<p>Thioredoxins [<cite idref="PUB00000038"/>, <cite idref="PUB00002504"/>, <cite idref="PUB00005258"/>, <cite idref="PUB00005259"/>] are small disulphide-containing redox proteins that have been found in all the kingdoms of living organisms. Thioredoxin serves as a general protein disulphide oxidoreductase. It interacts with a broad range of proteins by a redox mechanism based on reversible oxidation of two cysteine thiol groups to a disulphide, accompanied by the transfer of two electrons and two protons. The net result is the covalent interconversion of a disulphide and a dithiol. In the NADPH-dependent protein disulphide reduction, thioredoxin reductase (TR) catalyses the reduction of oxidised thioredoxin (trx) by NADPH using FAD and its redox-active disulphide; reduced thioredoxin then directly reduces the disulphide in the substrate protein [<cite idref="PUB00000038"/>].</p><p> Thioredoxin is present in prokaryotes and eukaryotes and the sequence around the redox-active disulphide bond is well conserved. All thioredoxins contain a cis-proline located in a loop preceding beta-strand 4, which makes contact with the active site cysteines, and is important for stability and function [<cite idref="PUB00005250"/>]. Thioredoxin belongs to a structural family that includes glutaredoxin, glutathione peroxidase, bacterial protein disulphide isomerase DsbA, and the N-terminal domain of glutathione transferase [<cite idref="PUB00005259"/>]. Thioredoxins have a beta-alpha unit preceding the motif common to all these proteins.</p><p> A number of eukaryotic proteins contain domains evolutionary related to thioredoxin, most of them are protein disulphide isomerases (PDI). PDI (<db_xref db="EC" dbkey="5.3.4.1"/>) [<cite idref="PUB00000561"/>, <cite idref="PUB00001495"/>, <cite idref="PUB00005423"/>] is an endoplasmic reticulum multi-functional enzyme that catalyses the formation and rearrangement of disulphide bonds during protein folding [<cite idref="PUB00002862"/>]. All PDI contains two or three (ERp72) copies of the thioredoxin domain, each of which contributes to disulphide isomerase activity, but which are functionally non-equivalent [<cite idref="PUB00002883"/>]. Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulphide bonds, i.e. behaving independently of its disulphide isomerase activity [<cite idref="PUB00001458"/>]. The various forms of PDI which are currently known are:</p><p> <ul> <li>PDI major isozyme; a multifunctional protein that also function as the beta subunit of prolyl 4-hydroxylase (<db_xref db="EC" dbkey="1.14.11.2"/>), as a component of oligosaccharyl transferase (<db_xref db="EC" dbkey="2.4.1.119"/>), as thyroxine deiodinase (<db_xref db="EC" dbkey="3.8.1.4"/>), as glutathione-insulin transhydrogenase (<db_xref db="EC" dbkey="1.8.4.2"/>) and as a thyroid hormone-binding protein</li><li>ERp60 (ER-60; 58 Kd microsomal protein). ERp60 was originally thought to be a phosphoinositide-specific phospholipase C isozyme and later to be a protease.</li><li>ERp72.</li><li>ERp5.</li> </ul> </p><p> Bacterial proteins that act as thiol:disulphide interchange proteins that allows disulphide bond formation in some periplasmic proteins also contain a thioredoxin domain. These proteins include:</p><p> <ul> <li> <taxon tax_id="562">Escherichia coli</taxon> DsbA (or PrfA) and its orthologs in <taxon tax_id="666">Vibrio cholerae</taxon> (TtcpG) and <taxon tax_id="727">Haemophilus influenzae</taxon> (Por).</li><li>E. coli DsbC (or XpRA) and its orthologues in <taxon tax_id="556">Erwinia chrysanthemi</taxon> and H. influenzae.</li><li>E. coli DsbD (or DipZ) and its H. influenzae orthologue.</li><li>E. coli DsbE (or CcmG) and orthologues in H. influenzae.</li><li> <taxon tax_id="1061">Rhodobacter capsulatus</taxon> (Rhodopseudomonas capsulata) (HelX), Rhiziobiacae (CycY and TlpA).</li> </ul> </p><p>This entry represents a conserved site found in the thioredoxin domain. This site contains two cysteines that form the redox-active disulphide bond.</p> Thioredoxin, conserved site