ID OARD1_HUMAN Reviewed; 152 AA. AC Q9Y530; A6NEK4; A8K4H4; Q96F23; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 07-NOV-2003, sequence version 2. DT 27-MAR-2024, entry version 164. DE RecName: Full=ADP-ribose glycohydrolase OARD1 {ECO:0000305}; DE AltName: Full=O-acetyl-ADP-ribose deacetylase 1; DE EC=3.5.1.- {ECO:0000305|PubMed:21849506}; DE AltName: Full=Terminal ADP-ribose protein glycohydrolase 1 {ECO:0000303|PubMed:23481255}; DE AltName: Full=[Protein ADP-ribosylglutamate] hydrolase OARD1 {ECO:0000305}; DE EC=3.2.2.- {ECO:0000269|PubMed:23474714, ECO:0000269|PubMed:23481255}; GN Name=OARD1 {ECO:0000312|HGNC:HGNC:21257}; GN Synonyms=C6orf130 {ECO:0000312|HGNC:HGNC:21257}, TARG1 GN {ECO:0000303|PubMed:23481255}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [6] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-4, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [10] RP FUNCTION. RX PubMed=23474714; DOI=10.1038/nsmb.2521; RA Rosenthal F., Feijs K.L., Frugier E., Bonalli M., Forst A.H., Imhof R., RA Winkler H.C., Fischer D., Caflisch A., Hassa P.O., Luescher B., RA Hottiger M.O.; RT "Macrodomain-containing proteins are new mono-ADP-ribosylhydrolases."; RL Nat. Struct. Mol. Biol. 20:502-507(2013). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=29712969; DOI=10.1038/s41598-018-25137-w; RA Buetepage M., Preisinger C., von Kriegsheim A., Scheufen A., Lausberg E., RA Li J., Kappes F., Feederle R., Ernst S., Eckei L., Krieg S., RA Mueller-Newen G., Rossetti G., Feijs K.L.H., Verheugd P., Luescher B.; RT "Nucleolar-nucleoplasmic shuttling of TARG1 and its control by DNA damage- RT induced poly-ADP-ribosylation and by nucleolar transcription."; RL Sci. Rep. 8:6748-6748(2018). RN [12] RP CATALYTIC ACTIVITY. RX PubMed=31599159; DOI=10.1021/acschembio.9b00429; RA Stevens L.A., Kato J., Kasamatsu A., Oda H., Lee D.Y., Moss J.; RT "The ARH and Macrodomain Families of alpha-ADP-ribose-acceptor Hydrolases RT Catalyze alpha-NAD+ Hydrolysis."; RL ACS Chem. Biol. 14:2576-2584(2019). RN [13] RP STRUCTURE BY NMR OF 11-152. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the A1PP domain from human protein C6orf130."; RL Submitted (AUG-2007) to the PDB data bank. RN [14] RP STRUCTURE BY NMR. RG Center for eukaryotic structural genomics (CESG); RT "Solution structure of human C6orf130, a putative Macro domain."; RL Submitted (APR-2008) to the PDB data bank. RN [15] RP STRUCTURE BY NMR IN COMPLEX WITH ADENOSINE-5-DIPHOSPHORIBOSE, FUNCTION, RP CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF HIS-32; CYS-33; SER-35; RP THR-83; GLY-123 AND ASP-125, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY RP REGULATION. RX PubMed=21849506; DOI=10.1074/jbc.m111.276238; RA Peterson F.C., Chen D., Lytle B.L., Rossi M.N., Ahel I., Denu J.M., RA Volkman B.F.; RT "Orphan macrodomain (human C6ORF130) is an o-acyl-ADP-ribose deacylase: RT solution structure and catalytic properties."; RL J. Biol. Chem. 286:35955-35965(2011). RN [16] {ECO:0007744|PDB:4J5Q, ECO:0007744|PDB:4J5R, ECO:0007744|PDB:4J5S} RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 11-152 IN COMPLEX WITH ADP-RIBOSE RP ANALOGUE, FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, TISSUE SPECIFICITY, RP INVOLVEMENT IN SEVERE NEURODEGENERATION, VARIANT 76-ARG--LEU-152 DEL, AND RP MUTAGENESIS OF LYS-84 AND ASP-125. RX PubMed=23481255; DOI=10.1038/emboj.2013.51; RA Sharifi R., Morra R., Appel C.D., Tallis M., Chioza B., Jankevicius G., RA Simpson M.A., Matic I., Ozkan E., Golia B., Schellenberg M.J., Weston R., RA Williams J.G., Rossi M.N., Galehdari H., Krahn J., Wan A., Trembath R.C., RA Crosby A.H., Ahel D., Hay R., Ladurner A.G., Timinszky G., Williams R.S., RA Ahel I.; RT "Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in RT neurodegenerative disease."; RL EMBO J. 32:1225-1237(2013). CC -!- FUNCTION: ADP-ribose glycohydrolase that hydrolyzes ADP-ribose and acts CC on different substrates, such as proteins ADP-ribosylated on glutamate CC and O-acetyl-ADP-D-ribose (PubMed:23481255, PubMed:23474714, CC PubMed:21849506). Specifically acts as a glutamate mono-ADP- CC ribosylhydrolase by mediating the removal of mono-ADP-ribose attached CC to glutamate residues on proteins (PubMed:23481255, PubMed:23474714). CC Does not act on poly-ADP-ribosylated proteins: the poly-ADP-ribose CC chain of poly-ADP-ribosylated glutamate residues must by hydrolyzed CC into mono-ADP-ribosylated glutamate by PARG to become a substrate for CC OARD1 (PubMed:23481255). Deacetylates O-acetyl-ADP ribose, a signaling CC molecule generated by the deacetylation of acetylated lysine residues CC in histones and other proteins (PubMed:21849506). Catalyzes the CC deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose and O- CC butyryl-ADP-ribose, yielding ADP-ribose plus acetate, propionate and CC butyrate, respectively (PubMed:21849506). {ECO:0000269|PubMed:21849506, CC ECO:0000269|PubMed:23474714, ECO:0000269|PubMed:23481255}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2''-O-acetyl-ADP-D-ribose + H2O = acetate + ADP-D-ribose + CC H(+); Xref=Rhea:RHEA:57060, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30089, ChEBI:CHEBI:57967, ChEBI:CHEBI:83767; CC Evidence={ECO:0000305|PubMed:21849506}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57061; CC Evidence={ECO:0000305|PubMed:21849506}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + H2O = ADP-D-ribose CC + H(+) + L-glutamyl-[protein]; Xref=Rhea:RHEA:58248, Rhea:RHEA- CC COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:57967, CC ChEBI:CHEBI:142540; Evidence={ECO:0000269|PubMed:23474714, CC ECO:0000269|PubMed:23481255}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249; CC Evidence={ECO:0000269|PubMed:23474714, ECO:0000269|PubMed:23481255}; CC -!- CATALYTIC ACTIVITY: CC Reaction=alpha-NAD(+) + H2O = ADP-D-ribose + H(+) + nicotinamide; CC Xref=Rhea:RHEA:68792, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57967, ChEBI:CHEBI:77017; CC Evidence={ECO:0000269|PubMed:31599159}; CC -!- ACTIVITY REGULATION: Subject to competitive inhibition by the product CC ADP-ribose. {ECO:0000269|PubMed:21849506}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=182 uM for O-acetyl-ADP-ribose {ECO:0000269|PubMed:21849506}; CC -!- INTERACTION: CC Q9Y530; P09874: PARP1; NbExp=5; IntAct=EBI-8502288, EBI-355676; CC Q9Y530; Q53GL7: PARP10; NbExp=3; IntAct=EBI-8502288, EBI-2857573; CC Q9Y530; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-8502288, EBI-79165; CC Q9Y530; O95271: TNKS; NbExp=3; IntAct=EBI-8502288, EBI-1105254; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm CC {ECO:0000269|PubMed:23481255, ECO:0000269|PubMed:29712969}. Nucleus, CC nucleolus {ECO:0000269|PubMed:29712969}. Chromosome CC {ECO:0000269|PubMed:23481255}. Note=Localizes both in the nucleoplasm CC and in the nucleolus (PubMed:29712969). Relocalizes to the nucleoplasm CC in response to DNA damage (PubMed:29712969). Recruited to DNA lesion CC regions following DNA damage (PubMed:23481255). CC {ECO:0000269|PubMed:23481255, ECO:0000269|PubMed:29712969}. CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:23481255}. CC -!- DISEASE: Note=Defects in OARD1 are found in patients with severe CC neurodegeneration (PubMed:23481255). Defects were found in an extended CC consanguineous family with several affected cases in two generations CC (PubMed:23481255). {ECO:0000269|PubMed:23481255}. 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; AK290939; BAF83628.1; -; mRNA. DR EMBL; AK313361; BAG36161.1; -; mRNA. DR EMBL; AL031778; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471081; EAX04011.1; -; Genomic_DNA. DR EMBL; BC011709; AAH11709.1; -; mRNA. DR CCDS; CCDS34445.1; -. DR RefSeq; NP_001316613.1; NM_001329684.1. DR RefSeq; NP_001316614.1; NM_001329685.1. DR RefSeq; NP_001316615.1; NM_001329686.1. DR RefSeq; NP_001316617.1; NM_001329688.1. DR RefSeq; NP_659500.1; NM_145063.3. DR PDB; 2EEE; NMR; -; A=11-152. DR PDB; 2L8R; NMR; -; A=3-152. DR PDB; 2LGR; NMR; -; A=2-152. DR PDB; 4J5Q; X-ray; 1.35 A; A=7-152. DR PDB; 4J5R; X-ray; 1.25 A; A/B=11-152. DR PDB; 4J5S; X-ray; 1.55 A; A/B/C/D=11-152. DR PDBsum; 2EEE; -. DR PDBsum; 2L8R; -. DR PDBsum; 2LGR; -. DR PDBsum; 4J5Q; -. DR PDBsum; 4J5R; -. DR PDBsum; 4J5S; -. DR AlphaFoldDB; Q9Y530; -. DR BMRB; Q9Y530; -. DR SMR; Q9Y530; -. DR BioGRID; 128727; 23. DR IntAct; Q9Y530; 5. DR MINT; Q9Y530; -. DR STRING; 9606.ENSP00000420484; -. DR ChEMBL; CHEMBL4295991; -. DR iPTMnet; Q9Y530; -. DR PhosphoSitePlus; Q9Y530; -. DR BioMuta; OARD1; -. DR DMDM; 38258957; -. DR EPD; Q9Y530; -. DR jPOST; Q9Y530; -. DR MassIVE; Q9Y530; -. DR MaxQB; Q9Y530; -. DR PaxDb; 9606-ENSP00000420484; -. DR PeptideAtlas; Q9Y530; -. DR ProteomicsDB; 86280; -. DR Pumba; Q9Y530; -. DR Antibodypedia; 29984; 51 antibodies from 13 providers. DR DNASU; 221443; -. DR Ensembl; ENST00000424266.7; ENSP00000416829.2; ENSG00000124596.17. DR Ensembl; ENST00000463088.5; ENSP00000420193.1; ENSG00000124596.17. DR Ensembl; ENST00000468811.5; ENSP00000420601.1; ENSG00000124596.17. DR Ensembl; ENST00000479950.5; ENSP00000420484.1; ENSG00000124596.17. DR GeneID; 221443; -. DR KEGG; hsa:221443; -. DR MANE-Select; ENST00000424266.7; ENSP00000416829.2; NM_001329686.2; NP_001316615.1. DR UCSC; uc003opm.4; human. DR AGR; HGNC:21257; -. DR CTD; 221443; -. DR DisGeNET; 221443; -. DR GeneCards; OARD1; -. DR HGNC; HGNC:21257; OARD1. DR HPA; ENSG00000124596; Low tissue specificity. DR MIM; 614393; gene. DR neXtProt; NX_Q9Y530; -. DR OpenTargets; ENSG00000124596; -. DR PharmGKB; PA134879529; -. DR VEuPathDB; HostDB:ENSG00000124596; -. DR eggNOG; ENOG502RXG1; Eukaryota. DR GeneTree; ENSGT00390000006988; -. DR InParanoid; Q9Y530; -. DR OMA; CHCLKNG; -. DR OrthoDB; 1347733at2759; -. DR PhylomeDB; Q9Y530; -. DR TreeFam; TF324128; -. DR PathwayCommons; Q9Y530; -. DR SABIO-RK; Q9Y530; -. DR SignaLink; Q9Y530; -. DR BioGRID-ORCS; 221443; 17 hits in 1155 CRISPR screens. DR EvolutionaryTrace; Q9Y530; -. DR GenomeRNAi; 221443; -. DR Pharos; Q9Y530; Tdark. DR PRO; PR:Q9Y530; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q9Y530; Protein. DR Bgee; ENSG00000124596; Expressed in primordial germ cell in gonad and 195 other cell types or tissues. DR ExpressionAtlas; Q9Y530; baseline and differential. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0090734; C:site of DNA damage; IDA:UniProtKB. DR GO; GO:0140293; F:ADP-ribosylglutamate hydrolase activity; IDA:UniProtKB. DR GO; GO:0061463; F:O-acetyl-ADP-ribose deacetylase activity; IDA:UniProtKB. DR GO; GO:0001883; F:purine nucleoside binding; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IMP:UniProtKB. DR GO; GO:0140291; P:peptidyl-glutamate ADP-deribosylation; IDA:UniProtKB. DR GO; GO:0051725; P:protein de-ADP-ribosylation; IDA:UniProtKB. DR GO; GO:0042278; P:purine nucleoside metabolic process; IDA:UniProtKB. DR CDD; cd02901; Macro_Poa1p-like; 1. DR Gene3D; 3.40.220.10; Leucine Aminopeptidase, subunit E, domain 1; 1. DR InterPro; IPR002589; Macro_dom. DR InterPro; IPR043472; Macro_dom-like. DR PANTHER; PTHR12521:SF0; ADP-RIBOSE GLYCOHYDROLASE OARD1; 1. DR PANTHER; PTHR12521; PROTEIN C6ORF130; 1. DR Pfam; PF01661; Macro; 1. DR SMART; SM00506; A1pp; 1. DR SUPFAM; SSF52949; Macro domain-like; 1. DR PROSITE; PS51154; MACRO; 1. DR Genevisible; Q9Y530; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Chromosome; Disease variant; Hydrolase; Nucleus; KW Phosphoprotein; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT CHAIN 2..152 FT /note="ADP-ribose glycohydrolase OARD1" FT /id="PRO_0000089529" FT DOMAIN 2..152 FT /note="Macro" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490" FT ACT_SITE 84 FT /note="Nucleophile" FT /evidence="ECO:0000269|PubMed:23481255" FT ACT_SITE 125 FT /note="Proton acceptor" FT /evidence="ECO:0000269|PubMed:21849506, FT ECO:0000269|PubMed:23481255" FT BINDING 21 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:21849506" FT BINDING 119..125 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:21849506, FT ECO:0000269|PubMed:23481255" FT BINDING 152 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:21849506, FT ECO:0000269|PubMed:23481255" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 4 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT VARIANT 76..152 FT /note="Missing (found in a family with severe FT neurodegeneration; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:23481255" FT /id="VAR_081206" FT MUTAGEN 32 FT /note="H->A: Abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:21849506" FT MUTAGEN 33 FT /note="C->S: No effect." FT /evidence="ECO:0000269|PubMed:21849506" FT MUTAGEN 35 FT /note="S->A: Reduced catalytic activity. No effect on FT affinity towards substrate." FT /evidence="ECO:0000269|PubMed:21849506" FT MUTAGEN 83 FT /note="T->A: Reduced catalytic activity. No effect on FT affinity towards substrate." FT /evidence="ECO:0000269|PubMed:21849506" FT MUTAGEN 84 FT /note="K->A: Abolishes enzyme activity and ability to form FT a stable covalent adduct with the ADP-ribosylated FT substrate." FT /evidence="ECO:0000269|PubMed:23481255" FT MUTAGEN 123 FT /note="G->E: Abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:21849506" FT MUTAGEN 125 FT /note="D->A: Abolishes enzyme activity without affecting FT ability to form a stable covalent adduct with the FT ADP-ribosylated substrate." FT /evidence="ECO:0000269|PubMed:21849506, FT ECO:0000269|PubMed:23481255" FT STRAND 14..19 FT /evidence="ECO:0007829|PDB:4J5R" FT HELIX 21..23 FT /evidence="ECO:0007829|PDB:4J5R" FT STRAND 28..35 FT /evidence="ECO:0007829|PDB:4J5R" FT STRAND 41..43 FT /evidence="ECO:0007829|PDB:2LGR" FT HELIX 45..52 FT /evidence="ECO:0007829|PDB:4J5R" FT HELIX 55..61 FT /evidence="ECO:0007829|PDB:4J5R" FT STRAND 67..73 FT /evidence="ECO:0007829|PDB:4J5R" FT STRAND 76..86 FT /evidence="ECO:0007829|PDB:4J5R" FT HELIX 93..110 FT /evidence="ECO:0007829|PDB:4J5R" FT STRAND 114..117 FT /evidence="ECO:0007829|PDB:4J5R" FT HELIX 123..125 FT /evidence="ECO:0007829|PDB:4J5Q" FT HELIX 129..140 FT /evidence="ECO:0007829|PDB:4J5R" FT STRAND 146..151 FT /evidence="ECO:0007829|PDB:4J5R" SQ SEQUENCE 152 AA; 17025 MW; 8CC43CBDABA73E0B CRC64; MASSLNEDPE GSRITYVKGD LFACPKTDSL AHCISEDCRM GAGIAVLFKK KFGGVQELLN QQKKSGEVAV LKRDGRYIYY LITKKRASHK PTYENLQKSL EAMKSHCLKN GVTDLSMPRI GCGLDRLQWE NVSAMIEEVF EATDIKITVY TL //