GPX3_YEAST
ID GPX3_YEAST Reviewed; 163 AA.
AC P40581; D6VVW8;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Glutathione peroxidase-like peroxiredoxin HYR1 {ECO:0000305};
DE EC=1.11.1.24 {ECO:0000269|PubMed:12437921, ECO:0000269|PubMed:18767166};
DE AltName: Full=Glutathione peroxidase homolog 3 {ECO:0000303|PubMed:10480913};
DE Short=GPx 3;
DE AltName: Full=Hydrogen peroxide resistance protein 1 {ECO:0000303|Ref.1};
DE AltName: Full=Oxidant receptor peroxidase 1 {ECO:0000303|PubMed:17720812};
DE AltName: Full=Phospholipid hydroperoxide glutathione peroxidase 3 {ECO:0000303|PubMed:9315326};
DE Short=PHGPx3;
GN Name=HYR1 {ECO:0000303|Ref.1};
GN Synonyms=GPX3 {ECO:0000303|PubMed:10480913},
GN ORP1 {ECO:0000303|PubMed:17720812};
GN OrderedLocusNames=YIR037W {ECO:0000312|SGD:S000001476};
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].
RC STRAIN=ATCC 38626 / AH22 / NRRL Y-12843;
RA Budde E., Stahl U.;
RT "Cloning and phenotypic characterization of a glutathione-peroxidase like
RT gene involved in the oxidative stress response of Saccharomyces
RT cerevisiae.";
RL Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169870;
RA Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D.,
RA Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E.,
RA Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C.,
RA Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V.,
RA Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.";
RL Nature 387:84-87(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 FUNCTION.
RX PubMed=9315326;
RA Ursini F., Maiorino M., Roveri A.;
RT "Phospholipid hydroperoxide glutathione peroxidase (PHGPx): more than an
RT antioxidant enzyme?";
RL Biomed. Environ. Sci. 10:327-332(1997).
RN [5]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10480913; DOI=10.1074/jbc.274.38.27002;
RA Inoue Y., Matsuda T., Sugiyama K., Izawa S., Kimura A.;
RT "Genetic analysis of glutathione peroxidase in oxidative stress response of
RT Saccharomyces cerevisiae.";
RL J. Biol. Chem. 274:27002-27009(1999).
RN [6]
RP FUNCTION.
RX PubMed=11445588; DOI=10.1074/jbc.m105672200;
RA Avery A.M., Avery S.V.;
RT "Saccharomyces cerevisiae expresses three phospholipid hydroperoxide
RT glutathione peroxidases.";
RL J. Biol. Chem. 276:33730-33735(2001).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND OXIDATION OF YAP1.
RX PubMed=12437921; DOI=10.1016/s0092-8674(02)01048-6;
RA Delaunay A., Pflieger D., Barrault M.-B., Vinh J., Toledano M.B.;
RT "A thiol peroxidase is an H2O2 receptor and redox-transducer in gene
RT activation.";
RL Cell 111:471-481(2002).
RN [8]
RP FUNCTION, AND INTERACTION WITH YBP1.
RX PubMed=12743123; DOI=10.1074/jbc.m303542200;
RA Veal E.A., Ross S.J., Malakasi P., Peacock E., Morgan B.A.;
RT "Ybp1 is required for the hydrogen peroxide-induced oxidation of the Yap1
RT transcription factor.";
RL J. Biol. Chem. 278:30896-30904(2003).
RN [9]
RP FUNCTION, AND ACTIVATING SUBSTANCES.
RX PubMed=14556853; DOI=10.1016/s0891-5849(03)00434-9;
RA Azevedo D., Tacnet F., Delaunay A., Rodrigues-Pousada C., Toledano M.B.;
RT "Two redox centers within Yap1 for H2O2 and thiol-reactive chemicals
RT signaling.";
RL Free Radic. Biol. Med. 35:889-900(2003).
RN [10]
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 [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.
RX PubMed=15337745; DOI=10.1074/jbc.m408340200;
RA Avery A.M., Willetts S.A., Avery S.V.;
RT "Genetic dissection of the phospholipid hydroperoxidase activity of yeast
RT gpx3 reveals its functional importance.";
RL J. Biol. Chem. 279:46652-46658(2004).
RN [13]
RP FUNCTION, AND ACTIVE SITE.
RX PubMed=17720812; DOI=10.1074/jbc.m705953200;
RA Ma L.H., Takanishi C.L., Wood M.J.;
RT "Molecular mechanism of oxidative stress perception by the Orp1 protein.";
RL J. Biol. Chem. 282:31429-31436(2007).
RN [14]
RP FUNCTION.
RX PubMed=19230722; DOI=10.1016/j.chembiol.2009.01.003;
RA Paulsen C.E., Carroll K.S.;
RT "Chemical dissection of an essential redox switch in yeast.";
RL Chem. Biol. 16:217-225(2009).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=22659048; DOI=10.1016/j.bbalip.2012.05.004;
RA Ohdate T., Inoue Y.;
RT "Involvement of glutathione peroxidase 1 in growth and peroxisome formation
RT in Saccharomyces cerevisiae in oleic acid medium.";
RL Biochim. Biophys. Acta 1821:1295-1305(2012).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE
RP ANALYSIS].
RX PubMed=22984289; DOI=10.1074/mcp.m112.021105;
RA Voegtle F.N., Burkhart J.M., Rao S., Gerbeth C., Hinrichs J.,
RA Martinou J.C., Chacinska A., Sickmann A., Zahedi R.P., Meisinger C.;
RT "Intermembrane space proteome of yeast mitochondria.";
RL Mol. Cell. Proteomics 11:1840-1852(2012).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS), CATALYTIC ACTIVITY, AND MUTAGENESIS
RP OF CYS-82.
RX PubMed=18767166; DOI=10.1002/prot.22220;
RA Zhang W.J., He Y.-X., Yang Z., Yu J., Chen Y., Zhou C.-Z.;
RT "Crystal structure of glutathione-dependent phospholipid peroxidase Hyr1
RT from the yeast Saccharomyces cerevisiae.";
RL Proteins 73:1058-1062(2008).
CC -!- FUNCTION: Involved in oxidative stress response and redox homeostasis.
CC Functions as a sensor and transducer of hydroperoxide stress. In
CC response to hydroperoxide stress it oxidizes (activates) the
CC transcription activator YAP1, which is involved in transcription
CC activation of genes of the oxidative stress response pathway. May also
CC play a direct role in hydroperoxide scavenging, being the most active
CC of three closely related S.cerevisiae peroxiredoxins (GPX1, GPX2, and
CC HYR1/GPX3) with respect to peroxide and lipid hydroperoxide reduction.
CC The three enzymes are not required for the glutaredoxin-mediated
CC antioxidant function. In the presence of peroxides, HYR1/GPX3 is
CC directly oxidized at Cys-36 to form a cysteine sulfenic acid (-SOH).
CC Cys-36-SOH then forms either an intramolecular disulfide bond (Cys-36
CC with Cys-82) or a transient, intermolecular disulfide bond with 'Cys-
CC 598' of YAP1, which is further resolved into a YAP1 intramolecular
CC disulfide bond ('Cys-303' with 'Cys-598'), which causes its nuclear
CC accumulation and activation, and a reduced Cys-36 in HYR1/GPX3.
CC {ECO:0000269|PubMed:10480913, ECO:0000269|PubMed:11445588,
CC ECO:0000269|PubMed:12437921, ECO:0000269|PubMed:12743123,
CC ECO:0000269|PubMed:14556853, ECO:0000269|PubMed:15337745,
CC ECO:0000269|PubMed:17720812, ECO:0000269|PubMed:19230722,
CC ECO:0000269|PubMed:9315326}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-dithiol + a hydroperoxide = [thioredoxin]-
CC disulfide + an alcohol + H2O; Xref=Rhea:RHEA:62620, Rhea:RHEA-
CC COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:30879, ChEBI:CHEBI:35924,
CC ChEBI:CHEBI:50058; EC=1.11.1.24;
CC Evidence={ECO:0000269|PubMed:12437921, ECO:0000269|PubMed:18767166};
CC -!- SUBUNIT: Interacts with YAP1 and probably YBP1.
CC {ECO:0000269|PubMed:12743123}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}.
CC Mitochondrion intermembrane space {ECO:0000269|PubMed:22984289}.
CC Peroxisome matrix {ECO:0000269|PubMed:22659048}.
CC -!- INDUCTION: In contrast to the other two peroxiredoxins, HYR1/GPX3
CC expression is constitutive, not stress-induced.
CC {ECO:0000269|PubMed:10480913}.
CC -!- DISRUPTION PHENOTYPE: Sensitive to hydrogen peroxide and tert-butyl
CC hydroperoxide (t-BHP). {ECO:0000269|PubMed:10480913}.
CC -!- MISCELLANEOUS: Present with 8000 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- MISCELLANEOUS: The active site is a conserved redox-active cysteine
CC residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic
CC attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to
CC cysteine sulfenic acid (C(P)-SOH), which then reacts with another
CC cysteine residue, the resolving cysteine (C(R)), to form a disulfide
CC bridge. The disulfide is subsequently reduced by an appropriate
CC electron donor to complete the catalytic cycle. In this atypical 2-Cys
CC peroxiredoxin, C(R) is present in the same subunit to form an
CC intramolecular disulfide. {ECO:0000305|PubMed:17720812}.
CC -!- SIMILARITY: Belongs to the glutathione peroxidase family.
CC {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a glutathione peroxidase
CC (PubMed:10480913) or a phospholipid hydroperoxide glutathione
CC peroxidase (PubMed:11445588), but functions as an atypical 2-Cys
CC peroxiredoxin using thioredoxin as reducing power instead
CC (PubMed:12437921). {ECO:0000305|PubMed:10480913,
CC ECO:0000305|PubMed:11445588, ECO:0000305|PubMed:12437921}.
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DR EMBL; U22446; AAA64283.1; -; Genomic_DNA.
DR EMBL; Z38061; CAA86197.1; -; Genomic_DNA.
DR EMBL; BK006942; DAA08584.1; -; Genomic_DNA.
DR PIR; S48499; S48499.
DR RefSeq; NP_012303.1; NM_001179559.1.
DR PDB; 3CMI; X-ray; 2.02 A; A=1-163.
DR PDBsum; 3CMI; -.
DR AlphaFoldDB; P40581; -.
DR SMR; P40581; -.
DR BioGRID; 35028; 103.
DR DIP; DIP-1275N; -.
DR IntAct; P40581; 14.
DR MINT; P40581; -.
DR STRING; 4932.YIR037W; -.
DR PeroxiBase; 3742; SceGPx03.
DR iPTMnet; P40581; -.
DR MaxQB; P40581; -.
DR PaxDb; P40581; -.
DR PRIDE; P40581; -.
DR TopDownProteomics; P40581; -.
DR EnsemblFungi; YIR037W_mRNA; YIR037W; YIR037W.
DR GeneID; 854855; -.
DR KEGG; sce:YIR037W; -.
DR SGD; S000001476; HYR1.
DR VEuPathDB; FungiDB:YIR037W; -.
DR eggNOG; KOG1651; Eukaryota.
DR GeneTree; ENSGT00940000165680; -.
DR HOGENOM; CLU_029507_2_2_1; -.
DR InParanoid; P40581; -.
DR OMA; FPMMSKI; -.
DR BioCyc; YEAST:YIR037W-MON; -.
DR EvolutionaryTrace; P40581; -.
DR PRO; PR:P40581; -.
DR Proteomes; UP000002311; Chromosome IX.
DR RNAct; P40581; protein.
DR GO; GO:0005829; C:cytosol; HDA:SGD.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0005782; C:peroxisomal matrix; IDA:SGD.
DR GO; GO:0004602; F:glutathione peroxidase activity; IDA:SGD.
DR GO; GO:0004601; F:peroxidase activity; IBA:GO_Central.
DR GO; GO:0051920; F:peroxiredoxin activity; IEA:UniProtKB-EC.
DR GO; GO:0047066; F:phospholipid-hydroperoxide glutathione peroxidase activity; IDA:SGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:SGD.
DR CDD; cd00340; GSH_Peroxidase; 1.
DR InterPro; IPR000889; Glutathione_peroxidase.
DR InterPro; IPR029759; GPX_AS.
DR InterPro; IPR029760; GPX_CS.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR013766; Thioredoxin_domain.
DR PANTHER; PTHR11592; PTHR11592; 1.
DR Pfam; PF00255; GSHPx; 1.
DR PIRSF; PIRSF000303; Glutathion_perox; 1.
DR PRINTS; PR01011; GLUTPROXDASE.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS00460; GLUTATHIONE_PEROXID_1; 1.
DR PROSITE; PS00763; GLUTATHIONE_PEROXID_2; 1.
DR PROSITE; PS51355; GLUTATHIONE_PEROXID_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antioxidant; Cytoplasm; Disulfide bond; Mitochondrion;
KW Oxidoreductase; Peroxidase; Peroxisome; Redox-active center;
KW Reference proteome.
FT CHAIN 1..163
FT /note="Glutathione peroxidase-like peroxiredoxin HYR1"
FT /id="PRO_0000066643"
FT ACT_SITE 36
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000269|PubMed:17720812,
FT ECO:0000305|PubMed:18767166"
FT DISULFID 36..82
FT /note="Redox-active"
FT /evidence="ECO:0000305|PubMed:18767166"
FT DISULFID 36
FT /note="Interchain (with C-598 in YAP1); transient"
FT /evidence="ECO:0000269|PubMed:12437921,
FT ECO:0000269|PubMed:17720812"
FT MUTAGEN 82
FT /note="C->S: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:18767166"
FT HELIX 3..6
FT /evidence="ECO:0007829|PDB:3CMI"
FT HELIX 19..22
FT /evidence="ECO:0007829|PDB:3CMI"
FT STRAND 26..36
FT /evidence="ECO:0007829|PDB:3CMI"
FT HELIX 39..52
FT /evidence="ECO:0007829|PDB:3CMI"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:3CMI"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:3CMI"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:3CMI"
FT HELIX 105..113
FT /evidence="ECO:0007829|PDB:3CMI"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:3CMI"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:3CMI"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:3CMI"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:3CMI"
FT HELIX 148..151
FT /evidence="ECO:0007829|PDB:3CMI"
FT HELIX 152..159
FT /evidence="ECO:0007829|PDB:3CMI"
SQ SEQUENCE 163 AA; 18641 MW; 46C42B81E895C1A3 CRC64;
MSEFYKLAPV DKKGQPFPFD QLKGKVVLIV NVASKCGFTP QYKELEALYK RYKDEGFTII
GFPCNQFGHQ EPGSDEEIAQ FCQLNYGVTF PIMKKIDVNG GNEDPVYKFL KSQKSGMLGL
RGIKWNFEKF LVDKKGKVYE RYSSLTKPSS LSETIEELLK EVE
