Protein / target
Protein mono-ADP-ribosyltransferase PARP3
Protein at a glance
Biological role
NAD+-protein-aspartate ADP-ribosyltransferase
Strongest disease association
Ovarian Neoplasms
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage.
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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.
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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.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
4 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
PARP 1, 2 and 3 inhibitor
Indicated for Breast Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Prostatic Neoplasms, Castration-Resistant
PARP 1, 2 and 3 inhibitor
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene PARP3
Gene-level evidence surfaced through the gene PARP3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
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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 per-type scores above show the calculation.
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Drug development
5 compounds recorded · 4 approved · 1 in clinical development
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Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Protein degraders — Emerging
View underlying tractability evidence (7)Hide
Raw Open Targets tractability assessment buckets, by modality.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Trial status changed
A Phase 1, Open-Label, Multicenter Study of INCB123667 as Monotherapy and in Combination With Anticancer Therapies in Participants With Selected Advanced Solid Tumors
- 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 publicationOlaparib for Metastatic Castration-Resistant Prostate Cancer.
- New publicationMaintenance Olaparib for Germline <i>BRCA</i>-Mutated Metastatic Pancreatic Cancer.
- Regulatory approval
Approval: Lynparza (EMA)
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.
Related family literature
Papers about “Poly(ADP-ribose) Polymerases” — a broader family this protein belongs to. Shown as context; not counted as papers specifically about this protein.
via Poly(ADP-ribose) Polymerases
via Poly(ADP-ribose) Polymerases
via Poly(ADP-ribose) Polymerases
via Poly(ADP-ribose) Polymerases
Europe PMC literature, reached through curated HGNC family membership. Membership is a taxonomic relationship — it does not imply this protein participates in every mechanism these papers discuss.