PDIA3

Protein disulfide-isomerase A3 (PDIA3), also known as glucose-regulated protein, 58-kD (GRP58), is an isomerase enzyme encoded by the autosomal gene PDIA3 in humans.^[5][6][7][8] This protein localizes to the endoplasmic reticulum (ER) and interacts with lectin chaperones calreticulin and calnexin (CNX) to modulate folding of newly synthesized glycoproteins. It is thought that complexes of lectins and this protein mediate protein folding by promoting formation of disulfide bonds in their glycoprotein substrates.^[9]

Structure

The PDIA3 protein consists of four thioredoxin-like domains: a, b, b′, and a′. The a and a′ domains have Cys-Gly-His-Cys

PDIA3 may also participate in Vitamin D (specifically, calcitriol) signaling as a membrane-bound receptor.^[14]

Clinical significance

It has been demonstrated that the downregulation of ERp57 expression is correlated with poor prognosis in early-stage cervical cancer.^[15] It has also been demonstrated that ERp57/PDIA3 binds specific DNA fragments in a melanoma cell line.^[16] PDIA3 is also involved in bone metastasis, which is the most common source of distant relapse in breast cancer.^[13] In addition to cancer, overexpression of PDIA3 is linked to renal fibrosis, which is characterized by excess synthesis and secretion of ECM leading to ER stress.^[17]

Interactions

It has been demonstrated that PDIA3 interacts with:

• BACE1,^[18]
• ERp27,^[19]
• tapasin,^[18][11]
• CRT,^[18] and
• CNX.^[10][18][11]

• Antigen processing
• Major histocompatibility complex

References