Protein mono-ADP-ribosyltransferase PARP3
Also known as: ADPRT3, ADPRTL3, PARP3
Function
Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage. Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins. In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation. Involved in DNA repair by mediating mono-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism, such as histone H2B, XRCC5 and XRCC6. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on 'Glu-2' (H2BE2ADPr) of nucleosomes containing nicked DNA. Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ. Suppresses G-quadruplex (G4) structures in response to DNA damage. Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks. Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ). May link the DNA damage surveillance network to the mitotic fidelity checkpoint. Acts as a negative regulator of immunoglobulin class switch recombination, probably by controlling the level of AICDA /AID on the chromatin (By similarity). In addition to proteins, also able to ADP-ribosylate DNA: mediates DNA mono-ADP-ribosylation of DNA strand break termini via covalent addition of a single ADP-ribose moiety to a 5'- or 3'-terminal phosphate residues in DNA containing multiple strand breaks.
Classification
- Family (Pfam)
- PF00644 PARP, PF02877 PARP_reg, PF05406 WGR
- InterPro
- ARTD/PARP, Poly(ADP-ribose)pol_cat_dom, Poly(ADP-ribose)pol_reg_dom, Poly(ADP-ribose)pol_reg_dom_sf, WGR_dom_sf, WGR_domain
- Functional cluster
- Zinc-Finger & Ubiquitination Proteins
Experimental structures · PDB · 16
- 2EOC NMR
- 3C49 X-ray 2.80A
- 3C4H X-ray 2.10A
- 3CE0 X-ray 2.80A
- 3FHB X-ray 2.30A
- 4GV0 X-ray 1.90A
- 4GV2 X-ray 1.80A
- 4GV4 X-ray 1.80A
- 4L6Z X-ray 2.00A
- 4L70 X-ray 2.00A
- 4L7L X-ray 2.10A
- 4L7N X-ray 1.80A
- … and 4 more
A predicted model is available from AlphaFold.
Gene Ontology · 24
- GO:0005814 centriole
- GO:0005813 centrosome
- GO:0016604 nuclear body
- GO:0005730 nucleolus
- GO:0005654 nucleoplasm
- GO:0035861 site of double-strand break
- GO:0003824 catalytic activity
- GO:0140294 NAD DNA ADP-ribosyltransferase activity
- GO:0003950 NAD+ poly-ADP-ribosyltransferase activity
- GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity
- GO:0140806 NAD+-protein-aspartate ADP-ribosyltransferase activity
- GO:0140807 NAD+-protein-glutamate ADP-ribosyltransferase activity
- GO:0140804 NAD+-protein-lysine ADP-ribosyltransferase activity
- GO:0016779 nucleotidyltransferase activity
- GO:0030592 DNA ADP-ribosylation
- GO:0006302 double-strand break repair
- GO:0006303 double-strand break repair via nonhomologous end joining
- GO:0045829 negative regulation of isotype switching
- GO:0032211 negative regulation of telomere maintenance via telomerase
- GO:2001034 positive regulation of double-strand break repair via nonhomologous end joining
- GO:0070213 protein auto-ADP-ribosylation
- GO:1990166 protein localization to site of double-strand break
- GO:0060236 regulation of mitotic spindle organization
- GO:0000723 telomere maintenance
Drugs targeting this protein · 5
- RUCAPARIB inhibitor
- E-7016 inhibitor
- RUCAPARIB CAMSYLATE inhibitor
- VELIPARIB inhibitor
- OLAPARIB inhibitor
Related proteins · sequence + function similarity
- Protein mono-ADP-ribosyltransferase PARP3 0.97
- Poly [ADP-ribose] polymerase 2 0.85
- Poly [ADP-ribose] polymerase 2 0.85
- Protein mono-ADP-ribosyltransferase PARP3 0.82
- tRNA 2'-phosphotransferase 1 0.64
- tRNA 2'-phosphotransferase 1 0.64
- tRNA 2'-phosphotransferase 1 0.62
- Protein mono-ADP-ribosyltransferase PARP4 0.61
- Indoleamine 2,3-dioxygenase 2 0.58
- TRPM8 channel-associated factor 2 0.58
- Protein mono-ADP-ribosyltransferase PARP4 0.58
- TRPM8 channel-associated factor 2 0.56
Co-cited proteins · studied together in the literature
- Protein mono-ADP-ribosyltransferase PARP3 2 shared papers
- Aprataxin and PNK-like factor 1 shared papers
- Poly [ADP-ribose] polymerase 2 4 shared papers
- Aprataxin and PNK-like factor 1 shared papers
- Poly [ADP-ribose] polymerase 1 3 shared papers
- Protein mono-ADP-ribosyltransferase PARP3 1 shared papers
- Protein mono-ADP-ribosyltransferase PARP8 2 shared papers
- Protein mono-ADP-ribosyltransferase PARP6 2 shared papers
- Protein mono-ADP-ribosyltransferase TIPARP 2 shared papers
- Protein mono-ADP-ribosyltransferase PARP11 2 shared papers
- Protein mono-ADP-ribosyltransferase PARP16 2 shared papers
- DNA repair protein Ku70 1 shared papers
Literature · 19 cited papers
- Dna is a new target of Parp3. Sci. Rep. · 2018
- Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: new insights into DNA ADP-ribosylation. Nucleic Acids Res. · 2018
- PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA. Nat. Commun. · 2017
- PARP3 is a sensor of nicked nucleosomes and monoribosylates histone H2B(Glu2). Nat. Commun. · 2016
- Family-wide analysis of poly(ADP-ribose) polymerase activity. Nat. Commun. · 2014
- PARP3 affects the relative contribution of homologous recombination and nonhomologous end-joining pathways. Nucleic Acids Res. · 2014
- Chemical probes to study ADP-ribosylation: synthesis and biochemical evaluation of inhibitors of the human ADP-ribosyltransferase ARTD3/PARP3. J. Med. Chem. · 2013
- PARP inhibitor with selectivity toward ADP-ribosyltransferase ARTD3/PARP3. ACS Chem. Biol. · 2013
- Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression. Proc. Natl. Acad. Sci. U.S.A. · 2011
- PARP-3 and APLF function together to accelerate nonhomologous end-joining. Mol. Cell · 2011
- Toward a unified nomenclature for mammalian ADP-ribosyltransferases. Trends Biochem. Sci. · 2010
- PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of DNA. J. Biol. Chem. · 2010
- … and 7 more in the literature graph