ERG2_YEAST
ID ERG2_YEAST Reviewed; 222 AA.
AC P32352; D6W027;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=C-8 sterol isomerase ERG2 {ECO:0000303|Ref.5};
DE EC=5.-.-.- {ECO:0000269|Ref.5};
DE AltName: Full=Delta-8--delta-7 sterol isomerase ERG2 {ECO:0000303|Ref.5};
DE AltName: Full=Ergosterol biosynthetic protein 2 {ECO:0000303|Ref.5};
GN Name=ERG2 {ECO:0000303|Ref.5}; OrderedLocusNames=YMR202W;
GN ORFNames=YM8325.03;
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=1743517; DOI=10.1016/0378-1119(91)90314-2;
RA Arthington B.A., Hoskins J.A., Skatrud P.L., Bard M.;
RT "Nucleotide sequence of the gene encoding yeast C-8 sterol isomerase.";
RL Gene 107:173-174(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169872;
RA Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL Nature 387:90-93(1997).
RN [3]
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 [4]
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX DOI=10.1016/S0031-9422(00)80523-3;
RA Baloch R.I., Mercer E.I., Wiggins T.E., Baldwin B.C.;
RT "Inhibition of ergosterol biosynthesis of Saccharomyces cereviriae and
RT Ustago maydis by tridemorph, fenpropimorph, and fenpropidin.";
RL Phytochemistry 23:2219-2226(1984).
RN [6]
RP INDUCTION.
RX PubMed=10734216; DOI=10.1016/s0014-5793(00)01300-4;
RA Soustre I., Dupuy P.H., Silve S., Karst F., Loison G.;
RT "Sterol metabolism and ERG2 gene regulation in the yeast Saccharomyces
RT cerevisiae.";
RL FEBS Lett. 470:102-106(2000).
RN [7]
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 [8]
RP SUBCELLULAR LOCATION.
RX PubMed=15716577; DOI=10.1074/mcp.m400123-mcp200;
RA Natter K., Leitner P., Faschinger A., Wolinski H., McCraith S., Fields S.,
RA Kohlwein S.D.;
RT "The spatial organization of lipid synthesis in the yeast Saccharomyces
RT cerevisiae derived from large scale green fluorescent protein tagging and
RT high resolution microscopy.";
RL Mol. Cell. Proteomics 4:662-672(2005).
RN [9]
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: C-8 sterol isomerase; part of the third module of ergosterol
CC biosynthesis pathway that includes the late steps of the pathway
CC (Ref.5). ERG2 catalyzes the reaction which results in unsaturation at
CC C-7 in the B ring of sterols and thus converts fecosterol to episterol
CC (Ref.5). The third module or late pathway involves the ergosterol
CC synthesis itself through consecutive reactions that mainly occur in the
CC endoplasmic reticulum (ER) membrane. Firstly, the squalene synthase
CC ERG9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to
CC form squalene, which is the precursor of all steroids. Squalene
CC synthase is crucial for balancing the incorporation of farnesyl
CC diphosphate (FPP) into sterol and nonsterol isoprene synthesis.
CC Secondly, the squalene epoxidase ERG1 catalyzes the stereospecific
CC oxidation of squalene to (S)-2,3-epoxysqualene, which is considered to
CC be a rate-limiting enzyme in steroid biosynthesis. Then, the lanosterol
CC synthase ERG7 catalyzes the cyclization of (S)-2,3 oxidosqualene to
CC lanosterol, a reaction that forms the sterol core. In the next steps,
CC lanosterol is transformed to zymosterol through a complex process
CC involving various demethylation, reduction and desaturation reactions.
CC The lanosterol 14-alpha-demethylase ERG11 (also known as CYP51)
CC catalyzes C14-demethylation of lanosterol to produce 4,4'-dimethyl
CC cholesta-8,14,24-triene-3-beta-ol, which is critical for ergosterol
CC biosynthesis. The C-14 reductase ERG24 reduces the C14=C15 double bond
CC of 4,4-dimethyl-cholesta-8,14,24-trienol to produce 4,4-dimethyl-
CC cholesta-8,24-dienol. 4,4-dimethyl-cholesta-8,24-dienol is substrate of
CC the C-4 demethylation complex ERG25-ERG26-ERG27 in which ERG25
CC catalyzes the three-step monooxygenation required for the demethylation
CC of 4,4-dimethyl and 4alpha-methylsterols, ERG26 catalyzes the oxidative
CC decarboxylation that results in a reduction of the 3-beta-hydroxy group
CC at the C-3 carbon to an oxo group, and ERG27 is responsible for the
CC reduction of the keto group on the C-3. ERG28 has a role as a scaffold
CC to help anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum and
CC ERG29 regulates the activity of the iron-containing C4-methylsterol
CC oxidase ERG25. Then, the sterol 24-C-methyltransferase ERG6 catalyzes
CC the methyl transfer from S-adenosyl-methionine to the C-24 of
CC zymosterol to form fecosterol. The C-8 sterol isomerase ERG2 catalyzes
CC the reaction which results in unsaturation at C-7 in the B ring of
CC sterols and thus converts fecosterol to episterol. The sterol-C5-
CC desaturase ERG3 then catalyzes the introduction of a C-5 double bond in
CC the B ring to produce 5-dehydroepisterol. The C-22 sterol desaturase
CC ERG5 further converts 5-dehydroepisterol into ergosta-5,7,22,24(28)-
CC tetraen-3beta-ol by forming the C-22(23) double bond in the sterol side
CC chain. Finally, ergosta-5,7,22,24(28)-tetraen-3beta-ol is substrate of
CC the C-24(28) sterol reductase ERG4 to produce ergosterol
CC (PubMed:32679672). {ECO:0000269|Ref.5, ECO:0000303|PubMed:32679672}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=fecosterol = episterol; Xref=Rhea:RHEA:33435,
CC ChEBI:CHEBI:17038, ChEBI:CHEBI:23929; Evidence={ECO:0000269|Ref.5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33436;
CC Evidence={ECO:0000269|Ref.5};
CC -!- ACTIVITY REGULATION: Catalytic activity is inhibited by the morphilines
CC tridemorph, fenpropimorph, and fenpropidin. {ECO:0000269|Ref.5}.
CC -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis; ergosterol from
CC zymosterol: step 2/5. {ECO:0000269|Ref.5}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15716577}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- INDUCTION: Expression is increased during ergosterol starvation, during
CC anaerobic growth or in the presence of SR31747A, a sterol isomerase
CC inhibitor (PubMed:10734216). Exogenously-supplied zymosterol is
CC entirely transformed into ergosterol, which represses ERG2 expression
CC (PubMed:10734216). However, exogenously-supplied ergosterol does not
CC affect ERG2 expression (PubMed:10734216).
CC {ECO:0000269|PubMed:10734216}.
CC -!- MISCELLANEOUS: Present with 2640 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the ERG2 family. {ECO:0000305}.
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DR EMBL; M74037; AAA34593.1; -; Genomic_DNA.
DR EMBL; Z48755; CAA88643.1; -; Genomic_DNA.
DR EMBL; AY558122; AAS56448.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA10101.1; -; Genomic_DNA.
DR PIR; JH0488; JH0488.
DR RefSeq; NP_013929.1; NM_001182709.1.
DR AlphaFoldDB; P32352; -.
DR SMR; P32352; -.
DR BioGRID; 35380; 451.
DR DIP; DIP-5068N; -.
DR IntAct; P32352; 7.
DR STRING; 4932.YMR202W; -.
DR BindingDB; P32352; -.
DR ChEMBL; CHEMBL3224; -.
DR DrugCentral; P32352; -.
DR MaxQB; P32352; -.
DR PaxDb; P32352; -.
DR PRIDE; P32352; -.
DR TopDownProteomics; P32352; -.
DR EnsemblFungi; YMR202W_mRNA; YMR202W; YMR202W.
DR GeneID; 855242; -.
DR KEGG; sce:YMR202W; -.
DR SGD; S000004815; ERG2.
DR VEuPathDB; FungiDB:YMR202W; -.
DR eggNOG; KOG4143; Eukaryota.
DR HOGENOM; CLU_085469_0_0_1; -.
DR InParanoid; P32352; -.
DR OMA; WKTTRIT; -.
DR BioCyc; MetaCyc:YMR202W-MON; -.
DR BioCyc; YEAST:YMR202W-MON; -.
DR UniPathway; UPA00768; UER00761.
DR PRO; PR:P32352; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; P32352; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0000247; F:C-8 sterol isomerase activity; IMP:SGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IMP:SGD.
DR InterPro; IPR006716; ERG2_sigma1_rcpt-like.
DR PANTHER; PTHR10868; PTHR10868; 1.
DR Pfam; PF04622; ERG2_Sigma1R; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Isomerase; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..222
FT /note="C-8 sterol isomerase ERG2"
FT /id="PRO_0000087021"
FT TRANSMEM 3..23
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 222 AA; 24896 MW; 9E17143542DDBB75 CRC64;
MKFFPLLLLI GVVGYIMNVL FTTWLPTNYM FDPKTLNEIC NSVISKHNAA EGLSTEDLLQ
DVRDALASHY GDEYINRYVK EEWVFNNAGG AMGQMIILHA SVSEYLILFG TAVGTEGHTG
VHFADDYFTI LHGTQIAALP YATEAEVYTP GMTHHLKKGY AKQYSMPGGS FALELAQGWI
PCMLPFGFLD TFSSTLDLYT LYRTVYLTAR DMGKNLLQNK KF
