PROSITE documentation PDOC00172

Thioredoxins [1,2,3,4] are small proteins of approximately one hundred amino-acid residues which participate in various redox reactions via the reversible oxidation of an active center disulfide bond. They exist in either a reduced form or an oxidized form where the two cysteine residues are linked in an intramolecular disulfide bond. Thioredoxin is present in prokaryotes and eukaryotes and the sequence around the redox-active disulfide bond is well conserved. Bacteriophage T4 also encodes for a thioredoxin but its primary structure is not homologous to bacterial, plant and vertebrate thioredoxins.

A number of eukaryotic proteins contain domains evolutionary related to thioredoxin, most of them are protein disulfide isomerases (PDI). PDI (EC 5.3.4.1) [5,6,7] is an endoplasmic reticulum enzyme that catalyzes the rearrangement of disulfide bonds in various proteins. The various forms of PDI which are currently known are:

PDI major isozyme; a multifunctional protein that also function as the β 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 !
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.
ERp72.
P5.

All PDI contains two or three (ERp72) copies of the thioredoxin domain.

Bacterial proteins that act as thiol:disulfide interchange proteins that allows disulfide bond formation in some periplasmic proteins also contain a thioredoxin domain. These proteins are:

Escherichia coli dsbA (or prfA) and its orthologs in Vibrio cholerae (tcpG) and Haemophilus influenzae (por).
Escherichia coli dsbC (or xpRA) and its orthologs in Erwinia chrysanthemi and Haemophilus influenzae.
Escherichia coli dsbD (or dipZ) and its Haemophilus influenzae ortholog.
Escherichia coli dsbE (or ccmG) and orthologs in Haemophilus influenzae, Rhodobacter capsulatus (helX), Rhiziobiacae (cycY and tlpA).

The pattern we developed is directed against the two cysteines that form the redox-active bond. We also developed a profile that covers the whole domain.

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1	Authors	Holmgren A.
	Title	Thioredoxin.
	Source	Annu. Rev. Biochem. 54:237-271(1985).
	PubMed ID	3896121
	DOI	10.1146/annurev.bi.54.070185.001321

2	Authors	Gleason F.K., Holmgren A.
	Title	Thioredoxin and related proteins in procaryotes.
	Source	FEMS Microbiol. Rev. 4:271-297(1988).
	PubMed ID	3152490

3	Authors	Holmgren A.
	Title	Thioredoxin and glutaredoxin systems.
	Source	J. Biol. Chem. 264:13963-13966(1989).
	PubMed ID	2668278

4	Authors	Eklund H., Gleason F.K., Holmgren A.
	Title	Structural and functional relations among thioredoxins of different species.
	Source	Proteins 11:13-28(1991).
	PubMed ID	1961698

5	Authors	Freedman R.B., Hawkins H.C., Murant S.J., Reid L.
	Title	Protein disulphide-isomerase: a homologue of thioredoxin implicated in the biosynthesis of secretory proteins.
	Source	Biochem. Soc. Trans. 16:96-99(1988).
	PubMed ID	3371540

Thioredoxin family active site signature and domain profile

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6	Authors	Kivirikko K.I., Myllyla R., Pihlajaniemi T.
	Title	Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit.
	Source	FASEB J. 3:1609-1617(1989).
	PubMed ID	2537773

7	Authors	Freedman R.B., Hirst T.R., Tuite M.F.
	Title	Protein disulphide isomerase: building bridges in protein folding.
	Source	Trends Biochem. Sci. 19:331-336(1994).
	PubMed ID	7940678