GSHR_YEAST
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 03-AUG-2022, entry version 197.
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; 92.
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 iPTMnet; P41921; -.
DR COMPLUYEAST-2DPAGE; P41921; -.
DR MaxQB; P41921; -.
DR PaxDb; P41921; -.
DR PRIDE; P41921; -.
DR EnsemblFungi; YPL091W_mRNA; YPL091W; YPL091W. [P41921-1]
DR GeneID; 856014; -.
DR KEGG; sce:YPL091W; -.
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 BioCyc; YEAST:YPL091W-MON; -.
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 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 (NADPH) 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; -; 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; IPR001100; Pyr_nuc-diS_OxRdtase.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR PANTHER; PTHR42737; PTHR42737; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PIRSF; PIRSF000350; Mercury_reductase_MerA; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR TIGRFAMs; TIGR01421; gluta_reduc_1; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
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
