Anti-GRP78

GRP78 (Glucose-regulated protein 78 kDa, also BiP and HSPA5) is a 72 kDa member of the heat shock protein 70 family of proteins. Intracellularly, GRP78 is an endoplasmic reticulum chaperone that participates in protein folding, extracellularly, it induces IL-10 production from T cells and interacts with Cripto to block TGF-beta signaling. Human GRP78 precursor is 654 amino acids (aa) in length. It contains an 18 aa signal sequence and a 636 aa mature region that shows a hydantoinase A region (aa 145245) and a C-terminal KDEL motif that is present on intracellular GRP78, but absent on secreted GRP78. There is alternative splicing in the signal sequence (aa 110), and multiple single aa substitituion. Over aa 1654, human GRP78 is more than 97% aa identical to mouse and rat GRP78. Protein function: Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate. Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:1550958, PubMed:19538957). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1. Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1. Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (PubMed:26045166). [The UniProt Consortium]