Full text data of TXNRD1
TXNRD1
(GRIM12, KDRF)
[Confidence: low (only semi-automatic identification from reviews)]
Thioredoxin reductase 1, cytoplasmic; TR; 1.8.1.9 (Gene associated with retinoic and interferon-induced mortality 12 protein; GRIM-12; Gene associated with retinoic and IFN-induced mortality 12 protein; KM-102-derived reductase-like factor; Thioredoxin reductase TR1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Thioredoxin reductase 1, cytoplasmic; TR; 1.8.1.9 (Gene associated with retinoic and interferon-induced mortality 12 protein; GRIM-12; Gene associated with retinoic and IFN-induced mortality 12 protein; KM-102-derived reductase-like factor; Thioredoxin reductase TR1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q16881
ID TRXR1_HUMAN Reviewed; 649 AA.
AC Q16881; Q6FI31; Q6VB40; Q6VB41; Q6VB42; Q6VBP2; Q6VBP3; Q6VBP4;
read moreAC Q6VBP5; Q6VBP9; Q6VBQ0; Q6YNQ1; Q76P53; Q7LA96; Q8WVC8; Q99475;
AC Q9UES8; Q9UH79;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 22-JAN-2014, entry version 162.
DE RecName: Full=Thioredoxin reductase 1, cytoplasmic;
DE Short=TR;
DE EC=1.8.1.9;
DE AltName: Full=Gene associated with retinoic and interferon-induced mortality 12 protein;
DE Short=GRIM-12;
DE Short=Gene associated with retinoic and IFN-induced mortality 12 protein;
DE AltName: Full=KM-102-derived reductase-like factor;
DE AltName: Full=Thioredoxin reductase TR1;
GN Name=TXNRD1; Synonyms=GRIM12, KDRF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), PROTEIN SEQUENCE OF 153-161;
RP 307-315 AND 585-607, AND VARIANT GLY-365.
RC TISSUE=Placenta;
RX PubMed=7589432; DOI=10.1016/0014-5793(95)01003-W;
RA Gasdaska P.Y., Gasdaska J.R., Cochran S., Powis G.;
RT "Cloning and sequencing of a human thioredoxin reductase.";
RL FEBS Lett. 373:5-9(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), PROTEIN SEQUENCE OF 122-127
RP AND 147-151, AND TISSUE SPECIFICITY.
RC TISSUE=Bone marrow stroma;
RX PubMed=8999974; DOI=10.1074/jbc.272.4.2570;
RA Koishi R., Kawashima I., Yoshimura C., Sugawara M., Serizawa N.;
RT "Cloning and characterization of a novel oxidoreductase KDRF from a
RT human bone marrow-derived stromal cell line KM-102.";
RL J. Biol. Chem. 272:2570-2577(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION, AND INDUCTION.
RC TISSUE=Mammary carcinoma;
RX PubMed=9774665;
RA Hofman E.R., Boyanapalli M., Lindner D.J., Weihua X., Hassel B.A.,
RA Jagus R., Gutierrez P.L., Kalvakolanu D.V.;
RT "Thioredoxin reductase mediates cell death effects of the combination
RT of beta interferon and retinoic acid.";
RL Mol. Cell. Biol. 18:6493-6504(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE
RP [MRNA] (ISOFORMS 2; 3; 4 AND 5), AND VARIANT GLY-365.
RC TISSUE=Mammary gland, Ovary, Testis, and Thymus;
RX PubMed=14980707; DOI=10.1016/j.freeradbiomed.2003.12.004;
RA Rundloef A.-K., Janard M., Miranda-Vizuete A., Arner E.S.;
RT "Evidence for intriguingly complex transcription of human thioredoxin
RT reductase 1.";
RL Free Radic. Biol. Med. 36:641-656(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RA Schuetze N., Bachthaler M., Lechner A., Koehrle J., Jakob F.;
RT "Identification by ddPCR of thioredoxin reductase as a vitamin D
RT regulated gene in human osteoblasts.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Brain;
RA Xu L., Dai R., Xu J.Y.;
RT "Cloning and sequencing of thioredoxin reductase gene from human
RT brain.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PROTEIN SEQUENCE OF 307-316; 449-456; 466-476 AND 638-649, MASS
RP SPECTROMETRY, BLOCKAGE OF N-TERMINUS, AND SELENOCYSTEINE AT SEC-648.
RX PubMed=8650234; DOI=10.1073/pnas.93.12.6146;
RA Gladyshev V.N., Jeang K.-T., Stadtman T.C.;
RT "Selenocysteine, identified as the penultimate C-terminal residue in
RT human T-cell thioredoxin reductase, corresponds to TGA in the human
RT placental gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:6146-6151(1996).
RN [12]
RP FUNCTION, HOMODIMERIZATION, CHARACTERIZATION, AND PRESENCE OF
RP SELENOCYSTEINE.
RX PubMed=8577704; DOI=10.1073/pnas.93.3.1006;
RA Tamura T., Stadtman T.C.;
RT "A new selenoprotein from human lung adenocarcinoma cells:
RT purification, properties, and thioredoxin reductase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:1006-1011(1996).
RN [13]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3; 4; 5 AND 6), AND DOMAIN.
RX PubMed=15379556; DOI=10.1021/bi048478t;
RA Su D., Gladyshev V.N.;
RT "Alternative splicing involving the thioredoxin reductase module in
RT mammals: a glutaredoxin-containing thioredoxin reductase 1.";
RL Biochemistry 43:12177-12188(2004).
RN [14]
RP FUNCTION, INTERACTION WITH ESR1 AND ESR2, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY (ISOFORM 4).
RX PubMed=15199063; DOI=10.1074/jbc.M402753200;
RA Damdimopoulos A.E., Miranda-Vizuete A., Treuter E., Gustafsson J.-A.,
RA Spyrou G.;
RT "An alternative splicing variant of the selenoprotein thioredoxin
RT reductase is a modulator of estrogen signaling.";
RL J. Biol. Chem. 279:38721-38729(2004).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-281, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [16]
RP INTERACTION WITH HERC5, AND ISGYLATION.
RX PubMed=16815975; DOI=10.1073/pnas.0600397103;
RA Wong J.J., Pung Y.F., Sze N.S., Chin K.C.;
RT "HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates
RT type I IFN-induced ISGylation of protein targets.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10735-10740(2006).
RN [17]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION (ISOFORM 1).
RX PubMed=18042542; DOI=10.1074/jbc.M708939200;
RA Dammeyer P., Damdimopoulos A.E., Nordman T., Jimenez A.,
RA Miranda-Vizuete A., Arner E.S.J.;
RT "Induction of cell membrane protrusions by the N-terminal glutaredoxin
RT domain of a rare splice variant of human thioredoxin reductase 1.";
RL J. Biol. Chem. 283:2814-2821(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) (ISOFORM 5).
RX PubMed=17512005; DOI=10.1016/j.jmb.2007.04.044;
RA Fritz-Wolf K., Urig S., Becker K.;
RT "The structure of human thioredoxin reductase 1 provides insights into
RT C-terminal rearrangements during catalysis.";
RL J. Mol. Biol. 370:116-127(2007).
CC -!- FUNCTION: Isoform 1 may possess glutaredoxin activity as well as
CC thioredoxin reductase activity and induces actin and tubulin
CC polymerization, leading to formation of cell membrane protrusions.
CC Isoform 4 enhances the transcriptional activity of estrogen
CC receptors alpha and beta while isoform 5 enhances the
CC transcriptional activity of the beta receptor only. Isoform 5 also
CC mediates cell death induced by a combination of interferon-beta
CC and retinoic acid.
CC -!- CATALYTIC ACTIVITY: Thioredoxin + NADP(+) = thioredoxin disulfide
CC + NADPH.
CC -!- COFACTOR: Binds 1 FAD per subunit.
CC -!- SUBUNIT: Homodimer. Isoform 4 interacts with ESR1 and ESR2.
CC Interacts with HERC5.
CC -!- INTERACTION:
CC Q03135:CAV1; NbExp=4; IntAct=EBI-716617, EBI-603614;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- SUBCELLULAR LOCATION: Isoform 4: Cytoplasm. Nucleus.
CC -!- SUBCELLULAR LOCATION: Isoform 5: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=V, TXNRD1_v3;
CC IsoId=Q16881-1; Sequence=Displayed;
CC Note=Minor isoform;
CC Name=2; Synonyms=II, TXNRD1_v4;
CC IsoId=Q16881-2; Sequence=VSP_031560, VSP_031565;
CC Name=3; Synonyms=III, TXNRD1_v5;
CC IsoId=Q16881-3; Sequence=VSP_031562, VSP_031563;
CC Name=4; Synonyms=IV, TXNRD1_v2, TrxR1b;
CC IsoId=Q16881-4; Sequence=VSP_031561, VSP_031564;
CC Name=5; Synonyms=I, TXNRD1_v1, TrxR1a;
CC IsoId=Q16881-5; Sequence=VSP_031558;
CC Note=Major isoform. The N-terminus of the sequence is processed
CC into a mature form that lacks residues Met-151 and Asn-152 at
CC the N-terminus;
CC Name=6; Synonyms=VI;
CC IsoId=Q16881-6; Sequence=VSP_031559;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed predominantly in Leydig
CC cells (at protein level). Also expressed in ovary, spleen, heart,
CC liver, kidney and pancreas and in a number of cancer cell lines.
CC Isoform 4 is widely expressed with highest levels in kidney,
CC testis, uterus, ovary, prostate, placenta and fetal liver.
CC -!- INDUCTION: Isoform 5 is induced by a combination of interferon-
CC beta and retinoic acid (at protein level). Isoform 1 is induced by
CC estradiol or testosterone in HeLa cells.
CC -!- DOMAIN: The N-terminal glutaredoxin domain found in isoform 1 does
CC not contain the C-P-Y-C redox-active motif normally found in
CC glutaredoxins and has been found to be inactive in classical
CC glutaredoxin assays.
CC -!- PTM: The N-terminus of isoform 5 is blocked.
CC -!- PTM: ISGylated (Probable).
CC -!- MISCELLANEOUS: The thioredoxin reductase active site is a redox-
CC active disulfide bond. The selenocysteine residue is also
CC essential for catalytic activity.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family.
CC -!- SIMILARITY: Contains 1 glutaredoxin domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB35418.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=AAC69621.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=AAF15900.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=AAV38446.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=AAZ67916.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=BAA13674.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=CAA04503.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=CAA62629.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=CAG38744.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/txnrd1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X91247; CAA62629.1; ALT_SEQ; mRNA.
DR EMBL; S79851; AAB35418.1; ALT_SEQ; mRNA.
DR EMBL; D88687; BAA13674.1; ALT_SEQ; mRNA.
DR EMBL; AF077367; AAC69621.1; ALT_SEQ; mRNA.
DR EMBL; AY057105; AAL15432.1; -; mRNA.
DR EMBL; AY344081; AAQ62461.1; -; mRNA.
DR EMBL; AY344083; AAQ62462.1; -; mRNA.
DR EMBL; AY344084; AAQ62463.1; -; mRNA.
DR EMBL; AY344086; AAQ62464.1; -; mRNA.
DR EMBL; AY344087; AAQ62465.1; -; mRNA.
DR EMBL; AY344089; AAQ62466.1; -; mRNA.
DR EMBL; AY344092; AAQ62467.1; -; mRNA.
DR EMBL; AY344093; AAQ62468.1; -; mRNA.
DR EMBL; AY344095; AAQ62469.1; -; mRNA.
DR EMBL; AY344096; AAQ62470.1; -; mRNA.
DR EMBL; AY344670; AAQ62471.1; -; mRNA.
DR EMBL; AY344673; AAQ62472.1; -; mRNA.
DR EMBL; AY344679; AAQ62473.1; -; mRNA.
DR EMBL; AJ001050; CAA04503.1; ALT_SEQ; mRNA.
DR EMBL; AF208018; AAF15900.1; ALT_SEQ; mRNA.
DR EMBL; CR536506; CAG38744.1; ALT_SEQ; mRNA.
DR EMBL; BT019640; AAV38446.1; ALT_SEQ; mRNA.
DR EMBL; DQ157758; AAZ67916.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC018122; AAH18122.2; -; mRNA.
DR PIR; S66677; S66677.
DR RefSeq; NP_001087240.1; NM_001093771.2.
DR RefSeq; NP_001248374.1; NM_001261445.1.
DR RefSeq; NP_001248375.1; NM_001261446.1.
DR RefSeq; NP_003321.3; NM_003330.3.
DR RefSeq; NP_877393.1; NM_182729.2.
DR RefSeq; NP_877419.1; NM_182742.2.
DR RefSeq; NP_877420.1; NM_182743.2.
DR UniGene; Hs.654922; -.
DR PDB; 1W1C; Model; -; A/B=161-649.
DR PDB; 2CFY; X-ray; 2.70 A; A/B/C/D/E/F=151-649.
DR PDB; 2J3N; X-ray; 2.80 A; A/B/C/D/E/F=151-649.
DR PDB; 2ZZ0; X-ray; 2.80 A; A/B/C/D=150-649.
DR PDB; 2ZZB; X-ray; 3.20 A; A/B/C/D=150-649.
DR PDB; 2ZZC; X-ray; 2.60 A; A/B/C/D=150-649.
DR PDB; 3QFA; X-ray; 2.20 A; A/B=151-646.
DR PDB; 3QFB; X-ray; 2.60 A; A/B=151-646.
DR PDBsum; 1W1C; -.
DR PDBsum; 2CFY; -.
DR PDBsum; 2J3N; -.
DR PDBsum; 2ZZ0; -.
DR PDBsum; 2ZZB; -.
DR PDBsum; 2ZZC; -.
DR PDBsum; 3QFA; -.
DR PDBsum; 3QFB; -.
DR ProteinModelPortal; Q16881; -.
DR SMR; Q16881; 59-644.
DR IntAct; Q16881; 5.
DR MINT; MINT-1525880; -.
DR BindingDB; Q16881; -.
DR ChEMBL; CHEMBL2096978; -.
DR PhosphoSite; Q16881; -.
DR DMDM; 172046253; -.
DR REPRODUCTION-2DPAGE; IPI00554786; -.
DR PaxDb; Q16881; -.
DR PRIDE; Q16881; -.
DR DNASU; 7296; -.
DR Ensembl; ENST00000388854; ENSP00000373506; ENSG00000198431.
DR Ensembl; ENST00000503506; ENSP00000421934; ENSG00000198431.
DR Ensembl; ENST00000524698; ENSP00000433425; ENSG00000198431.
DR Ensembl; ENST00000525566; ENSP00000434516; ENSG00000198431.
DR Ensembl; ENST00000526390; ENSP00000435123; ENSG00000198431.
DR Ensembl; ENST00000526580; ENSP00000433887; ENSG00000198431.
DR Ensembl; ENST00000526691; ENSP00000435929; ENSG00000198431.
DR GeneID; 7296; -.
DR KEGG; hsa:7296; -.
DR UCSC; uc010swp.3; human.
DR CTD; 7296; -.
DR GeneCards; GC12P104609; -.
DR H-InvDB; HIX0010939; -.
DR HGNC; HGNC:12437; TXNRD1.
DR HPA; CAB004607; -.
DR HPA; CAB015834; -.
DR HPA; HPA001395; -.
DR MIM; 601112; gene.
DR neXtProt; NX_Q16881; -.
DR PharmGKB; PA37093; -.
DR eggNOG; COG1249; -.
DR HOVERGEN; HBG004959; -.
DR InParanoid; Q16881; -.
DR KO; K00384; -.
DR OrthoDB; EOG779NXG; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; TXNRD1; human.
DR EvolutionaryTrace; Q16881; -.
DR GeneWiki; TXNRD1; -.
DR GenomeRNAi; 7296; -.
DR NextBio; 28527; -.
DR PRO; PR:Q16881; -.
DR ArrayExpress; Q16881; -.
DR Bgee; Q16881; -.
DR Genevestigator; Q16881; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0009055; F:electron carrier activity; IEA:InterPro.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0045340; F:mercury ion binding; IEA:Ensembl.
DR GO; GO:0016174; F:NAD(P)H oxidase activity; IEA:Ensembl.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0015035; F:protein disulfide oxidoreductase activity; IEA:InterPro.
DR GO; GO:0033797; F:selenate reductase activity; IEA:Ensembl.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase activity; EXP:Reactome.
DR GO; GO:0042537; P:benzene-containing compound metabolic process; IEA:Ensembl.
DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR GO; GO:0071455; P:cellular response to hyperoxia; IEA:Ensembl.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:Ensembl.
DR GO; GO:0070276; P:halogen metabolic process; IEA:Ensembl.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0042191; P:methylmercury metabolic process; IEA:Ensembl.
DR GO; GO:0070995; P:NADPH oxidation; IEA:Ensembl.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0001890; P:placenta development; IEA:Ensembl.
DR GO; GO:0010942; P:positive regulation of cell death; IEA:Ensembl.
DR GO; GO:0051262; P:protein tetramerization; IEA:Ensembl.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0010269; P:response to selenium ion; IEA:Ensembl.
DR GO; GO:0016259; P:selenocysteine metabolic process; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer.
DR InterPro; IPR013027; FAD_pyr_nucl-diS_OxRdtase.
DR InterPro; IPR002109; Glutaredoxin.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR023753; Pyr_nucl-diS_OxRdtase_FAD/NAD.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR InterPro; IPR001327; Pyr_OxRdtase_NAD-bd_dom.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR InterPro; IPR006338; Thioredoxin/glutathione_Rdtase.
DR PANTHER; PTHR22912:SF23; PTHR22912:SF23; 1.
DR Pfam; PF00462; Glutaredoxin; 1.
DR Pfam; PF00070; Pyr_redox; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PRINTS; PR00368; FADPNR.
DR SUPFAM; SSF52833; SSF52833; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR TIGRFAMs; TIGR01438; TGR; 1.
DR PROSITE; PS00195; GLUTAREDOXIN_1; FALSE_NEG.
DR PROSITE; PS51354; GLUTAREDOXIN_2; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Electron transport; FAD;
KW Flavoprotein; NADP; Nucleus; Oxidoreductase; Phosphoprotein;
KW Polymorphism; Redox-active center; Reference proteome; Selenocysteine;
KW Transport; Ubl conjugation.
FT CHAIN 1 649 Thioredoxin reductase 1, cytoplasmic.
FT /FTId=PRO_0000030286.
FT DOMAIN 56 156 Glutaredoxin.
FT NP_BIND 192 209 FAD (By similarity).
FT ACT_SITE 622 622 Proton acceptor (By similarity).
FT NON_STD 648 648 Selenocysteine.
FT MOD_RES 281 281 Phosphotyrosine.
FT DISULFID 209 214 Redox-active (By similarity).
FT CROSSLNK 647 648 Cysteinyl-selenocysteine (Cys-Sec) (By
FT similarity).
FT VAR_SEQ 1 150 Missing (in isoform 5).
FT /FTId=VSP_031558.
FT VAR_SEQ 1 139 MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLP
FT ENPAGFTSTATADSRALLQAYIDGHSVVIFSRSTCTRCTEV
FT KKLFKSLCVPYFVLELDQTEDGRALEGTLSELAAETDLPVV
FT FVKQRKIGGHGPTLKA -> MPVDDYWLCLPASCARPFVQT
FT VRVVQSCPHCCWFPGVLPSVPEPLRMPAMLPTGSHSAVLPP
FT SHCSTAPPSTSQEPSSSADPKLCLSPPTSDSRQERNVQFGL
FT A (in isoform 6).
FT /FTId=VSP_031559.
FT VAR_SEQ 1 106 Missing (in isoform 2).
FT /FTId=VSP_031560.
FT VAR_SEQ 1 98 Missing (in isoform 4).
FT /FTId=VSP_031561.
FT VAR_SEQ 1 51 Missing (in isoform 3).
FT /FTId=VSP_031562.
FT VAR_SEQ 52 100 TADSRALLQAYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVP
FT YFVLELDQ -> MQQVMLTCKGVNRGHAVPAGPGRKPRPRR
FT SSRLLAGEKHLTRSALLLCH (in isoform 3).
FT /FTId=VSP_031563.
FT VAR_SEQ 99 101 DQT -> MSC (in isoform 4).
FT /FTId=VSP_031564.
FT VAR_SEQ 107 138 LEGTLSELAAETDLPVVFVKQRKIGGHGPTLK -> MLSRL
FT VLNSWAQAIIRPRPPKVLGLQVTTFSE (in isoform
FT 2).
FT /FTId=VSP_031565.
FT VARIANT 365 365 D -> G (in dbSNP:rs1127954).
FT /FTId=VAR_051776.
FT CONFLICT 153 153 G -> S (in Ref. 4; AAQ62473).
FT CONFLICT 181 181 A -> P (in Ref. 6; AAF15900).
FT CONFLICT 194 194 V -> G (in Ref. 6; AAF15900).
FT CONFLICT 200 200 G -> E (in Ref. 4; AAQ62469).
FT CONFLICT 202 202 R -> K (in Ref. 4; AAQ62463).
FT CONFLICT 215 215 I -> N (in Ref. 4; AAQ62463).
FT CONFLICT 306 306 R -> S (in Ref. 1; AAB35418/CAA62629 and
FT 4; AAL15432).
FT CONFLICT 365 365 D -> N (in Ref. 3; AAC69621).
FT CONFLICT 449 449 K -> R (in Ref. 7; CAG38744).
FT CONFLICT 641 641 S -> R (in Ref. 3; AAC69621).
FT STRAND 162 168
FT HELIX 172 183
FT STRAND 188 191
FT HELIX 208 212
FT HELIX 214 233
FT TURN 234 237
FT HELIX 248 272
FT STRAND 276 278
FT STRAND 280 286
FT STRAND 289 293
FT STRAND 295 297
FT STRAND 301 309
FT STRAND 313 315
FT HELIX 323 326
FT HELIX 330 333
FT STRAND 342 346
FT HELIX 350 361
FT STRAND 366 372
FT TURN 374 377
FT HELIX 380 392
FT STRAND 396 410
FT STRAND 412 414
FT STRAND 416 427
FT STRAND 429 439
FT STRAND 443 446
FT STRAND 448 450
FT TURN 453 456
FT TURN 461 463
FT STRAND 479 481
FT HELIX 483 485
FT STRAND 486 489
FT HELIX 493 508
FT STRAND 522 524
FT STRAND 526 528
FT STRAND 530 534
FT HELIX 537 544
FT HELIX 546 548
FT STRAND 549 556
FT HELIX 559 562
FT TURN 563 565
FT TURN 568 570
FT STRAND 571 578
FT TURN 579 582
FT STRAND 584 592
FT HELIX 595 607
FT HELIX 612 617
FT HELIX 625 631
FT TURN 636 639
SQ SEQUENCE 649 AA; 70906 MW; 5A51C3F77EB03EFE CRC64;
MGCAEGKAVA AAAPTELQTK GKNGDGRRRS AKDHHPGKTL PENPAGFTST ATADSRALLQ
AYIDGHSVVI FSRSTCTRCT EVKKLFKSLC VPYFVLELDQ TEDGRALEGT LSELAAETDL
PVVFVKQRKI GGHGPTLKAY QEGRLQKLLK MNGPEDLPKS YDYDLIIIGG GSGGLAAAKE
AAQYGKKVMV LDFVTPTPLG TRWGLGGTCV NVGCIPKKLM HQAALLGQAL QDSRNYGWKV
EETVKHDWDR MIEAVQNHIG SLNWGYRVAL REKKVVYENA YGQFIGPHRI KATNNKGKEK
IYSAERFLIA TGERPRYLGI PGDKEYCISS DDLFSLPYCP GKTLVVGASY VALECAGFLA
GIGLDVTVMV RSILLRGFDQ DMANKIGEHM EEHGIKFIRQ FVPIKVEQIE AGTPGRLRVV
AQSTNSEEII EGEYNTVMLA IGRDACTRKI GLETVGVKIN EKTGKIPVTD EEQTNVPYIY
AIGDILEDKV ELTPVAIQAG RLLAQRLYAG STVKCDYENV PTTVFTPLEY GACGLSEEKA
VEKFGEENIE VYHSYFWPLE WTIPSRDNNK CYAKIICNTK DNERVVGFHV LGPNAGEVTQ
GFAAALKCGL TKKQLDSTIG IHPVCAEVFT TLSVTKRSGA SILQAGCUG
//
ID TRXR1_HUMAN Reviewed; 649 AA.
AC Q16881; Q6FI31; Q6VB40; Q6VB41; Q6VB42; Q6VBP2; Q6VBP3; Q6VBP4;
read moreAC Q6VBP5; Q6VBP9; Q6VBQ0; Q6YNQ1; Q76P53; Q7LA96; Q8WVC8; Q99475;
AC Q9UES8; Q9UH79;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 22-JAN-2014, entry version 162.
DE RecName: Full=Thioredoxin reductase 1, cytoplasmic;
DE Short=TR;
DE EC=1.8.1.9;
DE AltName: Full=Gene associated with retinoic and interferon-induced mortality 12 protein;
DE Short=GRIM-12;
DE Short=Gene associated with retinoic and IFN-induced mortality 12 protein;
DE AltName: Full=KM-102-derived reductase-like factor;
DE AltName: Full=Thioredoxin reductase TR1;
GN Name=TXNRD1; Synonyms=GRIM12, KDRF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), PROTEIN SEQUENCE OF 153-161;
RP 307-315 AND 585-607, AND VARIANT GLY-365.
RC TISSUE=Placenta;
RX PubMed=7589432; DOI=10.1016/0014-5793(95)01003-W;
RA Gasdaska P.Y., Gasdaska J.R., Cochran S., Powis G.;
RT "Cloning and sequencing of a human thioredoxin reductase.";
RL FEBS Lett. 373:5-9(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), PROTEIN SEQUENCE OF 122-127
RP AND 147-151, AND TISSUE SPECIFICITY.
RC TISSUE=Bone marrow stroma;
RX PubMed=8999974; DOI=10.1074/jbc.272.4.2570;
RA Koishi R., Kawashima I., Yoshimura C., Sugawara M., Serizawa N.;
RT "Cloning and characterization of a novel oxidoreductase KDRF from a
RT human bone marrow-derived stromal cell line KM-102.";
RL J. Biol. Chem. 272:2570-2577(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), FUNCTION, AND INDUCTION.
RC TISSUE=Mammary carcinoma;
RX PubMed=9774665;
RA Hofman E.R., Boyanapalli M., Lindner D.J., Weihua X., Hassel B.A.,
RA Jagus R., Gutierrez P.L., Kalvakolanu D.V.;
RT "Thioredoxin reductase mediates cell death effects of the combination
RT of beta interferon and retinoic acid.";
RL Mol. Cell. Biol. 18:6493-6504(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL NUCLEOTIDE SEQUENCE
RP [MRNA] (ISOFORMS 2; 3; 4 AND 5), AND VARIANT GLY-365.
RC TISSUE=Mammary gland, Ovary, Testis, and Thymus;
RX PubMed=14980707; DOI=10.1016/j.freeradbiomed.2003.12.004;
RA Rundloef A.-K., Janard M., Miranda-Vizuete A., Arner E.S.;
RT "Evidence for intriguingly complex transcription of human thioredoxin
RT reductase 1.";
RL Free Radic. Biol. Med. 36:641-656(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RA Schuetze N., Bachthaler M., Lechner A., Koehrle J., Jakob F.;
RT "Identification by ddPCR of thioredoxin reductase as a vitamin D
RT regulated gene in human osteoblasts.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RC TISSUE=Brain;
RA Xu L., Dai R., Xu J.Y.;
RT "Cloning and sequencing of thioredoxin reductase gene from human
RT brain.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PROTEIN SEQUENCE OF 307-316; 449-456; 466-476 AND 638-649, MASS
RP SPECTROMETRY, BLOCKAGE OF N-TERMINUS, AND SELENOCYSTEINE AT SEC-648.
RX PubMed=8650234; DOI=10.1073/pnas.93.12.6146;
RA Gladyshev V.N., Jeang K.-T., Stadtman T.C.;
RT "Selenocysteine, identified as the penultimate C-terminal residue in
RT human T-cell thioredoxin reductase, corresponds to TGA in the human
RT placental gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:6146-6151(1996).
RN [12]
RP FUNCTION, HOMODIMERIZATION, CHARACTERIZATION, AND PRESENCE OF
RP SELENOCYSTEINE.
RX PubMed=8577704; DOI=10.1073/pnas.93.3.1006;
RA Tamura T., Stadtman T.C.;
RT "A new selenoprotein from human lung adenocarcinoma cells:
RT purification, properties, and thioredoxin reductase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:1006-1011(1996).
RN [13]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3; 4; 5 AND 6), AND DOMAIN.
RX PubMed=15379556; DOI=10.1021/bi048478t;
RA Su D., Gladyshev V.N.;
RT "Alternative splicing involving the thioredoxin reductase module in
RT mammals: a glutaredoxin-containing thioredoxin reductase 1.";
RL Biochemistry 43:12177-12188(2004).
RN [14]
RP FUNCTION, INTERACTION WITH ESR1 AND ESR2, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY (ISOFORM 4).
RX PubMed=15199063; DOI=10.1074/jbc.M402753200;
RA Damdimopoulos A.E., Miranda-Vizuete A., Treuter E., Gustafsson J.-A.,
RA Spyrou G.;
RT "An alternative splicing variant of the selenoprotein thioredoxin
RT reductase is a modulator of estrogen signaling.";
RL J. Biol. Chem. 279:38721-38729(2004).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-281, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [16]
RP INTERACTION WITH HERC5, AND ISGYLATION.
RX PubMed=16815975; DOI=10.1073/pnas.0600397103;
RA Wong J.J., Pung Y.F., Sze N.S., Chin K.C.;
RT "HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates
RT type I IFN-induced ISGylation of protein targets.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10735-10740(2006).
RN [17]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION (ISOFORM 1).
RX PubMed=18042542; DOI=10.1074/jbc.M708939200;
RA Dammeyer P., Damdimopoulos A.E., Nordman T., Jimenez A.,
RA Miranda-Vizuete A., Arner E.S.J.;
RT "Induction of cell membrane protrusions by the N-terminal glutaredoxin
RT domain of a rare splice variant of human thioredoxin reductase 1.";
RL J. Biol. Chem. 283:2814-2821(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) (ISOFORM 5).
RX PubMed=17512005; DOI=10.1016/j.jmb.2007.04.044;
RA Fritz-Wolf K., Urig S., Becker K.;
RT "The structure of human thioredoxin reductase 1 provides insights into
RT C-terminal rearrangements during catalysis.";
RL J. Mol. Biol. 370:116-127(2007).
CC -!- FUNCTION: Isoform 1 may possess glutaredoxin activity as well as
CC thioredoxin reductase activity and induces actin and tubulin
CC polymerization, leading to formation of cell membrane protrusions.
CC Isoform 4 enhances the transcriptional activity of estrogen
CC receptors alpha and beta while isoform 5 enhances the
CC transcriptional activity of the beta receptor only. Isoform 5 also
CC mediates cell death induced by a combination of interferon-beta
CC and retinoic acid.
CC -!- CATALYTIC ACTIVITY: Thioredoxin + NADP(+) = thioredoxin disulfide
CC + NADPH.
CC -!- COFACTOR: Binds 1 FAD per subunit.
CC -!- SUBUNIT: Homodimer. Isoform 4 interacts with ESR1 and ESR2.
CC Interacts with HERC5.
CC -!- INTERACTION:
CC Q03135:CAV1; NbExp=4; IntAct=EBI-716617, EBI-603614;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- SUBCELLULAR LOCATION: Isoform 4: Cytoplasm. Nucleus.
CC -!- SUBCELLULAR LOCATION: Isoform 5: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=V, TXNRD1_v3;
CC IsoId=Q16881-1; Sequence=Displayed;
CC Note=Minor isoform;
CC Name=2; Synonyms=II, TXNRD1_v4;
CC IsoId=Q16881-2; Sequence=VSP_031560, VSP_031565;
CC Name=3; Synonyms=III, TXNRD1_v5;
CC IsoId=Q16881-3; Sequence=VSP_031562, VSP_031563;
CC Name=4; Synonyms=IV, TXNRD1_v2, TrxR1b;
CC IsoId=Q16881-4; Sequence=VSP_031561, VSP_031564;
CC Name=5; Synonyms=I, TXNRD1_v1, TrxR1a;
CC IsoId=Q16881-5; Sequence=VSP_031558;
CC Note=Major isoform. The N-terminus of the sequence is processed
CC into a mature form that lacks residues Met-151 and Asn-152 at
CC the N-terminus;
CC Name=6; Synonyms=VI;
CC IsoId=Q16881-6; Sequence=VSP_031559;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed predominantly in Leydig
CC cells (at protein level). Also expressed in ovary, spleen, heart,
CC liver, kidney and pancreas and in a number of cancer cell lines.
CC Isoform 4 is widely expressed with highest levels in kidney,
CC testis, uterus, ovary, prostate, placenta and fetal liver.
CC -!- INDUCTION: Isoform 5 is induced by a combination of interferon-
CC beta and retinoic acid (at protein level). Isoform 1 is induced by
CC estradiol or testosterone in HeLa cells.
CC -!- DOMAIN: The N-terminal glutaredoxin domain found in isoform 1 does
CC not contain the C-P-Y-C redox-active motif normally found in
CC glutaredoxins and has been found to be inactive in classical
CC glutaredoxin assays.
CC -!- PTM: The N-terminus of isoform 5 is blocked.
CC -!- PTM: ISGylated (Probable).
CC -!- MISCELLANEOUS: The thioredoxin reductase active site is a redox-
CC active disulfide bond. The selenocysteine residue is also
CC essential for catalytic activity.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family.
CC -!- SIMILARITY: Contains 1 glutaredoxin domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB35418.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=AAC69621.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=AAF15900.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=AAV38446.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=AAZ67916.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=BAA13674.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=CAA04503.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=CAA62629.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC Sequence=CAG38744.1; Type=Erroneous termination; Positions=648; Note=Translated as Sec;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/txnrd1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X91247; CAA62629.1; ALT_SEQ; mRNA.
DR EMBL; S79851; AAB35418.1; ALT_SEQ; mRNA.
DR EMBL; D88687; BAA13674.1; ALT_SEQ; mRNA.
DR EMBL; AF077367; AAC69621.1; ALT_SEQ; mRNA.
DR EMBL; AY057105; AAL15432.1; -; mRNA.
DR EMBL; AY344081; AAQ62461.1; -; mRNA.
DR EMBL; AY344083; AAQ62462.1; -; mRNA.
DR EMBL; AY344084; AAQ62463.1; -; mRNA.
DR EMBL; AY344086; AAQ62464.1; -; mRNA.
DR EMBL; AY344087; AAQ62465.1; -; mRNA.
DR EMBL; AY344089; AAQ62466.1; -; mRNA.
DR EMBL; AY344092; AAQ62467.1; -; mRNA.
DR EMBL; AY344093; AAQ62468.1; -; mRNA.
DR EMBL; AY344095; AAQ62469.1; -; mRNA.
DR EMBL; AY344096; AAQ62470.1; -; mRNA.
DR EMBL; AY344670; AAQ62471.1; -; mRNA.
DR EMBL; AY344673; AAQ62472.1; -; mRNA.
DR EMBL; AY344679; AAQ62473.1; -; mRNA.
DR EMBL; AJ001050; CAA04503.1; ALT_SEQ; mRNA.
DR EMBL; AF208018; AAF15900.1; ALT_SEQ; mRNA.
DR EMBL; CR536506; CAG38744.1; ALT_SEQ; mRNA.
DR EMBL; BT019640; AAV38446.1; ALT_SEQ; mRNA.
DR EMBL; DQ157758; AAZ67916.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC018122; AAH18122.2; -; mRNA.
DR PIR; S66677; S66677.
DR RefSeq; NP_001087240.1; NM_001093771.2.
DR RefSeq; NP_001248374.1; NM_001261445.1.
DR RefSeq; NP_001248375.1; NM_001261446.1.
DR RefSeq; NP_003321.3; NM_003330.3.
DR RefSeq; NP_877393.1; NM_182729.2.
DR RefSeq; NP_877419.1; NM_182742.2.
DR RefSeq; NP_877420.1; NM_182743.2.
DR UniGene; Hs.654922; -.
DR PDB; 1W1C; Model; -; A/B=161-649.
DR PDB; 2CFY; X-ray; 2.70 A; A/B/C/D/E/F=151-649.
DR PDB; 2J3N; X-ray; 2.80 A; A/B/C/D/E/F=151-649.
DR PDB; 2ZZ0; X-ray; 2.80 A; A/B/C/D=150-649.
DR PDB; 2ZZB; X-ray; 3.20 A; A/B/C/D=150-649.
DR PDB; 2ZZC; X-ray; 2.60 A; A/B/C/D=150-649.
DR PDB; 3QFA; X-ray; 2.20 A; A/B=151-646.
DR PDB; 3QFB; X-ray; 2.60 A; A/B=151-646.
DR PDBsum; 1W1C; -.
DR PDBsum; 2CFY; -.
DR PDBsum; 2J3N; -.
DR PDBsum; 2ZZ0; -.
DR PDBsum; 2ZZB; -.
DR PDBsum; 2ZZC; -.
DR PDBsum; 3QFA; -.
DR PDBsum; 3QFB; -.
DR ProteinModelPortal; Q16881; -.
DR SMR; Q16881; 59-644.
DR IntAct; Q16881; 5.
DR MINT; MINT-1525880; -.
DR BindingDB; Q16881; -.
DR ChEMBL; CHEMBL2096978; -.
DR PhosphoSite; Q16881; -.
DR DMDM; 172046253; -.
DR REPRODUCTION-2DPAGE; IPI00554786; -.
DR PaxDb; Q16881; -.
DR PRIDE; Q16881; -.
DR DNASU; 7296; -.
DR Ensembl; ENST00000388854; ENSP00000373506; ENSG00000198431.
DR Ensembl; ENST00000503506; ENSP00000421934; ENSG00000198431.
DR Ensembl; ENST00000524698; ENSP00000433425; ENSG00000198431.
DR Ensembl; ENST00000525566; ENSP00000434516; ENSG00000198431.
DR Ensembl; ENST00000526390; ENSP00000435123; ENSG00000198431.
DR Ensembl; ENST00000526580; ENSP00000433887; ENSG00000198431.
DR Ensembl; ENST00000526691; ENSP00000435929; ENSG00000198431.
DR GeneID; 7296; -.
DR KEGG; hsa:7296; -.
DR UCSC; uc010swp.3; human.
DR CTD; 7296; -.
DR GeneCards; GC12P104609; -.
DR H-InvDB; HIX0010939; -.
DR HGNC; HGNC:12437; TXNRD1.
DR HPA; CAB004607; -.
DR HPA; CAB015834; -.
DR HPA; HPA001395; -.
DR MIM; 601112; gene.
DR neXtProt; NX_Q16881; -.
DR PharmGKB; PA37093; -.
DR eggNOG; COG1249; -.
DR HOVERGEN; HBG004959; -.
DR InParanoid; Q16881; -.
DR KO; K00384; -.
DR OrthoDB; EOG779NXG; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; TXNRD1; human.
DR EvolutionaryTrace; Q16881; -.
DR GeneWiki; TXNRD1; -.
DR GenomeRNAi; 7296; -.
DR NextBio; 28527; -.
DR PRO; PR:Q16881; -.
DR ArrayExpress; Q16881; -.
DR Bgee; Q16881; -.
DR Genevestigator; Q16881; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0009055; F:electron carrier activity; IEA:InterPro.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0045340; F:mercury ion binding; IEA:Ensembl.
DR GO; GO:0016174; F:NAD(P)H oxidase activity; IEA:Ensembl.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0015035; F:protein disulfide oxidoreductase activity; IEA:InterPro.
DR GO; GO:0033797; F:selenate reductase activity; IEA:Ensembl.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase activity; EXP:Reactome.
DR GO; GO:0042537; P:benzene-containing compound metabolic process; IEA:Ensembl.
DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl.
DR GO; GO:0045454; P:cell redox homeostasis; IEA:InterPro.
DR GO; GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR GO; GO:0071455; P:cellular response to hyperoxia; IEA:Ensembl.
DR GO; GO:0006749; P:glutathione metabolic process; IEA:Ensembl.
DR GO; GO:0070276; P:halogen metabolic process; IEA:Ensembl.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0042191; P:methylmercury metabolic process; IEA:Ensembl.
DR GO; GO:0070995; P:NADPH oxidation; IEA:Ensembl.
DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome.
DR GO; GO:0001890; P:placenta development; IEA:Ensembl.
DR GO; GO:0010942; P:positive regulation of cell death; IEA:Ensembl.
DR GO; GO:0051262; P:protein tetramerization; IEA:Ensembl.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0010269; P:response to selenium ion; IEA:Ensembl.
DR GO; GO:0016259; P:selenocysteine metabolic process; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR Gene3D; 3.30.390.30; -; 1.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR016156; FAD/NAD-linked_Rdtase_dimer.
DR InterPro; IPR013027; FAD_pyr_nucl-diS_OxRdtase.
DR InterPro; IPR002109; Glutaredoxin.
DR InterPro; IPR004099; Pyr_nucl-diS_OxRdtase_dimer.
DR InterPro; IPR023753; Pyr_nucl-diS_OxRdtase_FAD/NAD.
DR InterPro; IPR012999; Pyr_OxRdtase_I_AS.
DR InterPro; IPR001327; Pyr_OxRdtase_NAD-bd_dom.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR InterPro; IPR006338; Thioredoxin/glutathione_Rdtase.
DR PANTHER; PTHR22912:SF23; PTHR22912:SF23; 1.
DR Pfam; PF00462; Glutaredoxin; 1.
DR Pfam; PF00070; Pyr_redox; 1.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR Pfam; PF02852; Pyr_redox_dim; 1.
DR PRINTS; PR00368; FADPNR.
DR SUPFAM; SSF52833; SSF52833; 1.
DR SUPFAM; SSF55424; SSF55424; 1.
DR TIGRFAMs; TIGR01438; TGR; 1.
DR PROSITE; PS00195; GLUTAREDOXIN_1; FALSE_NEG.
DR PROSITE; PS51354; GLUTAREDOXIN_2; 1.
DR PROSITE; PS00076; PYRIDINE_REDOX_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Electron transport; FAD;
KW Flavoprotein; NADP; Nucleus; Oxidoreductase; Phosphoprotein;
KW Polymorphism; Redox-active center; Reference proteome; Selenocysteine;
KW Transport; Ubl conjugation.
FT CHAIN 1 649 Thioredoxin reductase 1, cytoplasmic.
FT /FTId=PRO_0000030286.
FT DOMAIN 56 156 Glutaredoxin.
FT NP_BIND 192 209 FAD (By similarity).
FT ACT_SITE 622 622 Proton acceptor (By similarity).
FT NON_STD 648 648 Selenocysteine.
FT MOD_RES 281 281 Phosphotyrosine.
FT DISULFID 209 214 Redox-active (By similarity).
FT CROSSLNK 647 648 Cysteinyl-selenocysteine (Cys-Sec) (By
FT similarity).
FT VAR_SEQ 1 150 Missing (in isoform 5).
FT /FTId=VSP_031558.
FT VAR_SEQ 1 139 MGCAEGKAVAAAAPTELQTKGKNGDGRRRSAKDHHPGKTLP
FT ENPAGFTSTATADSRALLQAYIDGHSVVIFSRSTCTRCTEV
FT KKLFKSLCVPYFVLELDQTEDGRALEGTLSELAAETDLPVV
FT FVKQRKIGGHGPTLKA -> MPVDDYWLCLPASCARPFVQT
FT VRVVQSCPHCCWFPGVLPSVPEPLRMPAMLPTGSHSAVLPP
FT SHCSTAPPSTSQEPSSSADPKLCLSPPTSDSRQERNVQFGL
FT A (in isoform 6).
FT /FTId=VSP_031559.
FT VAR_SEQ 1 106 Missing (in isoform 2).
FT /FTId=VSP_031560.
FT VAR_SEQ 1 98 Missing (in isoform 4).
FT /FTId=VSP_031561.
FT VAR_SEQ 1 51 Missing (in isoform 3).
FT /FTId=VSP_031562.
FT VAR_SEQ 52 100 TADSRALLQAYIDGHSVVIFSRSTCTRCTEVKKLFKSLCVP
FT YFVLELDQ -> MQQVMLTCKGVNRGHAVPAGPGRKPRPRR
FT SSRLLAGEKHLTRSALLLCH (in isoform 3).
FT /FTId=VSP_031563.
FT VAR_SEQ 99 101 DQT -> MSC (in isoform 4).
FT /FTId=VSP_031564.
FT VAR_SEQ 107 138 LEGTLSELAAETDLPVVFVKQRKIGGHGPTLK -> MLSRL
FT VLNSWAQAIIRPRPPKVLGLQVTTFSE (in isoform
FT 2).
FT /FTId=VSP_031565.
FT VARIANT 365 365 D -> G (in dbSNP:rs1127954).
FT /FTId=VAR_051776.
FT CONFLICT 153 153 G -> S (in Ref. 4; AAQ62473).
FT CONFLICT 181 181 A -> P (in Ref. 6; AAF15900).
FT CONFLICT 194 194 V -> G (in Ref. 6; AAF15900).
FT CONFLICT 200 200 G -> E (in Ref. 4; AAQ62469).
FT CONFLICT 202 202 R -> K (in Ref. 4; AAQ62463).
FT CONFLICT 215 215 I -> N (in Ref. 4; AAQ62463).
FT CONFLICT 306 306 R -> S (in Ref. 1; AAB35418/CAA62629 and
FT 4; AAL15432).
FT CONFLICT 365 365 D -> N (in Ref. 3; AAC69621).
FT CONFLICT 449 449 K -> R (in Ref. 7; CAG38744).
FT CONFLICT 641 641 S -> R (in Ref. 3; AAC69621).
FT STRAND 162 168
FT HELIX 172 183
FT STRAND 188 191
FT HELIX 208 212
FT HELIX 214 233
FT TURN 234 237
FT HELIX 248 272
FT STRAND 276 278
FT STRAND 280 286
FT STRAND 289 293
FT STRAND 295 297
FT STRAND 301 309
FT STRAND 313 315
FT HELIX 323 326
FT HELIX 330 333
FT STRAND 342 346
FT HELIX 350 361
FT STRAND 366 372
FT TURN 374 377
FT HELIX 380 392
FT STRAND 396 410
FT STRAND 412 414
FT STRAND 416 427
FT STRAND 429 439
FT STRAND 443 446
FT STRAND 448 450
FT TURN 453 456
FT TURN 461 463
FT STRAND 479 481
FT HELIX 483 485
FT STRAND 486 489
FT HELIX 493 508
FT STRAND 522 524
FT STRAND 526 528
FT STRAND 530 534
FT HELIX 537 544
FT HELIX 546 548
FT STRAND 549 556
FT HELIX 559 562
FT TURN 563 565
FT TURN 568 570
FT STRAND 571 578
FT TURN 579 582
FT STRAND 584 592
FT HELIX 595 607
FT HELIX 612 617
FT HELIX 625 631
FT TURN 636 639
SQ SEQUENCE 649 AA; 70906 MW; 5A51C3F77EB03EFE CRC64;
MGCAEGKAVA AAAPTELQTK GKNGDGRRRS AKDHHPGKTL PENPAGFTST ATADSRALLQ
AYIDGHSVVI FSRSTCTRCT EVKKLFKSLC VPYFVLELDQ TEDGRALEGT LSELAAETDL
PVVFVKQRKI GGHGPTLKAY QEGRLQKLLK MNGPEDLPKS YDYDLIIIGG GSGGLAAAKE
AAQYGKKVMV LDFVTPTPLG TRWGLGGTCV NVGCIPKKLM HQAALLGQAL QDSRNYGWKV
EETVKHDWDR MIEAVQNHIG SLNWGYRVAL REKKVVYENA YGQFIGPHRI KATNNKGKEK
IYSAERFLIA TGERPRYLGI PGDKEYCISS DDLFSLPYCP GKTLVVGASY VALECAGFLA
GIGLDVTVMV RSILLRGFDQ DMANKIGEHM EEHGIKFIRQ FVPIKVEQIE AGTPGRLRVV
AQSTNSEEII EGEYNTVMLA IGRDACTRKI GLETVGVKIN EKTGKIPVTD EEQTNVPYIY
AIGDILEDKV ELTPVAIQAG RLLAQRLYAG STVKCDYENV PTTVFTPLEY GACGLSEEKA
VEKFGEENIE VYHSYFWPLE WTIPSRDNNK CYAKIICNTK DNERVVGFHV LGPNAGEVTQ
GFAAALKCGL TKKQLDSTIG IHPVCAEVFT TLSVTKRSGA SILQAGCUG
//
MIM
601112
*RECORD*
*FIELD* NO
601112
*FIELD* TI
*601112 THIOREDOXIN REDUCTASE 1; TXNRD1
;;TXNR;;
TR1
*FIELD* TX
CLONING
Thioredoxin reductase (EC 1.6.4.5) is a key enzyme in the regulation of
read morethe intracellular redox environment. Gasdaska et al. (1995) purified
human thioredoxin reductase from placenta and obtained amino acid
sequence from tryptic peptides. Based on protein sequence data, the
authors designed degenerate PCR primers and used them to screen a human
placenta cDNA library. The authors obtained a 3.8-kb cDNA encoding a
predicted 495-amino acid protein that is 40% identical to glutathione
reductase (GSR; 138300) and 24% identical to thioredoxin reductase from
E. coli. The protein has a predicted FAD-binding domain, but this
activity could not be demonstrated with recombinantly expressed enzyme.
By Northern blot analysis, Gasdaska et al. (1996) found that thioredoxin
reductase was expressed in all tissues examined, but at varying levels.
The authors found no correlation between the relative expression levels
of thioredoxin and thioredoxin reductase.
Tamura and Stadtman (1996) purified a selenocysteine-containing enzyme
from a human lung adenocarcinoma cell line. The protein was purified as
a homodimer of 57-kD subunits with no detectable N-linked
oligosaccharides. Tamura and Stadtman (1996) identified a prosthetic FAD
group in the protein, and they found that the protein catalyzed
NADPH-dependent reduction of insulin in the presence of thioredoxin. The
subunit composition and catalytic properties of the selenoprotein were
similar to those of mammalian thioredoxin reductase, but it failed to
crossreact with anti-rat liver thioredoxin reductase polyclonal
antibodies in immunoblot assays.
Selenium has been indirectly implicated in immunologic function and
numerous nutritional studies over many years. Furthermore, human
immunodeficiency virus (HIV)-infected persons have been reported to have
decreased levels of plasma selenium and selenium-containing glutathione
peroxidase (e.g., 138321). For this reason, Gladyshev et al. (1996)
initiated studies on selenium metabolism in human T cells. They
identified one of the selenoproteins detected in T cells as thioredoxin
reductase and demonstrated that the location of selenocysteine in this
protein corresponds to a TGA codon in the cloned placental gene. The
finding that T-cell thioredoxin reductase is a selenoenzyme that
contains selenium in a conserved C-terminal region provides another
example of the role of selenium in the major antioxidant enzyme system
(i.e., thioredoxin-thioredoxin reductase), in addition to the well-known
glutathione peroxidase enzyme system.
Dammeyer et al. (2008) stated that there are at least 3 TXNRD1 splice
variants with different 5-prime ends that encode TXNRD1 isoforms with
unique N-terminal domains. They studied variant-3 (v3), which includes
alternative exons upstream of the core promoter that encode an atypical
N-terminal monothiol glutaredoxin (GRX, or GLRX; 600443) domain fused to
the thioredoxin module. Northern blot analysis detected a 4.5-kb v3
transcript in testis only. PCR analysis also showed v3 expression in
ovary, spleen, heart, liver, kidney, pancreas, and some cancer cell
lines of various tissue origin. Immunohistochemical analysis of human
testis detected v3 predominantly in Leydig cells. Dammeyer et al. (2008)
stated that orthologs of v3 are found in chimpanzee and dog, but not in
mouse or rat.
GENE FUNCTION
Gorlatov and Stadtman (1998) demonstrated the essential role of
selenocysteine in thioredoxin reductase isolated from HeLa cells by
alkylation studies. Selective alkylation of selenocysteine in the
protein inhibited enzyme activity, and reduction with NADPH influenced
affinity to heparin.
Dammeyer et al. (2008) found that treatment of HeLa cells with estradiol
or testosterone induced expression of TXNRD1 v3. Fluorescence-tagged v3,
or its isolated GRX domain, localized to distinct cellular sites in
proximity to actin (see ACTG1; 102560) and had the capacity to rapidly
induce cell membrane protrusions. Analysis of these structures suggested
that the GRX domain of TXNRD1 v3 localized first to the emerging
protrusion and was followed into the protrusion by actin and
subsequently by tubulin (see TUBA1A; 602529). Dammeyer et al. (2008)
concluded that TXNRD1 v3 can guide actin polymerization in relation to
cell membrane restructuring.
MAPPING
Gasdaska et al. (1996) used fluorescence in situ hybridization to map
the TXNRD1 gene to human chromosome 12q23-q24.1.
*FIELD* RF
1. Dammeyer, P.; Damdimopoulos, A. E.; Nordman, T.; Jimenez, A.; Miranda-Vizuete,
A.; Arner, E. S. J.: Induction of cell membrane protrusions by the
N-terminal glutaredoxin domain of a rare splice variant of human thioredoxin
reductase 1. J. Biol. Chem. 283: 2814-2821, 2008.
2. Gasdaska, J. R.; Gasdaska, P. Y.; Gallegos, A.; Powis, G.: Human
thioredoxin reductase gene localization to chromosomal position 12q23-q24.1
and mRNA distribution in human tissue. Genomics 37: 257-259, 1996.
3. Gasdaska, P. Y.; Gasdaska, J. R.; Cochran, S.; Powis, G.: Cloning
and sequencing of a human thioredoxin reductase. FEBS Lett. 373:
5-9, 1995.
4. Gladyshev, V. N.; Jeang, K.-T.; Stadtman, T. C.: Selenocysteine,
identified as the penultimate C-terminal residue in human T-cell thioredoxin
reductase, corresponds to TGA in the human placental gene. Proc.
Nat. Acad. Sci. 93: 6146-6151, 1996.
5. Gorlatov, S. N.; Stadtman, T. C.: Human thioredoxin reductase
from HeLa cells: selective alkylation of selenocysteine in the protein
inhibits enzyme activity and reduction with NADPH influences affinity
to heparin. Proc. Nat. Acad. Sci. 95: 8520-8525, 1998.
6. Tamura, T.; Stadtman, T. C.: A new selenoprotein from human lung
adenocarcinoma cells: purification, properties, and thioredoxin reductase
activity. Proc. Nat. Acad. Sci. 93: 1006-1011, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 5/27/2008
Victor A. McKusick - updated: 8/11/1998
Jennifer P. Macke - updated: 8/21/1997
*FIELD* CD
Alan F. Scott: 3/10/1996
*FIELD* ED
mgross: 02/04/2009
mgross: 6/24/2008
terry: 5/27/2008
mgross: 2/21/2007
mgross: 8/30/2001
carol: 8/12/1998
terry: 8/11/1998
dholmes: 8/28/1997
dholmes: 8/21/1997
mark: 1/2/1997
terry: 8/28/1996
terry: 7/16/1996
mark: 7/9/1996
terry: 5/24/1996
mark: 3/10/1996
*RECORD*
*FIELD* NO
601112
*FIELD* TI
*601112 THIOREDOXIN REDUCTASE 1; TXNRD1
;;TXNR;;
TR1
*FIELD* TX
CLONING
Thioredoxin reductase (EC 1.6.4.5) is a key enzyme in the regulation of
read morethe intracellular redox environment. Gasdaska et al. (1995) purified
human thioredoxin reductase from placenta and obtained amino acid
sequence from tryptic peptides. Based on protein sequence data, the
authors designed degenerate PCR primers and used them to screen a human
placenta cDNA library. The authors obtained a 3.8-kb cDNA encoding a
predicted 495-amino acid protein that is 40% identical to glutathione
reductase (GSR; 138300) and 24% identical to thioredoxin reductase from
E. coli. The protein has a predicted FAD-binding domain, but this
activity could not be demonstrated with recombinantly expressed enzyme.
By Northern blot analysis, Gasdaska et al. (1996) found that thioredoxin
reductase was expressed in all tissues examined, but at varying levels.
The authors found no correlation between the relative expression levels
of thioredoxin and thioredoxin reductase.
Tamura and Stadtman (1996) purified a selenocysteine-containing enzyme
from a human lung adenocarcinoma cell line. The protein was purified as
a homodimer of 57-kD subunits with no detectable N-linked
oligosaccharides. Tamura and Stadtman (1996) identified a prosthetic FAD
group in the protein, and they found that the protein catalyzed
NADPH-dependent reduction of insulin in the presence of thioredoxin. The
subunit composition and catalytic properties of the selenoprotein were
similar to those of mammalian thioredoxin reductase, but it failed to
crossreact with anti-rat liver thioredoxin reductase polyclonal
antibodies in immunoblot assays.
Selenium has been indirectly implicated in immunologic function and
numerous nutritional studies over many years. Furthermore, human
immunodeficiency virus (HIV)-infected persons have been reported to have
decreased levels of plasma selenium and selenium-containing glutathione
peroxidase (e.g., 138321). For this reason, Gladyshev et al. (1996)
initiated studies on selenium metabolism in human T cells. They
identified one of the selenoproteins detected in T cells as thioredoxin
reductase and demonstrated that the location of selenocysteine in this
protein corresponds to a TGA codon in the cloned placental gene. The
finding that T-cell thioredoxin reductase is a selenoenzyme that
contains selenium in a conserved C-terminal region provides another
example of the role of selenium in the major antioxidant enzyme system
(i.e., thioredoxin-thioredoxin reductase), in addition to the well-known
glutathione peroxidase enzyme system.
Dammeyer et al. (2008) stated that there are at least 3 TXNRD1 splice
variants with different 5-prime ends that encode TXNRD1 isoforms with
unique N-terminal domains. They studied variant-3 (v3), which includes
alternative exons upstream of the core promoter that encode an atypical
N-terminal monothiol glutaredoxin (GRX, or GLRX; 600443) domain fused to
the thioredoxin module. Northern blot analysis detected a 4.5-kb v3
transcript in testis only. PCR analysis also showed v3 expression in
ovary, spleen, heart, liver, kidney, pancreas, and some cancer cell
lines of various tissue origin. Immunohistochemical analysis of human
testis detected v3 predominantly in Leydig cells. Dammeyer et al. (2008)
stated that orthologs of v3 are found in chimpanzee and dog, but not in
mouse or rat.
GENE FUNCTION
Gorlatov and Stadtman (1998) demonstrated the essential role of
selenocysteine in thioredoxin reductase isolated from HeLa cells by
alkylation studies. Selective alkylation of selenocysteine in the
protein inhibited enzyme activity, and reduction with NADPH influenced
affinity to heparin.
Dammeyer et al. (2008) found that treatment of HeLa cells with estradiol
or testosterone induced expression of TXNRD1 v3. Fluorescence-tagged v3,
or its isolated GRX domain, localized to distinct cellular sites in
proximity to actin (see ACTG1; 102560) and had the capacity to rapidly
induce cell membrane protrusions. Analysis of these structures suggested
that the GRX domain of TXNRD1 v3 localized first to the emerging
protrusion and was followed into the protrusion by actin and
subsequently by tubulin (see TUBA1A; 602529). Dammeyer et al. (2008)
concluded that TXNRD1 v3 can guide actin polymerization in relation to
cell membrane restructuring.
MAPPING
Gasdaska et al. (1996) used fluorescence in situ hybridization to map
the TXNRD1 gene to human chromosome 12q23-q24.1.
*FIELD* RF
1. Dammeyer, P.; Damdimopoulos, A. E.; Nordman, T.; Jimenez, A.; Miranda-Vizuete,
A.; Arner, E. S. J.: Induction of cell membrane protrusions by the
N-terminal glutaredoxin domain of a rare splice variant of human thioredoxin
reductase 1. J. Biol. Chem. 283: 2814-2821, 2008.
2. Gasdaska, J. R.; Gasdaska, P. Y.; Gallegos, A.; Powis, G.: Human
thioredoxin reductase gene localization to chromosomal position 12q23-q24.1
and mRNA distribution in human tissue. Genomics 37: 257-259, 1996.
3. Gasdaska, P. Y.; Gasdaska, J. R.; Cochran, S.; Powis, G.: Cloning
and sequencing of a human thioredoxin reductase. FEBS Lett. 373:
5-9, 1995.
4. Gladyshev, V. N.; Jeang, K.-T.; Stadtman, T. C.: Selenocysteine,
identified as the penultimate C-terminal residue in human T-cell thioredoxin
reductase, corresponds to TGA in the human placental gene. Proc.
Nat. Acad. Sci. 93: 6146-6151, 1996.
5. Gorlatov, S. N.; Stadtman, T. C.: Human thioredoxin reductase
from HeLa cells: selective alkylation of selenocysteine in the protein
inhibits enzyme activity and reduction with NADPH influences affinity
to heparin. Proc. Nat. Acad. Sci. 95: 8520-8525, 1998.
6. Tamura, T.; Stadtman, T. C.: A new selenoprotein from human lung
adenocarcinoma cells: purification, properties, and thioredoxin reductase
activity. Proc. Nat. Acad. Sci. 93: 1006-1011, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 5/27/2008
Victor A. McKusick - updated: 8/11/1998
Jennifer P. Macke - updated: 8/21/1997
*FIELD* CD
Alan F. Scott: 3/10/1996
*FIELD* ED
mgross: 02/04/2009
mgross: 6/24/2008
terry: 5/27/2008
mgross: 2/21/2007
mgross: 8/30/2001
carol: 8/12/1998
terry: 8/11/1998
dholmes: 8/28/1997
dholmes: 8/21/1997
mark: 1/2/1997
terry: 8/28/1996
terry: 7/16/1996
mark: 7/9/1996
terry: 5/24/1996
mark: 3/10/1996