Protein disulfide-isomerase A3 (ERp57) (ERp57)

Protein disulfide-isomerase A3 (ERp57) is a thiol isomerase belonging to the protein disulfide isomerase (PDI) family, which is essential for platelet activation and the stabilization of thrombi (Wang et al., 2009, PMID: 19381018). Although traditionally recognized as an endoplasmic reticulum-resident chaperone involved in glycoprotein folding, ERp57 is secreted from platelet alpha-granules and translocated to the plasma membrane upon vascular injury (UniProt: P30101). On the platelet surface, it facilitates the activation of key adhesion receptors, most notably integrin alpha-IIb/beta-3 (GPIIb/IIIa), by catalyzing disulfide bond rearrangements (Zhou et al., 2015, PMID: 25631143). This activity is crucial for platelet aggregation and the subsequent growth of a thrombus (Stopa et al., 2017, PMID: 28239653). Given its prominent role in pathological thrombosis, ERp57 is considered a significant therapeutic target for developing next-generation antithrombotic agents (Jasuja et al., 2012, PMID: 22535994). Research indicates that inhibiting ERp57 can reduce thrombus formation with a potentially more favorable safety profile regarding bleeding complications compared to conventional antiplatelet drugs.

Other names

PDIA3GRP58ERp60P58Endoplasmic reticulum resident protein 57Glucose-regulated protein 58 kDa

Inhibition of the thiol-disulfide exchange activity of ERp57 on the platelet surface, which prevents the conformational change and activation of integrin alpha-IIb/beta-3 (GPIIb/IIIa), thereby reducing platelet aggregation and thrombus stabilization (Wang et al., 2009, PMID: 19381018; Zhou et al., 2015, PMID: 25631143).