Protein: Poly(ADP-ribose) glycohydrolase (EC 3.2.1.143) (O88622)
Organism: Mus musculus (Mouse)
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: Nucleus {ECO:0000250|UniProtKB:Q86W56}. Note=Colocalizes with PCNA at replication foci. Relocalizes to the cytoplasm in response to DNA damage (By similarity). {ECO:0000250|UniProtKB:Q86W56}.
InterPro domains:
- IPR048362: Poly (ADP-ribose) glycohydrolase, helical domain (domain) [574-692]
- IPR046372: Poly (ADP-ribose) glycohydrolase (PARG), catalytic domain (domain) [699-901]
- IPR007724: Poly(ADP-ribose) glycohydrolase (family) [453-951]
Sequence:
MSAGPGWEPCTKRPRWGAAGTSAPTASDSRSFPGRQRRVLDPKDAPVQFRVPPSSPACVSGRAGPHRGNATSFVFKQKTITTWMDTKGPKTAESESKENNNTRIDSMMSSVQKDNFYPHKVEKLENVPQLNLDKSPTEKSSQYLNQQQTASVCKWQNEGKHAEQLLASEPPAGTPLPKQLSNANIGQSPHTDDHSDTDHEEDRDNQQFLTPIKLANTKPTVGDGQARSNCKCSGSRQSVKDCTGCQQEEVDVLPESPLSDVGAEDIGTGPKNDNKLTGQESSLGDSPPFEKESEPESPMDVDNSKNSCQDSEADEETSPVFDEQDDRSSQTANKLSSCQAREADGDLRKRYLTKGSEVRLHFQFEGENNAGTSDLNAKPSGNSSSLNVECRSSKQHGKRDSKITDHFMRISKSEDRRKEQCEVRHQRTERKIPKYIPPNLPPEKKWLGTPIEEMRKMPRCGIHLPSLRPSASHTVTVRVDLLRAGEVPKPFPTHYKDLWDNKHVKMPCSEQNLYPVEDENGERTAGSRWELIQTALLNKFTRPQNLKDAILKYNVAYSKKWDFTALVDFWDKVLEEAEAQHLYQSILPDMVKIALCLPNICTQPIPLLKQKMNHSVTMSQEQIASLLANAFFCTFPRRNAKMKSEYSSYPDINFNRLFEGRSSRKPEKLKTLFCYFRRVTEKKPTGLVTFTRQSLEDFPEWERCEKPLTRLHVTYEGTIEGNGRGMLQVDFANRFVGGGVTGAGLVQEEIRFLINPELIVSRLFTEVLDHNECLIITGTEQYSEYTGYAETYRWARSHEDGSEKDDWQRRCTEIVAIDALHFRRYLDQFVPEKVRRELNKAYCGFLRPGVPSENLSAVATGNWGCGAFGGDARLKALIQILAAAAAERDVVYFTFGDSELMRDIYSMHTFLTERKLDVGKVYKLLLRYYNEECRNCSTPGPDIKLYPFIYHAVESSAETTDMPGQKAGT
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016787 (hydrolase activity), GO:0016798 (hydrolase activity, acting on glycosyl bonds), GO:0004553 (hydrolase activity, hydrolyzing O-glycosyl compounds)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0051179 (localization), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0051641 (cellular localization), GO:0051651 (maintenance of location in cell), GO:0044237 (cellular metabolic process), GO:0019222 (regulation of metabolic process), GO:0051235 (maintenance of location), GO:0050794 (regulation of cellular process), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:0033036 (macromolecule localization), GO:0009892 (negative regulation of metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0044085 (cellular component biogenesis), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0032507 (maintenance of protein location in cell), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0070727 (cellular macromolecule localization), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0016043 (cellular component organization), GO:0080090 (regulation of primary metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0045185 (maintenance of protein location), GO:0072595 (maintenance of protein localization in organelle), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0008104 (protein localization), GO:0006996 (organelle organization), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0010468 (regulation of gene expression), GO:0022607 (cellular component assembly), GO:0070925 (organelle assembly), GO:0033365 (protein localization to organelle), GO:0051457 (maintenance of protein location in nucleus), GO:0043484 (regulation of RNA splicing), GO:2001141 (regulation of RNA biosynthetic process), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0051276 (chromosome organization), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0034504 (protein localization to nucleus), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:0140694 (non-membrane-bounded organelle assembly), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0060271 (cilium assembly), GO:0045892 (negative regulation of DNA-templated transcription), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)