ID   TRXB1_YEAST             Reviewed;         319 AA.
AC   P29509; D6VSY3;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   10-JUN-2026, entry version 215.
DE   RecName: Full=Thioredoxin reductase 1;
DE            Short=TR;
DE            Short=TrxR;
DE            EC=1.8.1.9 {ECO:0000269|PubMed:7961686};
DE   AltName: Full=Thioredoxin peroxidase 1 {ECO:0000303|PubMed:7961686};
DE            Short=TPx {ECO:0000303|PubMed:7961686};
DE   AltName: Full=Thioredoxin-dependent peroxide reductase 1 {ECO:0000303|PubMed:7961686};
GN   Name=TRR1; OrderedLocusNames=YDR353W; ORFNames=D9476.5;
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], PARTIAL PROTEIN SEQUENCE OF 2-16; 90-97;
RP   126-137; 176-179; 233-238 AND 296-303, FUNCTION, AND CATALYTIC ACTIVITY.
RC   STRAIN=ATCC 200358 / YNN 295;
RX   PubMed=7961686; DOI=10.1016/s0021-9258(18)47038-x;
RA   Chae H.Z., Chung S.J., Rhee S.G.;
RT   "Thioredoxin-dependent peroxide reductase from yeast.";
RL   J. Biol. Chem. 269:27670-27678(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169867; DOI=10.1038/387s075;
RA   Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA   Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA   Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA   Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA   Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA   Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA   Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA   Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA   Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA   Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA   Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA   Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA   Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA   Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA   Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA   Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA   Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA   Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA   Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA   Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA   Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA   Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA   Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA   Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA   Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA   Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA   Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA   Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA   Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA   Mewes H.-W., Zollner A., Zaccaria P.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL   Nature 387:75-78(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   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 261-319.
RX   PubMed=2428012; DOI=10.1093/nar/14.16.6357;
RA   Furter R., Paravicini G., Aebi M., Braus G., Prantl F., Niederberger P.,
RA   Huetter R.;
RT   "The TRP4 gene of Saccharomyces cerevisiae: isolation and structural
RT   analysis.";
RL   Nucleic Acids Res. 14:6357-6373(1986).
RN   [6]
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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303, AND IDENTIFICATION BY
RP   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   [8]
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   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 2-319 IN COMPLEX WITH FAD,
RP   COFACTOR, AND SUBUNIT.
RX   PubMed=18930846; DOI=10.1016/j.bbapap.2008.09.011;
RA   Zhang Z., Bao R., Zhang Y., Yu J., Zhou C.Z., Chen Y.;
RT   "Crystal structure of Saccharomyces cerevisiae cytoplasmic thioredoxin
RT   reductase Trr1 reveals the structural basis for species-specific
RT   recognition of thioredoxin.";
RL   Biochim. Biophys. Acta 1794:124-128(2009).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 2-319 IN COMPLEX WITH FAD,
RP   FUNCTION, COFACTOR, SUBUNIT, AND DISULFIDE BOND.
RX   PubMed=20235561; DOI=10.1021/bi901962p;
RA   Oliveira M.A., Discola K.F., Alves S.V., Medrano F.J., Guimaraes B.G.,
RA   Netto L.E.;
RT   "Insights into the specificity of thioredoxin reductase-thioredoxin
RT   interactions. A structural and functional investigation of the yeast
RT   thioredoxin system.";
RL   Biochemistry 49:3317-3326(2010).
CC   -!- FUNCTION: Central component in the thioredoxin system. Reduces
CC       thioredoxins 1 and 2. {ECO:0000269|PubMed:20235561,
CC       ECO:0000269|PubMed:7961686}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide +
CC         NADPH + H(+); Xref=Rhea:RHEA:20345, Rhea:RHEA-COMP:10698, Rhea:RHEA-
CC         COMP:10700, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC         ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.8.1.9;
CC         Evidence={ECO:0000269|PubMed:7961686};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20346;
CC         Evidence={ECO:0000269|PubMed:7961686};
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000269|PubMed:18930846, ECO:0000269|PubMed:20235561};
CC       Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:18930846,
CC       ECO:0000269|PubMed:20235561};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18930846,
CC       ECO:0000269|PubMed:20235561, ECO:0000269|PubMed:7961686}.
CC   -!- INTERACTION:
CC       P29509; P53879: RHO5; NbExp=4; IntAct=EBI-19497, EBI-29054;
CC       P29509; P38816: TRR2; NbExp=5; IntAct=EBI-19497, EBI-19502;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion intermembrane space
CC       {ECO:0000269|PubMed:22984289}.
CC   -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC       {ECO:0000305|PubMed:7961686}.
CC   -!- MISCELLANEOUS: Present with 292000 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the class-II pyridine nucleotide-disulfide
CC       oxidoreductase family. {ECO:0000305}.
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DR   EMBL; U10274; AAA64747.1; -; Genomic_DNA.
DR   EMBL; U28372; AAB64789.1; -; Genomic_DNA.
DR   EMBL; X04273; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AY557749; AAS56075.1; -; Genomic_DNA.
DR   EMBL; BK006938; DAA12193.1; -; Genomic_DNA.
DR   PIR; S61150; S61150.
DR   RefSeq; NP_010640.1; NM_001180661.1.
DR   PDB; 3D8X; X-ray; 2.80 A; A/B=2-319.
DR   PDB; 3ITJ; X-ray; 2.40 A; A/B/C/D=2-319.
DR   AlphaFoldDB; P29509; -.
DR   SMR; P29509; -.
DR   BioGRID; 32410; 70.
DR   DIP; DIP-4319N; -.
DR   FunCoup; P29509; 284.
DR   IntAct; P29509; 18.
DR   MINT; P29509; -.
DR   STRING; 4932.YDR353W; -.
DR   iPTMnet; P29509; -.
DR   PaxDb; 4932-YDR353W; -.
DR   PeptideAtlas; P29509; -.
DR   EnsemblFungi; YDR353W_mRNA; YDR353W; YDR353W.
DR   GeneID; 851955; -.
DR   KEGG; sce:YDR353W; -.
DR   AGR; SGD:S000002761; -.
DR   SGD; S000002761; TRR1.
DR   VEuPathDB; FungiDB:YDR353W; -.
DR   eggNOG; KOG0404; Eukaryota.
DR   HOGENOM; CLU_031864_5_1_1; -.
DR   InParanoid; P29509; -.
DR   OMA; GPCHVLK; -.
DR   OrthoDB; 371245at2759; -.
DR   BioCyc; YEAST:YDR353W-MONOMER; -.
DR   BRENDA; 1.8.1.9; 984.
DR   BioGRID-ORCS; 851955; 6 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P29509; -.
DR   PRO; PR:P29509; -.
DR   Proteomes; UP000002311; Chromosome IV.
DR   RNAct; P29509; protein.
DR   GO; GO:0005829; C:cytosol; IDA:SGD.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; IDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR   GO; GO:0008198; F:ferrous iron binding; IDA:SGD.
DR   GO; GO:0004791; F:thioredoxin-disulfide reductase (NADPH) activity; IDA:SGD.
DR   GO; GO:0045454; P:cell redox homeostasis; IDA:SGD.
DR   GO; GO:0034599; P:cellular response to oxidative stress; IGI:SGD.
DR   GO; GO:0019430; P:removal of superoxide radicals; IEA:InterPro.
DR   FunFam; 3.50.50.60:FF:000064; Thioredoxin reductase; 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; IPR050097; Ferredoxin-NADP_redctase_2.
DR   InterPro; IPR008255; Pyr_nucl-diS_OxRdtase_2_AS.
DR   InterPro; IPR005982; Thioredox_Rdtase.
DR   NCBIfam; TIGR01292; TRX_reduct; 1.
DR   PANTHER; PTHR48105; THIOREDOXIN REDUCTASE 1-RELATED-RELATED; 1.
DR   Pfam; PF07992; Pyr_redox_2; 1.
DR   PRINTS; PR00368; FADPNR.
DR   PRINTS; PR00469; PNDRDTASEII.
DR   SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1.
DR   PROSITE; PS00573; PYRIDINE_REDOX_2; 1.
DR   PDBsum; 3D8X; -.
DR   PDBsum; 3ITJ; -.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Direct protein sequencing; Disulfide bond; FAD;
KW   Flavoprotein; Mitochondrion; NADP; Oxidoreductase; Phosphoprotein;
KW   Redox-active center; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:7961686"
FT   CHAIN           2..319
FT                   /note="Thioredoxin reductase 1"
FT                   /id="PRO_0000166770"
FT   BINDING         11..14
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000269|PubMed:18930846,
FT                   ECO:0000269|PubMed:20235561"
FT   BINDING         40..41
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000269|PubMed:18930846,
FT                   ECO:0000269|PubMed:20235561"
FT   BINDING         45
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000269|PubMed:18930846,
FT                   ECO:0000269|PubMed:20235561"
FT   BINDING         54
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000269|PubMed:18930846,
FT                   ECO:0000269|PubMed:20235561"
FT   BINDING         87
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000269|PubMed:18930846,
FT                   ECO:0000269|PubMed:20235561"
FT   BINDING         145
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000269|PubMed:18930846,
FT                   ECO:0000269|PubMed:20235561"
FT   BINDING         288
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000269|PubMed:18930846,
FT                   ECO:0000269|PubMed:20235561"
FT   BINDING         295..297
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000269|PubMed:18930846,
FT                   ECO:0000269|PubMed:20235561"
FT   MOD_RES         303
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   DISULFID        142..145
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000269|PubMed:20235561"
FT   CONFLICT        18
FT                   /note="A -> V (in Ref. 1; AAA64747)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        101
FT                   /note="T -> A (in Ref. 1; AAA64747)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        111
FT                   /note="T -> A (in Ref. 1; AAA64747)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        180..196
FT                   /note="VFMLVRKDHLRASTIMQ -> CLCLSEKTICVLLPLCK (in Ref. 1;
FT                   AAA64747)"
FT                   /evidence="ECO:0000305"
FT   STRAND          3..9
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           13..24
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          30..32
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          35..37
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           45..48
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          49..52
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           64..77
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          81..83
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          87..91
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          93..101
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          105..107
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          110..117
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          121..123
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           131..134
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   TURN            136..138
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          139..141
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           143..146
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           150..152
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          155..160
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           164..173
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   TURN            174..176
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          177..183
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          185..188
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           193..201
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          205..208
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          210..230
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   TURN            231..234
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          235..240
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          242..246
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          250..252
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           255..257
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   TURN            258..260
FT                   /evidence="ECO:0007829|PDB:3D8X"
FT   STRAND          275..277
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   STRAND          283..285
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           287..290
FT                   /evidence="ECO:0007829|PDB:3ITJ"
FT   HELIX           297..315
FT                   /evidence="ECO:0007829|PDB:3ITJ"
SQ   SEQUENCE   319 AA;  34238 MW;  9F9E58A4BAD859E1 CRC64;
     MVHNKVTIIG SGPAAHTAAI YLARAEIKPI LYEGMMANGI AAGGQLTTTT EIENFPGFPD
     GLTGSELMDR MREQSTKFGT EIITETVSKV DLSSKPFKLW TEFNEDAEPV TTDAIILATG
     ASAKRMHLPG EETYWQKGIS ACAVCDGAVP IFRNKPLAVI GGGDSACEEA QFLTKYGSKV
     FMLVRKDHLR ASTIMQKRAE KNEKIEILYN TVALEAKGDG KLLNALRIKN TKKNEETDLP
     VSGLFYAIGH TPATKIVAGQ VDTDEAGYIK TVPGSSLTSV PGFFAAGDVQ DSKYRQAITS
     AGSGCMAALD AEKYLTSLE
//