TRXR2_MOUSE
ID TRXR2_MOUSE Reviewed; 524 AA.
AC Q9JLT4; Q6KG49; Q80VZ4; Q91YX4; Q9JHA7; Q9JMH5;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 4.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Thioredoxin reductase 2, mitochondrial {ECO:0000305};
DE EC=1.8.1.9 {ECO:0000250|UniProtKB:Q9N2I8, ECO:0000250|UniProtKB:Q9Z0J5};
DE AltName: Full=Thioredoxin reductase TR3;
DE Flags: Precursor;
GN Name=Txnrd2 {ECO:0000312|MGI:MGI:1347023}; Synonyms=Trxr2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAD51323.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=10500251; DOI=10.1016/s0167-4781(99)00129-3;
RA Miranda-Vizuete A., Damdimopoulos A.E., Spyrou G.;
RT "cDNA cloning, expression and chromosomal localization of the mouse
RT mitochondrial thioredoxin reductase gene.";
RL Biochim. Biophys. Acta 1447:113-118(1999).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE (ISOFORM 1), TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Thymocyte;
RX PubMed=10721726; DOI=10.1016/s0378-1119(99)00498-9;
RA Kawai H., Ota T., Suzuki F., Tatsuka M.;
RT "Molecular cloning of mouse thioredoxin reductases.";
RL Gene 242:321-330(2000).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 35-44; 65-76;
RP 255-277 AND 341-373, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=10455115; DOI=10.1074/jbc.274.35.24522;
RA Sun Q.-A., Wu Y., Zappacosta F., Jeang K.-T., Lee B.J., Hatfield D.L.,
RA Gladyshev V.N.;
RT "Redox regulation of cell signaling by selenocysteine in mammalian
RT thioredoxin reductases.";
RL J. Biol. Chem. 274:24522-24530(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 4), AND
RP ALTERNATIVE SPLICING.
RC STRAIN=BALB/cJ;
RX PubMed=12132591;
RA Miranda-Vizuete A., Spyrou G.;
RT "Genomic organization and identification of a novel alternative splicing
RT variant of mouse mitochondrial thioredoxin reductase (TrxR2) gene.";
RL Mol. Cells 13:488-492(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=FVB/N; TISSUE=Limb, and Mammary tumor;
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 [6]
RP ALTERNATIVE SPLICING.
RX PubMed=11060283; DOI=10.1074/jbc.m004750200;
RA Sun Q.-A., Zappacosta F., Factor V.M., Wirth P.J., Hatfield D.L.,
RA Gladyshev V.N.;
RT "Heterogeneity within animal thioredoxin reductases: evidence for
RT alternative first exon splicing.";
RL J. Biol. Chem. 276:3106-3114(2001).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-79; LYS-175 AND LYS-329, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Involved in the control of reactive oxygen species levels and
CC the regulation of mitochondrial redox homeostasis (By similarity).
CC Maintains thioredoxin in a reduced state. May play a role in redox-
CC regulated cell signaling (By similarity).
CC {ECO:0000250|UniProtKB:Q9NNW7, ECO:0000250|UniProtKB:Q9Z0J5}.
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:0000250|UniProtKB:Q9N2I8,
CC ECO:0000250|UniProtKB:Q9Z0J5};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20347;
CC Evidence={ECO:0000250|UniProtKB:Q9N2I8,
CC ECO:0000250|UniProtKB:Q9Z0J5};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000255|RuleBase:RU000402, ECO:0000305};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P38816}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10721726}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9JLT4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JLT4-2; Sequence=VSP_008293;
CC Name=3;
CC IsoId=Q9JLT4-3; Sequence=VSP_008294, VSP_008295;
CC Name=4;
CC IsoId=Q9JLT4-4; Sequence=VSP_008296;
CC -!- TISSUE SPECIFICITY: Expressed in liver, heart, testis and kidney.
CC {ECO:0000269|PubMed:10455115, ECO:0000269|PubMed:10500251,
CC ECO:0000269|PubMed:10721726}.
CC -!- MISCELLANEOUS: The active site is a redox-active disulfide bond. The
CC selenocysteine residue is also essential for catalytic activity (By
CC similarity). {ECO:0000250|UniProtKB:Q9ZOJ5}.
CC -!- SIMILARITY: Belongs to the class-I pyridine nucleotide-disulfide
CC oxidoreductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF03359.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH52157.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAL90457.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAQ03230.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA86986.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF136399; AAF03359.1; ALT_INIT; mRNA.
DR EMBL; AF171053; AAD51323.1; -; mRNA.
DR EMBL; AB027566; BAA86986.2; ALT_INIT; mRNA.
DR EMBL; AF414359; AAL90457.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF414356; AAL90457.1; JOINED; Genomic_DNA.
DR EMBL; AF414357; AAL90457.1; JOINED; Genomic_DNA.
DR EMBL; AF414358; AAL90457.1; JOINED; Genomic_DNA.
DR EMBL; AF412308; AAQ03230.1; ALT_INIT; mRNA.
DR EMBL; BC013688; AAH13688.1; -; mRNA.
DR EMBL; BC052157; AAH52157.3; ALT_INIT; mRNA.
DR RefSeq; NP_038739.2; NM_013711.3.
DR PDB; 1ZDL; X-ray; 3.00 A; A=31-522.
DR PDB; 1ZKQ; X-ray; 2.60 A; A=31-522.
DR PDB; 3DGZ; X-ray; 2.25 A; A=34-521.
DR PDBsum; 1ZDL; -.
DR PDBsum; 1ZKQ; -.
DR PDBsum; 3DGZ; -.
DR SMR; Q9JLT4; -.
DR BioGRID; 205007; 1.
DR IntAct; Q9JLT4; 2.
DR MINT; Q9JLT4; -.
DR STRING; 10090.ENSMUSP00000111269; -.
DR iPTMnet; Q9JLT4; -.
DR PhosphoSitePlus; Q9JLT4; -.
DR EPD; Q9JLT4; -.
DR jPOST; Q9JLT4; -.
DR MaxQB; Q9JLT4; -.
DR PaxDb; Q9JLT4; -.
DR PeptideAtlas; Q9JLT4; -.
DR PRIDE; Q9JLT4; -.
DR ProteomicsDB; 298240; -. [Q9JLT4-1]
DR ProteomicsDB; 298241; -. [Q9JLT4-2]
DR ProteomicsDB; 298242; -. [Q9JLT4-3]
DR ProteomicsDB; 298243; -. [Q9JLT4-4]
DR DNASU; 26462; -.
DR GeneID; 26462; -.
DR KEGG; mmu:26462; -.
DR UCSC; uc007ynx.1; mouse. [Q9JLT4-3]
DR UCSC; uc007yny.1; mouse. [Q9JLT4-1]
DR CTD; 10587; -.
DR MGI; MGI:1347023; Txnrd2.
DR eggNOG; KOG4716; Eukaryota.
DR HOGENOM; CLU_016755_2_4_1; -.
DR InParanoid; Q9JLT4; -.
DR OrthoDB; 581771at2759; -.
DR PhylomeDB; Q9JLT4; -.
DR TreeFam; TF314782; -.
DR BRENDA; 1.8.1.9; 3474.
DR Reactome; R-MMU-3299685; Detoxification of Reactive Oxygen Species.
DR BioGRID-ORCS; 26462; 15 hits in 65 CRISPR screens.
DR ChiTaRS; Txnrd2; mouse.
DR EvolutionaryTrace; Q9JLT4; -.
DR PRO; PR:Q9JLT4; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9JLT4; protein.
DR Genevisible; Q9JLT4; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase activity; ISS:UniProtKB.
DR GO; GO:0045454; P:cell redox homeostasis; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0030097; P:hemopoiesis; IMP:MGI.
DR GO; GO:0000305; P:response to oxygen radical; TAS:UniProtKB.
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 splicing; Direct protein sequencing;
KW Disulfide bond; FAD; Flavoprotein; Mitochondrion; NADP; Oxidoreductase;
KW Redox-active center; Reference proteome; Selenocysteine; Transit peptide.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:10455115"
FT CHAIN 35..524
FT /note="Thioredoxin reductase 2, mitochondrial"
FT /id="PRO_0000030289"
FT ACT_SITE 497
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 41..70
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT NON_STD 523
FT /note="Selenocysteine"
FT /evidence="ECO:0000250"
FT MOD_RES 79
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 175
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 329
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT DISULFID 86..91
FT /note="Redox-active"
FT /evidence="ECO:0000250"
FT CROSSLNK 522..523
FT /note="Cysteinyl-selenocysteine (Cys-Sec)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..36
FT /note="MVAAMVAALRGPSRRFRPRTRALTRGTRGAASAAGG -> MEG (in
FT isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_008293"
FT VAR_SEQ 318..356
FT /note="RVPETRTLNLEKAGISTNPKNQKIIVDAQEATSVPHIYA -> KDAASHTDT
FT VSSSRKPYFLGRRVFAFLPITSWILHSAGS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008294"
FT VAR_SEQ 357..524
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008295"
FT VAR_SEQ 395..425
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12132591"
FT /id="VSP_008296"
FT CONFLICT 4..6
FT /note="AMV -> GRMW (in Ref. 1; AAF03359)"
FT /evidence="ECO:0000305"
FT STRAND 39..45
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 49..60
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 85..89
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 91..112
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 125..149
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 158..170
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 176..186
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 201..204
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 208..211
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 220..224
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 228..239
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 244..250
FT /evidence="ECO:0007829|PDB:3DGZ"
FT TURN 252..255
FT /evidence="ECO:0007829|PDB:1ZDL"
FT HELIX 258..270
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 274..277
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 279..286
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 292..298
FT /evidence="ECO:0007829|PDB:3DGZ"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 304..314
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 318..321
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 323..325
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 327..330
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:1ZDL"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 361..364
FT /evidence="ECO:0007829|PDB:1ZKQ"
FT HELIX 368..383
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 401..409
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 412..419
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 424..430
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 434..438
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 447..455
FT /evidence="ECO:0007829|PDB:3DGZ"
FT STRAND 459..467
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 470..482
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 487..491
FT /evidence="ECO:0007829|PDB:3DGZ"
FT HELIX 502..505
FT /evidence="ECO:0007829|PDB:3DGZ"
FT TURN 511..514
FT /evidence="ECO:0007829|PDB:3DGZ"
SQ SEQUENCE 524 AA; 56603 MW; 74D4713DC8EF6A80 CRC64;
MVAAMVAALR GPSRRFRPRT RALTRGTRGA ASAAGGQQSF DLLVIGGGSG GLACAKEAAQ
LGKKVAVADY VEPSPRGTKW GLGGTCVNVG CIPKKLMHQA ALLGGMIRDA HHYGWEVAQP
VQHNWKTMAE AVQNHVKSLN WGHRVQLQDR KVKYFNIKAS FVDEHTVRGV DKGGKATLLS
AEHIVIATGG RPRYPTQVKG ALEYGITSDD IFWLKESPGK TLVVGASYVA LECAGFLTGI
GLDTTVMMRS IPLRGFDQQM SSLVTEHMES HGTQFLKGCV PSHIKKLPTN QLQVTWEDHA
SGKEDTGTFD TVLWAIGRVP ETRTLNLEKA GISTNPKNQK IIVDAQEATS VPHIYAIGDV
AEGRPELTPT AIKAGKLLAQ RLFGKSSTLM DYSNVPTTVF TPLEYGCVGL SEEEAVALHG
QEHVEVYHAY YKPLEFTVAD RDASQCYIKM VCMREPPQLV LGLHFLGPNA GEVTQGFALG
IKCGASYAQV MQTVGIHPTC SEEVVKLHIS KRSGLEPTVT GCUG
