TRXR1_RAT
ID TRXR1_RAT Reviewed; 499 AA.
AC O89049; Q5U344; Q9JKZ3; Q9JKZ4; Q9R1I3;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 5.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Thioredoxin reductase 1, cytoplasmic {ECO:0000305};
DE Short=TR;
DE EC=1.8.1.9 {ECO:0000269|PubMed:10849437};
DE AltName: Full=NADPH-dependent thioredoxin reductase;
DE AltName: Full=Peroxidase TXNRD1 {ECO:0000305|PubMed:10849437};
DE EC=1.11.1.2 {ECO:0000269|PubMed:10849437};
DE AltName: Full=Thioredoxin reductase TR1;
GN Name=Txnrd1 {ECO:0000312|RGD:61959}; Synonyms=Trxr1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Neuroblastoma;
RX PubMed=9535831; DOI=10.1074/jbc.273.15.8581;
RA Zhong L., Arner E.S.J., Ljung J., Aaslund F., Holmgren A.;
RT "Rat and calf thioredoxin reductase are homologous to glutathione reductase
RT with a carboxyl-terminal elongation containing a conserved catalytically
RT active penultimate selenocysteine residue.";
RL J. Biol. Chem. 273:8581-8591(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SELENOCYSTEINE AT SEC-498.
RC TISSUE=Kidney, and Liver;
RX PubMed=10333487; DOI=10.1042/bj3400439;
RA Fujiwara N., Fujii T., Fujii J., Taniguchi N.;
RT "Functional expression of rat thioredoxin reductase: selenocysteine
RT insertion sequence element is essential for the active enzyme.";
RL Biochem. J. 340:439-444(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Rundlof A., Arner E.S.J.;
RT "Molecular cloning of thioredoxin reductase 1 from rat liver.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 1-20; 56-67; 101-116; 316-335; 365-384; 425-430;
RP 435-459 AND 488-499, FUNCTION, MUTAGENESIS OF SEC-498, CHARACTERIZATION,
RP CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10849437; DOI=10.1074/jbc.m000690200;
RA Zhong L., Holmgren A.;
RT "Essential role of selenium in the catalytic activities of mammalian
RT thioredoxin reductase revealed by characterization of recombinant enzymes
RT with selenocysteine mutations.";
RL J. Biol. Chem. 275:18121-18128(2000).
RN [6] {ECO:0007744|PDB:1H6V}
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF MUTANT CYS-498 IN COMPLEX WITH FAD
RP AND NADP, DISULFIDE BOND, HOMODIMERIZATION, AND COFACTOR.
RX PubMed=11481439; DOI=10.1073/pnas.171178698;
RA Sandalova T., Zhong L., Lindqvist Y., Holmgren A., Schneider G.;
RT "Three-dimensional structure of a mammalian thioredoxin reductase:
RT implications for mechanism and evolution of a selenocysteine-dependent
RT enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:9533-9538(2001).
CC -!- FUNCTION: Reduces disulfideprotein thioredoxin (Trx) to its dithiol-
CC containing form. Homodimeric flavoprotein involved in the regulation of
CC cellular redox reactions, growth and differentiation. Contains a
CC selenocysteine residue at the C-terminal active site that is essential
CC for catalysis (PubMed:10849437). Also has reductase activity on
CC hydrogen peroxide (H2O2) (PubMed:10849437).
CC {ECO:0000269|PubMed:10849437}.
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:10849437};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20347;
CC Evidence={ECO:0000269|PubMed:10849437};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + H2O2 + NADPH = 2 H2O + NADP(+); Xref=Rhea:RHEA:15173,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.11.1.2;
CC Evidence={ECO:0000269|PubMed:10849437};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15174;
CC Evidence={ECO:0000305|PubMed:10849437};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:10849437, ECO:0000269|PubMed:11481439};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:11481439};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.3 uM for thioredoxin {ECO:0000269|PubMed:10849437};
CC Note=kcat is 2500 min(-1) with thioredoxin as substrate.
CC {ECO:0000269|PubMed:10849437};
CC pH dependence:
CC Optimum pH is 7.5. {ECO:0000269|PubMed:10849437};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11481439}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q16881}.
CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:Q16881}.
CC -!- MISCELLANEOUS: The active site is a redox-active disulfide bond. The
CC selenocysteine residue is also essential for catalytic activity.
CC {ECO:0000269|PubMed:10849437, ECO:0000269|PubMed:11481439}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD43039.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH85726.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U63923; AAC35244.2; -; mRNA.
DR EMBL; AF108213; AAD43039.1; ALT_SEQ; mRNA.
DR EMBL; AF220760; AAF32362.1; -; mRNA.
DR EMBL; AF220761; AAF32363.1; -; mRNA.
DR EMBL; BC085726; AAH85726.1; ALT_INIT; mRNA.
DR PDB; 1H6V; X-ray; 3.00 A; A/B/C/D/E/F=1-499.
DR PDB; 3EAN; X-ray; 2.75 A; A/B/C/D/E/F=1-499.
DR PDB; 3EAO; X-ray; 3.10 A; A/B/C/D/E/F=1-499.
DR PDB; 4KPR; X-ray; 2.40 A; A/B/E/F=1-499.
DR PDBsum; 1H6V; -.
DR PDBsum; 3EAN; -.
DR PDBsum; 3EAO; -.
DR PDBsum; 4KPR; -.
DR SMR; O89049; -.
DR BioGRID; 248626; 1.
DR STRING; 10116.ENSRNOP00000013612; -.
DR BindingDB; O89049; -.
DR ChEMBL; CHEMBL6035; -.
DR iPTMnet; O89049; -.
DR PhosphoSitePlus; O89049; -.
DR jPOST; O89049; -.
DR PaxDb; O89049; -.
DR PeptideAtlas; O89049; -.
DR PRIDE; O89049; -.
DR UCSC; RGD:61959; rat.
DR RGD; 61959; Txnrd1.
DR eggNOG; KOG4716; Eukaryota.
DR InParanoid; O89049; -.
DR BioCyc; MetaCyc:MON-15194; -.
DR BRENDA; 1.8.1.9; 5301.
DR Reactome; R-RNO-3299685; Detoxification of Reactive Oxygen Species.
DR Reactome; R-RNO-499943; Interconversion of nucleotide di- and triphosphates.
DR Reactome; R-RNO-5263617; Metabolism of ingested MeSeO2H into MeSeH.
DR Reactome; R-RNO-5628897; TP53 Regulates Metabolic Genes.
DR SABIO-RK; O89049; -.
DR EvolutionaryTrace; O89049; -.
DR PRO; PR:O89049; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0071949; F:FAD binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0045340; F:mercury ion binding; IDA:RGD.
DR GO; GO:0016174; F:NAD(P)H oxidase H2O2-forming activity; IDA:RGD.
DR GO; GO:0050137; F:NADPH peroxidase activity; IDA:UniProtKB.
DR GO; GO:0033797; F:selenate reductase activity; IDA:RGD.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase activity; IDA:UniProtKB.
DR GO; GO:0042537; P:benzene-containing compound metabolic process; IDA:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0071280; P:cellular response to copper ion; IEP:RGD.
DR GO; GO:0071455; P:cellular response to hyperoxia; IEP:RGD.
DR GO; GO:0007369; P:gastrulation; ISO:RGD.
DR GO; GO:0070276; P:halogen metabolic process; IEP:RGD.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IMP:RGD.
DR GO; GO:0001707; P:mesoderm formation; ISO:RGD.
DR GO; GO:0070995; P:NADPH oxidation; IDA:RGD.
DR GO; GO:0001890; P:placenta development; IEP:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; IMP:RGD.
DR GO; GO:0048678; P:response to axon injury; IEP:RGD.
DR GO; GO:0055093; P:response to hyperoxia; IEP:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IDA:RGD.
DR GO; GO:0010269; P:response to selenium ion; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0016259; P:selenocysteine metabolic process; IMP:RGD.
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; Cytoplasm; Direct protein sequencing; Disulfide bond; FAD;
KW Flavoprotein; NADP; Oxidoreductase; Phosphoprotein; Redox-active center;
KW Reference proteome; Selenocysteine; Ubl conjugation.
FT CHAIN 1..499
FT /note="Thioredoxin reductase 1, cytoplasmic"
FT /id="PRO_0000067985"
FT ACT_SITE 472
FT /note="Proton acceptor"
FT BINDING 18..23
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 42..43
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 58..59
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q16881"
FT BINDING 63..67
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 131..132
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 161
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 166
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 198..204
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 200
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q16881"
FT BINDING 221..222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 226..228
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q16881"
FT BINDING 226
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 291..293
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 315
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q16881"
FT BINDING 334
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 341..343
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 341
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0007744|PDB:1H6V"
FT BINDING 472
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0007744|PDB:1H6V"
FT NON_STD 498
FT /note="Selenocysteine"
FT /evidence="ECO:0000305|PubMed:10849437,
FT ECO:0000305|PubMed:11481439"
FT MOD_RES 68
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9JMH6"
FT MOD_RES 131
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q16881"
FT DISULFID 59..64
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:11481439"
FT CROSSLNK 497..498
FT /note="Cysteinyl-selenocysteine (Cys-Sec)"
FT MUTAGEN 498
FT /note="U->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10849437"
FT MUTAGEN 498
FT /note="Missing: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10849437"
FT CONFLICT 52..53
FT /note="RW -> NG (in Ref. 1; AAC35244, 2; AAD43039 and 3;
FT AAF32362)"
FT /evidence="ECO:0000305"
FT CONFLICT 426
FT /note="I -> V (in Ref. 4; AAH85726)"
FT /evidence="ECO:0000305"
FT CONFLICT 451..455
FT /note="GFAAA -> ALQP (in Ref. 2; AAD43039 and 3; AAF32362)"
FT /evidence="ECO:0000305"
FT STRAND 12..18
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 22..33
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 57..62
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 64..83
FT /evidence="ECO:0007829|PDB:4KPR"
FT TURN 84..87
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 98..122
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 130..136
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 139..143
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 149..159
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 169..172
FT /evidence="ECO:0007829|PDB:3EAO"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 192..196
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 200..211
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 216..222
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 230..242
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 246..260
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 266..277
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 279..289
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 293..296
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:4KPR"
FT TURN 311..313
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 343..358
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 372..374
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 380..384
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 387..394
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 396..398
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 399..406
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 409..411
FT /evidence="ECO:0007829|PDB:4KPR"
FT TURN 412..415
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 421..428
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:4KPR"
FT STRAND 434..442
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 445..457
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 462..467
FT /evidence="ECO:0007829|PDB:4KPR"
FT HELIX 475..480
FT /evidence="ECO:0007829|PDB:4KPR"
FT TURN 486..489
FT /evidence="ECO:0007829|PDB:4KPR"
SQ SEQUENCE 499 AA; 54670 MW; B23E5B5E661B174E CRC64;
MNDSKDAPKS YDFDLIIIGG GSGGLAAAKE AAKFDKKVMV LDFVTPTPLG TRWGLGGTCV
NVGCIPKKLM HQAALLGQAL KDSRNYGWKL EDTVKHDWEK MTESVQNHIG SLNWGYRVAL
REKKVVYENA YGKFIGPHKI MATNNKGKEK VYSAERFLIA TGERPRYLGI PGDKEYCISS
DDLFSLPYCP GKTLVVGASY VALECAGFLA GIGLDVTVMV RSILLRGFDQ DMANKIGEHM
EEHGIKFIRQ FVPTKIEQIE AGTPGRLKVT AKSTNSEETI EDEFNTVLLA VGRDSCTRTI
GLETVGVKIN EKTGKIPVTD EEQTNVPYIY AIGDILEGKL ELTPVAIQAG RLLAQRLYGG
STVKCDYDNV PTTVFTPLEY GCCGLSEEKA VEKFGEENIE VYHSFFWPLE WTVPSRDNNK
CYAKVICNLK DNERVVGFHV LGPNAGEVTQ GFAAALKCGL TKQQLDSTIG IHPVCAEIFT
TLSVTKRSGG DILQSGCUG
