Thioredoxin domain (IPR013766)
Short name: Thioredoxin_domain
Overlapping homologous superfamilies
- Thioredoxin-like superfamily (IPR036249)
Thioredoxins [PMID: 3896121, PMID: 2668278, PMID: 7788289, PMID: 7788290] 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 [PMID: 3896121].
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 [PMID: 8590004]. Thioredoxin belongs to a structural family that includes glutaredoxin, glutathione peroxidase, bacterial protein disulphide isomerase DsbA, and the N-terminal domain of glutathione transferase [PMID: 7788290]. Thioredoxins have a beta-alpha unit preceding the motif common to all these proteins.
A number of eukaryotic proteins contain domains evolutionary related to thioredoxin, most of them are protein disulphide isomerases (PDI). PDI (EC:184.108.40.206) [PMID: 3371540, PMID: 2537773, PMID: 7940678] is an endoplasmic reticulum multi-functional enzyme that catalyses the formation and rearrangement of disulphide bonds during protein folding [PMID: 7913469]. 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 [PMID: 7983029]. Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulphide bonds, i.e. behaving independently of its disulphide isomerase activity [PMID: 7635143]. The various forms of PDI which are currently known are:
- PDI major isozyme; a multifunctional protein that also function as the beta subunit of prolyl 4-hydroxylase (EC:220.127.116.11), as a component of oligosaccharyl transferase (EC:18.104.22.168), as thyroxine deiodinase (EC:22.214.171.124), as glutathione-insulin transhydrogenase (EC:126.96.36.199) and as a thyroid hormone-binding protein
- 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.
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:
- Escherichia coli DsbA (or PrfA) and its orthologs in Vibrio cholerae (TtcpG) and Haemophilus influenzae (Por).
- E. coli DsbC (or XpRA) and its orthologues in Erwinia chrysanthemi and H. influenzae.
- E. coli DsbD (or DipZ) and its H. influenzae orthologue.
- E. coli DsbE (or CcmG) and orthologues in H. influenzae.
- Rhodobacter capsulatus (Rhodopseudomonas capsulata) (HelX), Rhiziobiacae (CycY and TlpA).
This entry represents the thioredoxin domain.
GO:0045454 cell redox homeostasis
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