ADPRS
Function
ADP-ribosylhydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine and threonine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose (PubMed:21498885, PubMed:29907568, PubMed:30045870, PubMed:30401461, PubMed:30830864, PubMed:33186521, PubMed:33769608, PubMed:33894202, PubMed:34019811, PubMed:34321462, PubMed:34479984, PubMed:34625544). Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response (PubMed:28650317, PubMed:29234005, PubMed:30045870, PubMed:33186521, PubMed:34019811, PubMed:34625544). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802, PubMed:33186521, PubMed:34625544). Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (PubMed:16278211, PubMed:33769608). Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (PubMed:16278211). Also hydrolyzes free poly(ADP-ribose) in mitochondria (PubMed:22433848). Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (PubMed:17075046, PubMed:21498885). Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers (PubMed:21498885).
Involvement in disease
Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures
CONDSIAS
An autosomal recessive neurodegenerative disorder characterized by pediatric onset of progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the ADP-ribosylglycohydrolase family.
Tissue Specificity
Ubiquitous (PubMed:16278211). Expressed in skin fibroblasts (PubMed:30830864).
Cellular localization
- Nucleus
- Cytoplasm
- Chromosome
- Mitochondrion matrix
- Recruited to DNA lesion regions following DNA damage; ADP-D-ribose-recognition is required for recruitment to DNA damage sites.
Alternative names
ADPRHL2, ARH3, ADPRS, ADP-ribosylhydrolase ARH3, ADP-ribose glycohydrolase ARH3, ADP-ribosylhydrolase 3, O-acetyl-ADP-ribose deacetylase ARH3, Poly(ADP-ribose) glycohydrolase ARH3, [Protein ADP-ribosylarginine] hydrolase-like protein 2, [Protein ADP-ribosylserine] hydrolase