ID CP51_YEAST Reviewed; 530 AA.
AC P10614; D3DKV1;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 29-MAY-2013, entry version 132.
DE RecName: Full=Lanosterol 14-alpha demethylase;
DE EC=1.14.13.70;
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=YHR007C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina;
OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3322742;
RA Kalb V.F., Woods C.W., Turi T.G., Dey C.R., Sutter T.R., Loper J.C.;
RT "Primary structure of the P450 lanosterol demethylase gene from
RT Saccharomyces cerevisiae.";
RL DNA 6:529-537(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3046615; DOI=10.1016/S0006-291X(88)81087-8;
RA Ishida N., Aoyama Y., Hatanaka R., Oyama Y., Imajo S., Ishiguro M.,
RA Oshima T., Nakazato H., Noguchi T., Maitra U.S., Mohan V.P.,
RA Sprinson D.B., Yoshida Y.;
RT "A single amino acid substitution converts cytochrome P450(14DM) to an
RT inactive form, cytochrome P450SG1: complete primary structures deduced
RT from cloned DNAS.";
RL Biochem. Biophys. Res. Commun. 155:317-323(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=8091229; DOI=10.1126/science.8091229;
RA Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J.,
RA Du Z., Favello A., Fulton L., Gattung S., Geisel C., Kirsten J.,
RA Kucaba T., Hillier L.W., Jier M., Johnston L., Langston Y.,
RA Latreille P., Louis E.J., Macri C., Mardis E., Menezes S., Mouser L.,
RA Nhan M., Rifkin L., Riles L., St Peter H., Trevaskis E., Vaughan K.,
RA Vignati D., Wilcox L., Wohldman P., Waterston R., Wilson R.,
RA Vaudin M.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT VIII.";
RL Science 265:2077-2082(1994).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RG Saccharomyces Genome Database;
RL Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 444-530.
RX PubMed=3542713; DOI=10.1016/0378-1119(86)90021-1;
RA Kalb V.F., Loper J.C., Dey C.R., Woods C.W., Sutter T.R.;
RT "Isolation of a cytochrome P-450 structural gene from Saccharomyces
RT cerevisiae.";
RL Gene 45:237-245(1986).
RN [6]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A.,
RA Dephoure N., O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [7]
RP INTERACTION WITH ERG28.
RX PubMed=15995173; DOI=10.1194/jlr.M500153-JLR200;
RA Mo C., Bard M.;
RT "Erg28p is a key protein in the yeast sterol biosynthetic enzyme
RT complex.";
RL J. Lipid Res. 46:1991-1998(2005).
RN [8]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 208353 / W303-1A;
RX PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA Kim H., Melen K., Oesterberg M., von Heijne G.;
RT "A global topology map of the Saccharomyces cerevisiae membrane
RT proteome.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND MASS
RP SPECTROMETRY.
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND MASS
RP SPECTROMETRY.
RX PubMed=18407956; DOI=10.1074/mcp.M700468-MCP200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth
RT phosphoproteome analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
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: A 14-alpha-methylsteroid + 3 O(2) + 3 NADPH =
CC a Delta(14)-steroid + formate + 3 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 -!- SUBUNIT: Interacts with ERG28.
CC -!- INTERACTION:
CC P53045:ERG25; NbExp=3; IntAct=EBI-5127, EBI-6506;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein.
CC -!- MISCELLANEOUS: It is the main target for antifungal compounds of
CC the triazole family like ketoconazole which inhibits by
CC coordinating the iron atom at the sixth ligand position.
CC -!- MISCELLANEOUS: Present with 73200 molecules/cell in log phase SD
CC medium.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
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DR EMBL; M18109; AAA34379.1; -; Genomic_DNA.
DR EMBL; M15663; AAA34837.1; -; Genomic_DNA.
DR EMBL; M21483; AAA34546.1; -; Genomic_DNA.
DR EMBL; M21484; AAA34547.1; -; Genomic_DNA.
DR EMBL; U10555; AAB68433.1; -; Genomic_DNA.
DR EMBL; BK006934; DAA06695.1; -; Genomic_DNA.
DR PIR; A27491; A27491.
DR RefSeq; NP_011871.1; NM_001179137.1.
DR ProteinModelPortal; P10614; -.
DR SMR; P10614; 52-525.
DR DIP; DIP-7886N; -.
DR IntAct; P10614; 66.
DR MINT; MINT-1325794; -.
DR STRING; 4932.YHR007C; -.
DR PaxDb; P10614; -.
DR PeptideAtlas; P10614; -.
DR EnsemblFungi; YHR007C; YHR007C; YHR007C.
DR GeneID; 856398; -.
DR KEGG; sce:YHR007C; -.
DR CYGD; YHR007c; -.
DR SGD; S000001049; ERG11.
DR eggNOG; COG2124; -.
DR GeneTree; ENSGT00660000095370; -.
DR HOGENOM; HOG000042780; -.
DR KO; K05917; -.
DR OMA; DFTSMVT; -.
DR OrthoDB; EOG4QJVWH; -.
DR BioCyc; MetaCyc:YHR007C-MONOMER; -.
DR BioCyc; YEAST:YHR007C-MONOMER; -.
DR UniPathway; UPA00770; UER00754.
DR DrugBank; DB00257; Clotrimazole.
DR DrugBank; DB01127; Econazole.
DR DrugBank; DB00196; Fluconazole.
DR DrugBank; DB01026; Ketoconazole.
DR DrugBank; DB01263; Posaconazole.
DR DrugBank; DB01153; Sertaconazole.
DR DrugBank; DB00251; Terconazole.
DR DrugBank; DB01007; Tioconazole.
DR DrugBank; DB00582; Voriconazole.
DR NextBio; 981925; -.
DR Genevestigator; P10614; -.
DR GermOnline; YHR007C; Saccharomyces cerevisiae.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0009055; F:electron carrier activity; IEA:InterPro.
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; IDA:SGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IMP:SGD.
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 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 1: Evidence at protein level;
KW Complete proteome; Heme; Iron; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Metal-binding; Monooxygenase; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1 530 Lanosterol 14-alpha demethylase.
FT /FTId=PRO_0000052012.
FT TOPO_DOM 1 20 Extracellular (Potential).
FT TRANSMEM 21 41 Helical; (Potential).
FT TOPO_DOM 42 530 Cytoplasmic (Potential).
FT METAL 470 470 Iron (heme axial ligand) (By similarity).
FT MOD_RES 458 458 Phosphoserine.
FT CONFLICT 433 433 K -> N (in Ref. 2; AAA34546/AAA34547).
SQ SEQUENCE 530 AA; 60720 MW; 646960BBA0E17979 CRC64;
MSATKSIVGE ALEYVNIGLS HFLALPLAQR ISLIIIIPFI YNIVWQLLYS LRKDRPPLVF
YWIPWVGSAV VYGMKPYEFF EECQKKYGDI FSFVLLGRVM TVYLGPKGHE FVFNAKLADV
SAEAAYAHLT TPVFGKGVIY DCPNSRLMEQ KKFVKGALTK EAFKSYVPLI AEEVYKYFRD
SKNFRLNERT TGTIDVMVTQ PEMTIFTASR SLLGKEMRAK LDTDFAYLYS DLDKGFTPIN
FVFPNLPLEH YRKRDHAQKA ISGTYMSLIK ERRKNNDIQD RDLIDSLMKN STYKDGVKMT
DQEIANLLIG VLMGGQHTSA ATSAWILLHL AERPDVQQEL YEEQMRVLDG GKKELTYDLL
QEMPLLNQTI KETLRMHHPL HSLFRKVMKD MHVPNTSYVI PAGYHVLVSP GYTHLRDEYF
PNAHQFNIHR WNKDSASSYS VGEEVDYGFG AISKGVSSPY LPFGGGRHRC IGEHFAYCQL
GVLMSIFIRT LKWHYPEGKT VPPPDFTSMV TLPTGPAKII WEKRNPEQKI
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