ID THIO_HUMAN Reviewed; 105 AA. AC P10599; B1ALW1; O60744; Q53X69; Q96KI3; Q9UDG5; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 09-DEC-2015, entry version 191. DE RecName: Full=Thioredoxin; DE Short=Trx; DE AltName: Full=ATL-derived factor; DE Short=ADF; DE AltName: Full=Surface-associated sulphydryl protein; DE Short=SASP; GN Name=TXN; Synonyms=TRDX, TRX, TRX1; 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 1). RX PubMed=3170595; RA Wollman E.E., D'Auriol L., Rimsky L., Shaw A., Jacquot J.-P., RA Wingfield P., Graber P., Dessarps F.; RT "Cloning and expression of a cDNA for human thioredoxin."; RL J. Biol. Chem. 263:15506-15512(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2785919; RA Tagaya Y., Maeda Y., Mitsui A., Kndo N., Matsui H., Hamuro J., RA Brown N., 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 RT receptor induction."; RL EMBO J. 8:757-764(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1874447; DOI=10.1016/0378-1119(91)90081-L; RA Tonissen K.F., Wells J.R.E.; RT "Isolation and characterization of human thioredoxin-encoding genes."; RL Gene 102:221-228(1991). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Lens; RA Reddy P.G., Bhuyan D.K., Bhuyan K.C.; RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Lens; RA Liu A., Lou M.F.; RT "Cloning, purification and characterization of human lens RT thioredoxin."; RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Xu J.Y., Xu L., Li K.S., Dai R.; RT "Cloning and sequencing of thioredoxin cDNA from human brain."; RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Cervix; 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 [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-85 (ISOFORM 2), AND ALTERNATIVE RP SPLICING. RC TISSUE=Liver; RA Wang Y., Wang Y.G., Zhang Y., Yuan Y., Ma D.; RT "An alternative splice variant of human thioredoxin."; RL Chin. Sci. Bull. 43:292-295(1998). RN [14] RP PROTEIN SEQUENCE OF 2-21 AND 38-57. RC TISSUE=Monocyte; RX PubMed=7818492; RA Dean M.F., Martin H., Sansom P.A.; RT "Characterization of a thioredoxin-related surface protein."; RL Biochem. J. 304:861-867(1994). RN [15] RP PROTEIN SEQUENCE OF 2-15. RX PubMed=1998498; DOI=10.1016/S0006-291X(05)81209-4; RA Martin H., Dean M.; RT "Identification of a thioredoxin-related protein associated with RT plasma membranes."; RL Biochem. Biophys. Res. Commun. 175:123-128(1991). RN [16] RP PROTEIN SEQUENCE OF 9-48; 73-81 AND 95-105, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex; RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [17] RP FUNCTION. RX PubMed=2176490; DOI=10.1016/S0006-291X(05)80940-4; RA Jacquot J.-P., de Lamotte F., Fontecav M., Schuermann P., RA Decottignies P., Miginiac-Maslow M., Wollman E.; RT "Human thioredoxin reactivity-structure/function relationship."; RL Biochem. Biophys. Res. Commun. 173:1375-1381(1990). RN [18] RP SUBCELLULAR LOCATION. RX PubMed=1332947; RA Rubartelli A., Bajetto A., Allavena G., Wollman E., Sitia R.; RT "Secretion of thioredoxin by normal and neoplastic cells through a RT leaderless secretory pathway."; RL J. Biol. Chem. 267:24161-24164(1992). RN [19] RP FUNCTION, SUBUNIT, INTERACTION WITH APEX1, MUTAGENESIS OF CYS-32; RP CYS-35; CYS-62; CYS-69 AND CYS-73, AND SUBCELLULAR LOCATION. RX PubMed=9108029; DOI=10.1073/pnas.94.8.3633; RA Hirota K., Matsui M., Iwata S., Nishiyama A., Mori K., Yodoi J.; RT "AP-1 transcriptional activity is regulated by a direct association RT between thioredoxin and Ref-1."; RL Proc. Natl. Acad. Sci. U.S.A. 94:3633-3638(1997). RN [20] RP FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION. RX PubMed=11118054; RA Wei S.J., Botero A., Hirota K., Bradbury C.M., Markovina S., RA Laszlo A., Spitz D.R., Goswami P.C., Yodoi J., Gius D.; RT "Thioredoxin nuclear translocation and interaction with redox factor-1 RT activates the activator protein-1 transcription factor in response to RT ionizing radiation."; RL Cancer Res. 60:6688-6695(2000). RN [21] RP S-NITROSYLATION, AND INTERACTION WITH MAP3K5. RX PubMed=15246877; DOI=10.1016/j.abb.2004.06.004; RA Yasinska I.M., Kozhukhar A.V., Sumbayev V.V.; RT "S-nitrosation of thioredoxin in the nitrogen monoxide/superoxide RT system activates apoptosis signal-regulating kinase 1."; RL Arch. Biochem. Biophys. 428:198-203(2004). RN [22] RP FUNCTION, MUTAGENESIS OF CYS-73, AND S-NITROSYLATION AT CYS-73. RX PubMed=16408020; DOI=10.1038/nchembio720; RA Mitchell D.A., Marletta M.A.; RT "Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site RT cysteine."; RL Nat. Chem. Biol. 1:154-158(2005). RN [23] RP FUNCTION, MUTAGENESIS OF CYS-69; GLU-70; LYS-72 AND CYS-73, AND RP S-NITROSYLATION AT CYS-73 IN RESPONSE TO NITRIC OXIDE. RX PubMed=17606900; DOI=10.1073/pnas.0704898104; RA Mitchell D.A., Morton S.U., Fernhoff N.B., Marletta M.A.; RT "Thioredoxin is required for S-nitrosation of procaspase-3 and the RT inhibition of apoptosis in Jurkat cells."; RL Proc. Natl. Acad. Sci. U.S.A. 104:11609-11614(2007). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Mammary cancer; RA Ahamed M.E., Ahmed M.E., Eltoum A.M., Altahir G.O., Ahmed K.M., RA Harbi S.O., Stansalas J., Mohamed A.O.; RT "Abnormal proteins in primary breast cancer tissues from 25 Sudanese RT patients."; RL Eur. J. Inflamm. 6:115-121(2008). RN [25] RP INTERACTION WITH S.TYPHIMURIUM SLRP, AND UBIQUITINATION. RX PubMed=19690162; DOI=10.1074/jbc.M109.010363; RA Bernal-Bayard J., Ramos-Morales F.; RT "Salmonella type III secretion effector SlrP is an E3 ubiquitin ligase RT for mammalian thioredoxin."; RL J. Biol. Chem. 284:27587-27595(2009). RN [26] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-3 AND LYS-39, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [27] 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 [28] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [29] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [30] RP STRUCTURE BY NMR. RX PubMed=2684271; DOI=10.1021/bi00443a045; RA Forman-Kay J.D., Clore G.M., Dricoll P.C., Wingfield P., RA Richards F.M., Gronenborn A.M.; RT "A proton nuclear magnetic resonance assignment and secondary RT structure determination of recombinant human thioredoxin."; RL Biochemistry 28:7088-7097(1989). RN [31] RP STRUCTURE BY NMR. RX PubMed=2001356; DOI=10.1021/bi00224a017; RA Forman-Kay J.D., Clore G.M., Wingfield P., Gronenborn A.M.; RT "High-resolution three-dimensional structure of reduced recombinant RT human thioredoxin in solution."; RL Biochemistry 30:2685-2698(1991). RN [32] RP STRUCTURE BY NMR. RX PubMed=7922028; DOI=10.1016/S0969-2126(00)00051-4; RA Qin J., Clore G.M., Gronenborn A.M.; RT "The high-resolution three-dimensional solution structures of the RT oxidized and reduced states of human thioredoxin."; RL Structure 2:503-522(1994). RN [33] RP STRUCTURE BY NMR. RX PubMed=7788295; DOI=10.1016/S0969-2126(01)00159-9; RA Qin J., Clore G.M., Kennedy W.M., Huth J.R., Gronenborn A.M.; RT "Solution structure of human thioredoxin in a mixed disulfide RT intermediate complex with its target peptide from the transcription RT factor NF kappa B."; RL Structure 3:289-297(1995). RN [34] RP STRUCTURE BY NMR. RX PubMed=8736558; DOI=10.1016/S0969-2126(96)00065-2; RA Qin J., Clore G.M., Kennedy W.P., Kuszewski J., Gronenborn A.M.; RT "The solution structure of human thioredoxin complexed with its target RT from Ref-1 reveals peptide chain reversal."; RL Structure 4:613-620(1996). RN [35] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS). RX PubMed=8805557; DOI=10.1016/S0969-2126(96)00079-2; RA Weichsel A., Gasdaska J.R., Powis G., Montfort W.R.; RT "Crystal structures of reduced, oxidized, and mutated human RT thioredoxins: evidence for a regulatory homodimer."; RL Structure 4:735-751(1996). RN [36] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF MUTANT ASN-60, AND SUBUNIT. RX PubMed=9369469; DOI=10.1021/bi971004s; RA Andersen J.F., Sanders D.A., Gasdaska J.R., Weichsel A., Powis G., RA Montfort W.R.; RT "Human thioredoxin homodimers: regulation by pH, role of aspartate 60, RT and crystal structure of the aspartate 60 --> asparagine mutant."; RL Biochemistry 36:13979-13988(1997). RN [37] RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS), SUBUNIT, DISULFIDE BONDS, AND RP S-NITROSYLATION AT CYS-62 AND CYS-69. RX PubMed=17260951; DOI=10.1021/bi061878r; RA Weichsel A., Brailey J.L., Montfort W.R.; RT "Buried S-nitrosocysteine revealed in crystal structures of human RT thioredoxin."; RL Biochemistry 46:1219-1227(2007). CC -!- FUNCTION: Participates in various redox reactions through the CC reversible oxidation of its active center dithiol to a disulfide CC and catalyzes dithiol-disulfide exchange reactions. Plays a role CC 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 CC response to nitric oxide (NO), and thereby inhibits caspase-3 CC activity. Induces the FOS/JUN AP-1 DNA-binding activity in CC ionizing radiation (IR) cells through its oxidation/reduction CC status and stimulates AP-1 transcriptional activity. CC -!- FUNCTION: ADF augments the expression of the interleukin-2 CC receptor TAC (IL2R/P55). CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with TXNIP through CC the redox-active site. Interacts with MAP3K5 and CASP3. In case of CC infection, interacts with S.typhimurium protein slrP. Interacts CC with APEX1; the interaction stimulates the FOS/JUN AP-1 DNA- CC binding activity in a redox-dependent manner. CC {ECO:0000269|PubMed:15246877, ECO:0000269|PubMed:17260951, CC ECO:0000269|PubMed:19690162, ECO:0000269|PubMed:9108029, CC ECO:0000269|PubMed:9369469}. CC -!- INTERACTION: CC Q92905:COPS5; NbExp=8; IntAct=EBI-594644, EBI-594661; CC P00533:EGFR; NbExp=4; IntAct=EBI-594644, EBI-297353; CC Q99683:MAP3K5; NbExp=2; IntAct=EBI-594644, EBI-476263; CC Q99836:MYD88; NbExp=4; IntAct=EBI-594644, EBI-447677; CC P18031:PTPN1; NbExp=2; IntAct=EBI-594644, EBI-968788; CC D0ZRB2:slrP (xeno); NbExp=7; IntAct=EBI-594644, EBI-10762386; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Secreted. Note=Secreted CC by a leaderless secretory pathway. Predominantly in the cytoplasm CC in non irradiated cells. Radiation induces translocation of TRX CC from the cytoplasm to the nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P10599-1; Sequence=Displayed; CC Name=2; CC IsoId=P10599-2; Sequence=VSP_045607; CC -!- INDUCTION: Up-regulated by ionizing radiation. CC {ECO:0000269|PubMed:11118054}. 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 CC bonds are present in the protein, only Cys-73 is nitrosylated. CC Cys-73 can serve as donor for nitrosylation of target proteins. CC {ECO:0000269|PubMed:15246877, ECO:0000269|PubMed:16408020, CC ECO:0000269|PubMed:17260951, ECO:0000269|PubMed:17606900}. CC -!- PTM: In case of infection, ubiquitinated by S.typhimurium protein CC slrP, leading to its degradation. {ECO:0000269|PubMed:19690162}. CC -!- SIMILARITY: Belongs to the thioredoxin family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 thioredoxin domain. {ECO:0000255|PROSITE- CC ProRule:PRU00691}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/txn/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/TXNID44354ch9q31.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J04026; AAA74596.1; -; mRNA. DR EMBL; X77584; CAA54687.1; -; mRNA. DR EMBL; X54539; CAA38410.1; -; Genomic_DNA. DR EMBL; X54540; CAA38410.1; JOINED; Genomic_DNA. DR EMBL; X54541; CAA38410.1; JOINED; Genomic_DNA. DR EMBL; AF276919; AAF86466.1; -; mRNA. DR EMBL; AY004872; AAF87085.1; -; mRNA. DR EMBL; AF313911; AAG34699.1; -; mRNA. DR EMBL; AK289508; BAF82197.1; -; mRNA. DR EMBL; CR407665; CAG28593.1; -; mRNA. DR EMBL; AF548001; AAN33187.1; -; Genomic_DNA. DR EMBL; AL158158; CAI14066.1; -; Genomic_DNA. DR EMBL; AL158158; CAI14067.1; -; Genomic_DNA. DR EMBL; CH471105; EAW59059.1; -; Genomic_DNA. DR EMBL; CH471105; EAW59060.1; -; Genomic_DNA. DR EMBL; BC003377; AAH03377.1; -; mRNA. DR EMBL; BC054866; AAH54866.1; -; mRNA. DR EMBL; AF065241; AAC17430.1; -; mRNA. DR CCDS; CCDS35103.1; -. [P10599-1] DR CCDS; CCDS59139.1; -. [P10599-2] DR PIR; JH0568; JH0568. DR RefSeq; NP_001231867.1; NM_001244938.1. [P10599-2] DR RefSeq; NP_003320.2; NM_003329.3. [P10599-1] DR UniGene; Hs.435136; -. DR PDB; 1AIU; X-ray; 2.00 A; A=1-105. DR PDB; 1AUC; X-ray; 2.10 A; A=1-105. DR PDB; 1CQG; NMR; -; A=1-105. DR PDB; 1CQH; NMR; -; A=1-105. DR PDB; 1ERT; X-ray; 1.70 A; A=1-105. DR PDB; 1ERU; X-ray; 2.10 A; A=1-105. DR PDB; 1ERV; X-ray; 1.65 A; A=1-105. DR PDB; 1ERW; X-ray; 1.80 A; A=1-105. DR PDB; 1M7T; NMR; -; A=1-66. DR PDB; 1MDI; NMR; -; A=1-105. DR PDB; 1MDJ; NMR; -; A=1-105. DR PDB; 1MDK; NMR; -; A=1-105. DR PDB; 1TRS; NMR; -; A=1-105. DR PDB; 1TRU; NMR; -; A=1-105. DR PDB; 1TRV; NMR; -; A=1-105. DR PDB; 1TRW; NMR; -; A=1-105. DR PDB; 1W1C; Model; -; C=1-105. DR PDB; 1W1E; Model; -; C=1-105. DR PDB; 2HSH; X-ray; 1.35 A; A=1-105. DR PDB; 2HXK; X-ray; 1.65 A; A/B/C=1-105. DR PDB; 2IFQ; X-ray; 1.20 A; A/B/C=1-105. DR PDB; 2IIY; X-ray; 1.70 A; A=1-105. DR PDB; 3E3E; X-ray; 2.01 A; A/B=1-105. DR PDB; 3KD0; X-ray; 1.70 A; A=1-105. DR PDB; 3M9J; X-ray; 1.10 A; A/B=1-105. DR PDB; 3M9K; X-ray; 1.50 A; A/B=1-105. DR PDB; 3QFA; X-ray; 2.20 A; C/D=2-105. DR PDB; 3QFB; X-ray; 2.60 A; C/D=2-105. DR PDB; 3TRX; NMR; -; A=1-105. DR PDB; 4LL1; X-ray; 2.00 A; B/D=1-105. DR PDB; 4LL4; X-ray; 2.70 A; B/D=1-105. DR PDB; 4OO4; X-ray; 0.97 A; A/B=1-105. DR PDB; 4OO5; X-ray; 1.54 A; A=1-105. DR PDB; 4POK; X-ray; 2.52 A; A/B/C/D=1-105. DR PDB; 4POL; X-ray; 2.80 A; A/B/C/D=1-105. DR PDB; 4POM; X-ray; 1.85 A; A/B/C/D=1-105. DR PDB; 4PUF; X-ray; 3.30 A; C/D=1-105. DR PDB; 4TRX; NMR; -; A=1-105. DR PDBsum; 1AIU; -. DR PDBsum; 1AUC; -. DR PDBsum; 1CQG; -. DR PDBsum; 1CQH; -. DR PDBsum; 1ERT; -. DR PDBsum; 1ERU; -. DR PDBsum; 1ERV; -. DR PDBsum; 1ERW; -. DR PDBsum; 1M7T; -. DR PDBsum; 1MDI; -. DR PDBsum; 1MDJ; -. DR PDBsum; 1MDK; -. DR PDBsum; 1TRS; -. DR PDBsum; 1TRU; -. DR PDBsum; 1TRV; -. DR PDBsum; 1TRW; -. DR PDBsum; 1W1C; -. DR PDBsum; 1W1E; -. DR PDBsum; 2HSH; -. DR PDBsum; 2HXK; -. DR PDBsum; 2IFQ; -. DR PDBsum; 2IIY; -. DR PDBsum; 3E3E; -. DR PDBsum; 3KD0; -. DR PDBsum; 3M9J; -. DR PDBsum; 3M9K; -. DR PDBsum; 3QFA; -. DR PDBsum; 3QFB; -. DR PDBsum; 3TRX; -. DR PDBsum; 4LL1; -. DR PDBsum; 4LL4; -. DR PDBsum; 4OO4; -. DR PDBsum; 4OO5; -. DR PDBsum; 4POK; -. DR PDBsum; 4POL; -. DR PDBsum; 4POM; -. DR PDBsum; 4PUF; -. DR PDBsum; 4TRX; -. DR ProteinModelPortal; P10599; -. DR SMR; P10599; 1-105. DR BioGrid; 113146; 96. DR DIP; DIP-6129N; -. DR IntAct; P10599; 37. DR MINT; MINT-1522967; -. DR STRING; 9606.ENSP00000363641; -. DR BindingDB; P10599; -. DR ChEMBL; CHEMBL2010624; -. DR Allergome; 3543; Hom s Trx. DR PhosphoSite; P10599; -. DR BioMuta; TXN; -. DR DMDM; 135773; -. DR DOSAC-COBS-2DPAGE; P10599; -. DR REPRODUCTION-2DPAGE; IPI00216298; -. DR SWISS-2DPAGE; P10599; -. DR MaxQB; P10599; -. DR PaxDb; P10599; -. DR PeptideAtlas; P10599; -. DR PRIDE; P10599; -. DR DNASU; 7295; -. DR Ensembl; ENST00000374515; ENSP00000363639; ENSG00000136810. [P10599-2] DR Ensembl; ENST00000374517; ENSP00000363641; ENSG00000136810. [P10599-1] DR GeneID; 7295; -. DR KEGG; hsa:7295; -. DR UCSC; uc004bep.2; human. [P10599-1] DR UCSC; uc004beq.2; human. DR CTD; 7295; -. DR GeneCards; TXN; -. DR HGNC; HGNC:12435; TXN. DR HPA; CAB008678; -. DR HPA; HPA047478; -. DR MIM; 187700; gene. DR neXtProt; NX_P10599; -. DR PharmGKB; PA37091; -. DR eggNOG; KOG0907; Eukaryota. DR eggNOG; COG0526; LUCA. DR GeneTree; ENSGT00530000063008; -. DR HOGENOM; HOG000292977; -. DR HOVERGEN; HBG009243; -. DR InParanoid; P10599; -. DR KO; K03671; -. DR OMA; AISTHCA; -. DR OrthoDB; EOG7H4DX9; -. DR PhylomeDB; P10599; -. DR TreeFam; TF318932; -. DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species. DR Reactome; R-HSA-499943; Synthesis and interconversion of nucleotide di- and triphosphates. DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. DR Reactome; R-HSA-844456; The NLRP3 inflammasome. DR SignaLink; P10599; -. DR ChiTaRS; TXN; human. DR EvolutionaryTrace; P10599; -. DR GeneWiki; Thioredoxin; -. DR GenomeRNAi; 7295; -. DR NextBio; 28523; -. DR PRO; PR:P10599; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; P10599; -. DR CleanEx; HS_TXN; -. DR ExpressionAtlas; P10599; baseline and differential. DR Genevisible; P10599; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0016671; F:oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor; IBA:GO_Central. DR GO; GO:0015037; F:peptide disulfide oxidoreductase activity; IEA:Ensembl. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0015035; F:protein disulfide oxidoreductase activity; IBA:GO_Central. DR GO; GO:0032148; P:activation of protein kinase B activity; IC:ParkinsonsUK-UCL. DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc. DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0034599; P:cellular response to oxidative stress; IBA:GO_Central. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0006662; P:glycerol ether metabolic process; IEA:InterPro. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0006928; P:movement of cell or subcellular component; TAS:ProtInc. DR GO; GO:1903206; P:negative regulation of hydrogen peroxide-induced cell death; IGI:ParkinsonsUK-UCL. DR GO; GO:0046826; P:negative regulation of protein export from nucleus; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome. DR GO; GO:0055086; P:nucleobase-containing small molecule metabolic process; TAS:Reactome. DR GO; GO:0035872; P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway; TAS:Reactome. DR GO; GO:0055114; P:oxidation-reduction process; IDA:UniProtKB. DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IGI:ParkinsonsUK-UCL. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IC:ParkinsonsUK-UCL. DR GO; GO:0006457; P:protein folding; IBA:GO_Central. DR GO; GO:0033158; P:regulation of protein import into nucleus, translocation; IDA:UniProtKB. DR GO; GO:0009314; P:response to radiation; IDA:UniProtKB. DR GO; GO:0000302; P:response to reactive oxygen species; TAS:Reactome. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0000103; P:sulfate assimilation; IBA:GO_Central. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR Gene3D; 3.40.30.10; -; 1. DR InterPro; IPR005746; Thioredoxin. DR InterPro; IPR012336; Thioredoxin-like_fold. DR InterPro; IPR017937; Thioredoxin_CS. DR InterPro; IPR013766; Thioredoxin_domain. DR PANTHER; PTHR10438; PTHR10438; 1. DR Pfam; PF00085; Thioredoxin; 1. DR PIRSF; PIRSF000077; Thioredoxin; 1. DR SUPFAM; SSF52833; SSF52833; 1. DR PROSITE; PS00194; THIOREDOXIN_1; 1. DR PROSITE; PS51352; THIOREDOXIN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Complete proteome; Cytoplasm; Direct protein sequencing; KW Disulfide bond; Electron transport; Nucleus; Redox-active center; KW Reference proteome; S-nitrosylation; Secreted; Transcription; KW Transcription regulation; Transport; Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:1998498, FT ECO:0000269|PubMed:7818492}. FT CHAIN 2 105 Thioredoxin. FT /FTId=PRO_0000120005. FT DOMAIN 2 105 Thioredoxin. {ECO:0000255|PROSITE- FT ProRule:PRU00691}. FT ACT_SITE 32 32 Nucleophile. FT ACT_SITE 35 35 Nucleophile. FT SITE 26 26 Deprotonates C-terminal active site Cys. FT SITE 33 33 Contributes to redox potential value. FT SITE 34 34 Contributes to redox potential value. FT MOD_RES 3 3 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 8 8 N6-succinyllysine. FT {ECO:0000250|UniProtKB:P10639}. FT MOD_RES 39 39 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 62 62 S-nitrosocysteine. FT {ECO:0000269|PubMed:17260951}. FT MOD_RES 69 69 S-nitrosocysteine. FT {ECO:0000269|PubMed:17260951}. FT MOD_RES 73 73 S-nitrosocysteine; alternate. FT {ECO:0000269|PubMed:16408020, FT ECO:0000269|PubMed:17606900}. FT MOD_RES 94 94 N6-acetyllysine; alternate. FT {ECO:0000250|UniProtKB:P10639}. FT MOD_RES 94 94 N6-succinyllysine; alternate. FT {ECO:0000250|UniProtKB:P10639}. FT DISULFID 32 35 Redox-active. {ECO:0000255|PROSITE- FT ProRule:PRU00691, FT ECO:0000269|PubMed:17260951, FT ECO:0000269|PubMed:2001356}. FT DISULFID 73 73 Interchain; alternate. FT {ECO:0000269|PubMed:17260951}. FT VAR_SEQ 44 63 Missing (in isoform 2). FT {ECO:0000303|Ref.13}. FT /FTId=VSP_045607. FT MUTAGEN 32 32 C->S: Loses its reducing activity, FT interaction with APEX1 and transcription FT activation; when associated with S-35. FT {ECO:0000269|PubMed:9108029}. FT MUTAGEN 35 35 C->S: Loses its reducing activity, FT interaction with APEX1 and transcription FT activation; when associated with S-32. FT {ECO:0000269|PubMed:9108029}. FT MUTAGEN 60 60 D->N: Loss of pH-dependence of FT dimerization. FT MUTAGEN 62 62 C->S: Retains its reducing activity. FT Retains interaction with APEX1 and FT transcription activation; when associated FT with S-69 and S-73. FT {ECO:0000269|PubMed:9108029}. FT MUTAGEN 69 69 C->S: No effect on reducing activity, FT interaction with APEX1 and on S- FT nitrosylation of C-73. Retains FT interaction with APEX1 and transcription FT activation; when associated with S-62 and FT S-73. {ECO:0000269|PubMed:17606900, FT ECO:0000269|PubMed:9108029}. FT MUTAGEN 70 70 E->A: Strongly reduced interaction with FT CASP3; when associated with A-72. FT {ECO:0000269|PubMed:17606900}. FT MUTAGEN 72 72 K->A: Strongly reduced interaction with FT CASP3; when associated with A-70. FT {ECO:0000269|PubMed:17606900}. FT MUTAGEN 73 73 C->D: Strongly reduced S-nitrosylation of FT CASP3. {ECO:0000269|PubMed:16408020, FT ECO:0000269|PubMed:17606900, FT ECO:0000269|PubMed:9108029}. FT MUTAGEN 73 73 C->S: Loss of nitrosylation, and loss of FT S-nitrosylating activity towards CASP3. FT Retains interaction with APEX1 and FT transcription activation; when associated FT with S-62 and S-69. FT {ECO:0000269|PubMed:16408020, FT ECO:0000269|PubMed:17606900, FT ECO:0000269|PubMed:9108029}. FT MUTAGEN 73 73 C->S: Retains its reducing activity. FT {ECO:0000269|PubMed:16408020, FT ECO:0000269|PubMed:17606900, FT ECO:0000269|PubMed:9108029}. FT CONFLICT 39 39 K -> N (in Ref. 1; AAA74596 and 4; FT AAF86466). {ECO:0000305}. FT CONFLICT 74 74 M -> T (in Ref. 1; AAA74596 and 4; FT AAF86466). {ECO:0000305}. FT STRAND 3 5 {ECO:0000244|PDB:2IFQ}. FT HELIX 8 17 {ECO:0000244|PDB:4OO4}. FT TURN 18 20 {ECO:0000244|PDB:4OO4}. FT STRAND 23 28 {ECO:0000244|PDB:4OO4}. FT STRAND 30 32 {ECO:0000244|PDB:4TRX}. FT HELIX 33 48 {ECO:0000244|PDB:4OO4}. FT TURN 49 51 {ECO:0000244|PDB:3QFB}. FT STRAND 52 58 {ECO:0000244|PDB:4OO4}. FT TURN 59 62 {ECO:0000244|PDB:4OO4}. FT HELIX 63 69 {ECO:0000244|PDB:4OO4}. FT STRAND 73 81 {ECO:0000244|PDB:4OO4}. FT STRAND 84 91 {ECO:0000244|PDB:4OO4}. FT HELIX 94 104 {ECO:0000244|PDB:4OO4}. SQ SEQUENCE 105 AA; 11737 MW; 256F4E3C8A187693 CRC64; MVKQIESKTA FQEALDAAGD KLVVVDFSAT WCGPCKMIKP FFHSLSEKYS NVIFLEVDVD DCQDVASECE VKCMPTFQFF KKGQKVGEFS GANKEKLEAT INELV //