UniProt Summary: 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). {ECO:0000250|UniProtKB:A0A061I403, ECO:0000269|PubMed:22266942, ECO:0000269|PubMed:25435325, ECO:0000269|PubMed:25601083, ECO:0000305|PubMed:19362538}.
Pfam DomainsGO Terms
Pfam Domains
Fic
GO Terms
protein denucleotidylation
protein adenylylhydrolase activity
protein deadenylylation
protein adenylylation
protein nucleotidylation
protein adenylyltransferase activity
regulation of IRE1-mediated unfolded protein response
regulation of endoplasmic reticulum unfolded protein response
Hsp70 protein binding
negative regulation of GTPase activity
regulation of response to endoplasmic reticulum stress
chaperone binding
integral component of endoplasmic reticulum membrane
response to unfolded protein
response to topologically incorrect protein
response to endoplasmic reticulum stress
negative regulation of hydrolase activity
regulation of GTPase activity
regulation of cellular response to stress
negative regulation of catalytic activity
protein homodimerization activity
identical protein binding
negative regulation of molecular function
regulation of hydrolase activity
regulation of response to stress
ATP binding
cellular response to stress
CRISPR Data
Compound HitMost Correlated Genes in ChemogenomicsTissues where Essential in the Avana Dataset (DepMap 20Q1)