Enzymes
| UniProtKB help_outline | 1,590 proteins |
Reaction participants Show >> << Hide
-
Namehelp_outline
5-O-(ADP-D-ribosyl)-L-glutamyl-[protein]
Identifier
RHEA-COMP:15089
Reactive part
help_outline
- Name help_outline 5-O-(ADP-D-ribosyl)-L-glutamate residue Identifier CHEBI:142540 Charge -2 Formula C20H26N6O16P2 SMILEShelp_outline O(C(=O)CC[C@H](N*)C(*)=O)C1O[C@H](COP(OP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2O)O)N3C=NC4=C3N=CN=C4N)[O-])(=O)[O-])[C@H]([C@H]1O)O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline ADP-D-ribose Identifier CHEBI:57967 Charge -2 Formula C15H21N5O14P2 InChIKeyhelp_outline SRNWOUGRCWSEMX-TYASJMOZSA-L SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2OC(O)[C@H](O)[C@@H]2O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 22 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
-
Namehelp_outline
L-glutamyl-[protein]
Identifier
RHEA-COMP:10208
Reactive part
help_outline
- Name help_outline L-glutamate residue Identifier CHEBI:29973 Charge -1 Formula C5H6NO3 SMILEShelp_outline C(*)(=O)[C@@H](N*)CCC(=O)[O-] 2D coordinates Mol file for the small molecule Search links Involved in 11 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:58248 | RHEA:58249 | RHEA:58250 | RHEA:58251 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
|
Publications
-
Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease.
Sharifi R., Morra R., Appel C.D., Tallis M., Chioza B., Jankevicius G., Simpson M.A., Matic I., Ozkan E., Golia B., Schellenberg M.J., Weston R., Williams J.G., Rossi M.N., Galehdari H., Krahn J., Wan A., Trembath R.C., Crosby A.H., Ahel D., Hay R., Ladurner A.G., Timinszky G., Williams R.S., Ahel I.
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-ribo ... >> More
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. << Less
-
ADP-ribosylhydrolase activity of Chikungunya virus macrodomain is critical for virus replication and virulence.
McPherson R.L., Abraham R., Sreekumar E., Ong S.E., Cheng S.J., Baxter V.K., Kistemaker H.A., Filippov D.V., Griffin D.E., Leung A.K.
Chikungunya virus (CHIKV), an Old World alphavirus, is transmitted to humans by infected mosquitoes and causes acute rash and arthritis, occasionally complicated by neurologic disease and chronic arthritis. One determinant of alphavirus virulence is nonstructural protein 3 (nsP3) that contains a h ... >> More
Chikungunya virus (CHIKV), an Old World alphavirus, is transmitted to humans by infected mosquitoes and causes acute rash and arthritis, occasionally complicated by neurologic disease and chronic arthritis. One determinant of alphavirus virulence is nonstructural protein 3 (nsP3) that contains a highly conserved MacroD-type macrodomain at the N terminus, but the roles of nsP3 and the macrodomain in virulence have not been defined. Macrodomain is a conserved protein fold found in several plus-strand RNA viruses that binds to the small molecule ADP-ribose. Prototype MacroD-type macrodomains also hydrolyze derivative linkages on the distal ribose ring. Here, we demonstrated that the CHIKV nsP3 macrodomain is able to hydrolyze ADP-ribose groups from mono(ADP-ribosyl)ated proteins. Using mass spectrometry, we unambiguously defined its substrate specificity as mono(ADP-ribosyl)ated aspartate and glutamate but not lysine residues. Mutant viruses lacking hydrolase activity were unable to replicate in mammalian BHK-21 cells or mosquito <i>Aedes albopictus</i> cells and rapidly reverted catalytically inactivating mutations. Mutants with reduced enzymatic activity had slower replication in mammalian neuronal cells and reduced virulence in 2-day-old mice. Therefore, nsP3 mono(ADP-ribosyl)hydrolase activity is critical for CHIKV replication in both vertebrate hosts and insect vectors, and for virulence in mice. << Less
Proc. Natl. Acad. Sci. U.S.A. 114:1666-1671(2017) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.