{"metadata":{"accession":"IPR005746","entry_id":null,"type":"family","go_terms":[{"identifier":"GO:0015035","name":"protein-disulfide reductase activity","category":{"code":"F","name":"molecular_function"}}],"source_database":"interpro","member_databases":{"pirsf":{"PIRSF000077":"Thioredoxin"},"ncbifam":{"TIGR01068":"thioredoxin"}},"integrated":null,"hierarchy":{"accession":"IPR005746","name":"Thioredoxin","type":"Family","children":[]},"name":{"name":"Thioredoxin","short":"Thioredoxin"},"description":[{"text":"<p>This entry represents the thioredoxin protein family.</p>","llm":false,"checked":false,"updated":false},{"text":"<p>Thioredoxins [[cite:PUB00000038], [cite:PUB00002504], [cite:PUB00005258], [cite: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:PUB00000038]].</p>\r\n\r\n<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 β-strand 4, which makes contact with the active site cysteines, and is important for stability and function [[cite: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:PUB00005259]]. Thioredoxins have a β-α unit preceding the motif common to all these proteins.</p>\r\n\r\n<p>A number of eukaryotic proteins contain domains evolutionary related to thioredoxin, most of them are protein disulphide isomerases (PDI). PDI ([ec:5.3.4.1]) [[cite:PUB00000561], [cite:PUB00001495], [cite:PUB00005423]] is an endoplasmic reticulum multi-functional enzyme that catalyses the formation and rearrangement of disulphide bonds during protein folding [[cite: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:PUB00002883]]. Moreover, PDI exhibits chaperone-like activity towards proteins that contain no disulphide bonds, i.e. behaving independently of its disulphide isomerase activity [[cite:PUB00001458]]. The various forms of PDI which are currently known are:</p>\r\n\r\n\n<ul><li>PDI major isozyme; a multifunctional protein that also function as the beta subunit of prolyl 4-hydroxylase ([ec:1.14.11.2]), as a component of oligosaccharyl transferase ([ec:2.4.1.119]), as thyroxine deiodinase ([ec:3.8.1.4]), as glutathione-insulin transhydrogenase ([ec:1.8.4.2]) and as a thyroid hormone-binding protein</li>\r\n<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>\r\n<li>ERp72.</li>\r\n<li>ERp5.</li></ul>\r\n\r\n<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>\r\n\r\n\n<ul><li>Escherichia coli DsbA (or PrfA) and its orthologs in Vibrio cholerae (TtcpG) and Haemophilus influenzae (Por).</li>\r\n<li>E. coli DsbC (or XpRA) and its orthologues in Erwinia chrysanthemi and H. influenzae.</li>\r\n<li>E. coli DsbD (or DipZ) and its H. influenzae orthologue.</li>\r\n<li>E. coli DsbE  (or CcmG) and orthologues in H. influenzae.</li>\r\n<li>Rhodobacter capsulatus (Rhodopseudomonas capsulata) (HelX), Rhiziobiacae (CycY and TlpA).</li></ul>","llm":false,"checked":false,"updated":false}],"wikipedia":null,"literature":{"PUB00000038":{"PMID":3896121,"ISBN":null,"volume":"54","issue":null,"year":1985,"title":"Thioredoxin.","URL":null,"raw_pages":"237-71","medline_journal":"Annu Rev Biochem","ISO_journal":"Annu. Rev. Biochem.","authors":["Holmgren A."],"DOI_URL":"http://dx.doi.org/10.1146/annurev.bi.54.070185.001321"},"PUB00002504":{"PMID":2668278,"ISBN":null,"volume":"264","issue":"24","year":1989,"title":"Thioredoxin and glutaredoxin systems.","URL":null,"raw_pages":"13963-6","medline_journal":"J Biol Chem","ISO_journal":"J. Biol. Chem.","authors":["Holmgren A."],"DOI_URL":"http://intl.jbc.org/cgi/reprint/264/24/13963.pdf"},"PUB00005258":{"PMID":7788289,"ISBN":null,"volume":"3","issue":"3","year":1995,"title":"Thioredoxin structure and mechanism: conformational changes on oxidation of the active-site sulfhydryls to a disulfide.","URL":null,"raw_pages":"239-43","medline_journal":"Structure","ISO_journal":"Structure","authors":["Holmgren A."],"DOI_URL":"http://dx.doi.org/10.1016/S0969-2126(01)00153-8"},"PUB00005259":{"PMID":7788290,"ISBN":null,"volume":"3","issue":"3","year":1995,"title":"Thioredoxin--a fold for all reasons.","URL":null,"raw_pages":"245-50","medline_journal":"Structure","ISO_journal":"Structure","authors":["Martin JL."],"DOI_URL":"http://dx.doi.org/10.1016/S0969-2126(01)00154-X"},"PUB00002862":{"PMID":7913469,"ISBN":null,"volume":"269","issue":"29","year":1994,"title":"The role of the thiol/disulfide centers and peptide binding site in the chaperone and anti-chaperone activities of protein disulfide isomerase.","URL":null,"raw_pages":"19128-35","medline_journal":"J Biol Chem","ISO_journal":"J. Biol. Chem.","authors":["Puig A","Lyles MM","Noiva R","Gilbert HF."],"DOI_URL":"http://intl.jbc.org/cgi/content/abstract/269/29/19128"},"PUB00002883":{"PMID":7983029,"ISBN":null,"volume":"269","issue":"49","year":1994,"title":"Mutations in the thioredoxin sites of protein disulfide isomerase reveal functional nonequivalence of the N- and C-terminal domains.","URL":null,"raw_pages":"30946-52","medline_journal":"J Biol Chem","ISO_journal":"J. Biol. Chem.","authors":["Lyles MM","Gilbert HF."],"DOI_URL":"http://intl.jbc.org/cgi/reprint/269/49/30946.pdf"},"PUB00001458":{"PMID":7635143,"ISBN":null,"volume":"231","issue":"2","year":1995,"title":"Chaperone-like activity of protein disulfide-isomerase in the refolding of rhodanese.","URL":null,"raw_pages":"312-6","medline_journal":"Eur J Biochem","ISO_journal":"Eur. J. Biochem.","authors":["Song JL","Wang CC."],"DOI_URL":"http://dx.doi.org/10.1111/j.1432-1033.1995.tb20702.x"},"PUB00005250":{"PMID":8590004,"ISBN":null,"volume":"3","issue":"10","year":1995,"title":"Crystal structure of thioredoxin-2 from Anabaena.","URL":null,"raw_pages":"1097-108","medline_journal":"Structure","ISO_journal":"Structure","authors":["Saarinen M","Gleason FK","Eklund H."],"DOI_URL":"http://dx.doi.org/10.1016/S0969-2126(01)00245-3"},"PUB00000561":{"PMID":3371540,"ISBN":null,"volume":"16","issue":"2","year":1988,"title":"Protein disulphide-isomerase: a homologue of thioredoxin implicated in the biosynthesis of secretory proteins.","URL":null,"raw_pages":"96-9","medline_journal":"Biochem Soc Trans","ISO_journal":"Biochem. Soc. Trans.","authors":["Freedman RB","Hawkins HC","Murant SJ","Reid L."],"DOI_URL":null},"PUB00001495":{"PMID":2537773,"ISBN":null,"volume":"3","issue":"5","year":1989,"title":"Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit.","URL":null,"raw_pages":"1609-17","medline_journal":"FASEB J","ISO_journal":"FASEB J.","authors":["Kivirikko KI","Myllyla R","Pihlajaniemi T."],"DOI_URL":"http://www.fasebj.org/cgi/content/abstract/3/5/1609"},"PUB00005423":{"PMID":7940678,"ISBN":null,"volume":"19","issue":"8","year":1994,"title":"Protein disulphide isomerase: building bridges in protein folding.","URL":null,"raw_pages":"331-6","medline_journal":"Trends Biochem Sci","ISO_journal":"Trends Biochem. Sci.","authors":["Freedman RB","Hirst TR","Tuite MF."],"DOI_URL":"http://dx.doi.org/10.1016/0968-0004(94)90072-8"}},"set_info":null,"overlaps_with":[{"accession":"IPR036249","name":"Thioredoxin-like superfamily","type":"homologous_superfamily"}],"counters":{"subfamilies":0,"domain_architectures":0,"interactions":0,"matches":60035,"pathways":74,"proteins":60021,"proteomes":20749,"sets":0,"structural_models":{"alphafold":46776,"bfvd":6},"structures":267,"taxa":39240},"entry_annotations":{},"cross_references":{},"is_llm":false,"is_reviewed_llm":false,"is_updated_llm":false,"representative_structure":{"accession":"2yn1","name":"Crystal Structure of Ancestral Thioredoxin Relative to Last Gamma- Proteobacteria Common Ancestor (LGPCA) from the Precambrian Period"}}}