Protein disulfide-isomerase A3 (PDIA3)

Protein disulfide-isomerase A3 (PDIA3) is an enzyme of the protein disulfide isomerase family, primarily localized in the endoplasmic reticulum of eukaryotic cells, where it catalyzes the formation, isomerization, and reduction/oxidation of disulfide bonds, ensuring correct protein folding and acting as a molecular chaperone to prevent protein aggregation. PDIA3 is an essential component of the major histocompatibility complex (MHC) class I peptide loading complex, facilitating antigen presentation for immune surveillance and adaptive immunity. It is implicated in the cellular response to ER stress, redox regulation, signal transduction (notably via STAT3), and cell cycle regulation. PDIA3 is overexpressed in several tumors, correlating with poor prognosis and chemoresistance, and is being explored as a therapeutic target and biomarker in oncology and other diseases characterized by protein misfolding or ER stress. Emerging research also suggests roles in neurodegenerative diseases and inflammation, with ongoing efforts to develop selective inhibitors.

Other names

ERp57ERp60ERp61GRP57GRP58p58PI-PLCDisulfide isomerase ER-60Endoplasmic reticulum resident protein 57Endoplasmic reticulum resident protein 60ER protein 57ER protein 60Protein Disulfide-Isomerase A3Protein Disulfide Isomerase Family A Member 358 kDa glucose-regulated protein58 kDa microsomal proteinEpididymis Secretory Protein Li 269HsT17083HEL-S-269HEL-S-93n

Inhibition of PDIA3 enzymatic activity (disulfide isomerase function), disruption of protein folding and quality control, induction of cytotoxic/ER stress responses, enhancement of chemosensitivity (when co-administered with cytotoxics like temozolomide), modulation of immune cell function through roles in antigen presentation and redox balance