RPA2 replication protein A2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RPA2provided by HGNC
Official Full Name: replication protein A2provided by HGNC
Primary source: HGNC:HGNC:10290
See related: Ensembl:ENSG00000117748 MIM:179836; AllianceGenome:HGNC:10290
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: REPA2; RPA32; RP-A p32; RP-A p34
Summary: This gene encodes a 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 RPA complex protects 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. The heterotrimeric complex has two different modes of ssDNA binding, a low-affinity and high-affinity mode, determined by which oligonucleotide/oligosaccharide-binding (OB) domains of the complex are utilized, and differing in the length of DNA bound. This subunit contains a single OB domain that participates in high-affinity DNA binding and also contains a winged helix domain at its carboxy terminus, which interacts with many genome maintenance protein. Post-translational modifications of the RPA complex also plays a role in co-ordinating different damage response pathways. [provided by RefSeq, Sep 2017]
Expression: Ubiquitous expression in testis (RPKM 29.0), lymph node (RPKM 26.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p35.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (27891524..27914797, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (27733626..27756900, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (28218035..28241308, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Upregulated RPA2 in endometrial tissues of repeated implantation failure patients impairs the endometrial decidualization.
Title: Upregulated RPA2 in endometrial tissues of repeated implantation failure patients impairs the endometrial decidualization.
hSSB2 (NABP1) is required for the recruitment of RPA during the cellular response to DNA UV damage.
Title: hSSB2 (NABP1) is required for the recruitment of RPA during the cellular response to DNA UV damage.
RPA2 winged-helix domain facilitates UNG-mediated removal of uracil from ssDNA; implications for repair of mutagenic uracil at the replication fork.
Title: RPA2 winged-helix domain facilitates UNG-mediated removal of uracil from ssDNA; implications for repair of mutagenic uracil at the replication fork.
Dynamic elements of replication protein A at the crossroads of DNA replication, recombination, and repair.
Title: Dynamic elements of replication protein A at the crossroads of DNA replication, recombination, and repair.
HERC2 regulates RPA2 by mediating ATR-induced Ser33 phosphorylation and ubiquitin-dependent degradation.
Title: HERC2 regulates RPA2 by mediating ATR-induced Ser33 phosphorylation and ubiquitin-dependent degradation.
RPA, best known for its role in DNA replication and repair, recruits HIRA to promoters and enhancers and regulates deposition of newly synthesized H3.3 to these regulatory elements for gene regulation.
Title: RPA Interacts with HIRA and Regulates H3.3 Deposition at Gene Regulatory Elements in Mammalian Cells.
E3 ligase RFWD3 functions in timely removal and degradation of RPA and RAD51 to allow homologous recombination progression to subsequent steps following mitomycin C damage.
Title: RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination.
Single point mutations in the RPA32 subunit of RPA that abolish interaction with RFWD3 also inhibit interstrand crossling repair, demonstrating that RPA-mediated RFWD3 recruitment to stalled replication forks is important for ICL repair.
Title: RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for Interstrand Crosslink Repair and Human Health.
knockdown of RPA2 promoted formation of the menin-p65 complex and repressed the expression of NF-kappaB-mediated genes. RPA2 expression was induced via an E2F1-dependent mechanism in MCF7 and MDA-MB-231 cells treated with NF-kappaB activators, TNF-alpha or lipopolysaccharide (LPS).
Title: Upregulation of RPA2 promotes NF-κB activation in breast cancer by relieving the antagonistic function of menin on NF-κB-regulated transcription.
The authors show that Vpr can form a trimolecular complex with UNG2 and RPA32 and the positive effect of UNG2 and RPA32 on the reverse transcription process leading to optimal virus replication and dissemination between the primary target cells of HIV-1.
Title: Uracil DNA glycosylase interacts with the p32 subunit of the replication protein A complex to modulate HIV-1 reverse transcription for optimal virus dissemination.

Submit: New GeneRIF Correction See all GeneRIFs (40)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 replication is enhanced by RPA2 in monocyte derived macrophages	PubMed
HIV-1 replication is enhanced by RPA2 in PBMCs by influencing the efficiency of reverse transcription	PubMed
HIV-1 replication is enhanced by RPA2 (HeLa-CD4 cells and Jurkat T cells) as shown by shRNA-mediated knockdown of RPA2	PubMed
Depletion of RPA2 by shRNA in HIV-1-producing 293T cells inhibits viral infectivity and replication	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Vif	vif	HIV-1 Vif-induced G2 delay is inhibited by caffeine and correlates with the activation of RPA-32 protein	PubMed
Vpr	vpr	HIV-1 Vpr complexes with RPA2 via UNG2 to form a trimolecular complex (containing Vpr, UNG2 and RPA2)	PubMed
	vpr	HIV-1 Vpr forms nuclear foci containing VPRBP and partially co-localizes with DNA repair foci components 53BP1 and phosphorylated RPA32	PubMed
	vpr	HIV-1 Vpr induces phosphorylation of replication protein A (RPA2) at serine 4 and 8 in an ATR-dependent manner	PubMed
reverse transcriptase	gag-pol	Replication protein A and HIV-1 nucleocapsid protein interfere with the strand displacement DNA synthesis of HIV-1 reverse transcriptase by binding to the displaced strand and keeping it away from the newly synthesized strand	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AL034207 (e-PCR)
- UniSTS:94033

RH68976 (e-PCR)
- UniSTS:72807

stbA460I13SP6 (e-PCR)
- UniSTS:181376

SHGC-30251 (e-PCR)
- UniSTS:9675

G30996 (e-PCR)
- UniSTS:46314

SHGC-124 (e-PCR)
- UniSTS:89842

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G-rich strand telomeric DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables damaged DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables single-stranded DNA binding	IC Inferred by Curator more info	PubMed
enables single-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables single-stranded DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables telomeric DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA replication	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA replication	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA replication	NAS Non-traceable Author Statement more info	PubMed
involved_in base-excision repair	IDA Inferred from Direct Assay more info	PubMed
involved_in double-strand break repair via homologous recombination	IBA Inferred from Biological aspect of Ancestor more info
involved_in double-strand break repair via homologous recombination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair via homologous recombination	NAS Non-traceable Author Statement more info	PubMed
involved_in mismatch repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic G1 DNA damage checkpoint signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nucleotide-excision repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in nucleotide-excision repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nucleotide-excision repair	NAS Non-traceable Author Statement more info	PubMed
involved_in protein localization to chromosome	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA damage checkpoint	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of double-strand break repair via homologous recombination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in telomere maintenance	IC Inferred by Curator more info	PubMed
involved_in telomere maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in telomere maintenance	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of DNA replication factor A complex	IBA Inferred from Biological aspect of Ancestor more info
part_of DNA replication factor A complex	IDA Inferred from Direct Assay more info	PubMed
part_of DNA replication factor A complex	IPI Inferred from Physical Interaction more info	PubMed
colocalizes_with PML body	IDA Inferred from Direct Assay more info	PubMed
located_in PML body	IDA Inferred from Direct Assay more info	PubMed
part_of chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in chromosome, telomeric region	HDA more info	PubMed
colocalizes_with chromosome, telomeric region	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with site of double-strand break	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: replication protein A 32 kDa subunit

Names: RF-A protein 2; replication factor A protein 2; replication protein A 34 kDa subunit

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001286076.2 → NP_001273005.1 replication protein A 32 kDa subunit isoform 2

See identical proteins and their annotated locations for NP_001273005.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 5' region and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1.

Source sequence(s)

AK300691, AL109927, BC001630, BG107669, DB025488

UniProtKB/TrEMBL

B4DUL2

Conserved Domains (2) summary

cd04478
Location:4 → 71

RPA2_DBD_D; RPA2_DBD_D: A subfamily of OB folds corresponding to the OB fold of the central ssDNA-binding domain (DBD)-D of human RPA2 (also called RPA32). RPA2 is a subunit of Replication protein A (RPA). RPA is a nuclear ssDNA-binding protein (SSB) which appears ...

pfam08784
Location:70 → 166

RPA_C; Replication protein A C terminal
NM_001297558.1 → NP_001284487.1 replication protein A 32 kDa subunit isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in the 5' region and initiates translation at an alternate upstream start codon, compared to variant 1. The encoded isoform (3) has a distinct N-terminus and is longer than isoform 1.

Source sequence(s)

BC001630, BQ006360, BX333932, DB025488

Consensus CDS

CCDS72740.1

UniProtKB/TrEMBL

B2R7E8

Related

ENSP00000363017.3, ENST00000373909.7

Conserved Domains (3) summary

COG5235
Location:33 → 275

RFA2; Single-stranded DNA-binding replication protein A (RPA), medium (30 kD) subunit [DNA replication, recombination, and repair]

cd04478
Location:81 → 175

RPA2_DBD_D; RPA2_DBD_D: A subfamily of OB folds corresponding to the OB fold of the central ssDNA-binding domain (DBD)-D of human RPA2 (also called RPA32). RPA2 is a subunit of Replication protein A (RPA). RPA is a nuclear ssDNA-binding protein (SSB) which appears ...

pfam08784
Location:174 → 270

RPA_C; Replication protein A C terminal
NM_001355128.2 → NP_001342057.1 replication protein A 32 kDa subunit isoform 2

Status: REVIEWED

Source sequence(s)

BC001630, BG107669, BM839986, DB025488

UniProtKB/TrEMBL

B4DUL2

Conserved Domains (2) summary

cd04478
Location:4 → 71

RPA2_DBD_D; RPA2_DBD_D: A subfamily of OB folds corresponding to the OB fold of the central ssDNA-binding domain (DBD)-D of human RPA2 (also called RPA32). RPA2 is a subunit of Replication protein A (RPA). RPA is a nuclear ssDNA-binding protein (SSB) which appears ...

pfam08784
Location:70 → 166

RPA_C; Replication protein A C terminal
NM_001355129.2 → NP_001342058.1 replication protein A 32 kDa subunit isoform 4

Status: REVIEWED

Source sequence(s)

BC001630, BG107669, CB155053

UniProtKB/TrEMBL

B2R7E8

Conserved Domains (2) summary

cd04478
Location:77 → 171

RPA2_DBD_D; A subfamily of OB folds corresponding to the OB fold of the central ssDNA-binding domain (DBD)-D of human RPA2 (also called RPA32). RPA2 is a subunit of Replication protein A (RPA). RPA is a nuclear ssDNA-binding protein (SSB) which appears to be ...

cl27871
Location:29 → 271

RPA_C; Replication protein A C terminal
NM_002946.5 → NP_002937.1 replication protein A 32 kDa subunit isoform 1

See identical proteins and their annotated locations for NP_002937.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

BC001630, BG107669, DB025488

Consensus CDS

CCDS314.1

UniProtKB/Swiss-Prot

P15927, Q52II0, Q5TEI9, Q5TEJ5

UniProtKB/TrEMBL

B2R7E8

Related

ENSP00000363021.3, ENST00000373912.8

Conserved Domains (2) summary

COG5235
Location:25 → 267

RFA2; Single-stranded DNA-binding replication protein A (RPA), medium (30 kD) subunit [DNA replication, recombination, and repair]

cd04478
Location:73 → 167

RPA2_DBD_D; A subfamily of OB folds corresponding to the OB fold of the central ssDNA-binding domain (DBD)-D of human RPA2 (also called RPA32). RPA2 is a subunit of Replication protein A (RPA). RPA is a nuclear ssDNA-binding protein (SSB) which appears to be ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

27891524..27914797 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024448862.2 → XP_024304630.1 replication protein A 32 kDa subunit isoform X1

UniProtKB/TrEMBL

B2R7E8

Conserved Domains (2) summary

cd04478
Location:81 → 150

RPA2_DBD_D; A subfamily of OB folds corresponding to the OB fold of the central ssDNA-binding domain (DBD)-D of human RPA2 (also called RPA32). RPA2 is a subunit of Replication protein A (RPA). RPA is a nuclear ssDNA-binding protein (SSB) which appears to be ...

pfam08784
Location:149 → 245

RPA_C; Replication protein A C terminal
XM_024448864.2 → XP_024304632.1 replication protein A 32 kDa subunit isoform X2

UniProtKB/TrEMBL

B2R7E8

Conserved Domains (2) summary

cd04478
Location:73 → 142

RPA2_DBD_D; A subfamily of OB folds corresponding to the OB fold of the central ssDNA-binding domain (DBD)-D of human RPA2 (also called RPA32). RPA2 is a subunit of Replication protein A (RPA). RPA is a nuclear ssDNA-binding protein (SSB) which appears to be ...

pfam08784
Location:141 → 237

RPA_C; Replication protein A C terminal