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-273 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place (By similarity). Adenylyltransferase that mediates the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins. In vivo target proteins include the heat-shock 70 family proteins hsp-1 and hsp-3 and the translation elongation factors eef-1A, eef-1G and eef-2. Can AMPylate core histone H3 in vitro (By similarity). Can also act as a phosphodiesterase by mediating removal of ATP (de-AMPylation) from target proteins (By similarity). Decreases susceptibility to P.aeruginosa-mediated killing and might therefore play a role in the innate immune response (By similarity). ATP + L-tyrosyl-[protein] = diphosphate + O-(5'-adenylyl)-L-tyrosyl-[protein] ATP + L-threonyl-[protein] = 3-O-(5'-adenylyl)-L-threonyl-[protein] + diphosphate 3-O-(5'-adenylyl)-L-threonyl-[protein] + H2O = AMP + H(+) + L-threonyl-[protein] The side chain of Glu-273 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-273 binds ATP and competes with ATP-binding at Arg-414, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-273 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-273, 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 (By similarity). Forms homodimers; homodimerization might be required for adenylyltransferase activity. Predominantly localized to the endoplasmic reticulum and to the nucleus. The fido domain mediates the adenylyltransferase activity. Belongs to the fic family.