PARG_RAT
ID PARG_RAT Reviewed; 972 AA.
AC Q9QYM2;
DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Poly(ADP-ribose) glycohydrolase {ECO:0000303|PubMed:10502684};
DE EC=3.2.1.143 {ECO:0000250|UniProtKB:Q86W56};
GN Name=Parg {ECO:0000303|PubMed:10502684, ECO:0000312|RGD:620387};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 543-550; 556-562 AND
RP 948-957, AND TISSUE SPECIFICITY.
RC STRAIN=Buffalo; TISSUE=Colon;
RX PubMed=10502684; DOI=10.1093/oxfordjournals.jbchem.a022512;
RA Shimokawa T., Masutani M., Nagasawa S., Nozaki T., Ikota N., Aoki Y.,
RA Nakagama H., Sugimura T.;
RT "Isolation and cloning of rat poly(ADP-ribose) glycohydrolase: presence of
RT a potential nuclear export signal conserved in mammalian orthologs.";
RL J. Biochem. 126:748-755(1999).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256; SER-259 AND SER-286, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 385-972 IN COMPLEX WITH SUBSTRATE
RP ANALOG, ACTIVE SITE, AND SUBSTRATE-BINDING SITES.
RX PubMed=22609859; DOI=10.1038/nsmb.2305;
RA Kim I.K., Kiefer J.R., Ho C.M., Stegeman R.A., Classen S., Tainer J.A.,
RA Ellenberger T.;
RT "Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible
RT tyrosine clasp as a substrate-binding element.";
RL Nat. Struct. Mol. Biol. 19:653-656(2012).
CC -!- FUNCTION: Poly(ADP-ribose) glycohydrolase that degrades poly(ADP-
CC ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP-
CC ribose). PARG acts both as an endo- and exoglycosidase, releasing
CC poly(ADP-ribose) of different length as well as ADP-ribose monomers. It
CC is however unable to cleave the ester bond between the terminal ADP-
CC ribose and ADP-ribosylated residues, leaving proteins that are mono-
CC ADP-ribosylated. Poly(ADP-ribose) is synthesized after DNA damage is
CC only present transiently and is rapidly degraded by PARG. Required to
CC prevent detrimental accumulation of poly(ADP-ribose) upon prolonged
CC replicative stress, while it is not required for recovery from
CC transient replicative stress. Responsible for the prevalence of mono-
CC ADP-ribosylated proteins in cells, thanks to its ability to degrade
CC poly(ADP-ribose) without cleaving the terminal protein-ribose bond.
CC Required for retinoid acid-dependent gene transactivation, probably by
CC removing poly(ADP-ribose) from histone demethylase KDM4D, allowing
CC chromatin derepression at RAR-dependent gene promoters. Involved in the
CC synthesis of ATP in the nucleus, together with PARP1, NMNAT1 and NUDT5.
CC Nuclear ATP generation is required for extensive chromatin remodeling
CC events that are energy-consuming. {ECO:0000250|UniProtKB:Q86W56}.
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:0000250|UniProtKB:Q86W56};
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 -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:10502684}.
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}.
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DR EMBL; AB019366; BAA87901.1; -; mRNA.
DR RefSeq; NP_112629.1; NM_031339.1.
DR PDB; 3UEK; X-ray; 1.95 A; A=385-972.
DR PDB; 3UEL; X-ray; 3.00 A; A/B/C=385-972.
DR PDBsum; 3UEK; -.
DR PDBsum; 3UEL; -.
DR AlphaFoldDB; Q9QYM2; -.
DR SMR; Q9QYM2; -.
DR STRING; 10116.ENSRNOP00000027071; -.
DR BindingDB; Q9QYM2; -.
DR ChEMBL; CHEMBL3317337; -.
DR iPTMnet; Q9QYM2; -.
DR PhosphoSitePlus; Q9QYM2; -.
DR PaxDb; Q9QYM2; -.
DR PRIDE; Q9QYM2; -.
DR GeneID; 83507; -.
DR KEGG; rno:83507; -.
DR UCSC; RGD:620387; rat.
DR CTD; 8505; -.
DR RGD; 620387; Parg.
DR eggNOG; KOG2064; Eukaryota.
DR InParanoid; Q9QYM2; -.
DR OrthoDB; 730627at2759; -.
DR PhylomeDB; Q9QYM2; -.
DR BRENDA; 3.2.1.143; 5301.
DR Reactome; R-RNO-110362; POLB-Dependent Long Patch Base Excision Repair.
DR PRO; PR:Q9QYM2; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0003682; F:chromatin binding; IDA:RGD.
DR GO; GO:0004649; F:poly(ADP-ribose) glycohydrolase activity; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0016045; P:detection of bacterium; ISO:RGD.
DR GO; GO:0009225; P:nucleotide-sugar metabolic process; IBA:GO_Central.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:RGD.
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 3D-structure; Acetylation; Direct protein sequencing; DNA damage;
KW Hydrolase; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..972
FT /note="Poly(ADP-ribose) glycohydrolase"
FT /id="PRO_0000066604"
FT REGION 1..452
FT /note="A-domain"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT REGION 1..239
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 253..351
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 605..790
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 130..153
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 167..191
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..207
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..394
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 395..409
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 733
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT ACT_SITE 751
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT ACT_SITE 752
FT /evidence="ECO:0000269|PubMed:22609859"
FT BINDING 722..723
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22609859"
FT BINDING 736
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22609859"
FT BINDING 750
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22609859"
FT BINDING 791
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22609859"
FT BINDING 865..870
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22609859"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 137
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 197
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 286
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 297
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86W56"
FT MOD_RES 337
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O88622"
FT STRAND 448..452
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 454..456
FT /evidence="ECO:0007829|PDB:3UEK"
FT TURN 460..463
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 493..497
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 503..506
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 516..520
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 522..524
FT /evidence="ECO:0007829|PDB:3UEL"
FT STRAND 526..530
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 531..539
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 546..555
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 558..560
FT /evidence="ECO:0007829|PDB:3UEK"
FT TURN 561..563
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 567..574
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 579..587
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 589..598
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 600..603
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 617..622
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 623..634
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 644..646
FT /evidence="ECO:0007829|PDB:3UEK"
FT TURN 648..651
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 658..661
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 668..684
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 690..697
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 704..706
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 714..720
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 722..725
FT /evidence="ECO:0007829|PDB:3UEK"
FT TURN 726..728
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 729..735
FT /evidence="ECO:0007829|PDB:3UEK"
FT TURN 739..744
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 750..757
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 759..763
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 764..767
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 775..780
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 786..790
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 792..794
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 796..800
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 816..821
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 828..832
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 834..848
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 855..857
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 861..864
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 875..888
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 893..896
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 901..916
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 921..935
FT /evidence="ECO:0007829|PDB:3UEK"
FT TURN 936..938
FT /evidence="ECO:0007829|PDB:3UEK"
FT STRAND 941..943
FT /evidence="ECO:0007829|PDB:3UEK"
FT HELIX 948..957
FT /evidence="ECO:0007829|PDB:3UEK"
SQ SEQUENCE 972 AA; 109003 MW; 3DED7885684F59E9 CRC64;
MSAGPGCEPC TKRPRWGAAG TSAPTASDSR SFPGRQKRVL DPKDAPVQFR VPPSSSACVS
GRAGPHRGSV TSFVFKQKPI TTWMDTKGPK TAESESKENN NTRTDPMMSS VQKDNFYPHK
VEKLGNVPQL NLDKSPTEKS TPYLNQQQTA GVCKWHSAGE RAEQLSASEP SAVTQAPKQL
SNANIDQSPP TDGHSDTDHE EDRDNQQFLT PVKLANAKQT VGDGQARSNC KCSASCQCGQ
DCAGCQREEA DVIPESPLSD VGAEDIGTGS KNDNKLTGQE SGLGDSPPFE KESEPESPMD
VDNSKTSCQD SEADEEASPV FDEQDDQDDR SSQTANKLSS RQAREVDGDL RKRYLTKGSE
IRLHFQFEGG SNAGTSDLNA KPSGNSSSLN VDGRSSKQHG KRDSKITDHF VRIPKSEDKR
KEQCEVRHQR AERKIPKYVP PNLPPDKKWL GTPIEEMRKM PRCGVRLPLL RPSASHTVTV
RVDLLRAGEV PKPFPTHYKD LWDNKHVKMP CSEQNLYPVE DENGERTAGS RWELIQTALL
NKFTRPQNLK DAILKYNVAY SKKWDFTALV DFWDKVLEEA EAQHLYQSIL PDMVKIALCL
PNICTQPIPL LKQKMNHSVT MSQEQIASLL ANAFFCTFPR RNAKMKSEYS SYPDINFNRL
FEGRSSRKPE KLKTLFCYFR RVTEKKPTGL VTFTRQSLED FPEWERCDKP LTRLHVTYEG
TIEGNGRGML QVDFANRFVG GGVTGAGLVQ EEIRFLINPE LIVSRLFTEV LDHNECLIIT
GTEQYSEYTG YAETYRWARS HEDGSEKDDW QRCCTEIVAI DALHFRRYLD QFVPEKVRRE
LNKAYCGFLR PGVPPENLSA VATGNWGCGA FGGDARLKAL IQLLAAAAAE RDVVYFTFGD
SELMRDIYSM HTFLTERKLN VGKVYRLLLR YYREECRDCS SPGPDTKLYP FIYHAAESSA
ETSDQPGQRT GT
