Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen. Involved in the correct folding of proteins and degradation of misfolded proteins (By similarity). Acts as a key repressor of the unfolded protein response (UPR) (By similarity). ATP + H2O = ADP + H(+) + phosphate The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains. In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction. In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates. J domain-containing co-chaperones stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP. AMPylation at Thr-518 by Fic inactivates the chaperome activity (PubMed:25395623, PubMed:29089387). In response to endoplasmic reticulum stress, de-AMPylation by the same protein, Fic, restores the chaperone activity (PubMed:29089387). Belongs to the heat shock protein 70 family. Was initially thought to be AMPylated at 'Thr-366' by Fic (PubMed:25395623). However, it was later shown to be AMPylated at 'Thr-518'.