PARG_BOVIN
ID PARG_BOVIN Reviewed; 977 AA.
AC O02776;
DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Poly(ADP-ribose) glycohydrolase {ECO:0000303|PubMed:9115250};
DE EC=3.2.1.143 {ECO:0000269|PubMed:15658938};
GN Name=PARG {ECO:0000303|PubMed:9115250};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 601-616; 760-801 AND
RP 849-877.
RC TISSUE=Thymus;
RX PubMed=9115250; DOI=10.1074/jbc.272.18.11895;
RA Lin W., Ame J.-C., Aboul-Ela N., Jacobson E.L., Jacobson M.K.;
RT "Isolation and characterization of the cDNA encoding bovine poly(ADP-
RT ribose) glycohydrolase.";
RL J. Biol. Chem. 272:11895-11901(1997).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-738; GLU-756 AND GLU-757,
RP AND ACTIVE SITE.
RX PubMed=15658938; DOI=10.1042/bj20040942;
RA Patel C.N., Koh D.W., Jacobson M.K., Oliveira M.A.;
RT "Identification of three critical acidic residues of poly(ADP-ribose)
RT glycohydrolase involved in catalysis: determining the PARG catalytic
RT domain.";
RL Biochem. J. 388:493-500(2005).
CC -!- FUNCTION: Poly(ADP-ribose) glycohydrolase that degrades poly(ADP-
CC ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP-
CC ribose) (PubMed:15658938). PARG acts both as an endo- and
CC exoglycosidase, releasing poly(ADP-ribose) of different length as well
CC as ADP-ribose monomers. It is however unable to cleave the ester bond
CC between the terminal ADP-ribose and ADP-ribosylated residues, leaving
CC proteins that are mono-ADP-ribosylated. Poly(ADP-ribose) is synthesized
CC after DNA damage is only present transiently and is rapidly degraded by
CC PARG. Required to prevent detrimental accumulation of poly(ADP-ribose)
CC upon prolonged replicative stress, while it is not required for
CC recovery from transient replicative stress. Responsible for the
CC prevalence of mono-ADP-ribosylated proteins in cells, thanks to its
CC ability to degrade poly(ADP-ribose) without cleaving the terminal
CC protein-ribose bond. Required for retinoid acid-dependent gene
CC transactivation, probably by removing poly(ADP-ribose) from histone
CC demethylase KDM4D, allowing chromatin derepression at RAR-dependent
CC gene promoters. Involved in the synthesis of ATP in the nucleus,
CC together with PARP1, NMNAT1 and NUDT5. Nuclear ATP generation is
CC required for extensive chromatin remodeling events that are energy-
CC consuming (By similarity). {ECO:0000250|UniProtKB:Q86W56,
CC ECO:0000269|PubMed:15658938}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[(1''->2')-ADP-alpha-D-ribose](n) + H2O = [(1''->2')-ADP-
CC alpha-D-ribose](n-1) + ADP-D-ribose; Xref=Rhea:RHEA:52216, Rhea:RHEA-
CC COMP:16922, Rhea:RHEA-COMP:16923, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57967, ChEBI:CHEBI:142512; EC=3.2.1.143;
CC Evidence={ECO:0000269|PubMed:15658938};
CC -!- SUBUNIT: Interacts with PCNA. Interacts with NUDT5.
CC {ECO:0000250|UniProtKB:Q86W56}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q86W56}.
CC Note=Colocalizes with PCNA at replication foci. Relocalizes to the
CC cytoplasm in response to DNA damage (By similarity).
CC {ECO:0000250|UniProtKB:Q86W56}.
CC -!- DOMAIN: The PIP-box mediates interaction with PCNA and localization to
CC replication foci. {ECO:0000250|UniProtKB:Q86W56}.
CC -!- SIMILARITY: Belongs to the poly(ADP-ribose) glycohydrolase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U78975; AAB53370.1; -; mRNA.
DR RefSeq; NP_776563.1; NM_174138.3.
DR AlphaFoldDB; O02776; -.
DR SMR; O02776; -.
DR STRING; 9913.ENSBTAP00000031225; -.
DR BindingDB; O02776; -.
DR ChEMBL; CHEMBL4279; -.
DR PaxDb; O02776; -.
DR GeneID; 281377; -.
DR KEGG; bta:281377; -.
DR CTD; 8505; -.
DR eggNOG; KOG2064; Eukaryota.
DR InParanoid; O02776; -.
DR OrthoDB; 730627at2759; -.
DR BRENDA; 3.2.1.143; 908.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004649; F:poly(ADP-ribose) glycohydrolase activity; IDA:CACAO.
DR GO; GO:1990966; P:ATP generation from poly-ADP-D-ribose; ISS:UniProtKB.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:UniProtKB-KW.
DR GO; GO:0009225; P:nucleotide-sugar metabolic process; IBA:GO_Central.
DR GO; GO:0006282; P:regulation of DNA repair; IBA:GO_Central.
DR GO; GO:0031056; P:regulation of histone modification; IBA:GO_Central.
DR InterPro; IPR046372; PARG_cat.
DR InterPro; IPR007724; Poly_GlycHdrlase.
DR PANTHER; PTHR12837; PTHR12837; 1.
DR Pfam; PF05028; PARG_cat; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; DNA damage; Hydrolase; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..977
FT /note="Poly(ADP-ribose) glycohydrolase"
FT /id="PRO_0000066601"
FT REGION 1..457
FT /note="A-domain"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT REGION 1..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 184..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 611..796
FT /note="Catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOTIF 10..16
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOTIF 77..84
FT /note="PIP-box (PCNA interacting peptide)"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT COMPBIAS 220..240
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..294
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 329..345
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 346..371
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 385..399
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 738
FT /evidence="ECO:0000269|PubMed:15658938"
FT ACT_SITE 756
FT /evidence="ECO:0000269|PubMed:15658938"
FT ACT_SITE 757
FT /evidence="ECO:0000269|PubMed:15658938"
FT BINDING 727..728
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT BINDING 741
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT BINDING 755
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT BINDING 796
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9QYM2"
FT BINDING 870..875
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 198
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 200
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 292
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 341
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88622"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MUTAGEN 738
FT /note="D->N: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:15658938"
FT MUTAGEN 756
FT /note="E->N: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:15658938"
FT MUTAGEN 757
FT /note="E->N: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:15658938"
SQ SEQUENCE 977 AA; 110837 MW; 87D2100F979DF377 CRC64;
MSAGPGCEPC TKRPRWDAAA TSPPAASDAR SFPGRQRRVL DSKDAPVQFR VPPSSSGCAL
GRAGQHRGSA TSLVFKQKTI TSWMDTKGIK TVESESLHSK ENNNTREESM MSSVQKDNFY
QHNMEKLENV SQLGFDKSPV EKGTQYLKQH QTAAMCKWQN EGPHSERLLE SEPPAVTLVP
EQFSNANVDQ SSPKDDHSDT NSEESRDNQQ FLTHVKLANA KQTMEDEQGR EARSHQKCGK
ACHPAEACAG CQQEETDVVS ESPLSDTGSE DVGTGLKNAN RLNRQESSLG NSPPFEKESE
PESPMDVDNS KNSCQDSEAD EETSPGFDEQ EDSSSAQTAN KPSRFQPREA DTELRKRSSA
KGGEIRLHFQ FEGGESRAGM NDVNAKRPGS TSSLNVECRN SKQHGRKDSK ITDHFMRVPK
AEDKRKEQCE MKHQRTERKI PKYIPPHLSP DKKWLGTPIE EMRRMPRCGI RLPPLRPSAN
HTVTIRVDLL RIGEVPKPFP THFKDLWDNK HVKMPCSEQN LYPVEDENGE RAAGSRWELI
QTALLNRLTR PQNLKDAILK YNVAYSKKWD FTALIDFWDK VLEEAEAQHL YQSILPDMVK
IALCLPNICT QPIPLLKQKM NHSITMSQEQ IASLLANAFF CTFPRRNAKM KSEYSSYPDI
NFNRLFEGRS SRKPEKLKTL FCYFRRVTEK KPTGLVTFTR QSLEDFPEWE RCEKLLTRLH
VTYEGTIEGN GQGMLQVDFA NRFVGGGVTS AGLVQEEIRF LINPELIVSR LFTEVLDHNE
CLIITGTEQY SEYTGYAETY RWARSHEDRS ERDDWQRRTT EIVAIDALHF RRYLDQFVPE
KIRRELNKAY CGFLRPGVSS ENLSAVATGN WGCGAFGGDA RLKALIQILA AAVAERDVVY
FTFGDSELMR DIYSMHTFLT ERKLTVGEVY KLLLRYYNEE CRNCSTPGPD IKLYPFIYHA
VESCTQTTNQ PGQRTGA
