Protein disulphide isomerase, a multifunctional endoplasmic reticulum protein.

Protein disulphide isomerase (E.C. 5.3.4.1) has been purified, cloned, and sequenced from a variety of vertebrate tissues. The enzyme and its isoforms have been assigned a role in four functional activities: (1) hydroxylation of proline residues in procollagen; (2) disulphide bond oxidation, isomerization, and reduction; (3) the major non-nuclear binding protein of the thyroid hormone 3,3',5-triiodo-L-thyronine; and (4) a component of oligosaccharide transferase. The concentration of the enzyme has been shown to be positively correlated with an endoplasmic reticulum network which is active in secreting disulphide-bonded polypeptides. The enzyme is directed into the endoplasmic reticulum by virtue of a 19 residue N-terminal signal peptide; a four amino acid C-terminal KDEL sequence prevents the enzyme from being secreted. Careful inspection of the sequence data of the isoforms from human tissues reveals a 97% similarity; whereas, analyses of the data from chick tissues reveals only a 80% level of similarity. Chromosomal localizations using human cDNA probes against different human isoforms have assigned the gene(s) to opposite ends of the long arm of chromosome 17. The compiled data suggest the presence of a family of related polypeptides, all of which reside within the lumen of the endoplasmic reticulum.