Fig. 1

Schematic representation of the different roles of ERp57 / PDIA3 in cellular processes in different cell compartments. Cell membrane: ERp57/PDIA3 participates in assembling of MHC I, interacts with different receptors (e.g., angiotensin II, vasopressin, and EGF receptors), acts as receptor of vitamin D₃, participates in ICD in complex with calreticulin, and interacts with αIIbβ3 integrin in platelet cells. ERp57/PDIA3 participates in different cellular processes, including signal transduction, recycling, degradation, and internalization. Cytosol: ERp57/PDIA3 interacts with STAT3 and contributes to redox balance acting on thioredoxin (TR) and other targets. Nucleus: ERp57/PDIA3 interacts with different proteins (e.g., STAT3; Ape/Ref1, Ku80, and maybe TDP-43) and different DNA sequences (AT-rich regions) or structures (G-quadruplex). ERp57/PDIA3 participates in gene expression (e.g., DKC1; MCOLN3), DNA repair, and transcriptional factor reduction. Endoplasmic reticulum: ERp57/PDIA3 promotes oxidative folding of glycoproteins in concert with lectin chaperones calnexin and calreticulin and is involved in retrotranslocation to cytosol of toxin, virus, and receptor. ER–mitochondrion: ERp57/PDIA3 is present in mitochondria-associated membranes (MAM), the regions of ER that are closely associated with mitochondria; ERp57/PDIA3 complexed with μ-calpain is able to cleave apoptosis-inducing factor (AIF) and interferes with the mitochondrial bioenergetic function via the inhibition of STAT3 Ser727 phosphorylation