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   27-MAR-2024, entry version 213.
DE   RecName: Full=Lanosterol 14-alpha demethylase CYP51 {ECO:0000303|PubMed:369554};
DE            EC=1.14.14.154 {ECO:0000269|PubMed:105731, ECO:0000269|PubMed:369554, ECO:0000305|PubMed:3543000};
DE   AltName: Full=Cytochrome P450 51 {ECO:0000305};
DE   AltName: Full=Cytochrome P450-14DM {ECO:0000303|PubMed:3046615, ECO:0000303|PubMed:3543000};
DE   AltName: Full=Cytochrome P450-LIA1 {ECO:0000303|PubMed:3322742};
DE            Short=CYPLI {ECO:0000303|PubMed:3322742};
DE   AltName: Full=Ergosterol biosynthetic protein 11 {ECO:0000303|PubMed:1730736};
DE   AltName: Full=Lanosterol C14-C32 lyase {ECO:0000303|PubMed:3543000};
DE   AltName: Full=Sterol 14-alpha demethylase {ECO:0000305};
GN   Name=ERG11 {ECO:0000303|PubMed:1730736}; Synonyms=CYP51;
GN   OrderedLocusNames=YHR007C;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3322742; DOI=10.1089/dna.1987.6.529;
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., Sprinson D.B.,
RA   Yoshida Y.;
RT   "A single amino acid substitution converts cytochrome P450(14DM) to an
RT   inactive form, cytochrome P450SG1: complete primary structures deduced from
RT   cloned DNAS.";
RL   Biochem. Biophys. Res. Commun. 155:317-323(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8091229; DOI=10.1126/science.8091229;
RA   Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z.,
RA   Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T.,
RA   Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P., Louis E.J.,
RA   Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L.,
RA   St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P.,
RA   Waterston R., Wilson R., 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;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
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   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=369554; DOI=10.1016/s0006-291x(78)80005-9;
RA   Ohba M., Sato R., Yoshida Y., Nishino T., Katsuki H.;
RT   "Involvement of cytochrome P-450 and a cyanide-sensitive enzyme in
RT   different steps of lanosterol demethylation by yeast microsomes.";
RL   Biochem. Biophys. Res. Commun. 85:21-27(1978).
RN   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=105731; DOI=10.1016/s0006-291x(78)80006-0;
RA   Aoyama Y., Yoshida Y.;
RT   "The 14alpha-demethylation of lanosterol by a reconstituted cytochrome P-
RT   450 system from yeast microsomes.";
RL   Biochem. Biophys. Res. Commun. 85:28-34(1978).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=3543000; DOI=10.1016/s0021-9258(19)75777-9;
RA   Aoyama Y., Yoshida Y., Sonoda Y., Sato Y.;
RT   "Metabolism of 32-hydroxy-24,25-dihydrolanosterol by purified cytochrome P-
RT   45014DM from yeast. Evidence for contribution of the cytochrome to whole
RT   process of lanosterol 14 alpha-demethylation.";
RL   J. Biol. Chem. 262:1239-1243(1987).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=1872829; DOI=10.1016/0006-291x(91)91000-3;
RA   Aoyama Y., Yoshida Y.;
RT   "Different substrate specificities of lanosterol 14a-demethylase (P-
RT   45014DM) of Saccharomyces cerevisiae and rat liver for 24-methylene-24,25-
RT   dihydrolanosterol and 24,25-dihydrolanosterol.";
RL   Biochem. Biophys. Res. Commun. 178:1064-1071(1991).
RN   [10]
RP   INDUCTION.
RX   PubMed=1730736; DOI=10.1016/s0021-9258(18)46051-6;
RA   Turi T.G., Loper J.C.;
RT   "Multiple regulatory elements control expression of the gene encoding the
RT   Saccharomyces cerevisiae cytochrome P450, lanosterol 14 alpha-demethylase
RT   (ERG11).";
RL   J. Biol. Chem. 267:2046-2056(1992).
RN   [11]
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., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [12]
RP   FUNCTION, AND 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 complex.";
RL   J. Lipid Res. 46:1991-1998(2005).
RN   [13]
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 proteome.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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   [15]
RP   UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-116; LYS-353 AND LYS-454, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22106047; DOI=10.1002/pmic.201100166;
RA   Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT   "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL   Proteomics 12:236-240(2012).
RN   [16]
RP   REVIEW ON ERGOSTEROL BIOSYNTHESIS.
RX   PubMed=32679672; DOI=10.3390/genes11070795;
RA   Jorda T., Puig S.;
RT   "Regulation of ergosterol biosynthesis in Saccharomyces cerevisiae.";
RL   Genes (Basel) 11:0-0(2020).
RN   [17] {ECO:0007744|PDB:4LXJ, ECO:0007744|PDB:5EQB}
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH HEME, SUBCELLULAR
RP   LOCATION, AND TOPOLOGY.
RX   PubMed=24613931; DOI=10.1073/pnas.1324245111;
RA   Monk B.C., Tomasiak T.M., Keniya M.V., Huschmann F.U., Tyndall J.D.,
RA   O'Connell J.D. III, Cannon R.D., McDonald J.G., Rodriguez A.,
RA   Finer-Moore J.S., Stroud R.M.;
RT   "Architecture of a single membrane spanning cytochrome P450 suggests
RT   constraints that orient the catalytic domain relative to a bilayer.";
RL   Proc. Natl. Acad. Sci. U.S.A. 111:3865-3870(2014).
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 (PubMed:369554, PubMed:105731). The third module
CC       or late pathway involves the ergosterol synthesis itself through
CC       consecutive reactions that mainly occur in the endoplasmic reticulum
CC       (ER) membrane (PubMed:32679672). Starting from lanosterol
CC       (lanosta-8,24-dien-3beta-ol), it catalyzes the three-step oxidative
CC       removal of the 14alpha-methyl group (C-32) of the sterol in the form of
CC       formate, and converts the sterol to 4,4-dimethyl-5alpha-
CC       cholesta-8,14,24-trien-3beta-ol, which is critical for ergosterol
CC       biosynthesis (PubMed:369554, PubMed:105731, PubMed:3543000). Can
CC       demethylate substrates not intrinsic to yeast, such as eburicol (24-
CC       methylene-24,25-dihydrolanosterol) at a similar rate to lanosterol, and
CC       at a lower rate the 24,25-dihydrolanosterol (DHL) to 4,4-dimethyl-8,14-
CC       cholestadien-3beta-ol (PubMed:3543000, PubMed:1872829).
CC       {ECO:0000269|PubMed:105731, ECO:0000269|PubMed:1872829,
CC       ECO:0000269|PubMed:3543000, ECO:0000269|PubMed:369554,
CC       ECO:0000303|PubMed:32679672}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 14alpha-methyl steroid + 3 O2 + 3 reduced
CC         [NADPH--hemoprotein reductase] = a Delta(14) steroid + formate + 4
CC         H(+) + 4 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         Evidence={ECO:0000269|PubMed:105731, ECO:0000269|PubMed:1872829,
CC         ECO:0000269|PubMed:3543000, ECO:0000269|PubMed:369554};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029;
CC         Evidence={ECO:0000269|PubMed:105731, ECO:0000269|PubMed:1872829,
CC         ECO:0000269|PubMed:3543000, ECO:0000269|PubMed:369554};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 14alpha-methyl steroid + O2 + reduced [NADPH--hemoprotein
CC         reductase] = a 14alpha-hydroxymethyl steroid + H(+) + H2O + oxidized
CC         [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68060, Rhea:RHEA-
CC         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:0000269|PubMed:3543000};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68061;
CC         Evidence={ECO:0000269|PubMed:3543000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 14alpha-hydroxymethyl steroid + O2 + reduced
CC         [NADPH--hemoprotein reductase] = a 14alpha-formyl steroid + H(+) + 2
CC         H2O + oxidized [NADPH--hemoprotein reductase]; 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:0000269|PubMed:3543000};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68065;
CC         Evidence={ECO:0000269|PubMed:3543000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 14alpha-formyl steroid + O2 + reduced [NADPH--hemoprotein
CC         reductase] = a Delta(14) steroid + formate + 2 H(+) + H2O + oxidized
CC         [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:68068, 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:138031,
CC         ChEBI:CHEBI:176902; Evidence={ECO:0000269|PubMed:3543000};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68069;
CC         Evidence={ECO:0000269|PubMed:3543000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=lanosterol + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] =
CC         4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 4
CC         H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase];
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:0000269|PubMed:105731, ECO:0000269|PubMed:1872829,
CC         ECO:0000269|PubMed:369554, ECO:0000305|PubMed:3543000};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25287;
CC         Evidence={ECO:0000269|PubMed:105731, ECO:0000269|PubMed:1872829,
CC         ECO:0000269|PubMed:369554, ECO:0000305|PubMed:3543000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=lanosterol + O2 + reduced [NADPH--hemoprotein reductase] = 32-
CC         hydroxylanosterol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; 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:0000305|PubMed:3543000};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75104;
CC         Evidence={ECO:0000305|PubMed:3543000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=32-hydroxylanosterol + O2 + reduced [NADPH--hemoprotein
CC         reductase] = 32-oxolanosterol + H(+) + 2 H2O + oxidized
CC         [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:75107, Rhea:RHEA-
CC         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:166681, ChEBI:CHEBI:166806;
CC         Evidence={ECO:0000305|PubMed:3543000};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75108;
CC         Evidence={ECO:0000305|PubMed:3543000};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=32-oxolanosterol + O2 + reduced [NADPH--hemoprotein reductase]
CC         = 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 2
CC         H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
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:0000305|PubMed:3543000};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:75112;
CC         Evidence={ECO:0000305|PubMed:3543000};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000269|PubMed:24613931};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=6.7 uM for lanosterol {ECO:0000269|PubMed:1872829};
CC         KM=8.7 uM for eburicol {ECO:0000269|PubMed:1872829};
CC         Vmax=11.8 nmol/min/nmol enzyme with lanosterol
CC         {ECO:0000269|PubMed:1872829};
CC         Vmax=16.7 nmol/min/nmol enzyme with eburicol
CC         {ECO:0000269|PubMed:1872829};
CC   -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC       lanosterol: step 1/6. {ECO:0000269|PubMed:105731,
CC       ECO:0000269|PubMed:369554}.
CC   -!- SUBUNIT: Interacts with ERG28. {ECO:0000269|PubMed:15995173}.
CC   -!- INTERACTION:
CC       P10614; P53045: ERG25; NbExp=3; IntAct=EBI-5127, EBI-6506;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC       Single-pass membrane protein {ECO:0000269|PubMed:16847258,
CC       ECO:0000269|PubMed:24613931}.
CC   -!- INDUCTION: Expression is increased during growth on glucose, in the
CC       presence of heme, and during oxygen limiting growth conditions and,
CC       unexpectedly, during anaerobic growth (PubMed:1730736). Two upstream
CC       activating sequences, UASl and UASZ, and an upstream repressor element,
CC       URS1, plus a second possible or cryptic repressor element, URSP, are
CC       present in promoter (PubMed:1730736). HAP1 participates in activation
CC       from UASl but not from UAS2, whereas the ROXl repressor represses
CC       expressio of ERG11 (PubMed:1730736). {ECO:0000269|PubMed:1730736}.
CC   -!- MISCELLANEOUS: It is the main target for antifungal compounds of the
CC       triazole family like ketoconazole which inhibits by coordinating the
CC       iron atom at the sixth ligand position. {ECO:0000305}.
CC   -!- MISCELLANEOUS: Present with 73200 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; M18109; AAA34379.1; -; Genomic_DNA.
DR   EMBL; M15663; AAA34837.2; -; 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   PDB; 4LXJ; X-ray; 1.90 A; A=1-530.
DR   PDB; 5EQB; X-ray; 2.19 A; A=1-530.
DR   PDB; 7RY8; X-ray; 1.98 A; A=1-530.
DR   PDB; 7RY9; X-ray; 2.40 A; A=1-530.
DR   PDB; 7RYA; X-ray; 2.10 A; A=1-530.
DR   PDB; 7RYB; X-ray; 2.90 A; A=1-530.
DR   PDB; 7RYX; X-ray; 2.10 A; A=1-530.
DR   PDB; 8DL4; X-ray; 1.91 A; A=1-530.
DR   PDBsum; 4LXJ; -.
DR   PDBsum; 5EQB; -.
DR   PDBsum; 7RY8; -.
DR   PDBsum; 7RY9; -.
DR   PDBsum; 7RYA; -.
DR   PDBsum; 7RYB; -.
DR   PDBsum; 7RYX; -.
DR   PDBsum; 8DL4; -.
DR   AlphaFoldDB; P10614; -.
DR   SMR; P10614; -.
DR   BioGRID; 36434; 505.
DR   DIP; DIP-7886N; -.
DR   IntAct; P10614; 73.
DR   MINT; P10614; -.
DR   STRING; 4932.YHR007C; -.
DR   DrugBank; DB06890; (2R)-2-PHENYL-N-PYRIDIN-4-YLBUTANAMIDE.
DR   DrugBank; DB07568; (2S)-2-[(2,1,3-BENZOTHIADIAZOL-4-YLSULFONYL)AMINO]-2-PHENYL-N-PYRIDIN-4-YLACETAMIDE.
DR   DrugBank; DB07572; 3-{[(4-methylphenyl)sulfonyl]amino}propyl pyridin-4-ylcarbamate.
DR   DrugBank; DB07635; 4,4'-Dihydroxybenzophenone.
DR   DrugBank; DB07569; CIS-4-METHYL-N-[(1S)-3-(METHYLSULFANYL)-1-(PYRIDIN-4-YLCARBAMOYL)PROPYL]CYCLOHEXANECARBOXAMIDE.
DR   DrugBank; DB07560; N-[(1S)-2-methyl-1-(pyridin-4-ylcarbamoyl)propyl]cyclohexanecarboxamide.
DR   iPTMnet; P10614; -.
DR   MaxQB; P10614; -.
DR   PaxDb; 4932-YHR007C; -.
DR   PeptideAtlas; P10614; -.
DR   TopDownProteomics; P10614; -.
DR   EnsemblFungi; YHR007C_mRNA; YHR007C; YHR007C.
DR   GeneID; 856398; -.
DR   KEGG; sce:YHR007C; -.
DR   AGR; SGD:S000001049; -.
DR   SGD; S000001049; ERG11.
DR   VEuPathDB; FungiDB:YHR007C; -.
DR   eggNOG; KOG0684; Eukaryota.
DR   GeneTree; ENSGT00930000151026; -.
DR   HOGENOM; CLU_001570_15_0_1; -.
DR   InParanoid; P10614; -.
DR   OMA; AWTLIEL; -.
DR   OrthoDB; 5474434at2759; -.
DR   BioCyc; MetaCyc:YHR007C-MONOMER; -.
DR   BioCyc; YEAST:YHR007C-MONOMER; -.
DR   BRENDA; 1.14.14.154; 984.
DR   Reactome; R-SCE-191273; Cholesterol biosynthesis.
DR   Reactome; R-SCE-211976; Endogenous sterols.
DR   UniPathway; UPA00770; UER00754.
DR   BioGRID-ORCS; 856398; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P10614; -.
DR   Proteomes; UP000002311; Chromosome VIII.
DR   RNAct; P10614; Protein.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR   GO; GO:0005789; C:endoplasmic reticulum 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:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR   GO; GO:0008398; F:sterol 14-demethylase activity; IDA:SGD.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IDA:UniProt.
DR   CDD; cd11042; CYP51-like; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 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   PANTHER; PTHR24286; CYTOCHROME P450 26; 1.
DR   PANTHER; PTHR24286:SF24; LANOSTEROL 14-ALPHA DEMETHYLASE; 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   1: Evidence at protein level;
KW   3D-structure; Endoplasmic reticulum; Heme; Iron; Isopeptide bond;
KW   Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding;
KW   Monooxygenase; Oxidoreductase; Phosphoprotein; Reference proteome;
KW   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism; Transmembrane; Transmembrane helix; Ubl conjugation.
FT   CHAIN           1..530
FT                   /note="Lanosterol 14-alpha demethylase CYP51"
FT                   /id="PRO_0000052012"
FT   TOPO_DOM        1..20
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000269|PubMed:16847258,
FT                   ECO:0000269|PubMed:24613931"
FT   TRANSMEM        21..41
FT                   /note="Helical"
FT                   /evidence="ECO:0000269|PubMed:16847258,
FT                   ECO:0000269|PubMed:24613931"
FT   TOPO_DOM        42..530
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000269|PubMed:16847258,
FT                   ECO:0000269|PubMed:24613931"
FT   BINDING         126
FT                   /ligand="lanosterol"
FT                   /ligand_id="ChEBI:CHEBI:16521"
FT                   /evidence="ECO:0000269|PubMed:24613931,
FT                   ECO:0007744|PDB:4LXJ"
FT   BINDING         314
FT                   /ligand="itraconazole"
FT                   /ligand_id="ChEBI:CHEBI:6076"
FT                   /evidence="ECO:0000269|PubMed:24613931,
FT                   ECO:0007744|PDB:5EQB"
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                   /evidence="ECO:0000269|PubMed:24613931,
FT                   ECO:0007744|PDB:4LXJ, ECO:0007744|PDB:5EQB"
FT   MOD_RES         458
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17330950"
FT   CROSSLNK        116
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0007744|PubMed:22106047"
FT   CROSSLNK        353
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0007744|PubMed:22106047"
FT   CROSSLNK        454
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0007744|PubMed:22106047"
FT   CONFLICT        433
FT                   /note="K -> N (in Ref. 2; AAA34546/AAA34547)"
FT                   /evidence="ECO:0000305"
FT   HELIX           9..23
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           27..49
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          53..55
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   TURN            64..66
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           69..74
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           76..87
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          89..95
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          98..103
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           105..113
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   TURN            117..119
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           122..134
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          136..138
FT                   /evidence="ECO:0007829|PDB:7RYX"
FT   HELIX           144..155
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           160..180
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   TURN            182..184
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   TURN            186..188
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          190..195
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           196..212
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           215..220
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           225..234
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           238..242
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          243..245
FT                   /evidence="ECO:0007829|PDB:7RYB"
FT   HELIX           249..274
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          280..282
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           283..289
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           301..331
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           334..347
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           349..351
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           357..360
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           364..376
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          383..387
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          394..397
FT                   /evidence="ECO:0007829|PDB:7RYB"
FT   STRAND          405..408
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           410..413
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   TURN            417..419
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   TURN            421..424
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           428..431
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          444..449
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          451..454
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           466..468
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   HELIX           473..490
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          491..494
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          507..510
FT                   /evidence="ECO:0007829|PDB:4LXJ"
FT   STRAND          518..525
FT                   /evidence="ECO:0007829|PDB:4LXJ"
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
//