FICD
Description
The FICD (FIC domain protein adenylyltransferase) is a protein-coding gene located on chromosome 12.
FIC domain protein adenylyltransferase (FICD) is an enzyme in metazoans possessing adenylylation and deadenylylation activity (also known as (de)AMPylation), and is a member of the Fic (filamentation induced by cAMP) domain family of proteins. AMPylation is a reversible post-translational modification that FICD performs on target cellular protein substrates. FICD is the only known Fic domain encoded by the metazoan genome, and is located on chromosome 12 in humans. Catalytic activity is reliant on the enzyme's Fic domain, which catalyzes the addition of an AMP (adenylyl group) moiety to the substrate. FICD has been linked to many cellular pathways, most notably the ATF6 and PERK branches of the UPR (unfolded protein response) pathway regulating ER homeostasis. FICD is present at very low basal levels in most cell types in humans, and its expression is highly regulated. Examples of FICD include HYPE (Huntingtin Yeast Interacting Partner E) in humans, Fic-1 in C. elegans, and dfic in D. melanogaster.
== Structure == The structure of FICD proteins consists of different regions, which are the SS/TM (signal sequence/transmembrane domain),TPR (tetratricopeptide repeat) domain and fic (filamentation induced by cAMP) domain. The secondary structure is primarily composed of nine α-helices. All FICD proteins share the same catalytic motif in their fic domain, consisting of the amino acid sequence HxFx(D/E)(G/A)N(G/K)R1xxR2, located at the C terminus of the protein.
FICD is a dual-function enzyme that can both add (AMPylation) and remove (de-AMPylation) adenosine monophosphate (AMP) from specific residues on target proteins, depending on the cellular context. The activity of FICD is determined by the amino acid Glu-231, which switches between AMPylase and de-AMPylase functions. FICD is a crucial regulator of the ERN1/IRE1-mediated unfolded protein response (UPR) by controlling the AMPylation or de-AMPylation of HSPA5/BiP. In normal cells, FICD acts as an adenylyltransferase, AMPylating HSPA5/BiP at Thr-518 and inactivating it. In response to endoplasmic reticulum stress, FICD functions as a phosphodiesterase, removing AMP (de-AMPylation) from HSPA5/BiP at Thr-518, thereby restoring HSPA5/BiP activity. Although FICD can AMPylate RhoA, Rac, and Cdc42 Rho GTPases in laboratory settings, these proteins are not considered to be physiological substrates in living cells.
FICD is also known as HIP13, HYPE, UNQ3041.
