ID   THIO_MOUSE              Reviewed;         105 AA.
AC   P10639; Q52KC4; Q9D8R0;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   02-SEP-2026, entry version 214.
DE   RecName: Full=Thioredoxin;
DE            Short=Trx;
DE   AltName: Full=ATL-derived factor;
DE            Short=ADF;
GN   Name=Txn; Synonyms=Txn1;
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;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2785919; DOI=10.1002/j.1460-2075.1989.tb03436.x;
RA   Tagaya Y., Maeda Y., Mitsui A., Kndo N., Matsui H., Hamuro J., Brown N.,
RA   Arai K., Yokota T., Wakasugi H., Yodoi J.;
RT   "ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to
RT   thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor
RT   induction.";
RL   EMBO J. 8:757-764(1989).
RN   [2]
RP   ERRATUM OF PUBMED:2785919, AND SEQUENCE REVISION.
RX   PubMed=8187776; DOI=10.1002/j.1460-2075.1994.tb06502.x;
RA   Tagaya Y., Maeda Y., Mitsui A., Kndo N., Matsui H., Hamuro J., Brown N.,
RA   Arai K., Yokota T., Wakasugi H., Yodoi J.;
RL   EMBO J. 13:2244-2244(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/Sv; TISSUE=Liver;
RX   PubMed=7835695; DOI=10.1016/0378-1119(94)00707-y;
RA   Matsui M., Taniguchi Y., Hirota K., Taketo M., Yodoi J.;
RT   "Structure of the mouse thioredoxin-encoding gene and its processed
RT   pseudogene.";
RL   Gene 152:165-171(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Pancreas;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Colon, and Thymus;
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   INTERACTION WITH TXNIP.
RX   PubMed=10843682; DOI=10.4049/jimmunol.164.12.6287;
RA   Junn E., Han S.H., Im J.Y., Yang Y., Cho E.W., Um H.D., Kim D.K., Lee K.W.,
RA   Han P.L., Rhee S.G., Choi I.;
RT   "Vitamin D3 up-regulated protein 1 mediates oxidative stress via
RT   suppressing the thioredoxin function.";
RL   J. Immunol. 164:6287-6295(2000).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, 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   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-39 AND LYS-94, SUCCINYLATION
RP   [LARGE SCALE ANALYSIS] AT LYS-8 AND LYS-94, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast, and 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: Participates in various redox reactions through the
CC       reversible oxidation of its active center dithiol to a disulfide and
CC       catalyzes dithiol-disulfide exchange reactions (By similarity). Plays a
CC       role in the reversible S-nitrosylation of cysteine residues in target
CC       proteins, and thereby contributes to the response to intracellular
CC       nitric oxide. Nitrosylates the active site Cys of CASP3 in response to
CC       nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the
CC       FOS/JUN AP-1 DNA binding activity in ionizing radiation (IR) cells
CC       through its oxidation/reduction status and stimulates AP-1
CC       transcriptional activity (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: ADF augments the expression of the interleukin-2 receptor TAC
CC       (IL2R/P55).
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with TXNIP through the
CC       redox-active site. Interacts with MAP3K5 and CASP3. Interacts with
CC       APEX1; the interaction stimulates the FOS/JUN AP-1 DNA-binding activity
CC       in a redox-dependent manner (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P10599}. Cytoplasm
CC       {ECO:0000250|UniProtKB:P10599}. Secreted
CC       {ECO:0000250|UniProtKB:P10599}. Note=Translocates from the cytoplasm
CC       into the nucleus after phorbol 12-myristate 13-acetate induction (PMA).
CC       Predominantly in the cytoplasm in non irradiated cells. Radiation
CC       induces translocation of TRX from the cytoplasm to the nucleus.
CC       Secreted by a leaderless secretory pathway.
CC       {ECO:0000250|UniProtKB:P10599}.
CC   -!- PTM: In the fully reduced protein, both Cys-69 and Cys-73 are
CC       nitrosylated in response to nitric oxide (NO). When two disulfide bonds
CC       are present in the protein, only Cys-73 is nitrosylated. Cys-73 can
CC       serve as donor for nitrosylation of target proteins (By similarity).
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the thioredoxin family. {ECO:0000305}.
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DR   EMBL; X77585; CAA54688.1; -; mRNA.
DR   EMBL; D21859; BAA04881.1; -; Genomic_DNA.
DR   EMBL; AK007537; BAB25096.1; -; mRNA.
DR   EMBL; AK007790; BAB25256.1; -; mRNA.
DR   EMBL; BC010756; AAH10756.1; -; mRNA.
DR   EMBL; BC094415; AAH94415.1; -; mRNA.
DR   CCDS; CCDS18207.1; -.
DR   PIR; JC4068; S04107.
DR   RefSeq; NP_035790.1; NM_011660.3.
DR   AlphaFoldDB; P10639; -.
DR   SMR; P10639; -.
DR   BioGRID; 204389; 39.
DR   FunCoup; P10639; 1766.
DR   IntAct; P10639; 3.
DR   MINT; P10639; -.
DR   STRING; 10090.ENSMUSP00000030051; -.
DR   ChEMBL; CHEMBL6067621; -.
DR   GlyGen; P10639; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P10639; -.
DR   PhosphoSitePlus; P10639; -.
DR   SwissPalm; P10639; -.
DR   CPTAC; non-CPTAC-3884; -.
DR   jPOST; P10639; -.
DR   PaxDb; 10090-ENSMUSP00000030051; -.
DR   PeptideAtlas; P10639; -.
DR   ProteomicsDB; 262978; -.
DR   Pumba; P10639; -.
DR   TopDownProteomics; P10639; -.
DR   Antibodypedia; 3281; 868 antibodies from 43 providers.
DR   DNASU; 22166; -.
DR   Ensembl; ENSMUST00000030051.6; ENSMUSP00000030051.6; ENSMUSG00000028367.6.
DR   GeneID; 22166; -.
DR   KEGG; mmu:22166; -.
DR   UCSC; uc008syp.1; mouse.
DR   AGR; MGI:98874; -.
DR   CTD; 22166; -.
DR   MGI; MGI:98874; Txn1.
DR   VEuPathDB; HostDB:ENSMUSG00000028367; -.
DR   eggNOG; KOG0907; Eukaryota.
DR   GeneTree; ENSGT00940000154259; -.
DR   HOGENOM; CLU_090389_14_6_1; -.
DR   InParanoid; P10639; -.
DR   OMA; KQLWRQS; -.
DR   OrthoDB; 2121326at2759; -.
DR   PhylomeDB; P10639; -.
DR   Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
DR   Reactome; R-MMU-3299685; Detoxification of Reactive Oxygen Species.
DR   Reactome; R-MMU-499943; Interconversion of nucleotide di- and triphosphates.
DR   Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR   Reactome; R-MMU-5676934; Protein repair.
DR   Reactome; R-MMU-844456; The NLRP3 inflammasome.
DR   BioGRID-ORCS; 22166; 27 hits in 79 CRISPR screens.
DR   PRO; PR:P10639; -.
DR   Proteomes; UP000000589; Chromosome 4.
DR   RNAct; P10639; protein.
DR   Bgee; ENSMUSG00000028367; Expressed in jejunum and 71 other cell types or tissues.
DR   GO; GO:0030424; C:axon; ISO:GO_Central.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; IDA:MGI.
DR   GO; GO:0030425; C:dendrite; ISO:GO_Central.
DR   GO; GO:0005576; C:extracellular region; ISO:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0043025; C:neuronal cell body; ISO:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; ISO:GO_Central.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0019899; F:enzyme binding; ISO:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:GO_Central.
DR   GO; GO:0047134; F:protein-disulfide reductase [NAD(P)H] activity; ISO:GO_Central.
DR   GO; GO:0015035; F:protein-disulfide reductase activity; IDA:MGI.
DR   GO; GO:0045454; P:cell redox homeostasis; IDA:MGI.
DR   GO; GO:0061692; P:cellular detoxification of hydrogen peroxide; ISO:GO_Central.
DR   GO; GO:0046826; P:negative regulation of protein export from nucleus; IDA:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR   GO; GO:0043388; P:positive regulation of DNA binding; ISS:UniProtKB.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:GO_Central.
DR   GO; GO:0071731; P:response to nitric oxide; ISO:GO_Central.
DR   GO; GO:0009314; P:response to radiation; ISS:UniProtKB.
DR   CDD; cd02947; TRX_family; 1.
DR   FunFam; 3.40.30.10:FF:000130; Thioredoxin; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 1.
DR   InterPro; IPR005746; Thioredoxin.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   InterPro; IPR017937; Thioredoxin_CS.
DR   InterPro; IPR013766; Thioredoxin_domain.
DR   PANTHER; PTHR46115; THIOREDOXIN-LIKE PROTEIN 1; 1.
DR   Pfam; PF00085; Thioredoxin; 1.
DR   PIRSF; PIRSF000077; Thioredoxin; 1.
DR   PRINTS; PR00421; THIOREDOXIN.
DR   SUPFAM; SSF52833; Thioredoxin-like; 1.
DR   PROSITE; PS00194; THIOREDOXIN_1; 1.
DR   PROSITE; PS51352; THIOREDOXIN_2; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Activator; Cytoplasm; Disulfide bond; Electron transport;
KW   Nucleus; Redox-active center; Reference proteome; S-nitrosylation;
KW   Secreted; Transcription; Transcription regulation; Transport.
FT   CHAIN           1..105
FT                   /note="Thioredoxin"
FT                   /id="PRO_0000120007"
FT   DOMAIN          2..105
FT                   /note="Thioredoxin"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   ACT_SITE        32
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        35
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   SITE            26
FT                   /note="Deprotonates C-terminal active site Cys"
FT                   /evidence="ECO:0000250"
FT   SITE            33
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250"
FT   SITE            34
FT                   /note="Contributes to redox potential value"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         3
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P10599"
FT   MOD_RES         8
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         39
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         62
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P10599"
FT   MOD_RES         69
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P10599"
FT   MOD_RES         73
FT                   /note="S-nitrosocysteine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P10599"
FT   MOD_RES         94
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         94
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   DISULFID        32..35
FT                   /note="Redox-active"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT   DISULFID        73
FT                   /note="Interchain; alternate"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        100
FT                   /note="S -> C (in Ref. 4; BAB25256)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   105 AA;  11675 MW;  3A2B925935F952DA CRC64;
     MVKLIESKEA FQEALAAAGD KLVVVDFSAT WCGPCKMIKP FFHSLCDKYS NVVFLEVDVD
     DCQDVAADCE VKCMPTFQFY KKGQKVGEFS GANKEKLEAS ITEYA
//