Thioredoxin

TXN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4TRX, 1AIU, 1AUC, 1CQG, 1CQH, 1ERT, 1ERU, 1ERV, 1ERW, 1MDI, 1MDJ, 1MDK, 1TRS, 1TRU, 1TRV, 1TRW, 2HSH, 2HXK, 2IFQ, 2IIY, 3E3E, 3KD0, 3M9J, 3M9K, 3QFA, 3QFB, 3TRX, 4LL1, 4LL4, 4OO4, 4OO5, 4POK, 4POL, 4POM, 4PUF, 5DQY
Identifiers
Aliases	TXN, TRDX, TRX, TRX1, thioredoxin
External IDs	OMIM: 187700 MGI: 98874 HomoloGene: 128202 GeneCards: TXN
Gene ontology Molecular function • protein disulfide oxidoreductase activity • peptide disulfide oxidoreductase activity • oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor • protein binding • poly(A) RNA binding Cellular component • cytoplasm • cytosol • nucleoplasm • extracellular region • mitochondrion • extracellular exosome • nucleus Biological process • activation of protein kinase B activity • positive regulation of protein kinase B signaling • movement of cell or subcellular component • nucleobase-containing small molecule interconversion • glycerol ether metabolic process • regulation of transcription, DNA-templated • sulfate assimilation • response to reactive oxygen species • cell-cell signaling • negative regulation of transcription from RNA polymerase II promoter • regulation of protein import into nucleus, translocation • cell redox homeostasis • transcription, DNA-templated • positive regulation of peptidyl-serine phosphorylation • negative regulation of protein export from nucleus • protein folding • response to radiation • positive regulation of DNA binding • negative regulation of hydrogen peroxide-induced cell death • cell proliferation • oxidation-reduction process • signal transduction • protein repair Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7295	22166
Ensembl	ENSG00000136810	ENSMUSG00000028367
UniProt	P10599	P10639
RefSeq (mRNA)	NM_003329 NM_001244938	NM_011660
RefSeq (protein)	NP_001231867.1 NP_003320.2	NP_035790.1
Location (UCSC)	Chr 9: 110.24 – 110.26 Mb	Chr 4: 57.94 – 57.96 Mb
PubMed search	[1]	[2]
Wikidata

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.^[3] 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.^[4]

Function

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.^[5][6]

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.^[7]

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.^[8] Thioredoxins act as electron donors to peroxidases and ribonucleotide reductase.^[9] 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^[10] — 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.^[11]

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.^[4]

Interactions

Thioredoxin has been shown to interact with:

• ASK1,^[12][13][14]
• Collagen, type I, alpha 1,^[15]
• Glucocorticoid receptor,^[16]
• SENP1,^[17] and
• TXNIP.^[18]

See also

• RuBisCO - enzyme activity regulated by thioredoxin
• Peroxiredoxin - enzyme activity regulated by thioredoxin
• Thioredoxin fold

References

Further reading

External links

• Thioredoxin at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery
1aiu: HUMAN THIOREDOXIN (D60N MUTANT, REDUCED FORM)  1auc: HUMAN THIOREDOXIN (OXIDIZED WITH DIAMIDE)  1cqg: HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN HUMAN THIOREDOXIN (C35A, C62A, C69A, C73A) MUTANT AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN REF-1 (RESIDUES 59-71 OF THE P50 SUBUNIT OF NFKB), NMR, 31 STRUCTURES  1cqh: HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN HUMAN THIOREDOXIN (C35A, C62A, C69A, C73A) MUTANT AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN REF-1 (RESIDUES 59-71 OF THE P50 SUBUNIT OF NFKB), NMR, MINIMIZED AVERAGE STRUCTURE  1ert: HUMAN THIOREDOXIN (REDUCED FORM)  1eru: HUMAN THIOREDOXIN (OXIDIZED FORM)  1erv: HUMAN THIOREDOXIN MUTANT WITH CYS 73 REPLACED BY SER (REDUCED FORM)  1erw: HUMAN THIOREDOXIN DOUBLE MUTANT WITH CYS 32 REPLACED BY SER AND CYS 35 REPLACED BY SER  1mdi: HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN MUTANT HUMAN THIOREDOXIN AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN NFKB  1mdj: HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN HUMAN THIOREDOXIN (C35A, C62A, C69A, C73A) MUTANT AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN NFKB (RESIDUES 56-68 OF THE P50 SUBUNIT OF NFKB)  1mdk: HIGH RESOLUTION SOLUTION NMR STRUCTURE OF MIXED DISULFIDE INTERMEDIATE BETWEEN HUMAN THIOREDOXIN (C35A, C62A, C69A, C73A) MUTANT AND A 13 RESIDUE PEPTIDE COMPRISING ITS TARGET SITE IN HUMAN NFKB (RESIDUES 56-68 OF THE P50 SUBUNIT OF NFKB)  1trs: THE HIGH-RESOLUTION THREE-DIMENSIONAL SOLUTION STRUCTURES OF THE OXIDIZED AND REDUCED STATES OF HUMAN THIOREDOXIN  1tru: THE HIGH-RESOLUTION THREE-DIMENSIONAL SOLUTION STRUCTURES OF THE OXIDIZED AND REDUCED STATES OF HUMAN THIOREDOXIN  1trv: THE HIGH-RESOLUTION THREE-DIMENSIONAL SOLUTION STRUCTURES OF THE OXIDIZED AND REDUCED STATES OF HUMAN THIOREDOXIN  1trw: THE HIGH-RESOLUTION THREE-DIMENSIONAL SOLUTION STRUCTURES OF THE OXIDIZED AND REDUCED STATES OF HUMAN THIOREDOXIN  2hsh: Crystal structure of C73S mutant of human thioredoxin-1 oxidized with H2O2  2hxk: Crystal structure of S-nitroso thioredoxin  2ifq: Crystal structure of S-nitroso thioredoxin  2iiy: Crystal structure of S-nitroso thioredoxin  3trx: HIGH-RESOLUTION THREE-DIMENSIONAL STRUCTURE OF REDUCED RECOMBINANT HUMAN THIOREDOXIN IN SOLUTION  4trx: HIGH-RESOLUTION THREE-DIMENSIONAL STRUCTURE OF REDUCED RECOMBINANT HUMAN THIOREDOXIN IN SOLUTION