FIC domain protein adenylyltransferase (FICD)

FIC domain protein adenylyltransferase (FICD) is a human enzyme characterized by a conserved FIC domain that catalyzes the post-translational modification of target proteins through AMPylation (the transfer of an AMP group from ATP to a hydroxyl side chain, typically of serine, threonine, or tyrosine residues)[1][2][3]. FICD primarily localizes to the endoplasmic reticulum membrane, where it regulates the unfolded protein response (UPR) by catalyzing the reversible AMPylation and deAMPylation of the major ER chaperone BiP (HSPA5/GRP78), thereby tuning protein folding capacity in response to cellular stress[3]. Dysregulation of FICD activity has been linked to hereditary spastic paraplegia (SPG92) and cone-rod dystrophy, supporting its key role in neuronal function and proteostasis[3]. FICD and related Fic domain proteins are widely conserved from bacteria to humans, where they mediate diverse AMP transfer (AMPylation) modifications, signaling mechanisms, and potentially other post-translational processes[1][2].

Other names

HIP13HYPEAMPylator FICDDe-AMPylase FICDFIC domain-containing proteinHuntingtin yeast partner EHuntingtin-interacting protein 13HIP-13SPG92AMPylaseadenosine monophosphate-protein transferase FICDUNQ3041/PRO9857huntingtin interacting protein Ehuntingtin interactor protein E

Inhibitors would block AMPylation of target proteins (e.g., BiP/GRP78/HSPA5). Modulators could alter unfolded protein response signaling by affecting FICD-mediated AMPylation/deAMPylation activity.