GLRX1_YEAST
ID GLRX1_YEAST Reviewed; 110 AA.
AC P25373; D6VQY0;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Glutaredoxin-1 {ECO:0000303|PubMed:9571241};
DE EC=1.11.1.9 {ECO:0000269|PubMed:11875065};
DE EC=2.5.1.18 {ECO:0000269|PubMed:12684511};
DE AltName: Full=Glutathione-dependent oxidoreductase 1;
GN Name=GRX1; OrderedLocusNames=YCL035C; ORFNames=YCL35C;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=1574125; DOI=10.1038/357038a0;
RA Oliver S.G., van der Aart Q.J.M., Agostoni-Carbone M.L., Aigle M.,
RA Alberghina L., Alexandraki D., Antoine G., Anwar R., Ballesta J.P.G.,
RA Benit P., Berben G., Bergantino E., Biteau N., Bolle P.-A.,
RA Bolotin-Fukuhara M., Brown A., Brown A.J.P., Buhler J.-M., Carcano C.,
RA Carignani G., Cederberg H., Chanet R., Contreras R., Crouzet M.,
RA Daignan-Fornier B., Defoor E., Delgado M.D., Demolder J., Doira C.,
RA Dubois E., Dujon B., Duesterhoeft A., Erdmann D., Esteban M., Fabre F.,
RA Fairhead C., Faye G., Feldmann H., Fiers W., Francingues-Gaillard M.-C.,
RA Franco L., Frontali L., Fukuhara H., Fuller L.J., Galland P., Gent M.E.,
RA Gigot D., Gilliquet V., Glansdorff N., Goffeau A., Grenson M., Grisanti P.,
RA Grivell L.A., de Haan M., Haasemann M., Hatat D., Hoenicka J.,
RA Hegemann J.H., Herbert C.J., Hilger F., Hohmann S., Hollenberg C.P.,
RA Huse K., Iborra F., Indge K.J., Isono K., Jacq C., Jacquet M., James C.M.,
RA Jauniaux J.-C., Jia Y., Jimenez A., Kelly A., Kleinhans U., Kreisl P.,
RA Lanfranchi G., Lewis C., van der Linden C.G., Lucchini G.,
RA Lutzenkirchen K., Maat M.J., Mallet L., Mannhaupt G., Martegani E.,
RA Mathieu A., Maurer C.T.C., McConnell D., McKee R.A., Messenguy F.,
RA Mewes H.-W., Molemans F., Montague M.A., Muzi Falconi M., Navas L.,
RA Newlon C.S., Noone D., Pallier C., Panzeri L., Pearson B.M., Perea J.,
RA Philippsen P., Pierard A., Planta R.J., Plevani P., Poetsch B., Pohl F.M.,
RA Purnelle B., Ramezani Rad M., Rasmussen S.W., Raynal A., Remacha M.A.,
RA Richterich P., Roberts A.B., Rodriguez F., Sanz E.,
RA Schaaff-Gerstenschlaeger I., Scherens B., Schweitzer B., Shu Y., Skala J.,
RA Slonimski P.P., Sor F., Soustelle C., Spiegelberg R., Stateva L.I.,
RA Steensma H.Y., Steiner S., Thierry A., Thireos G., Tzermia M.,
RA Urrestarazu L.A., Valle G., Vetter I., van Vliet-Reedijk J.C., Voet M.,
RA Volckaert G., Vreken P., Wang H., Warmington J.R., von Wettstein D.,
RA Wicksteed B.L., Wilson C., Wurst H., Xu G., Yoshikawa A., Zimmermann F.K.,
RA Sgouros J.G.;
RT "The complete DNA sequence of yeast chromosome III.";
RL Nature 357:38-46(1992).
RN [2]
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 [3]
RP FUNCTION, AND INDUCTION.
RX PubMed=9571241; DOI=10.1091/mbc.9.5.1081;
RA Luikenhuis S., Perrone G., Dawes I.W., Grant C.M.;
RT "The yeast Saccharomyces cerevisiae contains two glutaredoxin genes that
RT are required for protection against reactive oxygen species.";
RL Mol. Biol. Cell 9:1081-1091(1998).
RN [4]
RP INDUCTION.
RX PubMed=10786615; DOI=10.1016/s0167-4781(99)00234-1;
RA Grant C.M., Luikenhuis S., Beckhouse A., Soderbergh M., Dawes I.W.;
RT "Differential regulation of glutaredoxin gene expression in response to
RT stress conditions in the yeast Saccharomyces cerevisiae.";
RL Biochim. Biophys. Acta 1490:33-42(2000).
RN [5]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11875065; DOI=10.1074/jbc.m111686200;
RA Collinson E.J., Wheeler G.L., Garrido E.O., Avery A.M., Avery S.V.,
RA Grant C.M.;
RT "The yeast glutaredoxins are active as glutathione peroxidases.";
RL J. Biol. Chem. 277:16712-16717(2002).
RN [6]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12684511; DOI=10.1074/jbc.m301387200;
RA Collinson E.J., Grant C.M.;
RT "Role of yeast glutaredoxins as glutathione S-transferases.";
RL J. Biol. Chem. 278:22492-22497(2003).
RN [7]
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 [8]
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 [9]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF CYS-30.
RX PubMed=18992757; DOI=10.1016/j.jmb.2008.10.055;
RA Discola K.F., de Oliveira M.A., Rosa Cussiol J.R., Monteiro G.,
RA Barcena J.A., Porras P., Padilla C.A., Guimaraes B.G., Netto L.E.;
RT "Structural aspects of the distinct biochemical properties of glutaredoxin
RT 1 and glutaredoxin 2 from Saccharomyces cerevisiae.";
RL J. Mol. Biol. 385:889-901(2009).
RN [10]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ASP-89.
RX PubMed=20417731; DOI=10.1016/j.bbapap.2010.04.010;
RA Li W.F., Yu J., Ma X.X., Teng Y.B., Luo M., Tang Y.J., Zhou C.Z.;
RT "Structural basis for the different activities of yeast Grx1 and Grx2.";
RL Biochim. Biophys. Acta 1804:1542-1547(2010).
RN [11]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-11, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE,
RP GLUTATHIONYLATION AT CYS-27, AND MUTAGENESIS OF CYS-30.
RX PubMed=17327665; DOI=10.1107/s0907444906051675;
RA Hakansson K.O., Winther J.R.;
RT "Structure of glutaredoxin Grx1p C30S mutant from yeast.";
RL Acta Crystallogr. D 63:288-294(2007).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE,
RP GLUTATHIONYLATION AT CYS-27, AND DISULFIDE BOND.
RX PubMed=18473363; DOI=10.1002/prot.22096;
RA Yu J., Zhang N.N., Yin P.D., Cui P.X., Zhou C.Z.;
RT "Glutathionylation-triggered conformational changes of glutaredoxin Grx1
RT from the yeast Saccharomyces cerevisiae.";
RL Proteins 72:1077-1083(2008).
CC -!- FUNCTION: Component of the glutathione system which performs several
CC activities such as glutathione-dependent oxidoreductase, glutathione
CC peroxidase and glutathione S-transferase (GST) activity
CC (PubMed:11875065, PubMed:12684511). The disulfide bond functions as an
CC electron carrier in the glutathione-dependent synthesis of
CC deoxyribonucleotides by the enzyme ribonucleotide reductase. In
CC addition, it is also involved in reducing cytosolic protein- and non-
CC protein-disulfides in a coupled system with glutathione reductase.
CC Required for resistance to reactive oxygen species (ROS) by directly
CC reducing hydroperoxides and for the detoxification of ROS-mediated
CC damage. GRX1 is less active as an oxidoreductase than GRX2
CC (PubMed:9571241, PubMed:18992757, PubMed:20417731).
CC {ECO:0000269|PubMed:11875065, ECO:0000269|PubMed:12684511,
CC ECO:0000269|PubMed:18992757, ECO:0000269|PubMed:20417731,
CC ECO:0000269|PubMed:9571241}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 glutathione + H2O2 = glutathione disulfide + 2 H2O;
CC Xref=Rhea:RHEA:16833, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:58297; EC=1.11.1.9;
CC Evidence={ECO:0000269|PubMed:11875065};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-chloro-2,4-dinitrobenzene + glutathione = 2,4-dinitrophenyl-
CC S-glutathione + chloride + H(+); Xref=Rhea:RHEA:51220,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17996, ChEBI:CHEBI:34718,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:133977; EC=2.5.1.18;
CC Evidence={ECO:0000269|PubMed:12684511};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione + RX = a halide anion + an S-substituted
CC glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:90779; EC=2.5.1.18;
CC Evidence={ECO:0000269|PubMed:12684511};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.88 mM for H(2)O(2) {ECO:0000269|PubMed:11875065};
CC KM=0.52 mM for cumene hydroperoxide {ECO:0000269|PubMed:11875065};
CC KM=0.37 mM for tert-butyl hydroperoxide
CC {ECO:0000269|PubMed:11875065};
CC KM=4.2 mM for 1-chloro-2,4-dinitrobenzene
CC {ECO:0000269|PubMed:12684511};
CC KM=1.3 mM for 1,2-dichloro-4-nitrobenzene
CC {ECO:0000269|PubMed:12684511};
CC KM=6.2 mM for reduced glutathione {ECO:0000269|PubMed:18992757};
CC Vmax=110 umol/min/mg enzyme for H(2)O(2)
CC {ECO:0000269|PubMed:11875065};
CC Vmax=32.5 umol/min/mg enzyme for cumene hydroperoxide
CC {ECO:0000269|PubMed:11875065};
CC Vmax=7.5 umol/min/mg enzyme for tert-butyl hydroperoxide
CC {ECO:0000269|PubMed:11875065};
CC -!- INTERACTION:
CC P25373; P34230: PXA2; NbExp=2; IntAct=EBI-7903, EBI-2464632;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus
CC {ECO:0000269|PubMed:14562095}.
CC -!- INDUCTION: In response to heat shock and osmotic stress.
CC {ECO:0000269|PubMed:10786615, ECO:0000269|PubMed:9571241}.
CC -!- MISCELLANEOUS: Present with 3030 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the glutaredoxin family. {ECO:0000305}.
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DR EMBL; X59720; CAA42381.1; -; Genomic_DNA.
DR EMBL; BK006937; DAA07449.1; -; Genomic_DNA.
DR PIR; S19363; S19363.
DR RefSeq; NP_009895.1; NM_001178680.1.
DR PDB; 2JAC; X-ray; 2.02 A; A=1-110.
DR PDB; 2JAD; X-ray; 2.70 A; A=1-110.
DR PDB; 3C1R; X-ray; 2.00 A; A=1-110.
DR PDB; 3C1S; X-ray; 2.50 A; A=1-110.
DR PDB; 6MWS; X-ray; 1.22 A; A=1-110.
DR PDBsum; 2JAC; -.
DR PDBsum; 2JAD; -.
DR PDBsum; 3C1R; -.
DR PDBsum; 3C1S; -.
DR PDBsum; 6MWS; -.
DR AlphaFoldDB; P25373; -.
DR SMR; P25373; -.
DR BioGRID; 30948; 62.
DR DIP; DIP-5646N; -.
DR IntAct; P25373; 5.
DR MINT; P25373; -.
DR STRING; 4932.YCL035C; -.
DR iPTMnet; P25373; -.
DR MaxQB; P25373; -.
DR PaxDb; P25373; -.
DR PRIDE; P25373; -.
DR EnsemblFungi; YCL035C_mRNA; YCL035C; YCL035C.
DR GeneID; 850322; -.
DR KEGG; sce:YCL035C; -.
DR SGD; S000000540; GRX1.
DR VEuPathDB; FungiDB:YCL035C; -.
DR eggNOG; KOG1752; Eukaryota.
DR GeneTree; ENSGT00940000162420; -.
DR HOGENOM; CLU_026126_7_2_1; -.
DR InParanoid; P25373; -.
DR OMA; KPGHLEC; -.
DR SABIO-RK; P25373; -.
DR EvolutionaryTrace; P25373; -.
DR PRO; PR:P25373; -.
DR Proteomes; UP000002311; Chromosome III.
DR RNAct; P25373; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0015038; F:glutathione disulfide oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0097573; F:glutathione oxidoreductase activity; IEA:InterPro.
DR GO; GO:0004602; F:glutathione peroxidase activity; IDA:SGD.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:SGD.
DR GO; GO:0004362; F:glutathione-disulfide reductase (NADPH) activity; IEA:InterPro.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:SGD.
DR GO; GO:0010731; P:protein glutathionylation; IGI:SGD.
DR InterPro; IPR011767; GLR_AS.
DR InterPro; IPR002109; Glutaredoxin.
DR InterPro; IPR011899; Glutaredoxin_euk/vir.
DR InterPro; IPR014025; Glutaredoxin_subgr.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR Pfam; PF00462; Glutaredoxin; 1.
DR PRINTS; PR00160; GLUTAREDOXIN.
DR SUPFAM; SSF52833; SSF52833; 1.
DR TIGRFAMs; TIGR02180; GRX_euk; 1.
DR PROSITE; PS00195; GLUTAREDOXIN_1; 1.
DR PROSITE; PS51354; GLUTAREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Disulfide bond; Electron transport;
KW Glutathionylation; Isopeptide bond; Nucleus; Oxidoreductase;
KW Redox-active center; Reference proteome; Transferase; Transport;
KW Ubl conjugation.
FT CHAIN 1..110
FT /note="Glutaredoxin-1"
FT /id="PRO_0000141613"
FT DOMAIN 7..110
FT /note="Glutaredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00686"
FT BINDING 24..29
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:17327665,
FT ECO:0000269|PubMed:18473363"
FT BINDING 63
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:17327665,
FT ECO:0000269|PubMed:18473363"
FT BINDING 75
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:17327665,
FT ECO:0000269|PubMed:18473363"
FT BINDING 88..89
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:17327665,
FT ECO:0000269|PubMed:18473363"
FT MOD_RES 27
FT /note="S-glutathionyl cysteine; alternate"
FT /evidence="ECO:0000269|PubMed:17327665,
FT ECO:0000269|PubMed:18473363"
FT DISULFID 27..30
FT /note="Redox-active; alternate"
FT /evidence="ECO:0000269|PubMed:18473363"
FT CROSSLNK 11
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT MUTAGEN 30
FT /note="C->S: Leads to increased oxidoreductase activity."
FT /evidence="ECO:0000269|PubMed:18992757"
FT MUTAGEN 89
FT /note="D->S: Leads to increased oxidoreductase activity."
FT /evidence="ECO:0000269|PubMed:20417731"
FT HELIX 4..16
FT /evidence="ECO:0007829|PDB:6MWS"
FT STRAND 18..23
FT /evidence="ECO:0007829|PDB:6MWS"
FT HELIX 28..38
FT /evidence="ECO:0007829|PDB:6MWS"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:2JAD"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:6MWS"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:6MWS"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:6MWS"
FT HELIX 59..70
FT /evidence="ECO:0007829|PDB:6MWS"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:6MWS"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:6MWS"
FT HELIX 88..97
FT /evidence="ECO:0007829|PDB:6MWS"
FT HELIX 99..108
FT /evidence="ECO:0007829|PDB:6MWS"
SQ SEQUENCE 110 AA; 12380 MW; 8E69BC80BF40F2DD CRC64;
MVSQETIKHV KDLIAENEIF VASKTYCPYC HAALNTLFEK LKVPRSKVLV LQLNDMKEGA
DIQAALYEIN GQRTVPNIYI NGKHIGGNDD LQELRETGEL EELLEPILAN
