Protein disulfide-isomerase A2 (PDIA2)

Protein disulfide-isomerase A2 (PDIA2) is an endoplasmic reticulum-resident enzyme and a member of the protein disulfide isomerase family, catalyzing thiol-disulfide interchange reactions important for oxidative protein folding[1][3]. It contains two active thioredoxin-like domains and two TRX-like domains, enabling the formation, breakage, and rearrangement of disulfide bonds in nascent proteins. PDIA2 acts as a molecular chaperone that prevents aggregation of misfolded proteins and possesses estradiol-binding (steroid-binding) activity, potentially modulating estrogen signaling within the cell[1]. PDIA2 is upregulated in various cancers—including colon and prostate—where it contributes to tumor progression, metabolic reprogramming (e.g., increased glycolysis), and poor prognosis[2][4]. Its upregulation in chronic inflammation links ER stress to tumorigenesis via effects on mitochondrial metabolism. PDIA2 is considered a potential therapeutic target in oncology and other diseases related to ER stress or protein misfolding, but no selective clinical inhibitors currently exist[2][4].

Other names

Protein disulfide isomerase A2PDIPPDIpPDA2PDIPDIRPancreas-specific protein disulfide isomeraseprotein disulfide-isomerase A2protein disulfide isomerase-associated 2

Enzyme inhibition (hypothetical for PDIA2-targeted drugs); Inhibition of protein folding and ER stress (for PDI family inhibitors); Regulation of metabolic reprogramming and glycolysis; Modulation of steroid hormone signaling