -.
DR UniPathway; UPA00770; UER00754.
DR Proteomes; UP000002428; Chromosome E.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:EnsemblFungi.
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:0006696; P:ergosterol biosynthetic process; IMP:CGD.
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 1: Evidence at protein level;
KW 3D-structure; Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism.
FT CHAIN 1..533
FT /note="Lanosterol 14-alpha demethylase"
FT /id="PRO_0000052004"
FT BINDING 472
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 CONFLICT 64
FT /note="I -> M (in Ref. 3; AAB32679)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="I -> T (in Ref. 3; AAB32679)"
FT /evidence="ECO:0000305"
FT HELIX 23..25
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 28..50
FT /evidence="ECO:0007829|PDB:5JLC"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 70..75
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 77..88
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 90..96
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 99..104
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 106..114
FT /evidence="ECO:0007829|PDB:5JLC"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 123..135
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 145..156
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 161..181
FT /evidence="ECO:0007829|PDB:5JLC"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:5JLC"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 191..196
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 197..213
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 216..221
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 227..235
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 240..243
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 250..276
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 284..290
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 302..332
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 335..348
FT /evidence="ECO:0007829|PDB:5JLC"
FT TURN 349..353
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 358..362
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 365..377
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 384..388
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 406..409
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 411..415
FT /evidence="ECO:0007829|PDB:5JLC"
FT TURN 418..420
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 429..432
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 446..451
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 453..456
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 468..470
FT /evidence="ECO:0007829|PDB:5JLC"
FT HELIX 475..492
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 493..496
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 510..513
FT /evidence="ECO:0007829|PDB:5JLC"
FT STRAND 521..527
FT /evidence="ECO:0007829|PDB:5JLC"
SQ SEQUENCE 533 AA; 61305 MW; A0506C17507E6EF7 CRC64;
MSTENTSLVV ELLEYVKLGL SYFQALPLAQ RVSIMVALPF VYTITWQLLY SLRKDRPPLV
FYWIPWVGSA IPYGTKPYEF FEDCQKKYGD IFSFMLLGRI MTVYLGPKGH EFIFNAKLAD
VSAEAAYSHL TTPVFGKGVI YDCPNHRLME QKKFVKGALT KEAFVRYVPL IAEEIYKYFR
NSKNFKINEN NSGIVDVMVS QPEMTIFTAS RSLLGKEMRD KLDTDFAYLY SDLDKGFTPI
NFVFPNLPLE HYRKRDHAQQ AISGTYMSLI KERREKNDIQ NRDLIDELMK NSTYKDGTKM
TDQEIANLLI GVLMGGQHTS AATSAWCLLH LAERPDVQEE LYQEQMRVLN NDTKELTYDD
LQNMPLLNQM IKETLRLHHP LHSLFRKVMR DVAIPNTSYV VPRDYHVLVS PGYTHLQEEF
FPKPNEFNIH RWDGDAASSS AAGGDEVDYG FGAISKGVSS PYLPFGGGRH RCIGELFAYC
QLGVLMSIFI RTMKWRYPTE GETVPPSDFT SMVTLPTAPA KIYWEKRHPE QKY
