The human protein disulfide isomerase gene family

James J. Galligan, Dennis R. Petersen

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

Abstract

Enzyme-mediated disulfide bond formation is a highly conserved process affecting over one-third of all eukaryotic proteins. The enzymes primarily responsible for facilitating thiol-disulfide exchange are members of an expanding family of proteins known as protein disulfide isomerases (PDIs). These proteins are part of a larger superfamily of proteins known as the thioredoxin protein family (TRX). As members of the PDI family of proteins, all proteins contain a TRX-like structural domain and are predominantly expressed in the endoplasmic reticulum. Subcellular localization and the presence of a TRX domain, however, comprise the short list of distinguishing features required for gene family classification. To date, the PDI gene family contains 21 members, varying in domain composition, molecular weight, tissue expression, and cellular processing. Given their vital role in protein-folding, loss of PDI activity has been associated with the pathogenesis of numerous disease states, most commonly related to the unfolded protein response (UPR). Over the past decade, UPR has become a very attractive therapeutic target for multiple pathologies including Alzheimer disease, Parkinson disease, alcoholic and non-alcoholic liver disease, and type-2 diabetes. Understanding the mechanisms of protein-folding, specifically thiol-disulfide exchange, may lead to development of a novel class of therapeutics that would help alleviate a wide range of diseases by targeting the UPR.

Original languageEnglish (US)
Article number6
JournalHuman genomics
Volume6
Issue number1
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • Calsequestrin
  • Disulfide bond
  • ER stress
  • Thioredoxin
  • UPR
  • Unfolded protein response

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

Fingerprint

Dive into the research topics of 'The human protein disulfide isomerase gene family'. Together they form a unique fingerprint.

Cite this