ADP-ribosylserine hydrolase (ARH3)

ADP-ribosylserine hydrolase (ARH3) is an enzyme of the ADP-ribosylglycohydrolase family, specializing in the removal of ADP-ribose modifications from serine residues on proteins, primarily in the context of DNA damage response. It hydrolyzes the alpha-O-linkage at the anomeric C1'' position of ADP-ribose in proteins, free poly(ADP-ribose), and O-acetyl-ADP-D-ribose, but does not act on ADP-ribosylation at arginine, cysteine, diphthamide, or asparagine. The main physiological roles include safeguarding cells from poly(ADP-ribose)-induced cell death (parthanatos), supporting DNA repair, and contributing to genomic stability. Its function is distinct from related hydrolases such as ARH1 or PARG in substrate specificity and activity. Dysfunction of ARH3 has been implicated in neurodegenerative pathology due to accumulation of toxic ADP-ribose polymers, emphasizing its therapeutic potential and highlighting safety concerns for direct inhibition.

Other names

ADPRSADPRHL2ADP-ribosylhydrolase ARH3ADP-ribosylhydrolase 3ADP-ribose glycohydrolase ARH3O-acetyl-ADP-ribose deacetylase ARH3Poly(ADP-ribose) glycohydrolase ARH3[Protein ADP-ribosylarginine] hydrolase-like protein 2[Protein ADP-ribosylserine] hydrolaseADP-ribosylarginine hydrolase like 2FLJ20446CONDSIAS

For potential inhibitors—block enzymatic hydrolysis of ADP-ribosyl-serine; interfere with removal of ADP-ribose modifications, modulating DNA repair and programmed cell death.