ERG7_YEAST
ID ERG7_YEAST Reviewed; 731 AA.
AC P38604; D3DL21; Q92327;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 6.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Lanosterol synthase ERG7 {ECO:0000303|PubMed:8134375};
DE EC=5.4.99.7 {ECO:0000269|PubMed:12842197, ECO:0000269|PubMed:1731628};
DE AltName: Full=2,3-epoxysqualene--lanosterol cyclase ERG7 {ECO:0000303|PubMed:1731628};
DE AltName: Full=Ergosterol biosynthetic protein 7 {ECO:0000303|PubMed:8134375};
DE AltName: Full=Oxidosqualene--lanosterol cyclase ERG7 {ECO:0000303|PubMed:1731628};
DE Short=OSC {ECO:0000303|PubMed:1731628};
GN Name=ERG7 {ECO:0000303|PubMed:8134375}; OrderedLocusNames=YHR072W;
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, AND PROTEIN SEQUENCE OF 2-9.
RX PubMed=8134375; DOI=10.1073/pnas.91.6.2211;
RA Corey E.J., Matsuda S.P.T., Bartel B.;
RT "Molecular cloning, characterization, and overexpression of ERG7, the
RT Saccharomyces cerevisiae gene encoding lanosterol synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:2211-2215(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8041797; DOI=10.1073/pnas.91.15.7370;
RA Shi Z., Buntel C.J., Griffin J.H.;
RT "Isolation and characterization of the gene encoding 2,3-oxidosqualene-
RT lanosterol cyclase from Saccharomyces cerevisiae.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7370-7374(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT 359-GLU--LEU-731 DEL.
RC STRAIN=SGL9;
RA Griffin J.H., Buntel C.J., Siregar J.J.;
RT "Mutations in the oxidosqualene-lanosterol cyclase gene of Saccharomyces
RT cerevisiae.";
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP GENOME REANNOTATION, AND SEQUENCE REVISION TO 530.
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [7]
RP PROTEIN SEQUENCE OF 2-13, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP THR-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RA Bienvenut W.V., Peters C.;
RL Submitted (JUN-2005) to UniProtKB.
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=1731628; DOI=10.1016/0003-9861(92)90374-6;
RA Balliano G., Viola F., Ceruti M., Cattel L.;
RT "Characterization and partial purification of squalene-2,3-oxide cyclase
RT from Saccharomyces cerevisiae.";
RL Arch. Biochem. Biophys. 293:122-129(1992).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=11706015; DOI=10.1074/jbc.m104195200;
RA Milla P., Athenstaedt K., Viola F., Oliaro-Bosso S., Kohlwein S.D.,
RA Daum G., Balliano G.;
RT "Yeast oxidosqualene cyclase (Erg7p) is a major component of lipid
RT particles.";
RL J. Biol. Chem. 277:2406-2412(2002).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=12842197; DOI=10.1016/s1388-1981(03)00088-x;
RA Mo C., Milla P., Athenstaedt K., Ott R., Balliano G., Daum G., Bard M.;
RT "In yeast sterol biosynthesis the 3-keto reductase protein (Erg27p) is
RT required for oxidosqualene cyclase (Erg7p) activity.";
RL Biochim. Biophys. Acta 1633:68-74(2003).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [12]
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 [13]
RP FUNCTION, AND MUTAGENESIS OF CYS-457 AND GLU-526.
RX PubMed=16235265; DOI=10.1002/cbic.200500107;
RA Oliaro-Bosso S., Schulz-Gasch T., Balliano G., Viola F.;
RT "Access of the substrate to the active site of yeast oxidosqualene cyclase:
RT an inhibition and site-directed mutagenesis approach.";
RL ChemBioChem 6:2221-2228(2005).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
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).
CC -!- FUNCTION: Lanosterol synthase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway
CC (PubMed:1731628, PubMed:12842197, PubMed:16235265). ERG7 catalyzes the
CC cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that
CC forms the sterol core (PubMed:1731628, PubMed:12842197). The third
CC module or late pathway involves the ergosterol synthesis itself through
CC consecutive reactions that mainly occur in the endoplasmic reticulum
CC (ER) membrane. Firstly, the squalene synthase ERG9 catalyzes the
CC condensation of 2 farnesyl pyrophosphate moieties to form squalene,
CC which is the precursor of all steroids. Squalene synthase is crucial
CC for balancing the incorporation of farnesyl diphosphate (FPP) into
CC sterol and nonsterol isoprene synthesis. Secondly, the squalene
CC epoxidase ERG1 catalyzes the stereospecific oxidation of squalene to
CC (S)-2,3-epoxysqualene, which is considered to be a rate-limiting enzyme
CC in steroid biosynthesis. Then, the lanosterol synthase ERG7 catalyzes
CC the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that
CC forms the sterol core. In the next steps, lanosterol is transformed to
CC zymosterol through a complex process involving various demethylation,
CC reduction and desaturation reactions. The lanosterol 14-alpha-
CC demethylase ERG11 (also known as CYP51) catalyzes C14-demethylation of
CC lanosterol to produce 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol,
CC which is critical for ergosterol biosynthesis. The C-14 reductase ERG24
CC reduces the C14=C15 double bond of 4,4-dimethyl-cholesta-8,14,24-
CC trienol to produce 4,4-dimethyl-cholesta-8,24-dienol. 4,4-dimethyl-
CC cholesta-8,24-dienol is substrate of the C-4 demethylation complex
CC ERG25-ERG26-ERG27 in which ERG25 catalyzes the three-step
CC monooxygenation required for the demethylation of 4,4-dimethyl and
CC 4alpha-methylsterols, ERG26 catalyzes the oxidative decarboxylation
CC that results in a reduction of the 3-beta-hydroxy group at the C-3
CC carbon to an oxo group, and ERG27 is responsible for the reduction of
CC the keto group on the C-3. ERG28 has a role as a scaffold to help
CC anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum and ERG29
CC regulates the activity of the iron-containing C4-methylsterol oxidase
CC ERG25. Then, the sterol 24-C-methyltransferase ERG6 catalyzes the
CC methyl transfer from S-adenosyl-methionine to the C-24 of zymosterol to
CC form fecosterol. The C-8 sterol isomerase ERG2 catalyzes the reaction
CC which results in unsaturation at C-7 in the B ring of sterols and thus
CC converts fecosterol to episterol. The sterol-C5-desaturase ERG3 then
CC catalyzes the introduction of a C-5 double bond in the B ring to
CC produce 5-dehydroepisterol. The C-22 sterol desaturase ERG5 further
CC converts 5-dehydroepisterol into ergosta-5,7,22,24(28)-tetraen-3beta-ol
CC by forming the C-22(23) double bond in the sterol side chain. Finally,
CC ergosta-5,7,22,24(28)-tetraen-3beta-ol is substrate of the C-24(28)
CC sterol reductase ERG4 to produce ergosterol (PubMed:32679672).
CC {ECO:0000269|PubMed:12842197, ECO:0000269|PubMed:16235265,
CC ECO:0000269|PubMed:1731628, ECO:0000303|PubMed:32679672}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2,3-epoxysqualene = lanosterol; Xref=Rhea:RHEA:14621,
CC ChEBI:CHEBI:15441, ChEBI:CHEBI:16521; EC=5.4.99.7;
CC Evidence={ECO:0000269|PubMed:12842197, ECO:0000269|PubMed:1731628};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14622;
CC Evidence={ECO:0000269|PubMed:12842197, ECO:0000269|PubMed:1731628};
CC -!- ACTIVITY REGULATION: Catalytic activity requires the presence of ERG27.
CC {ECO:0000269|PubMed:12842197}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7. {ECO:0000269|PubMed:1731628};
CC Temperature dependence:
CC Optimum temperature is 35 degrees Celsius.
CC {ECO:0000269|PubMed:1731628};
CC -!- PATHWAY: Terpene metabolism; lanosterol biosynthesis; lanosterol from
CC farnesyl diphosphate: step 3/3. {ECO:0000269|PubMed:12842197,
CC ECO:0000269|PubMed:1731628}.
CC -!- INTERACTION:
CC P38604; Q12452: ERG27; NbExp=4; IntAct=EBI-6572, EBI-38132;
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:11706015}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:11706015,
CC ECO:0000269|PubMed:14562095}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11706015}. Note=Predominantly in lipid particles.
CC {ECO:0000269|PubMed:11706015}.
CC -!- MISCELLANEOUS: Present with 2193 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the terpene cyclase/mutase family.
CC {ECO:0000305}.
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DR EMBL; U04841; AAA16975.1; -; Unassigned_DNA.
DR EMBL; U23488; AAA64377.1; -; Genomic_DNA.
DR EMBL; U60996; AAB08472.1; -; Genomic_DNA.
DR EMBL; U10556; AAB68891.1; -; Genomic_DNA.
DR EMBL; AY693043; AAT93062.1; -; Genomic_DNA.
DR EMBL; BK006934; DAA06765.2; -; Genomic_DNA.
DR PIR; S46813; S46813.
DR RefSeq; NP_011939.2; NM_001179202.2.
DR AlphaFoldDB; P38604; -.
DR SMR; P38604; -.
DR BioGRID; 36505; 287.
DR DIP; DIP-8319N; -.
DR IntAct; P38604; 19.
DR MINT; P38604; -.
DR STRING; 4932.YHR072W; -.
DR BindingDB; P38604; -.
DR ChEMBL; CHEMBL5355; -.
DR iPTMnet; P38604; -.
DR MaxQB; P38604; -.
DR PaxDb; P38604; -.
DR PRIDE; P38604; -.
DR EnsemblFungi; YHR072W_mRNA; YHR072W; YHR072W.
DR GeneID; 856470; -.
DR KEGG; sce:YHR072W; -.
DR SGD; S000001114; ERG7.
DR VEuPathDB; FungiDB:YHR072W; -.
DR eggNOG; KOG0497; Eukaryota.
DR GeneTree; ENSGT00390000011570; -.
DR HOGENOM; CLU_009074_2_1_1; -.
DR InParanoid; P38604; -.
DR OMA; CWARQTI; -.
DR BioCyc; MetaCyc:YHR072W-MON; -.
DR BioCyc; YEAST:YHR072W-MON; -.
DR Reactome; R-SCE-191273; Cholesterol biosynthesis.
DR SABIO-RK; P38604; -.
DR UniPathway; UPA00767; UER00753.
DR PRO; PR:P38604; -.
DR Proteomes; UP000002311; Chromosome VIII.
DR RNAct; P38604; protein.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; IDA:SGD.
DR GO; GO:0000250; F:lanosterol synthase activity; IMP:SGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IMP:SGD.
DR GO; GO:0016104; P:triterpenoid biosynthetic process; IEA:InterPro.
DR CDD; cd02892; SQCY_1; 1.
DR InterPro; IPR032696; SQ_cyclase_C.
DR InterPro; IPR032697; SQ_cyclase_N.
DR InterPro; IPR018333; Squalene_cyclase.
DR InterPro; IPR002365; Terpene_synthase_CS.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR PANTHER; PTHR11764; PTHR11764; 1.
DR Pfam; PF13243; SQHop_cyclase_C; 1.
DR Pfam; PF13249; SQHop_cyclase_N; 1.
DR SFLD; SFLDG01016; Prenyltransferase_Like_2; 1.
DR SUPFAM; SSF48239; SSF48239; 2.
DR TIGRFAMs; TIGR01787; squalene_cyclas; 1.
DR PROSITE; PS01074; TERPENE_SYNTHASES; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Endoplasmic reticulum; Isomerase;
KW Lipid biosynthesis; Lipid droplet; Lipid metabolism; Membrane;
KW Reference proteome; Repeat; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8134375, ECO:0000269|Ref.7"
FT CHAIN 2..731
FT /note="Lanosterol synthase ERG7"
FT /id="PRO_0000072657"
FT REPEAT 125..167
FT /note="PFTB 1"
FT /evidence="ECO:0000255"
FT REPEAT 615..661
FT /note="PFTB 2"
FT /evidence="ECO:0000255"
FT ACT_SITE 456
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P48449"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000269|Ref.7"
FT VARIANT 359..731
FT /note="Missing (in strain: SGL9; loss of activity)"
FT /evidence="ECO:0000269|Ref.3"
FT MUTAGEN 457
FT /note="C->D: Reduces thermal stability and enzyme activity;
FT when associated with A-526 or C-526. No effect; when
FT associated with D-526 or Q-526."
FT /evidence="ECO:0000269|PubMed:16235265"
FT MUTAGEN 526
FT /note="E->A,C: Reduces thermal stability and enzyme
FT activity; when associated with D-457."
FT /evidence="ECO:0000269|PubMed:16235265"
FT MUTAGEN 526
FT /note="E->D,Q: No effect; when associated with D-457."
FT /evidence="ECO:0000269|PubMed:16235265"
FT CONFLICT 61
FT /note="H -> N (in Ref. 1; AAA16975)"
FT /evidence="ECO:0000305"
FT CONFLICT 530
FT /note="N -> D (in Ref. 1; AAA16975 and 4; AAB68891)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 731 AA; 83460 MW; 9CE85BE1A7F5F52A CRC64;
MTEFYSDTIG LPKTDPRLWR LRTDELGRES WEYLTPQQAA NDPPSTFTQW LLQDPKFPQP
HPERNKHSPD FSAFDACHNG ASFFKLLQEP DSGIFPCQYK GPMFMTIGYV AVNYIAGIEI
PEHERIELIR YIVNTAHPVD GGWGLHSVDK STVFGTVLNY VILRLLGLPK DHPVCAKARS
TLLRLGGAIG SPHWGKIWLS ALNLYKWEGV NPAPPETWLL PYSLPMHPGR WWVHTRGVYI
PVSYLSLVKF SCPMTPLLEE LRNEIYTKPF DKINFSKNRN TVCGVDLYYP HSTTLNIANS
LVVFYEKYLR NRFIYSLSKK KVYDLIKTEL QNTDSLCIAP VNQAFCALVT LIEEGVDSEA
FQRLQYRFKD ALFHGPQGMT IMGTNGVQTW DCAFAIQYFF VAGLAERPEF YNTIVSAYKF
LCHAQFDTEC VPGSYRDKRK GAWGFSTKTQ GYTVADCTAE AIKAIIMVKN SPVFSEVHHM
ISSERLFEGI DVLLNLQNIG SFEYGSFATY EKIKAPLAME TLNPAEVFGN IMVEYPYVEC
TDSSVLGLTY FHKYFDYRKE EIRTRIRIAI EFIKKSQLPD GSWYGSWGIC FTYAGMFALE
ALHTVGETYE NSSTVRKGCD FLVSKQMKDG GWGESMKSSE LHSYVDSEKS LVVQTAWALI
ALLFAEYPNK EVIDRGIDLL KNRQEESGEW KFESVEGVFN HSCAIEYPSY RFLFPIKALG
MYSRAYETHT L
