Glucose regulated protein 94 (GRP94) is a constitutively expressed endoplasmic reticulum (ER) lumenal protein that is up-regulated in response to cellular stress such as heat shock, oxidative stress or glucose depletion. GRP94 is thought to play a role in protein translocation to the ER, in their subsequent folding and assembly, and in regulating protein secretion.¹GRP94 also plays a role in antigen presentation by accessing the endogenous pathway and eliciting specific cytotoxic T lymphocyte (CTL) responses to chaperone bound peptidesviathe major histocompatibility complex (MHC) class I pathway.²GRP94 is a member of the Hsp90 family of stress proteins and shares sequence homology with its cytosolic equivalent, Hsp90.³Both Hsp90 and GRP94 are calcium binding proteins.⁴Despite sharing 50% sequence homology over its N domains and complete conservation in its ligand binding domains with Hsp90, GRP94, and Hsp90 differ in their interactions with regulatory ligands as GRP94 has weak ATP binding and hydrolysis activity.⁵GRP94 exists as a homodimer and the two subunits interact at two distinct intermolecular sites, C-terminal dimerization domains and the N-terminal interacts with the middle domain of opposing subunits.⁶GRP94 contains a carboxy terminal KDEL (Lys-Asp-Glu-Leu) sequence which is believed to aid in its retention in the ER.⁷

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