Tchem RPA1 Replication protein A 70 kDa DNA-binding subunit

Protein Summary

Description

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 (PubMed:27723720, PubMed:27723717). Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage (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 (PubMed:17765923). 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). Plays also a role in base excision repair (BER) probably through interaction with UNG (PubMed:9765279). Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance (PubMed:17959650). 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). This gene encodes the largest subunit of the heterotrimeric Replication Protein A (RPA) complex, which binds to single-stranded DNA (ssDNA), forming a nucleoprotein complex that plays an important role in DNA metabolism, being involved in DNA replication, repair, recombination, telomere maintenance, and co-ordinating the cellular response to DNA damage through activation of the ataxia telangiectasia and Rad3-related protein (ATR) kinase. The nucleoprotein complex protects the single-stranded DNA from nucleases, prevents formation of secondary structures that would interfere with repair, and co-ordinates the recruitment and departure of different genome maintenance factors. This subunit contains four oligonucleotide/oligosaccharide-binding (OB) domains, though the majority of ssDNA binding occurs in two of these domains. The heterotrimeric complex has two different modes of ssDNA binding, a low-affinity and high-affinity mode, determined by which ssDNA binding domains are utilized. The different binding modes differ in the length of DNA bound and in the proteins with which it interacts, thereby playing a role in regulating different genomic maintenance pathways. [provided by RefSeq, Sep 2017]

Uniprot Accession IDs

• P27694
• A8K0Y9
• Q59ES9
• RP-A p70

Gene Name

• RPA1

Ensembl ID

• ENST00000254719
• ENSP00000254719
• ENSG00000132383

Symbol

• REPA1
• RPA70
• HSSB
• RF-A
• RP-A
• REPA1
• RPA70
• MST075

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	1
protein complex	0.97
kinase perturbation	0.95
biological term	0.9
hub protein	0.9

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Replication Protein A 70 Kda Dna-binding Subunit

DTO Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Replication Protein A 70 Kda Dna-binding Subunit

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 606.18   (req: < 5)

Gene RIFs: 173   (req: <= 3)

Antibodies: 449   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 606.18   (req: >= 5)

Gene RIFs: 173   (req: > 3)

Antibodies: 449   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 34

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 43

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0