Protein / target
Poly [ADP-ribose] polymerase 2
Protein at a glance
Biological role
Poly-ADP-D-ribose modification-dependent protein binding
Strongest disease association
ovarian cancer
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
9 approved · 3 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
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:10364231, PubMed:25043379, PubMed:27471034, PubMed:30104678, PubMed:32028527, PubMed:32939087, PubMed:34108479, PubMed:34486521, PubMed:34874266). Mediates glutamate, aspartate or serine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:25043379, PubMed:30104678, PubMed:30321391). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:32939087). Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 (PubMed:25043379). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site (PubMed:28190768, PubMed:32028527, PubMed:34108479, PubMed:34486521, PubMed:34874266). PARP2 initiates the repair of double-strand DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:10364231, PubMed:32939087, PubMed:34108479). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains (PubMed:34732825, PubMed:34795260). Specifically mediates formation of branched poly-ADP-ribosylation (PubMed:30104678). Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF (PubMed:30104678). In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5'-terminal phosphates at DNA strand breaks termini in nicked duplex (PubMed:27471034, PubMed:29361132)
Subcellular location
Domains and Gene Ontology detail (27)Hide
Domains & features
Gene Ontology
- Cnucleolus
- Cnucleoplasm
- Cnucleus
- Csite of DNA damage
- Fchromatin binding
- Fdamaged DNA binding
- 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
- FNAD+-protein-serine 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
- ·NAD DNA ADP-ribosyltransferase activity
- ·NAD+ poly-ADP-ribosyltransferase activity
- ·NAD+-protein mono-ADP-ribosyltransferase activity
- ·NAD+-protein-aspartate ADP-ribosyltransferase activity
View underlying pathways (5)Hide underlying pathways
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.
Poly [ADP-ribose] polymerase 2 inhibitor
Appears in clinical studies involving breast cancer, neoplasm, psoriatic arthritis, prostate cancer
Poly [ADP-ribose] polymerase 2 inhibitor
Appears in clinical studies involving fallopian tube neoplasm, peritoneal neoplasm, ovarian neoplasm, neoplasm
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 478 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 · 12 total
fallopian tube neoplasm · peritoneal neoplasm · ovarian neoplasm
neoplasm · breast cancer · malignant epithelial tumor of ovary
primary peritoneal carcinoma · fallopian tube cancer · ovarian cancer
ovarian cancer · ovarian carcinoma · pancreatic neoplasm
neoplasm · cancer · ovarian cancer
ovarian cancer · breast cancer · colorectal cancer
ovarian cancer · fallopian tube cancer · peritoneum cancer
ovarian cancer · ovarian neoplasm · ovarian carcinoma
breast cancer · neoplasm · psoriatic arthritis
melanoma · glioma
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 4 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
- Trial status changed
A Pharmacodynamics-Driven Trial of Talazoparib, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Aberrations in Genes Involved in DNA Damage Response
- New publicationNiraparib and abiraterone acetate plus prednisone for HRR-deficient metastatic castration-sensitive prostate cancer: a randomized phase 3 trial.
- New publicationResults of a phase Ib study of olaparib with concomitant radiotherapy in soft-tissue sarcoma: a French sarcoma group study.
- New publicationFirst-line talazoparib with enzalutamide in HRR-deficient metastatic castration-resistant prostate cancer: the phase 3 TALAPRO-2 trial.
- 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.
- Safety communication
Drug Safety Update: Niraparib (Zejula▼): reports of severe hypertension and posterior reversible encephalopathy syndrome (PRES), particularly in early treatment
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.