PARP3
Function
Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage (PubMed:16924674, PubMed:19354255, PubMed:20064938, PubMed:21211721, PubMed:21270334, PubMed:23742272, PubMed:24598253, PubMed:25043379, PubMed:28447610). Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins (PubMed:20064938, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:25043379). 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 (PubMed:16924674, PubMed:24598253). ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on 'Glu-2' (H2BE2ADPr) of nucleosomes containing nicked DNA (PubMed:27530147). Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ (PubMed:24598253). Suppresses G-quadruplex (G4) structures in response to DNA damage (PubMed:28447610). Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (PubMed:21211721). May link the DNA damage surveillance network to the mitotic fidelity checkpoint (PubMed:16924674). 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 (PubMed:29361132, PubMed:29520010).
Post-translational modifications
Auto-mono-ADP-ribosylated.
Sequence Similarities
Belongs to the ARTD/PARP family.
Tissue Specificity
Widely expressed; the highest levels are in the kidney, skeletal muscle, liver, heart and spleen; also detected in pancreas, lung, placenta, brain, leukocytes, colon, small intestine, ovary, testis, prostate and thymus.
Cellular localization
- Nucleus
- Chromosome
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Centriole
- Almost exclusively localized in the nucleus and appears in numerous small foci and a small number of larger foci whereas a centrosomal location has not been detected (PubMed:16924674). In response to DNA damage, localizes to sites of double-strand break (PubMed:21270334, PubMed:28447610). Also localizes to single-strand breaks (PubMed:27530147). Preferentially localized to the daughter centriole (PubMed:10329013).
Alternative names
ADPRT3, ADPRTL3, PARP3, Protein mono-ADP-ribosyltransferase PARP3, ADP-ribosyltransferase diphtheria toxin-like 3, DNA ADP-ribosyltransferase PARP3, IRT1, NAD(+) ADP-ribosyltransferase 3, Poly [ADP-ribose] polymerase 3, Poly[ADP-ribose] synthase 3, ARTD3, ADPRT-3, PARP-3, hPARP-3, pADPRT-3