PARG_DROME
ID PARG_DROME Reviewed; 723 AA.
AC O46043; M9NEU9; Q960N8;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 3.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Poly(ADP-ribose) glycohydrolase;
DE EC=3.2.1.143 {ECO:0000250|UniProtKB:Q867X0};
GN Name=Parg; ORFNames=CG2864;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1] {ECO:0000312|EMBL:AAC28734.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ame J.-C., Jacobson M.K.;
RT "Isolation and characterization of the cDNA encoding Drosophila poly(ADP-
RT ribose) glycohydrolase.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4] {ECO:0000312|EMBL:CAB10913.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Oregon-R {ECO:0000269|PubMed:10731137};
RX PubMed=10731137; DOI=10.1126/science.287.5461.2220;
RA Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G.,
RA Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Borkova D., Minana B., Kafatos F.C.,
RA Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L.,
RA Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P.,
RA Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H.,
RA Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S.,
RA McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C.,
RA Glover D.M.;
RT "From sequence to chromosome: the tip of the X chromosome of D.
RT melanogaster.";
RL Science 287:2220-2222(2000).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAK93379.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAK93379.1};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14676324; DOI=10.1073/pnas.2237114100;
RA Hanai S., Kanai M., Ohashi S., Okamoto K., Yamada M., Takahashi H.,
RA Miwa M.;
RT "Loss of poly(ADP-ribose) glycohydrolase causes progressive
RT neurodegeneration in Drosophila melanogaster.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:82-86(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24; SER-28; SER-579; SER-582
RP AND SER-583, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=30100084; DOI=10.1016/j.ajhg.2018.07.010;
RA Ghosh S.G., Becker K., Huang H., Dixon-Salazar T., Chai G., Salpietro V.,
RA Al-Gazali L., Waisfisz Q., Wang H., Vaux K.K., Stanley V., Manole A.,
RA Akpulat U., Weiss M.M., Efthymiou S., Hanna M.G., Minetti C., Striano P.,
RA Pisciotta L., De Grandis E., Altmueller J., Nuernberg P., Thiele H.,
RA Yis U., Okur T.D., Polat A.I., Amiri N., Doosti M., Karimani E.G.,
RA Toosi M.B., Haddad G., Karakaya M., Wirth B., van Hagen J.M., Wolf N.I.,
RA Maroofian R., Houlden H., Cirak S., Gleeson J.G.;
RT "Biallelic mutations in ADPRHL2, encoding ADP-ribosylhydrolase 3, lead to a
RT degenerative pediatric stress-induced epileptic ataxia syndrome.";
RL Am. J. Hum. Genet. 103:431-439(2018).
CC -!- FUNCTION: Poly(ADP-ribose) synthesized after DNA damage is only present
CC transiently and is rapidly degraded by poly(ADP-ribose) glycohydrolase.
CC Poly(ADP-ribose) metabolism is required for maintenance of the normal
CC function of neuronal cells. {ECO:0000269|PubMed:14676324}.
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:Q867X0};
CC -!- DISRUPTION PHENOTYPE: Progressive neurodegeneration (PubMed:14676324).
CC Knockdown of Parg leads to decreased survival when animals are exposed
CC to stress with either hydrogen peroxide or environmental hypoxia
CC (PubMed:30100084). {ECO:0000269|PubMed:14676324,
CC ECO:0000269|PubMed:30100084}.
CC -!- SIMILARITY: Belongs to the poly(ADP-ribose) glycohydrolase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC28734.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF079556; AAC28734.1; ALT_INIT; mRNA.
DR EMBL; AE014298; AAF45886.2; -; Genomic_DNA.
DR EMBL; AE014298; AFH07225.1; -; Genomic_DNA.
DR EMBL; Z98254; CAB10913.1; -; Genomic_DNA.
DR EMBL; AY051955; AAK93379.1; -; mRNA.
DR RefSeq; NP_001245511.1; NM_001258582.2.
DR RefSeq; NP_477321.2; NM_057973.4.
DR AlphaFoldDB; O46043; -.
DR SMR; O46043; -.
DR BioGRID; 57851; 4.
DR IntAct; O46043; 2.
DR STRING; 7227.FBpp0298281; -.
DR iPTMnet; O46043; -.
DR PaxDb; O46043; -.
DR DNASU; 31329; -.
DR EnsemblMetazoa; FBtr0307279; FBpp0298280; FBgn0023216.
DR EnsemblMetazoa; FBtr0307280; FBpp0298281; FBgn0023216.
DR GeneID; 31329; -.
DR KEGG; dme:Dmel_CG2864; -.
DR CTD; 8505; -.
DR FlyBase; FBgn0023216; Parg.
DR VEuPathDB; VectorBase:FBgn0023216; -.
DR eggNOG; KOG2064; Eukaryota.
DR GeneTree; ENSGT00390000003652; -.
DR HOGENOM; CLU_013388_3_0_1; -.
DR InParanoid; O46043; -.
DR OMA; WDSEHVR; -.
DR OrthoDB; 730627at2759; -.
DR PhylomeDB; O46043; -.
DR Reactome; R-DME-110362; POLB-Dependent Long Patch Base Excision Repair.
DR BioGRID-ORCS; 31329; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 31329; -.
DR PRO; PR:O46043; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0023216; Expressed in ovary and 27 other tissues.
DR Genevisible; O46043; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0004649; F:poly(ADP-ribose) glycohydrolase activity; IDA:FlyBase.
DR GO; GO:1990966; P:ATP generation from poly-ADP-D-ribose; IBA:GO_Central.
DR GO; GO:0030576; P:Cajal body organization; IMP:FlyBase.
DR GO; GO:0005975; P:carbohydrate metabolic process; IMP:UniProtKB.
DR GO; GO:0036099; P:female germ-line stem cell population maintenance; IMP:FlyBase.
DR GO; GO:0031507; P:heterochromatin assembly; IMP:FlyBase.
DR GO; GO:0051457; P:maintenance of protein location in nucleus; IMP:FlyBase.
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:0035065; P:regulation of histone acetylation; IMP:FlyBase.
DR GO; GO:0031056; P:regulation of histone modification; IBA:GO_Central.
DR GO; GO:0043484; P:regulation of RNA splicing; IMP:FlyBase.
DR GO; GO:0009408; P:response to heat; IMP:FlyBase.
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 Hydrolase; Phosphoprotein; Reference proteome.
FT CHAIN 1..723
FT /note="Poly(ADP-ribose) glycohydrolase"
FT /id="PRO_0000066607"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 554..593
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 609..723
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 576..593
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 643..669
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 682..723
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 583
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
SQ SEQUENCE 723 AA; 81109 MW; 90A5BA59775D611C CRC64;
MSKSPDGGIS EIETEEEPEN LANSLDDSWR GVSMEAIHRN RQPFELENLP PVTAGNLHRV
MYQLPIRETP PRPYKSPGKW DSEHVRLPCA PESKYPRENP DGSTTIDFRW EMIERALLQP
IKTCEELQAA IISYNTTYRD QWHFRALHQL LDEELDESET RVFFEDLLPR IIRLALRLPD
LIQSPVPLLK HHKNASLSLS QQQISCLLAN AFLCTFPRRN TLKRKSEYST FPDINFNRLY
QSTGPAVLEK LKCIMHYFRR VCPTERDASN VPTGVVTFVR RSGLPEHLID WSQSAAPLGD
VPLHVDAEGT IEDEGIGLLQ VDFANKYLGG GVLGHGCVQE EIRFVICPEL LVGKLFTECL
RPFEALVMLG AERYSNYTGY AGSFEWSGNF EDSTPRDSSG RRQTAIVAID ALHFAQSHHQ
YREDLMEREL NKAYIGFVHW MVTPPPGVAT GNWGCGAFGG DSYLKALLQL MVCAQLGRPL
AYYTFGNVEF RDDFHEMWLL FRNDGTTVQQ LWSILRSYSR LIKEKSSKEP RENKASKKKL
YDFIKEELKK VRDVPGEGAS AEAGSSRVAG LGEGKSETSA KSSPELNKQP ARPQITITQQ
STDLLPAQLS QDNSNSSEDQ ALLMLSDDEE ANAMMEAASL EAKSSVEISN SSTTSKTSST
ATKSMGSGGR QLSLLEMLDT HYEKGSASKR PRKSPNCSKA EGSAKSRKEI DVTDKDEKDD
IVD
