Thioredoxin

Thioredoxin
PDB rendering based on 1aiu.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1AIU, 1AUC, 1CQG, 1CQH, 1ERT, 1ERU, 1ERV, 1ERW, 1M7T, 1MDI, 1MDJ, 1MDK, 1TRS, 1TRU, 1TRV, 1TRW, 1W1C, 1W1E, 2HSH, 2HXK, 2IFQ, 2IIY, 3E3E, 3KD0, 3M9J, 3M9K, 3QFA, 3QFB, 3TRX, 4LL1, 4LL4, 4OO4, 4OO5, 4POK, 4POL, 4POM, 4PUF, 4TRX
Identifiers
Symbols	TXN ; TRDX; TRX; TRX1
External IDs	OMIM: 187700 MGI: 98874 HomoloGene: 128202 GeneCards: TXN Gene
Gene ontology Molecular function • protein binding • protein disulfide oxidoreductase activity • peptide disulfide oxidoreductase activity • oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor • poly(A) RNA binding Cellular component • nucleus • nucleoplasm • cytoplasm • mitochondrion • cytosol • extracellular exosome Biological process • sulfate assimilation • negative regulation of transcription from RNA polymerase II promoter • response to reactive oxygen species • transcription initiation from RNA polymerase II promoter • protein folding • glycerol ether metabolic process • movement of cell or subcellular component • signal transduction • cell-cell signaling • cell proliferation • response to radiation • gene expression • nucleobase-containing small molecule interconversion • activation of protein kinase B activity • positive regulation of peptidyl-serine phosphorylation • regulation of protein import into nucleus, translocation • cellular response to oxidative stress • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway • positive regulation of DNA binding • small molecule metabolic process • innate immune response • cell redox homeostasis • negative regulation of protein export from nucleus • positive regulation of protein kinase B signaling • nucleobase-containing small molecule metabolic process • oxidation-reduction process • negative regulation of hydrogen peroxide-induced cell death 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_001244938	NM_011660
RefSeq (protein)	NP_001231867	NP_035790
Location (UCSC)	Chr 9: 110.24 – 110.26 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. 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.

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.

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.

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. Thioredoxins act as electron donors to peroxidases and ribonucleotide reductase. 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 — 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.

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.

Interactions

Thioredoxin has been shown to interact with:

• ASK1,
• Collagen, type I, alpha 1,
• Glucocorticoid receptor,
• SENP1, and
• TXNIP.

See also

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

External links

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