Protein / target
Protein mono-ADP-ribosyltransferase PARP3
Protein at a glance
Biological role
NAD+-protein-aspartate ADP-ribosyltransferase activity
Strongest disease association
ovarian cancer
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
4 approved · 1 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
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)
Subcellular location
Domains and Gene Ontology detail (27)Hide
Domains & features
Gene Ontology
- Ccentriole
- Ccentrosome
- Cnuclear body
- Cnucleolus
- Cnucleoplasm
- Csite of double-strand break
- Fcatalytic activity
- FNAD DNA ADP-ribosyltransferase activity
- FNAD+ poly-ADP-ribosyltransferase activity
- FNAD+-protein mono-ADP-ribosyltransferase activity
- FNAD+-protein-aspartate ADP-ribosyltransferase activity
- FNAD+-protein-glutamate ADP-ribosyltransferase activity
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Metabolic enzyme activity
- ·catalytic activity
- ·NAD DNA ADP-ribosyltransferase activity
- ·NAD+ poly-ADP-ribosyltransferase activity
- ·NAD+-protein mono-ADP-ribosyltransferase activity
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
PARP 1, 2 and 3 inhibitor
Appears in clinical studies involving ovarian cancer, ovarian carcinoma, pancreatic neoplasm, prostate carcinoma
PARP 1, 2 and 3 inhibitor
Appears in clinical studies involving ovarian cancer, neoplasm, fallopian tube cancer, primary peritoneal carcinoma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 162 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 5 total
neoplasm · breast cancer · malignant epithelial tumor of ovary
melanoma · glioma
ovarian cancer · ovarian carcinoma · pancreatic neoplasm
ovarian cancer · neoplasm · fallopian tube cancer
ovarian cancer · ovarian neoplasm · ovarian carcinoma
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Trial results posted
Phase II Study of Rucaparib and Nivolumab in Patients With Leiomyosarcoma
- New publicationResults of a phase Ib study of olaparib with concomitant radiotherapy in soft-tissue sarcoma: a French sarcoma group study.
- New publicationOlaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in <i>BRCA1</i> and/or <i>BRCA2</i> in the PROfound Trial.
- New publicationDurvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial.
- New publicationRucaparib or Physician's Choice in Metastatic Prostate Cancer.
- New publicationOverall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer.
- Safety communication
Drug Safety Update: Rucaparib (Rubraca▼): withdrawal of third-line treatment indication
- New publicationAdjuvant Olaparib for Patients with <i>BRCA1</i>- or <i>BRCA2</i>-Mutated Breast Cancer.
- New publicationSurvival with Olaparib in Metastatic Castration-Resistant Prostate Cancer.
- New publicationRucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a <i>BRCA1</i> or <i>BRCA2</i> Gene Alteration.
- New publicationOlaparib for Metastatic Castration-Resistant Prostate Cancer.
- New publicationOlaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B): a multicentre, open-label, randomised, phase 2 trial.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.