Thioredoxin

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Thioredoxin
PBB Protein TXN image.jpg
PDB rendering based on 1aiu.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols TXN ; TRDX; TRX; TRX1
External IDs OMIM187700 MGI98874 HomoloGene128202 GeneCards: TXN Gene
RNA expression pattern
PBB GE TXN 208864 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 7295 22166
Ensembl ENSG00000136810 ENSMUSG00000028367
UniProt P10599 P10639
RefSeq (mRNA) NM_001244938 NM_011660
RefSeq (protein) NP_001231867 NP_035790
Location (UCSC) Chr 9:
113.01 – 113.02 Mb
Chr 4:
57.94 – 57.96 Mb
PubMed search [1] [2]

Thioredoxin is a class of small redox proteins known to be present in all organisms. It plays a role in many important biological processes, including redox signaling. In humans, it is encoded by the TXN gene.[1] Loss-of-function mutation of either of the two human thioredoxin genes is lethal at the four-cell stage of the developing embryo. Although not entirely understood, thioredoxin plays a central role in humans and is increasingly linked to medicine through their response to reactive oxygen species (ROS). In plants, thioredoxins regulate a spectrum of critical functions, ranging from photosynthesis to growth, flowering and the development and germination of seeds. It has also recently been found to play a role in cell-to-cell communication.[2]

Function[edit]

Thioredoxins are proteins that act as antioxidants by facilitating the reduction of other proteins by cysteine thiol-disulfide exchange. Thioredoxins are found in nearly all known organisms and are essential for life in mammals.[3][4]

Thioredoxin is a 12-kD oxidoreductase enzyme containing a dithiol-disulfide active site. It is ubiquitous and found in many organisms from plants and bacteria to mammals. Multiple in vitro substrates for thioredoxin have been identified, including ribonuclease, choriogonadotropins, coagulation factors, glucocorticoid receptor, and insulin. Reduction of insulin is classically used as an activity test.[5]

Thioredoxins are characterized at the level of their amino acid sequence by the presence of two vicinal cysteines in a CXXC motif. These two cysteines are the key to the ability of thioredoxin to reduce other proteins. Thioredoxin proteins also have a characteristic tertiary structure termed the thioredoxin fold.

The thioredoxins are kept in the reduced state by the flavoenzyme thioredoxin reductase, in a NADPH-dependent reaction.[6] Thioredoxins act as electron donors to peroxidases and ribonucleotide reductase.[7] The related glutaredoxins share many of the functions of thioredoxins, but are reduced by glutathione rather than a specific reductase.

The benefit of thioredoxins to reduce oxidative stress is shown by transgenic mice that overexpress thioredoxin, are more resistant to inflammation, and live 35% longer[8] — supporting the free radical theory of aging. However, the controls of this study were short lived, which may have contributed to the apparent increase in longevity.[9]

Plants have an unusually complex complement of Trxs composed of six well-defined types (Trxs f, m, x, y, h, and o) that reside in different cell compartments and function in an array of processes. In 2010 it was discovered for the first time that thioredoxin proteins are able to move from cell to cell, representing a novel form of cellular communication in plants.[2]

Interactions[edit]

Thioredoxin has been shown to interact with TXNIP,[10] ASK1,[11][12][13] Collagen, type I, alpha 1,[14] Glucocorticoid receptor.[15] and SENP1.[16]

See also[edit]

References[edit]

  1. ^ Wollman EE, d'Auriol L, Rimsky L, Shaw A, Jacquot JP, Wingfield P, Graber P, Dessarps F, Robin P, Galibert F (October 1988). "Cloning and expression of a cDNA for human thioredoxin". J. Biol. Chem. 263 (30): 15506–12. PMID 3170595. 
  2. ^ a b Meng, Ling; Wong, Joshua; Feldman, Lewis; Lemaux, Peggy; Buchanan, Bob (2010). "A membrane-associated thioredoxin required for plant growth moves from cell to cell, suggestive of a role in intercellular communication". Proceedings of the National Academy of Sciences of the USA 107 (8): 3900–5. doi:10.1073/pnas.0913759107. PMC 2840455. PMID 20133584. 
  3. ^ Holmgren A (1989). "Thioredoxin and glutaredoxin systems". J Biol Chem 264 (24): 13963–6. PMID 2668278. 
  4. ^ Nordberg J, Arnér E (2001). "Reactive oxygen species, antioxidants, and the mammalian thioredoxin system". Free Radic Biol Med 31 (11): 1287–312. doi:10.1016/S0891-5849(01)00724-9. PMID 11728801. 
  5. ^ "Entrez Gene: TXN thioredoxin". 
  6. ^ Mustacich D, Powis G (February 2000). "Thioredoxin reductase". Biochem J 346 (Pt 1): 1–8. doi:10.1042/0264-6021:3460001. PMC 1220815. PMID 10657232. 
  7. ^ Arnér E, Holmgren A (2000). "Physiological functions of thioredoxin and thioredoxin reductase". Eur J Biochem 267 (20): 6102–9. doi:10.1046/j.1432-1327.2000.01701.x. PMID 11012661. 
  8. ^ Yoshida T, Nakamura H, Masutani H, Yodoi J (2005). "The involvement of thioredoxin and thioredoxin binding protein-2 on cellular proliferation and aging process". Annals of the New York Academy of Sciences 1055: 1–12. doi:10.1196/annals.1323.002. PMID 16387713. 
  9. ^ Muller, F.L., Lustgarten, M.S., Jang, Y., Richardson, A. & Van Remmen, H. Trends in oxidative aging theories. Free Radic Biol Med 43, 477-503 (2007).
  10. ^ Nishiyama, A; Matsui M; Iwata S; Hirota K; Masutani H; Nakamura H; Takagi Y; Sono H; Gon Y; Yodoi J (July 1999). "Identification of thioredoxin-binding protein-2/vitamin D(3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression". J. Biol. Chem. (UNITED STATES) 274 (31): 21645–50. doi:10.1074/jbc.274.31.21645. ISSN 0021-9258. PMID 10419473. 
  11. ^ Liu, Yingmei; Min Wang (June 2002). "Thioredoxin promotes ASK1 ubiquitination and degradation to inhibit ASK1-mediated apoptosis in a redox activity-independent manner". Circ. Res. (United States) 90 (12): 1259–66. doi:10.1161/01.RES.0000022160.64355.62. PMID 12089063. 
  12. ^ Morita, K; Saitoh M; Tobiume K; Matsuura H; Enomoto S; Nishitoh H; Ichijo H (November 2001). "Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress". EMBO J. (England) 20 (21): 6028–36. doi:10.1093/emboj/20.21.6028. ISSN 0261-4189. PMC 125685. PMID 11689443. 
  13. ^ Saitoh, M; Nishitoh H; Fujii M; Takeda K; Tobiume K; Sawada Y; Kawabata M; Miyazono K; Ichijo H (May 1998). "Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1". EMBO J. (ENGLAND) 17 (9): 2596–606. doi:10.1093/emboj/17.9.2596. ISSN 0261-4189. PMC 1170601. PMID 9564042. 
  14. ^ Matsumoto, Ken; Masutani Hiroshi; Nishiyama Akira; Hashimoto Shu; Gon Yasuhiro; Horie Takashi; Yodoi Junji (July 2002). "C-propeptide region of human pro alpha 1 type 1 collagen interacts with thioredoxin". Biochem. Biophys. Res. Commun. (United States) 295 (3): 663–7. doi:10.1016/S0006-291X(02)00727-1. ISSN 0006-291X. PMID 12099690. 
  15. ^ Makino, Y; Yoshikawa N; Okamoto K; Hirota K; Yodoi J; Makino I; Tanaka H (January 1999). "Direct association with thioredoxin allows redox regulation of glucocorticoid receptor function". J. Biol. Chem. (UNITED STATES) 274 (5): 3182–8. doi:10.1074/jbc.274.5.3182. ISSN 0021-9258. PMID 9915858. 
  16. ^ Li, X; Luo Y, Yu L, Lin Y, Luo D, Zhang H, He Y, Kim YO, Kim Y, Tang S, Min W. (April 2008). "SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis". Cell Death & Diff. 15 (4): 739–50. doi:10.1038/sj.cdd.4402303. PMID 18219322. 

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