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| | ==TARG1 (C6orf130), Terminal ADP-ribose Glycohydrolase 1 ADP-ribose complex== | | ==TARG1 (C6orf130), Terminal ADP-ribose Glycohydrolase 1 ADP-ribose complex== |
| - | <StructureSection load='4j5s' size='340' side='right' caption='[[4j5s]], [[Resolution|resolution]] 1.55Å' scene=''> | + | <StructureSection load='4j5s' size='340' side='right'caption='[[4j5s]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4j5s]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J5S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4j5s]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J5S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J5S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BO4:BORATE+ION'>BO4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SBE:1,3,2-DIOXABOROLAN-2-OL'>SBE</scene>, <scene name='pdbligand=ZZC:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[[(2R,3R)-2,3-DIHYDROXY-4-OXO-PENTOXY]-OXIDO-PHOSPHORYL]+PHOSPHATE'>ZZC</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BO4:BORATE+ION'>BO4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SBE:1,3,2-DIOXABOROLAN-2-OL'>SBE</scene>, <scene name='pdbligand=ZZC:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[[(2R,3R)-2,3-DIHYDROXY-4-OXO-PENTOXY]-OXIDO-PHOSPHORYL]+PHOSPHATE'>ZZC</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4j5q|4j5q]], [[4j5r|4j5r]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4j5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5s OCA], [https://pdbe.org/4j5s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j5s RCSB], [https://www.ebi.ac.uk/pdbsum/4j5s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j5s ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OARD1, C6orf130 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j5s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j5s OCA], [http://pdbe.org/4j5s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j5s RCSB], [http://www.ebi.ac.uk/pdbsum/4j5s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j5s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/OARD1_HUMAN OARD1_HUMAN]] Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Catalyzes the deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose and O-butyryl-ADP-ribose, yielding ADP-ribose plus acetate, propionate and butyrate, respectively. | + | [https://www.uniprot.org/uniprot/OARD1_HUMAN OARD1_HUMAN] Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Catalyzes the deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose and O-butyryl-ADP-ribose, yielding ADP-ribose plus acetate, propionate and butyrate, respectively. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Appel, C D]] | + | [[Category: Large Structures]] |
| - | [[Category: Krahn, J]] | + | [[Category: Appel CD]] |
| - | [[Category: Schellenberg, M J]] | + | [[Category: Krahn J]] |
| - | [[Category: Williams, R S]] | + | [[Category: Schellenberg MJ]] |
| - | [[Category: Adp-ribose]] | + | [[Category: Williams RS]] |
| - | [[Category: Cellular signaling]]
| + | |
| - | [[Category: Dna repair]]
| + | |
| - | [[Category: Glycohydrolase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Macro domain]]
| + | |
| - | [[Category: Parp]]
| + | |
| - | [[Category: Poly-adp ribose]]
| + | |
| Structural highlights
Function
OARD1_HUMAN Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Catalyzes the deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose and O-butyryl-ADP-ribose, yielding ADP-ribose plus acetate, propionate and butyrate, respectively.
Publication Abstract from PubMed
Adenosine diphosphate (ADP)-ribosylation is a post-translational protein modification implicated in the regulation of a range of cellular processes. A family of proteins that catalyse ADP-ribosylation reactions are the poly(ADP-ribose) (PAR) polymerases (PARPs). PARPs covalently attach an ADP-ribose nucleotide to target proteins and some PARP family members can subsequently add additional ADP-ribose units to generate a PAR chain. The hydrolysis of PAR chains is catalysed by PAR glycohydrolase (PARG). PARG is unable to cleave the mono(ADP-ribose) unit directly linked to the protein and although the enzymatic activity that catalyses this reaction has been detected in mammalian cell extracts, the protein(s) responsible remain unknown. Here, we report the homozygous mutation of the c6orf130 gene in patients with severe neurodegeneration, and identify C6orf130 as a PARP-interacting protein that removes mono(ADP-ribosyl)ation on glutamate amino acid residues in PARP-modified proteins. X-ray structures and biochemical analysis of C6orf130 suggest a mechanism of catalytic reversal involving a transient C6orf130 lysyl-(ADP-ribose) intermediate. Furthermore, depletion of C6orf130 protein in cells leads to proliferation and DNA repair defects. Collectively, our data suggest that C6orf130 enzymatic activity has a role in the turnover and recycling of protein ADP-ribosylation, and we have implicated the importance of this protein in supporting normal cellular function in humans.
Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease.,Sharifi R, Morra R, Denise Appel C, Tallis M, Chioza B, Jankevicius G, Simpson MA, Matic I, Ozkan E, Golia B, Schellenberg MJ, Weston R, Williams JG, Rossi MN, Galehdari H, Krahn J, Wan A, Trembath RC, Crosby AH, Ahel D, Hay R, Ladurner AG, Timinszky G, Williams RS, Ahel I EMBO J. 2013 Mar 12. doi: 10.1038/emboj.2013.51. PMID:23481255[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sharifi R, Morra R, Denise Appel C, Tallis M, Chioza B, Jankevicius G, Simpson MA, Matic I, Ozkan E, Golia B, Schellenberg MJ, Weston R, Williams JG, Rossi MN, Galehdari H, Krahn J, Wan A, Trembath RC, Crosby AH, Ahel D, Hay R, Ladurner AG, Timinszky G, Williams RS, Ahel I. Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease. EMBO J. 2013 Mar 12. doi: 10.1038/emboj.2013.51. PMID:23481255 doi:10.1038/emboj.2013.51
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