ID   GSHR_YEAST              Reviewed;         483 AA.
AC   P41921; D6W3S6;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   27-MAR-2024, entry version 203.
DE   RecName: Full=Glutathione reductase {ECO:0000303|PubMed:7737505};
DE            Short=GR {ECO:0000303|PubMed:7737505};
DE            Short=GRase {ECO:0000303|PubMed:7737505};
DE            EC=1.8.1.7 {ECO:0000269|PubMed:7737505};
GN   Name=GLR1 {ECO:0000303|PubMed:7737505}; OrderedLocusNames=YPL091W;
GN   ORFNames=LPG17W;
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] OF 17-483, FUNCTION, DISRUPTION
RP   PHENOTYPE, AND CATALYTIC ACTIVITY.
RX   PubMed=7737505; DOI=10.1016/0378-1119(95)00026-3;
RA   Collinson L.P., Dawes I.W.;
RT   "Isolation, characterization and overexpression of the yeast gene, GLR1,
RT   encoding glutathione reductase.";
RL   Gene 156:123-127(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169875;
RA   Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W.,
RA   Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D.,
RA   Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E.,
RA   Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H.,
RA   DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N.,
RA   Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K.,
RA   Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M.,
RA   Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A.,
RA   Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S.,
RA   Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D.,
RA   Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S.,
RA   Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B.,
RA   Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A.,
RA   Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R.,
RA   Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A.,
RA   Vo D.H., Hani J.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.";
RL   Nature 387:103-105(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 OF 20-483.
RA   Aono M., Nakajima N.;
RL   Submitted (AUG-1994) to the EMBL/GenBank/DDBJ databases.
RN   [5]
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   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [7]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, ACETYLATION [LARGE SCALE
RP   ANALYSIS] AT SER-2 (ISOFORM 2), CLEAVAGE OF INITIATOR METHIONINE [LARGE
RP   SCALE ANALYSIS] (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP   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   [8] {ECO:0007744|PDB:2HQM}
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 16-483 IN COMPLEX WITH FAD AND
RP   GLUTATHIONE, AND GLYCOSYLATION AT ASN-278.
RX   PubMed=17554778; DOI=10.1002/prot.21354;
RA   Yu J., Zhou C.Z.;
RT   "Crystal structure of glutathione reductase Glr1 from the yeast
RT   Saccharomyces cerevisiae.";
RL   Proteins 68:972-979(2007).
CC   -!- FUNCTION: Maintains high levels of reduced glutathione in the cytosol.
CC       {ECO:0000269|PubMed:7737505}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 glutathione + NADP(+) = glutathione disulfide + H(+) +
CC         NADPH; Xref=Rhea:RHEA:11740, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:58349; EC=1.8.1.7;
CC         Evidence={ECO:0000269|PubMed:7737505};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:O52582};
CC       Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:O52582};
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=1;
CC         IsoId=P41921-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P41921-2; Sequence=VSP_058124;
CC   -!- DISRUPTION PHENOTYPE: Impairs glutathione reductase activity.
CC       {ECO:0000269|PubMed:7737505}.
CC   -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC   -!- MISCELLANEOUS: Present with 7600 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC       oxidoreductase family. {ECO:0000305}.
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DR   EMBL; L35342; AAA92575.1; -; Genomic_DNA.
DR   EMBL; U43281; AAB68208.1; -; Genomic_DNA.
DR   EMBL; D37871; BAA07109.1; -; mRNA.
DR   EMBL; BK006949; DAA11342.1; -; Genomic_DNA.
DR   PIR; S61975; S61975.
DR   RefSeq; NP_015234.1; NM_001183905.1. [P41921-1]
DR   PDB; 2HQM; X-ray; 2.40 A; A/B=17-483.
DR   PDBsum; 2HQM; -.
DR   AlphaFoldDB; P41921; -.
DR   SMR; P41921; -.
DR   BioGRID; 36090; 96.
DR   DIP; DIP-4020N; -.
DR   IntAct; P41921; 3.
DR   MINT; P41921; -.
DR   STRING; 4932.YPL091W; -.
DR   BindingDB; P41921; -.
DR   ChEMBL; CHEMBL4119; -.
DR   DrugCentral; P41921; -.
DR   GlyCosmos; P41921; 1 site, No reported glycans.
DR   GlyGen; P41921; 1 site.
DR   iPTMnet; P41921; -.
DR   MaxQB; P41921; -.
DR   PaxDb; 4932-YPL091W; -.
DR   PeptideAtlas; P41921; -.
DR   EnsemblFungi; YPL091W_mRNA; YPL091W; YPL091W. [P41921-1]
DR   GeneID; 856014; -.
DR   KEGG; sce:YPL091W; -.
DR   AGR; SGD:S000006012; -.
DR   SGD; S000006012; GLR1.
DR   VEuPathDB; FungiDB:YPL091W; -.
DR   eggNOG; KOG0405; Eukaryota.
DR   GeneTree; ENSGT00940000156986; -.
DR   HOGENOM; CLU_016755_2_2_1; -.
DR   InParanoid; P41921; -.
DR   OMA; MSKHYDY; -.
DR   OrthoDB; 5473641at2759; -.
DR   BioCyc; YEAST:YPL091W-MONOMER; -.
DR   BRENDA; 1.8.1.7; 984.
DR   Reactome; R-SCE-3299685; Detoxification of Reactive Oxygen Species.
DR   Reactome; R-SCE-499943; Interconversion of nucleotide di- and triphosphates.
DR   Reactome; R-SCE-5628897; TP53 Regulates Metabolic Genes.
DR   BioGRID-ORCS; 856014; 0 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P41921; -.
DR   PRO; PR:P41921; -.
DR   Proteomes; UP000002311; Chromosome XVI.
DR   RNAct; P41921; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005829; C:cytosol; IDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR   GO; GO:0005634; C:nucleus; IDA:SGD.
DR   GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR   GO; GO:0004362; F:glutathione-disulfide reductase (NADP) activity; IDA:SGD.
DR   GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR   GO; GO:0045454; P:cell redox homeostasis; IMP:SGD.
DR   GO; GO:0034599; P:cellular response to oxidative stress; IMP:SGD.
DR   GO; GO:0006749; P:glutathione metabolic process; IMP:SGD.
DR   GO; GO:0010731; P:protein glutathionylation; IGI:SGD.
DR   Gene3D; 3.30.390.30; -; 1.
DR   Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 2.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR023753; FAD/NAD-binding_dom.
DR   InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer_sf.
DR   InterPro; IPR006322; Glutathione_Rdtase_euk/bac.
DR   InterPro; IPR046952; GSHR/TRXR-like.
DR   InterPro; IPR001100; Pyr_nuc-diS_OxRdtase.
DR   InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR   InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR   NCBIfam; TIGR01421; gluta_reduc_1; 1.
DR   PANTHER; PTHR42737; GLUTATHIONE REDUCTASE; 1.
DR   PANTHER; PTHR42737:SF2; GLUTATHIONE REDUCTASE; 1.
DR   Pfam; PF07992; Pyr_redox_2; 1.
DR   Pfam; PF02852; Pyr_redox_dim; 1.
DR   PIRSF; PIRSF000350; Mercury_reductase_MerA; 1.
DR   PRINTS; PR00368; FADPNR.
DR   PRINTS; PR00411; PNDRDTASEI.
DR   SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1.
DR   SUPFAM; SSF55424; FAD/NAD-linked reductases, dimerisation (C-terminal) domain; 1.
DR   PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
DR   COMPLUYEAST-2DPAGE; P41921; -.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Alternative initiation; Cytoplasm; FAD;
KW   Flavoprotein; Glycoprotein; NADP; Oxidoreductase; Redox-active center;
KW   Reference proteome.
FT   CHAIN           1..483
FT                   /note="Glutathione reductase"
FT                   /id="PRO_0000067972"
FT   BINDING         30..74
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:O52582"
FT   BINDING         34
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         53..54
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         60
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         69
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         138..139
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         207
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         239
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         243
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         334
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         341..342
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         405
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         425
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   BINDING         472
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   CARBOHYD        278
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0007744|PDB:2HQM"
FT   VAR_SEQ         1..16
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_058124"
FT   CONFLICT        315
FT                   /note="Q -> E (in Ref. 4; BAA07109)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        428
FT                   /note="C -> G (in Ref. 4; BAA07109)"
FT                   /evidence="ECO:0000305"
FT   STRAND          23..29
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           33..44
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          49..55
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           59..64
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           66..82
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   TURN            83..89
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           98..100
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           105..129
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          132..141
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          147..154
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          157..166
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          170..172
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           181..183
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           187..192
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          198..203
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           207..218
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          222..226
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          228..232
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           238..251
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          254..256
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          261..266
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          273..277
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          282..291
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          295..297
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           303..306
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          329..331
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           333..335
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           342..357
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           360..362
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          374..376
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          382..386
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           389..396
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           398..400
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          401..408
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           411..415
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          422..429
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   TURN            430..433
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   STRAND          434..442
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           445..457
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           462..466
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   HELIX           476..480
FT                   /evidence="ECO:0007829|PDB:2HQM"
FT   INIT_MET        P41921-2:1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   MOD_RES         P41921-2:2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
SQ   SEQUENCE   483 AA;  53441 MW;  203BBB770120504A CRC64;
     MLSATKQTFR SLQIRTMSTN TKHYDYLVIG GGSGGVASAR RAASYGAKTL LVEAKALGGT
     CVNVGCVPKK VMWYASDLAT RVSHANEYGL YQNLPLDKEH LTFNWPEFKQ KRDAYVHRLN
     GIYQKNLEKE KVDVVFGWAR FNKDGNVEVQ KRDNTTEVYS ANHILVATGG KAIFPENIPG
     FELGTDSDGF FRLEEQPKKV VVVGAGYIGI ELAGVFHGLG SETHLVIRGE TVLRKFDECI
     QNTITDHYVK EGINVHKLSK IVKVEKNVET DKLKIHMNDS KSIDDVDELI WTIGRKSHLG
     MGSENVGIKL NSHDQIIADE YQNTNVPNIY SLGDVVGKVE LTPVAIAAGR KLSNRLFGPE
     KFRNDKLDYE NVPSVIFSHP EAGSIGISEK EAIEKYGKEN IKVYNSKFTA MYYAMLSEKS
     PTRYKIVCAG PNEKVVGLHI VGDSSAEILQ GFGVAIKMGA TKADFDNCVA IHPTSAEELV
     TMR
//