RPA2: Replication Protein A2, a Key Player in DNA Replication and Repair
Comprehensive genomic and proteomic overview of RPA2, including its role in DNA metabolism, associated diseases, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | RPA2 |
|---|---|
| Full Name | Replication Protein A2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p35.3 |
| NCBI Gene ID | 6118 ncbi.nlm.nih.gov/gene/6118 |
| Ensembl ID | ENSG00000117748 |
| UniProt ID | P15927 |
| OMIM ID | 179836 |
| HGNC ID | 10290 |
| Aliases | RPA32, REPA2, RP-A p32, MGC1022 |
Description
RPA2 encodes the 32 kDa subunit of replication protein A (RPA), a heterotrimeric single-stranded DNA-binding protein essential for DNA replication, repair, recombination, and the DNA damage response. RPA2 is phosphorylated in response to DNA damage and regulates RPA complex activity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | RPA2 overexpression and phosphorylation promote genomic instability and tumor progression | PMID: 25686104 |
| Ovarian cancer | RPA2 mutations and altered expression correlate with chemoresistance | PMID: 23934607 |
| Fanconi anemia | RPA2 interacts with FANCD2 in the Fanconi anemia pathway for interstrand crosslink repair | PMID: 19615732 |
| Lung cancer | RPA2 upregulation associated with poor prognosis and cisplatin resistance | PMID: 27498980 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.6 | High |
| Bone marrow | 22.3 | High |
| Lymph node | 18.9 | Medium |
| Brain | 12.4 | Medium |
| Liver | 8.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 25.3 | Cervical cancer cell line |
| A549 | 21.8 | Lung cancer cell line |
| MCF7 | 19.5 | Breast cancer cell line |
| HEK293 | 16.2 | Embryonic kidney cell line |
| K562 | 23.1 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.419C>T (p.Pro140Leu) | Missense | 0.01% | Reduced DNA-binding affinity |
| c.538G>A (p.Glu180Lys) | Missense | 0.005% | Altered phosphorylation and RPA complex stability |
| c.1A>G (p.Met1Val) | Start loss | <0.001% | Loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt RPA2 expression or DNA-binding impair RPA complex function, leading to defective DNA repair and replication stress.
Gain of Function (GOF)
Not well characterized; some missense variants may enhance RPA2 stability or alter phosphorylation dynamics.
Dominant Negative (DN)
Rare variants that interfere with wild-type RPA2 function in the heterotrimeric complex, potentially exacerbating genomic instability.
View complete mutation data：
Gene Ontology (GO)
| • single-stranded DNA binding | • DNA replication origin binding |
| • DNA damage response | • signal transduction by p53 class mediator |
| • nucleotide-excision repair | • double-strand break repair via homologous recombination |
Pathways
• DNA replication (Reactome: R-HSA-69306)
• Homology Directed Repair (Reactome: R-HSA-5693532)
• Nucleotide Excision Repair (Reactome: R-HSA-5696398)
• Fanconi Anemia Pathway (Reactome: R-HSA-6783310)
Protein Summary
RPA2 is the 32 kDa subunit of the heterotrimeric replication protein A complex. It contains a central DNA-binding domain and is heavily phosphorylated by ATM/ATR kinases in response to DNA damage. RPA2 stabilizes single-stranded DNA intermediates and coordinates the recruitment of repair factors. Its expression is elevated in proliferating tissues and many cancers.
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