TRXR1_DROME
ID TRXR1_DROME Reviewed; 596 AA.
AC P91938; Q1RKZ0; Q53YG2; Q961E3; Q9W3H2; Q9W3H3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JAN-2003, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Thioredoxin reductase 1, mitochondrial;
DE Short=TrxR-1;
DE EC=1.8.1.9;
DE Flags: Precursor;
GN Name=Trxr-1; Synonyms=GR; ORFNames=CG2151;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RX PubMed=9056265; DOI=10.1006/abbi.1996.9872;
RA Candas M., Sohal R.S., Radyuk S.N., Klichko V.I., Orr W.C.;
RT "Molecular organization of the glutathione reductase gene in Drosophila
RT melanogaster.";
RL Arch. Biochem. Biophys. 339:323-334(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND D), FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF CYS-594 AND
RP CYS-595.
RX PubMed=11158675; DOI=10.1126/science.291.5504.643;
RA Kanzok S.M., Fechner A., Bauer H., Ulschmid J.K., Muller H.M.,
RA Botella-Munoz J., Schneuwly S., Schirmer R., Becker K.;
RT "Substitution of the thioredoxin system for glutathione reductase in
RT Drosophila melanogaster.";
RL Science 291:643-646(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND C).
RC STRAIN=Berkeley;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-447 (ISOFORM B).
RC STRAIN=Berkeley; TISSUE=Ovary;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11525742; DOI=10.1016/s0960-9822(01)00393-1;
RA Missirlis F., Phillips J.P., Jackle H.;
RT "Cooperative action of antioxidant defense systems in Drosophila.";
RL Curr. Biol. 11:1272-1277(2001).
RN [8]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11782468; DOI=10.1074/jbc.m109234200;
RA Gromer S., Gross J.H.;
RT "Methylseleninate is a substrate rather than an inhibitor of mammalian
RT thioredoxin reductase. Implications for the antitumor effects of
RT selenium.";
RL J. Biol. Chem. 277:9701-9706(2002).
RN [9]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=11796729; DOI=10.1074/jbc.m111692200;
RA Missirlis F., Ulschmid J.K., Hirosawa-Takamori M., Groenke S., Schaefer U.,
RA Becker K., Phillips J.P., Jaeckle H.;
RT "Mitochondrial and cytoplasmic thioredoxin reductase variants encoded by a
RT single Drosophila gene are both essential for viability.";
RL J. Biol. Chem. 277:11521-11526(2002).
RN [10]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11877442; DOI=10.1074/jbc.m200636200;
RA Bauer H., Kanzok S.M., Schirmer R.H.;
RT "Thioredoxin-2 but not thioredoxin-1 is a substrate of thioredoxin
RT peroxidase-1 from Drosophila melanogaster: isolation and characterization
RT of a second thioredoxin in D.melanogaster and evidence for distinct
RT biological functions of Trx-1 and Trx-2.";
RL J. Biol. Chem. 277:17457-17463(2002).
RN [11]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF HIS-569.
RX PubMed=18211101; DOI=10.1021/bi702040u;
RA Huang H.H., Arscott L.D., Ballou D.P., Williams C.H. Jr.;
RT "Acid-base catalysis in the mechanism of thioredoxin reductase from
RT Drosophila melanogaster.";
RL Biochemistry 47:1721-1731(2008).
RN [12]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF GLU-574.
RX PubMed=18991392; DOI=10.1021/bi801449h;
RA Huang H.H., Arscott L.D., Ballou D.P., Williams C.H.;
RT "Function of Glu-469' in the acid-base catalysis of thioredoxin reductase
RT from Drosophila melanogaster.";
RL Biochemistry 47:12769-12776(2008).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 111-593 IN COMPLEX WITH FAD AND
RP NADP, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ACTIVE SITE, AND DISULFIDE
RP BOND.
RX PubMed=17385893; DOI=10.1021/bi602394p;
RA Eckenroth B.E., Rould M.A., Hondal R.J., Everse S.J.;
RT "Structural and biochemical studies reveal differences in the catalytic
RT mechanisms of mammalian and Drosophila melanogaster thioredoxin
RT reductases.";
RL Biochemistry 46:4694-4705(2007).
CC -!- FUNCTION: Thioredoxin system is a major player in glutathione
CC metabolism, due to the demonstrated absence of a glutathione reductase.
CC Functionally interacts with the Sod/Cat reactive oxidation species
CC (ROS) defense system and thereby has a role in preadult development and
CC life span. Lack of a glutathione reductase suggests antioxidant defense
CC in Drosophila, and probably in related insects, differs fundamentally
CC from that in other organisms. {ECO:0000269|PubMed:11158675,
CC ECO:0000269|PubMed:11525742, ECO:0000269|PubMed:11796729}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide +
CC H(+) + NADPH; 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:11158675};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Note=Binds 1 FAD per subunit.;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.5 uM for NADPH (at pH 7.4) {ECO:0000269|PubMed:11158675,
CC ECO:0000269|PubMed:11782468, ECO:0000269|PubMed:11796729,
CC ECO:0000269|PubMed:11877442, ECO:0000269|PubMed:17385893,
CC ECO:0000269|PubMed:18211101, ECO:0000269|PubMed:18991392};
CC KM=1 uM for NADPH (at pH 7.4, 2 mM EDTA, 100 mM KPO(4))
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC KM=1 uM for NADPH (isoform B at pH 7.4, 2 mM EDTA, 100 mM KPO(4))
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC KM=7.0 uM for dhd (at pH 7.4, 200 uM NADPH, 100 mM KPO(4))
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC KM=141 uM for dhd (at pH 7.0, 0.15 mM NADPH, 1 mM EDTA, 1 mg/ml
CC insulin, 50 mM KPO(4), 25 degrees Celsius)
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC KM=7 uM for dhd (at pH 7.4, 2 mM EDTA, 100 mM KPO(4))
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC KM=19 uM for dhd (isoform B at pH 7.4, 2 mM EDTA, 100 mM KPO(4))
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC KM=5.9 uM for Trx-2 (at pH 7.4, 100 uM NADPH, 2 mM EDTA, 100 mM
CC KPO(4)) {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC KM=310 uM for 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) (at pH 7.4,
CC 100 uM NADPH, 100 mM KPO(4)) {ECO:0000269|PubMed:11158675,
CC ECO:0000269|PubMed:11782468, ECO:0000269|PubMed:11796729,
CC ECO:0000269|PubMed:11877442, ECO:0000269|PubMed:17385893,
CC ECO:0000269|PubMed:18211101, ECO:0000269|PubMed:18991392};
CC KM=0.17 mM for DTNB (at pH 7.0, 0.2 mM NADPH, 10 mM EDTA, 100 mM
CC KPO(4), 25 degrees Celsius) {ECO:0000269|PubMed:11158675,
CC ECO:0000269|PubMed:11782468, ECO:0000269|PubMed:11796729,
CC ECO:0000269|PubMed:11877442, ECO:0000269|PubMed:17385893,
CC ECO:0000269|PubMed:18211101, ECO:0000269|PubMed:18991392};
CC KM=380 uM for DTNB (at pH 7.4, 2 mM EDTA, 100 mM KPO(4))
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC KM=410 uM for DTNB (isoform B at pH 7.4, 2 mM EDTA, 100 mM KPO(4))
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC KM=675 uM for methylseleninate (100 uM NADPH)
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC Vmax=24.3 umol/min/mg enzyme toward NADPH (at pH 7.4)
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC Vmax=16 umol/min/mg enzyme toward Trx-2 (at pH 7.4, 100 uM NADPH, 2
CC mM EDTA, 100 mM KPO(4), 25 degrees Celsius)
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC Note=Measurements were conducted with isoform A unless noted
CC otherwise.;
CC pH dependence:
CC Optimum pH is 7.6 for isoform A with Trx-2 and NADPH as substrates.
CC {ECO:0000269|PubMed:11158675, ECO:0000269|PubMed:11782468,
CC ECO:0000269|PubMed:11796729, ECO:0000269|PubMed:11877442,
CC ECO:0000269|PubMed:17385893, ECO:0000269|PubMed:18211101,
CC ECO:0000269|PubMed:18991392};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17385893}.
CC -!- SUBCELLULAR LOCATION: [Isoform B]: Mitochondrion.
CC -!- SUBCELLULAR LOCATION: [Isoform A]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=B; Synonyms=Mito;
CC IsoId=P91938-1; Sequence=Displayed;
CC Name=A; Synonyms=Cyto;
CC IsoId=P91938-2; Sequence=VSP_005572, VSP_005574;
CC Name=C;
CC IsoId=P91938-3; Sequence=VSP_005571, VSP_005573;
CC Name=D;
CC IsoId=P91938-4; Sequence=VSP_005572;
CC -!- TISSUE SPECIFICITY: During embryogenesis, expression is seen in germ
CC cell progenitors, developing midgut, hindgut and proventriculus.
CC {ECO:0000269|PubMed:11525742}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically during
CC all stages of development, highest expression during adult stages.
CC {ECO:0000269|PubMed:11525742, ECO:0000269|PubMed:11796729}.
CC -!- MISCELLANEOUS: The active site is a redox-active disulfide bond.
CC -!- MISCELLANEOUS: [Isoform B]: Can partially substitute for the
CC cytoplasmic enzyme activity.
CC -!- MISCELLANEOUS: [Isoform A]: Unable to compensate for the loss of the
CC mitochondrial enzyme activity. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform D]: Produced by alternative initiation at Met-
CC 106 of isoform B. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a glutathione reductase.
CC {ECO:0000305|PubMed:9056265}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK93067.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. Chimeric cDNA originating from chromosomes X and 3.; Evidence={ECO:0000305};
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DR EMBL; U81995; AAB48441.1; -; mRNA.
DR EMBL; AF301145; AAG25640.1; -; mRNA.
DR EMBL; AF301144; AAG25639.1; -; mRNA.
DR EMBL; AE014298; AAF46354.1; -; Genomic_DNA.
DR EMBL; AE014298; AAF46355.2; -; Genomic_DNA.
DR EMBL; AE014298; AAN09228.1; -; Genomic_DNA.
DR EMBL; BT003266; AAO25023.1; -; mRNA.
DR EMBL; BT025070; ABE73241.1; -; mRNA.
DR EMBL; AY051643; AAK93067.1; ALT_SEQ; mRNA.
DR RefSeq; NP_511082.2; NM_078527.3. [P91938-2]
DR RefSeq; NP_727251.1; NM_167149.2. [P91938-1]
DR RefSeq; NP_727252.1; NM_167150.2. [P91938-3]
DR PDB; 2NVK; X-ray; 2.40 A; X=111-593.
DR PDB; 3DGH; X-ray; 1.75 A; A/B=111-588.
DR PDB; 3DH9; X-ray; 2.25 A; A/B=111-591.
DR PDBsum; 2NVK; -.
DR PDBsum; 3DGH; -.
DR PDBsum; 3DH9; -.
DR AlphaFoldDB; P91938; -.
DR SMR; P91938; -.
DR BioGRID; 58221; 35.
DR DIP; DIP-19145N; -.
DR IntAct; P91938; 20.
DR STRING; 7227.FBpp0071116; -.
DR PaxDb; P91938; -.
DR PRIDE; P91938; -.
DR DNASU; 31760; -.
DR EnsemblMetazoa; FBtr0071167; FBpp0071115; FBgn0020653. [P91938-2]
DR EnsemblMetazoa; FBtr0071168; FBpp0071116; FBgn0020653. [P91938-1]
DR EnsemblMetazoa; FBtr0071169; FBpp0071117; FBgn0020653. [P91938-3]
DR GeneID; 31760; -.
DR KEGG; dme:Dmel_CG2151; -.
DR CTD; 31760; -.
DR FlyBase; FBgn0020653; Trxr-1.
DR VEuPathDB; VectorBase:FBgn0020653; -.
DR eggNOG; KOG4716; Eukaryota.
DR GeneTree; ENSGT00940000167606; -.
DR InParanoid; P91938; -.
DR OMA; GGATQRM; -.
DR PhylomeDB; P91938; -.
DR BRENDA; 1.8.1.9; 1994.
DR Reactome; R-DME-3299685; Detoxification of Reactive Oxygen Species.
DR BioGRID-ORCS; 31760; 1 hit in 3 CRISPR screens.
DR ChiTaRS; Trxr-1; fly.
DR EvolutionaryTrace; P91938; -.
DR GenomeRNAi; 31760; -.
DR PRO; PR:P91938; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0020653; Expressed in adult Malpighian tubule (Drosophila) and 23 other tissues.
DR ExpressionAtlas; P91938; baseline and differential.
DR Genevisible; P91938; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; HDA:FlyBase.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0016209; F:antioxidant activity; IDA:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:FlyBase.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase activity; IDA:UniProtKB.
DR GO; GO:0045454; P:cell redox homeostasis; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; TAS:FlyBase.
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; IPR001100; Pyr_nuc-diS_OxRdtase.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR InterPro; IPR006338; Thioredoxin/glutathione_Rdtase.
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; TIGR01438; TGR; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Alternative splicing; Cytoplasm;
KW Disulfide bond; FAD; Flavoprotein; Mitochondrion; NADP; Nucleotide-binding;
KW Oxidoreductase; Redox-active center; Reference proteome; Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..596
FT /note="Thioredoxin reductase 1, mitochondrial"
FT /id="PRO_0000030291"
FT REGION 59..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 59..75
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 569
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 120..126
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 143..147
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 159..170
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 233..235
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 262..266
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 282
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 286
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 302
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 322..328
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 355
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 392..399
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 429..432
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 438..443
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 472
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT BINDING 570
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:17385893"
FT DISULFID 162..167
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:17385893"
FT DISULFID 594..595
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:17385893"
FT VAR_SEQ 1..105
FT /note="Missing (in isoform A and isoform D)"
FT /evidence="ECO:0000303|PubMed:11158675,
FT ECO:0000303|PubMed:9056265, ECO:0000303|Ref.5"
FT /id="VSP_005572"
FT VAR_SEQ 1..88
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_005571"
FT VAR_SEQ 89..110
FT /note="QHPHCDRAAMYAQPVRKMSTKG -> MLKYMICAIVVGAKKSTSSKYN (in
FT isoform C)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_005573"
FT VAR_SEQ 106..110
FT /note="MSTKG -> MAPVQ (in isoform A)"
FT /evidence="ECO:0000303|PubMed:11158675,
FT ECO:0000303|PubMed:9056265, ECO:0000303|Ref.5"
FT /id="VSP_005574"
FT MUTAGEN 569
FT /note="H->Q: Almost complete loss of TrX reduction."
FT /evidence="ECO:0000269|PubMed:18211101"
FT MUTAGEN 574
FT /note="E->A: Reduced Trx reduction."
FT /evidence="ECO:0000269|PubMed:18991392"
FT MUTAGEN 574
FT /note="E->Q: Reduced Trx reduction."
FT /evidence="ECO:0000269|PubMed:18991392"
FT MUTAGEN 594
FT /note="C->S: Loss of Trx reduction."
FT /evidence="ECO:0000269|PubMed:11158675"
FT MUTAGEN 595
FT /note="C->S: Loss of Trx reduction."
FT /evidence="ECO:0000269|PubMed:11158675"
FT CONFLICT 88
FT /note="F -> L (in Ref. 6; AAK93067)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="V -> S (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="Missing (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 189..190
FT /note="Missing (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="E -> D (in Ref. 1; AAB48441 and 6; AAK93067)"
FT /evidence="ECO:0000305"
FT CONFLICT 203..207
FT /note="KLVQS -> RLCAV (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 213..216
FT /note="KSVN -> SRH (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="R -> V (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 239..247
FT /note="DSHTLLAKL -> TRTHCCPSM (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 264
FT /note="Missing (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 276..280
FT /note="VEYGI -> AEIGT (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 292
FT /note="Missing (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 317..318
FT /note="EP -> G (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 351..386
FT /note="RKTVPLSVEKQDDGKLLVKYKNVETGEEAEDVYDTV -> ADVDRCREADDA
FT AAREYRLTQIRFTTSHHR (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 379
FT /note="A -> S (in Ref. 6; AAK93067)"
FT /evidence="ECO:0000305"
FT CONFLICT 396..398
FT /note="VDD -> CDS (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 403..406
FT /note="NAGV -> MPAL (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 424..425
FT /note="AN -> PH (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 455
FT /note="Y -> F (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="R -> S (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 473..483
FT /note="TPLEYACVGLS -> SWSTSASGLA (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 488..495
FT /note="VKQFGADE -> SSSSEPR (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 559..560
FT /note="IN -> L (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT CONFLICT 583
FT /note="K -> KP (in Ref. 1; AAB48441)"
FT /evidence="ECO:0000305"
FT STRAND 114..120
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 124..135
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 140..143
FT /evidence="ECO:0007829|PDB:3DGH"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 161..165
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 167..188
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 201..225
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 233..239
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 242..246
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 252..261
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 282..285
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 294..298
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 302..313
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 317..324
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 332..344
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 349..351
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 353..360
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 366..372
FT /evidence="ECO:0007829|PDB:3DGH"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 378..388
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 397..399
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 401..403
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 409..413
FT /evidence="ECO:0007829|PDB:2NVK"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 430..432
FT /evidence="ECO:0007829|PDB:3DH9"
FT HELIX 440..455
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 469..471
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 473..481
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 484..491
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 493..495
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 496..502
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 506..508
FT /evidence="ECO:0007829|PDB:3DGH"
FT TURN 509..512
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 519..527
FT /evidence="ECO:0007829|PDB:3DGH"
FT STRAND 531..539
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 542..554
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 559..563
FT /evidence="ECO:0007829|PDB:3DGH"
FT HELIX 573..578
FT /evidence="ECO:0007829|PDB:3DGH"
FT TURN 583..585
FT /evidence="ECO:0007829|PDB:3DGH"
SQ SEQUENCE 596 AA; 64322 MW; 8DA6FC08CF6A7292 CRC64;
MNLCNSRFSV TFVRQCSTIL TSPSAGIIQN RGSLTTKVPH WISSSLSCAH HTFQRTMNLT
GQRGSRDSTG ATGGNAPAGS GAGAPPPFQH PHCDRAAMYA QPVRKMSTKG GSYDYDLIVI
GGGSAGLACA KEAVLNGARV ACLDFVKPTP TLGTKWGVGG TCVNVGCIPK KLMHQASLLG
EAVHEAAAYG WNVDEKIKPD WHKLVQSVQN HIKSVNWVTR VDLRDKKVEY INGLGSFVDS
HTLLAKLKSG ERTITAQTFV IAVGGRPRYP DIPGAVEYGI TSDDLFSLDR EPGKTLVVGA
GYIGLECAGF LKGLGYEPTV MVRSIVLRGF DQQMAELVAA SMEERGIPFL RKTVPLSVEK
QDDGKLLVKY KNVETGEEAE DVYDTVLWAI GRKGLVDDLN LPNAGVTVQK DKIPVDSQEA
TNVANIYAVG DIIYGKPELT PVAVLAGRLL ARRLYGGSTQ RMDYKDVATT VFTPLEYACV
GLSEEDAVKQ FGADEIEVFH GYYKPTEFFI PQKSVRYCYL KAVAERHGDQ RVYGLHYIGP
VAGEVIQGFA AALKSGLTIN TLINTVGIHP TTAEEFTRLA ITKRSGLDPT PASCCS
