FICD
Domain
The fido domain mediates the adenylyltransferase activity.
Function
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).
Post-translational modifications
Auto-AMPylated in vitro; it is unclear whether auto-AMPylation is relevant in vivo.
N-glycosylated; predominantly glycosylated at Asn-275.
Sequence Similarities
Belongs to the fic family.
Tissue Specificity
Ubiquitous.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass type II membrane protein
Alternative names
HIP13, HYPE, UNQ3041/PRO9857, FICD, Protein adenylyltransferase FICD, AMPylator FICD, De-AMPylase FICD, FIC domain-containing protein, Huntingtin yeast partner E, Huntingtin-interacting protein 13, Huntingtin-interacting protein E, HIP-13