RPA1
Replication protein A 70 kDa DNA-binding subunit
Also known as: HSSB, REPA1, RF-A, RFA1_HUMAN, RP-A, RPA70
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P27694
- Gene
- RPA1
- Ensembl
- ENSG00000132383
- Chromosome
- 17
- Canonical length
- 616 aa
- Protein class
- Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
616 residues, UniProt reviewed canonical sequence.
>P27694|RPA1
1 MVGQLSEGAI AAIMQKGDTN IKPILQVINI RPITTGNSPP RYRLLMSDGL NTLSSFMLAT
61 QLNPLVEEEQ LSSNCVCQIH RFIVNTLKDG RRVVILMELE VLKSAEAVGV KIGNPVPYNE
121 GLGQPQVAPP APAASPAASS RPQPQNGSSG MGSTVSKAYG ASKTFGKAAG PSLSHTSGGT
181 QSKVVPIASL TPYQSKWTIC ARVTNKSQIR TWSNSRGEGK LFSLELVDES GEIRATAFNE
241 QVDKFFPLIE VNKVYYFSKG TLKIANKQFT AVKNDYEMTF NNETSVMPCE DDHHLPTVQF
301 DFTGIDDLEN KSKDSLVDII GICKSYEDAT KITVRSNNRE VAKRNIYLMD TSGKVVTATL
361 WGEDADKFDG SRQPVLAIKG ARVSDFGGRS LSVLSSSTII ANPDIPEAYK LRGWFDAEGQ
421 ALDGVSISDL KSGGVGGSNT NWKTLYEVKS ENLGQGDKPD YFSSVATVVY LRKENCMYQA
481 CPTQDCNKKV IDQQNGLYRC EKCDTEFPNF KYRMILSVNI ADFQENQWVT CFQESAEAIL
541 GQNAAYLGEL KDKNEQAFEE VFQNANFRSF IFRVRVKVET YNDESRIKAT VMDVKPVDYR
601 EYGRRLVMSI RRSALMLocalizationUniProt · AlphaFold · HPA
Whether an antibody against RPA1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.34
- Highest tissue expression
- 49 nTPM
Expression across tissuesHPA
Tissue
- skeletal muscle: 49 nTPM
- tonsil: 36 nTPM
- thymus: 35 nTPM
- lymph node: 34 nTPM
- tongue: 32 nTPM
- ovary: 26 nTPM
Single-cell type
- oocytes: 184 nCPM
- platelets: 166 nCPM
- migrating cytotrophoblasts: 102 nCPM
- erythrocyte progenitors: 98 nCPM
- kupffer cells: 93 nCPM
- cytotrophoblasts: 89 nCPM
Immune cell
- NK-cell: 81 nTPM
- total PBMC: 61 nTPM
- T-reg: 57 nTPM
- memory CD4 T-cell: 55 nTPM
- eosinophil: 55 nTPM
- MAIT T-cell: 54 nTPM
Brain region
- white matter: 30 nTPM
- cerebellum: 29 nTPM
- hypothalamus: 27 nTPM
- pons: 27 nTPM
- spinal cord: 26 nTPM
- choroid plexus: 24 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about RPA1.
Disease | AllUniProt
Conditions RPA1 is implicated in, by any mechanism.
- Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 6 (PFBMFT6) MIM:619767
Disease | GeneticClinVar
2 pathogenic / likely-pathogenic of 114 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Pulmonary fibrosis and/or bone marrow failure, telomere-related, 6
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.43
- gnomAD pLI
- 0.09
- gnomAD missense Z
- 1.22
- DepMap mean gene effect
- -2.33
- DepMap dependency class
- pan
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- base-excision repair
- DNA damage response
- DNA recombination
- DNA repair
- DNA replication
- DNA-templated DNA replication
- double-strand break repair via homologous recombination
- hemopoiesis
- homeostasis of number of cells within a tissue
- in utero embryonic development
- meiotic cell cycle
- mismatch repair
- nucleotide-excision repair
- positive regulation of cell population proliferation
- protein localization to chromosome
- protein localization to site of double-strand break
- telomere maintenance
- telomere maintenance via telomerase
Molecular functions
- chromatin binding
- chromatin-protein adaptor activity
- damaged DNA binding
- G-rich strand telomeric DNA binding
- single-stranded DNA binding
- single-stranded telomeric DNA binding
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- OB-fold nucleic acid binding domain, AA-tRNA synthetase-type
- Nucleic acid-binding, OB-fold
- Replication factor A, C-terminal
- OB-fold nucleic acid binding domain
- Replication factor-A C terminal domain
- Replication factor A protein 1
- Replication factor-A protein 1, N-terminal
- Replication protein A, OB domain
- Replication factor A, C-terminal, eukaryotes
- Replication factor-A protein 1, N-terminal domain
- Replication protein A OB domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of RPA1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads RPA1 as an antibody target. Whether an autoantibody or antibody against RPA1 could matter depends on whether native RPA1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
RPA1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label RPA1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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