ID CP51_YEAST Reviewed; 530 AA. AC P10614; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 16-JUN-2009, entry version 93. 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; OrderedLocusNames=YHR007C; OS Saccharomyces cerevisiae (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=4932; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=88111027; 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 MEDLINE=88326319; 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 MEDLINE=94378003; 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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 444-530. RX MEDLINE=87106820; 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 [5] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX MEDLINE=22923965; 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 [6] 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 [7] RP TOPOLOGY [LARGE SCALE ANALYSIS]. 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 [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND MASS RP SPECTROMETRY. 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 [9] 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: 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 -!- SUBUNIT: Interacts with ERG28. CC -!- INTERACTION: CC Self; NbExp=1; IntAct=EBI-5127, EBI-5127; CC P36076:-; NbExp=1; IntAct=EBI-5127, EBI-26778; CC P47133:-; NbExp=1; IntAct=EBI-5127, EBI-25568; CC Q12164:-; NbExp=1; IntAct=EBI-5127, EBI-30000; CC Q12168:ACF2; NbExp=1; IntAct=EBI-5127, EBI-32973; CC P25376:AGP1; NbExp=1; IntAct=EBI-5127, EBI-2357; CC P53090:ARO8; NbExp=1; IntAct=EBI-5127, EBI-2042933; CC P04817:CAN1; NbExp=1; IntAct=EBI-5127, EBI-3993; CC P08456:CHO1; NbExp=1; IntAct=EBI-5127, EBI-14055; CC P43542:COS4; NbExp=1; IntAct=EBI-5127, EBI-2050225; CC P38723:COS8; NbExp=1; IntAct=EBI-5127, EBI-4985; CC P17898:CPT1; NbExp=1; IntAct=EBI-5127, EBI-2050738; CC P15365:DAL5; NbExp=1; IntAct=EBI-5127, EBI-5527; CC P38295:EHT1; NbExp=1; IntAct=EBI-5127, EBI-20890; CC P39540:ELO1; NbExp=1; IntAct=EBI-5127, EBI-2049096; CC P22140:EPT1; NbExp=1; IntAct=EBI-5127, EBI-6494; CC P53045:ERG25; NbExp=1; IntAct=EBI-5127, EBI-6506; CC P32353:ERG3; NbExp=1; IntAct=EBI-5127, EBI-6554; CC P54781:ERG5; NbExp=1; IntAct=EBI-5127, EBI-6563; CC Q05359:ERP1; NbExp=1; IntAct=EBI-5127, EBI-6581; CC P39704:ERP2; NbExp=1; IntAct=EBI-5127, EBI-6587; CC P54837:ERV25; NbExp=1; IntAct=EBI-5127, EBI-6642; CC P53337:ERV29; NbExp=1; IntAct=EBI-5127, EBI-23662; CC Q08967:FLC1; NbExp=1; IntAct=EBI-5127, EBI-36673; CC P19145:GAP1; NbExp=1; IntAct=EBI-5127, EBI-7314; CC Q04697:GSF2; NbExp=1; IntAct=EBI-5127, EBI-27807; CC P40582:GTT1; NbExp=1; IntAct=EBI-5127, EBI-7941; CC P32465:HXT1; NbExp=1; IntAct=EBI-5127, EBI-8759; CC P32466:HXT3; NbExp=1; IntAct=EBI-5127, EBI-8770; CC P39004:HXT7; NbExp=1; IntAct=EBI-5127, EBI-8790; CC P40581:HYR1; NbExp=1; IntAct=EBI-5127, EBI-7869; CC P47155:ILM1; NbExp=1; IntAct=EBI-5127, EBI-2051644; CC P00817:IPP1; NbExp=1; IntAct=EBI-5127, EBI-9338; CC P30605:ITR1; NbExp=1; IntAct=EBI-5127, EBI-2050956; CC P35844:KES1; NbExp=1; IntAct=EBI-5127, EBI-9648; CC P40540:KRE27; NbExp=1; IntAct=EBI-5127, EBI-24977; CC P28496:LAC1; NbExp=1; IntAct=EBI-5127, EBI-26585; CC P16603:NCP1; NbExp=1; IntAct=EBI-5127, EBI-11940; CC P32340:NDI1; NbExp=1; IntAct=EBI-5127, EBI-11961; CC P21147:OLE1; NbExp=1; IntAct=EBI-5127, EBI-2098; CC Q02201:OSH6; NbExp=1; IntAct=EBI-5127, EBI-12636; CC P41543:OST1; NbExp=1; IntAct=EBI-5127, EBI-12651; CC P05374:PEM1; NbExp=1; IntAct=EBI-5127, EBI-2049142; CC P25297:PHO84; NbExp=1; IntAct=EBI-5127, EBI-13320; CC P46956:PHO86; NbExp=1; IntAct=EBI-5127, EBI-13337; CC P38264:PHO88; NbExp=1; IntAct=EBI-5127, EBI-13350; CC P40857:PHS1; NbExp=1; IntAct=EBI-5127, EBI-26003; CC P06197:PIS1; NbExp=1; IntAct=EBI-5127, EBI-13458; CC Q03880:PKR1; NbExp=1; IntAct=EBI-5127, EBI-27252; CC P40975:PMP2; NbExp=1; IntAct=EBI-5127, EBI-2043041; CC P87284:PMP3; NbExp=1; IntAct=EBI-5127, EBI-13555; CC P13586:PMR1; NbExp=1; IntAct=EBI-5127, EBI-3091; CC P26570:PPZ1; NbExp=1; IntAct=EBI-5127, EBI-13807; CC Q04947:RTN1; NbExp=1; IntAct=EBI-5127, EBI-38020; CC P32368:SAC1; NbExp=1; IntAct=EBI-5127, EBI-16210; CC Q03529:SCS7; NbExp=1; IntAct=EBI-5127, EBI-16747; CC P21825:SEC62; NbExp=1; IntAct=EBI-5127, EBI-16632; CC P14906:SEC63; NbExp=1; IntAct=EBI-5127, EBI-16636; CC Q99287:SEY1; NbExp=1; IntAct=EBI-5127, EBI-37523; CC Q02774:SHR3; NbExp=1; IntAct=EBI-5127, EBI-17099; CC P38751:SHU1; NbExp=1; IntAct=EBI-5127, EBI-24305; CC P33333:SLC1; NbExp=1; IntAct=EBI-5127, EBI-13494; CC P39543:SOP4; NbExp=1; IntAct=EBI-5127, EBI-26193; CC P46965:SPC1; NbExp=1; IntAct=EBI-5127, EBI-17823; CC Q04969:SPC2; NbExp=1; IntAct=EBI-5127, EBI-27827; CC P39986:SPF1; NbExp=1; IntAct=EBI-5127, EBI-3128; CC P38985:SRP14; NbExp=1; IntAct=EBI-5127, EBI-17977; CC P38353:SSH1; NbExp=1; IntAct=EBI-5127, EBI-18175; CC P47154:STE24; NbExp=1; IntAct=EBI-5127, EBI-18298; CC P38992:SUR2; NbExp=1; IntAct=EBI-5127, EBI-18574; CC Q02795:SWP1; NbExp=1; IntAct=EBI-5127, EBI-12666; CC P53322:TNA1; NbExp=1; IntAct=EBI-5127, EBI-2051164; CC Q12256:TPO4; NbExp=1; IntAct=EBI-5127, EBI-37213; CC P25037:UBP1; NbExp=1; IntAct=EBI-5127, EBI-19819; CC Q08438:VHS3; NbExp=1; IntAct=EBI-5127, EBI-30482; CC P41806:VMA21; NbExp=1; IntAct=EBI-5127, EBI-20323; CC P40107:VRG4; NbExp=1; IntAct=EBI-5127, EBI-7764; CC P33767:WBP1; NbExp=1; IntAct=EBI-5127, EBI-12658; CC Q3E7B0:YER053C-A; NbExp=1; IntAct=EBI-5127, EBI-2047907; CC P35723:YET1; NbExp=1; IntAct=EBI-5127, EBI-26730; CC Q12402:YOP1; NbExp=1; IntAct=EBI-5127, EBI-37092; CC -!- SUBCELLULAR LOCATION: Membrane; Multi-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. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- 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 PIR; A27491; A27491. DR RefSeq; NP_011871.1; -. DR DIP; DIP:7886N; -. DR IntAct; P10614; 118. DR PeptideAtlas; P10614; -. DR Ensembl; YHR007C; Saccharomyces cerevisiae. DR GeneID; 856398; -. DR GenomeReviews; U00093_GR; YHR007C. DR KEGG; sce:YHR007C; -. DR NMPDR; fig|4932.3.peg.3015; -. DR CYGD; YHR007c; -. DR SGD; S000001049; ERG11. DR HOGENOM; P10614; -. DR OMA; P10614; NFVFPNL. DR BioCyc; MetaCyc:YHR007C-MON; -. DR BRENDA; 1.14.13.70; 250. 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 ArrayExpress; 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:0042802; F:identical protein binding; IPI:IntAct. 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 1: Evidence at protein level; KW Complete proteome; Heme; Iron; Lipid synthesis; Membrane; KW Metal-binding; Monooxygenase; NADP; Oxidoreductase; Phosphoprotein; KW Steroid biosynthesis; Sterol biosynthesis; Transmembrane. FT CHAIN 1 530 Lanosterol 14-alpha demethylase. FT /FTId=PRO_0000052012. FT TOPO_DOM 1 20 Extracellular (Potential). FT TRANSMEM 21 41 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 //