Thioredoxin

NameThioredoxin
Synonyms
  • ADF
  • ATL-derived factor
  • SASP
  • Surface-associated sulphydryl protein
  • TRDX
  • TRX
  • TRX1
Gene NameTXN
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008733|Thioredoxin
MVKQIESKTAFQEALDAAGDKLVVVDFSATWCGPCKMIKPFFHSLSEKYSNVIFLEVDVD
DCQDVASECEVKCMPTFQFFKKGQKVGEFSGANKEKLEATINELV
Number of residues105
Molecular Weight11737.42
Theoretical pINot Available
GO Classification
Functions
  • oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor
  • peptide disulfide oxidoreductase activity
  • protein disulfide oxidoreductase activity
  • poly(A) RNA binding
Processes
  • glycerol ether metabolic process
  • innate immune response
  • signal transduction
  • oxidation-reduction process
  • regulation of protein import into nucleus, translocation
  • positive regulation of peptidyl-serine phosphorylation
  • protein folding
  • nucleobase-containing small molecule metabolic process
  • negative regulation of transcription from RNA polymerase II promoter
  • movement of cell or subcellular component
  • cell-cell signaling
  • negative regulation of hydrogen peroxide-induced cell death
  • response to radiation
  • nucleobase-containing small molecule interconversion
  • cell redox homeostasis
  • cell proliferation
  • positive regulation of DNA binding
  • sulfate assimilation
  • positive regulation of protein kinase B signaling
  • gene expression
  • activation of protein kinase B activity
  • small molecule metabolic process
  • response to reactive oxygen species
  • transcription initiation from RNA polymerase II promoter
  • negative regulation of protein export from nucleus
  • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
Components
  • cytoplasm
  • nucleoplasm
  • mitochondrion
  • nucleus
  • cytosol
  • extracellular exosome
General FunctionProtein disulfide oxidoreductase activity
Specific FunctionParticipates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA-binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity.ADF augments the expression of the interleukin-2 receptor TAC (IL2R/P55).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP10599
UniProtKB Entry NameTHIO_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0017575|Thioredoxin (TXN)
ATGGTGAAGCAGATCGAGAGCAAGACTGCTTTTCAGGAAGCCTTGGACGCTGCAGGTGAT
AAACTTGTAGTAGTTGACTTCTCAGCCACGTGGTGTGGGCCTTGCAAAATGATCAAGCCT
TTCTTTCATGATGTTGCTTCAGAGTGTGAAGTCAAATGCATGCCAACATTCCAGTTTTTT
AAGAAGGGACAAAAGGTGGGTGAATTTTCTGGAGCCAATAAGGAAAAGCTTGAAGCCACC
ATTAATGAATTAGTCTAA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:12435
Chromosome Location9
LocusNot Available
References
  1. Wollman EE, d'Auriol L, Rimsky L, Shaw A, Jacquot JP, Wingfield P, Graber P, Dessarps F, Robin P, Galibert F, et al.: Cloning and expression of a cDNA for human thioredoxin. J Biol Chem. 1988 Oct 25;263(30):15506-12. 3170595
  2. Tagaya Y, Maeda Y, Mitsui A, Kondo N, Matsui H, Hamuro J, Brown N, Arai K, Yokota T, Wakasugi H, et al.: ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction. EMBO J. 1989 Mar;8(3):757-64. 2785919
  3. Tonissen KF, Wells JR: Isolation and characterization of human thioredoxin-encoding genes. Gene. 1991 Jun 30;102(2):221-8. 1874447
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  5. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. 15164053
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Dean MF, Martin H, Sansom PA: Characterization of a thioredoxin-related surface protein. Biochem J. 1994 Dec 15;304 ( Pt 3):861-7. 7818492
  8. Martin H, Dean M: Identification of a thioredoxin-related protein associated with plasma membranes. Biochem Biophys Res Commun. 1991 Feb 28;175(1):123-8. 1998498
  9. Jacquot JP, de Lamotte F, Fontecave M, Schurmann P, Decottignies P, Miginiac-Maslow M, Wollman E: Human thioredoxin reactivity-structure/function relationship. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1375-81. 2176490
  10. Rubartelli A, Bajetto A, Allavena G, Wollman E, Sitia R: Secretion of thioredoxin by normal and neoplastic cells through a leaderless secretory pathway. J Biol Chem. 1992 Dec 5;267(34):24161-4. 1332947
  11. Hirota K, Matsui M, Iwata S, Nishiyama A, Mori K, Yodoi J: AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3633-8. 9108029
  12. Wei SJ, Botero A, Hirota K, Bradbury CM, Markovina S, Laszlo A, Spitz DR, Goswami PC, Yodoi J, Gius D: Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation. Cancer Res. 2000 Dec 1;60(23):6688-95. 11118054
  13. Yasinska IM, Kozhukhar AV, Sumbayev VV: S-nitrosation of thioredoxin in the nitrogen monoxide/superoxide system activates apoptosis signal-regulating kinase 1. Arch Biochem Biophys. 2004 Aug 15;428(2):198-203. 15246877
  14. Mitchell DA, Marletta MA: Thioredoxin catalyzes the S-nitrosation of the caspase-3 active site cysteine. Nat Chem Biol. 2005 Aug;1(3):154-8. Epub 2005 Jul 10. 16408020
  15. Mitchell DA, Morton SU, Fernhoff NB, Marletta MA: Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11609-14. Epub 2007 Jul 2. 17606900
  16. Bernal-Bayard J, Ramos-Morales F: Salmonella type III secretion effector SlrP is an E3 ubiquitin ligase for mammalian thioredoxin. J Biol Chem. 2009 Oct 2;284(40):27587-95. doi: 10.1074/jbc.M109.010363. Epub 2009 Aug 18. 19690162
  17. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. 19608861
  18. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  19. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  20. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  21. Forman-Kay JD, Clore GM, Driscoll PC, Wingfield P, Richards FM, Gronenborn AM: A proton nuclear magnetic resonance assignment and secondary structure determination of recombinant human thioredoxin. Biochemistry. 1989 Aug 22;28(17):7088-97. 2684271
  22. Forman-Kay JD, Clore GM, Wingfield PT, Gronenborn AM: High-resolution three-dimensional structure of reduced recombinant human thioredoxin in solution. Biochemistry. 1991 Mar 12;30(10):2685-98. 2001356
  23. Qin J, Clore GM, Gronenborn AM: The high-resolution three-dimensional solution structures of the oxidized and reduced states of human thioredoxin. Structure. 1994 Jun 15;2(6):503-22. 7922028
  24. Qin J, Clore GM, Kennedy WM, Huth JR, Gronenborn AM: Solution structure of human thioredoxin in a mixed disulfide intermediate complex with its target peptide from the transcription factor NF kappa B. Structure. 1995 Mar 15;3(3):289-97. 7788295
  25. Qin J, Clore GM, Kennedy WP, Kuszewski J, Gronenborn AM: The solution structure of human thioredoxin complexed with its target from Ref-1 reveals peptide chain reversal. Structure. 1996 May 15;4(5):613-20. 8736558
  26. Weichsel A, Gasdaska JR, Powis G, Montfort WR: Crystal structures of reduced, oxidized, and mutated human thioredoxins: evidence for a regulatory homodimer. Structure. 1996 Jun 15;4(6):735-51. 8805557
  27. Andersen JF, Sanders DA, Gasdaska JR, Weichsel A, Powis G, Montfort WR: Human thioredoxin homodimers: regulation by pH, role of aspartate 60, and crystal structure of the aspartate 60 --> asparagine mutant. Biochemistry. 1997 Nov 18;36(46):13979-88. 9369469
  28. Weichsel A, Brailey JL, Montfort WR: Buried S-nitrosocysteine revealed in crystal structures of human thioredoxin. Biochemistry. 2007 Feb 6;46(5):1219-27. 17260951