Protein: Poly(ADP-ribose) glycohydrolase (EC 3.2.1.143) (Q86W56)
Organism: Homo sapiens (Human)
Function: Poly(ADP-ribose) glycohydrolase that degrades poly(ADP-ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP-ribose). PARG acts both as an endo- and exoglycosidase, releasing poly(ADP-ribose) of different length as well as ADP-ribose monomers. It is however unable to cleave the ester bond between the terminal ADP-ribose and ADP-ribosylated residues, leaving proteins that are mono-ADP-ribosylated. Poly(ADP-ribose) is synthesized after DNA damage is only present transiently and is rapidly degraded by PARG. Required to prevent detrimental accumulation of poly(ADP-ribose) upon prolonged replicative stress, while it is not required for recovery from transient replicative stress. Responsible for the prevalence of mono-ADP-ribosylated proteins in cells, thanks to its ability to degrade poly(ADP-ribose) without cleaving the terminal protein-ribose bond. Required for retinoid acid-dependent gene transactivation, probably by removing poly(ADP-ribose) from histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters. Involved in the synthesis of ATP in the nucleus, together with PARP1, NMNAT1 and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming.
Subcellular location: [Isoform 1]: Nucleus {ECO:0000269|PubMed:16460818, ECO:0000269|PubMed:21398629}. Note=Colocalizes with PCNA at replication foci (PubMed:21398629). Relocalizes to the cytoplasm in response to DNA damage (PubMed:16460818). {ECO:0000269|PubMed:16460818, ECO:0000269|PubMed:21398629}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:15212953, ECO:0000269|PubMed:16460818}. Note=Translocates to the nucleus in response to DNA damage. {ECO:0000269|PubMed:16460818}.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm {ECO:0000269|PubMed:15212953}.; SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm {ECO:0000269|PubMed:22433848}. Mitochondrion {ECO:0000269|PubMed:22433848}.; SUBCELLULAR LOCATION: [Isoform 5]: Mitochondrion matrix {ECO:0000269|PubMed:17509564}.
Interaction partners:
- Poly [ADP-ribose] polymerase 1
- Poly [ADP-ribose] polymerase 2
- Proliferating cell nuclear antigen
- Ecto-ADP-ribosyltransferase 5
- ADP-ribosylhydrolase ARH3
- Rho GTPase-activating protein 29
- ADP-ribose glycohydrolase MACROD1
- Protein mono-ADP-ribosyltransferase PARP3
- Apoptosis-inducing factor 1, mitochondrial
- Ecto-ADP-ribosyltransferase 3
Sequence:
MNAGPGCEPCTKRPRWGAATTSPAASDARSFPSRQRRVLDPKDAHVQFRVPPSSPACVPGRAGQHRGSATSLVFKQKTITSWMDTKGIKTAESESLDSKENNNTRIESMMSSVQKDNFYQHNVEKLENVSQLSLDKSPTEKSTQYLNQHQTAAMCKWQNEGKHTEQLLESEPQTVTLVPEQFSNANIDRSPQNDDHSDTDSEENRDNQQFLTTVKLANAKQTTEDEQAREAKSHQKCSKSCDPGEDCASCQQDEIDVVPESPLSDVGSEDVGTGPKNDNKLTRQESCLGNSPPFEKESEPESPMDVDNSKNSCQDSEADEETSPGFDEQEDGSSSQTANKPSRFQARDADIEFRKRYSTKGGEVRLHFQFEGGESRTGMNDLNAKLPGNISSLNVECRNSKQHGKKDSKITDHFMRLPKAEDRRKEQWETKHQRTERKIPKYVPPHLSPDKKWLGTPIEEMRRMPRCGIRLPLLRPSANHTVTIRVDLLRAGEVPKPFPTHYKDLWDNKHVKMPCSEQNLYPVEDENGERTAGSRWELIQTALLNKFTRPQNLKDAILKYNVAYSKKWDFTALIDFWDKVLEEAEAQHLYQSILPDMVKIALCLPNICTQPIPLLKQKMNHSITMSQEQIASLLANAFFCTFPRRNAKMKSEYSSYPDINFNRLFEGRSSRKPEKLKTLFCYFRRVTEKKPTGLVTFTRQSLEDFPEWERCEKPLTRLHVTYEGTIEENGQGMLQVDFANRFVGGGVTSAGLVQEEIRFLINPELIISRLFTEVLDHNECLIITGTEQYSEYTGYAETYRWSRSHEDGSERDDWQRRCTEIVAIDALHFRRYLDQFVPEKMRRELNKAYCGFLRPGVSSENLSAVATGNWGCGAFGGDARLKALIQILAAAAAERDVVYFTFGDSELMRDIYSMHIFLTERKLTVGDVYKLLLRYYNEECRNCSTPGPDIKLYPFIYHAVESCAETADHSGQRTGT