RPA3 replication protein A3
ENSG00000106399 · protein coding · Open Targets profile
As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage (PubMed:17596542, PubMed:9430682). In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response (PubMed:24332808). It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin, in response to DNA damage. Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair (PubMed:7697716). Also plays a role in base excision repair (BER), probably through interaction with UNG (PubMed:9765279). RPA stimulates 5'-3' helicase activity of BRIP1/FANCJ (PubMed:17596542). Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance. RPA3 has its own single-stranded DNA-binding activity and may be responsible for polarity of the binding of the complex to DNA (PubMed:19010961). As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA synthesis by polymerase delta in presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange (PubMed:19996105). {ECO:0000269|PubMed:17596542, ECO:0000269|PubMed:19010961, ECO:0000269|PubMed:19116208, ECO:0000269|PubMed:19996105, ECO:0000269|PubMed:7697716, ECO:0000269|PubMed:9430682, ECO:0000269|PubMed:9765279, ECO:0000303|PubMed:24332808}.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Structure with Ligand, Med-Quality Pocket
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data
gnomAD loss of function constraint: o/e 1.7488000392913818 (upper bound 2.459399938583374). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
No named investigators on registry trials of RPA3's approved or late-stage drugs in the last three years.
No terminated, withdrawn or suspended trials of RPA3's drugs are registered
All 0 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| No drugs or clinical candidates recorded. | ||||