GRP78 is a 78 kDa glucose regulated protein that belongs to the family of heat shock proteins that include HSP70. GRP78 is a resident protein of the endoplasmic reticulum (ER) and associates transiently with a variety of newly synthesized secretory and membrane proteins. GRP78 may also interact with mutant and misfolded proteins, marking them for degradation. The highly conserved sequence Lys-Asp-Glu-Leu (KDEL) is present at the C-terminus of GRP78 and other resident ER proteins including glucose regulated protein 94 (GRP94) and protein disulfide isomerase (PDI). The KDEL signal is recognized by the KDEL receptor and this interaction ensures recycling of escaped ER proteins back to the ER. GRP78's involvement in correct folding of proteins and degradation of misfolded proteins is via its interaction with DNAJC10, probably to facilitate the release of DNAJC10 from its substrate. GRP78 is critical for maintenance of cell homeostasis and the prevention of apoptosis. GRP78 protein levels have been shown to be a reliable biomarker of hypoglycemia and serves a neuroprotective function in neurons exposed to glutamate and oxidative stress. GRP78 levels are reduced in the brains of Alzheimer's Disease patients, and decreased expression of GRP78 is found associated with missense mutations in the human presenilin-1 (PS1) gene. Further, the induction of the GRP78 protein has been associated with the development of drug-resistance to antitumor drugs.
78 kDa glucose-regulated protein; Binding-immunoglobulin protein; BiP; Endoplasmic reticulum chaperone BiP; endoplasmic reticulum lumenal Ca(2+)-binding protein grp78; epididymis secretory sperm binding protein Li 89n; FLJ26106; glucose regulated protein, 78 kDa; glucose-regulated protein, 78kDa; GRP 78; GRP-78; heat shock 70 kDa protein 5; heat shock 70kD protein 5; heat shock 70kD protein 5 (glucose-regulated protein, 78kD); heat shock 70kDa protein 5 (glucose-regulated protein); heat shock 70kDa protein 5 (glucose-regulated protein, 78kDa); Heat shock protein 70 family protein 5; Heat shock protein family A member 5; HSP70 family protein 5; HSPA 5; Immunoglobulin heavy chain-binding protein; Steroidogenesis-activator polypeptide; XAP-1 antigen