Protein that can both mediate the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context (By similarity). The side chain of Glu-231 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place (By similarity). Acts as a key regulator of the ERN1/IRE1-mediated unfolded protein response (UPR) by mediating AMPylation or de-AMPylation of HSPA5/BiP (PubMed:25601083). In unstressed cells, acts as an adenylyltransferase by mediating AMPylation of HSPA5/BiP at 'Thr-518', thereby inactivating it (By similarity). In response to endoplasmic reticulum stress, acts as a phosphodiesterase by mediating removal of ATP (de-AMPylation) from HSPA5/BiP at 'Thr-518', leading to restore HSPA5/BiP activity (By similarity). Although it is able to AMPylate RhoA, Rac and Cdc42 Rho GTPases in vitro, Rho GTPases do not constitute physiological substrates (PubMed:19362538, PubMed:25601083). ATP + L-tyrosyl-[protein] = diphosphate + O-(5'-adenylyl)-L-tyrosyl-[protein] 3-O-(5'-adenylyl)-L-threonyl-[protein] + H2O = AMP + H(+) + L-threonyl-[protein] ATP + L-threonyl-[protein] = 3-O-(5'-adenylyl)-L-threonyl-[protein] + diphosphate Divalent metal cation. Prefers Mn(2+) over Mg(2+). The side chain of Glu-234 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-234 binds ATP and competes with ATP-binding at Arg-374, thereby preventing adenylyltransferase activity (PubMed:22266942, PubMed:25435325). In unstressed cells, disengagement of Glu-234 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-234, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (PubMed:22266942, PubMed:25435325). Homodimer (PubMed:25435325). Interacts with HD (PubMed:9700202). Ubiquitous. Up-regulated in response to activation of unfolded protein response (UPR). The fido domain mediates the adenylyltransferase activity. Auto-AMPylated in vitro; it is unclear whether auto-AMPylation is relevant in vivo. N-glycosylated; predominantly glycosylated at Asn-275. Belongs to the fic family. Was initially thought to mediate AMPylation of HSPA5/BiP at 'Ser-365' and 'Thr-366' in vitro, leading to activate HSPA5/BiP (PubMed:25601083). However, it was later shown that it mediates AMPylation of HSPA5/BiP at 'Thr-518', leading to inactivate HSPA5/BiP.