UniProtKB - P35244 (RFA3_HUMAN)
Replication protein A 14 kDa subunit
RPA3
Functioni
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: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).
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. 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).
1 Publication6 PublicationsGO - Molecular functioni
- damaged DNA binding Source: UniProtKB
- single-stranded DNA binding Source: UniProtKB
GO - Biological processi
- base-excision repair Source: UniProtKB
- DNA repair Source: ComplexPortal
- DNA replication Source: UniProtKB
- double-strand break repair via homologous recombination Source: UniProtKB
- mismatch repair Source: UniProtKB
- nucleotide-excision repair Source: UniProtKB
- regulation of cell population proliferation Source: Ensembl
- regulation of mitotic cell cycle Source: Ensembl
- telomere maintenance Source: BHF-UCL
Keywordsi
Biological process | DNA damage, DNA recombination, DNA repair, DNA replication |
Enzyme and pathway databases
PathwayCommonsi | P35244 |
Reactomei | R-HSA-110312, Translesion synthesis by REV1 R-HSA-110314, Recognition of DNA damage by PCNA-containing replication complex R-HSA-110320, Translesion Synthesis by POLH R-HSA-174437, Removal of the Flap Intermediate from the C-strand R-HSA-176187, Activation of ATR in response to replication stress R-HSA-3371453, Regulation of HSF1-mediated heat shock response R-HSA-3371511, HSF1 activation R-HSA-5358565, Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) R-HSA-5358606, Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) R-HSA-5651801, PCNA-Dependent Long Patch Base Excision Repair R-HSA-5655862, Translesion synthesis by POLK R-HSA-5656121, Translesion synthesis by POLI R-HSA-5656169, Termination of translesion DNA synthesis R-HSA-5685938, HDR through Single Strand Annealing (SSA) R-HSA-5685942, HDR through Homologous Recombination (HRR) R-HSA-5693607, Processing of DNA double-strand break ends R-HSA-5693616, Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-5696395, Formation of Incision Complex in GG-NER R-HSA-5696397, Gap-filling DNA repair synthesis and ligation in GG-NER R-HSA-5696400, Dual Incision in GG-NER R-HSA-6782135, Dual incision in TC-NER R-HSA-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-6783310, Fanconi Anemia Pathway R-HSA-6804756, Regulation of TP53 Activity through Phosphorylation R-HSA-68962, Activation of the pre-replicative complex R-HSA-69166, Removal of the Flap Intermediate R-HSA-69473, G2/M DNA damage checkpoint R-HSA-912446, Meiotic recombination |
SignaLinki | P35244 |
SIGNORi | P35244 |
Names & Taxonomyi
Protein namesi | Recommended name: Replication protein A 14 kDa subunitShort name: RP-A p14 Alternative name(s): Replication factor A protein 3 Short name: RF-A protein 3 |
Gene namesi | Name:RPA3 Synonyms:REPA3, RPA14 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10291, RPA3 |
MIMi | 179837, gene |
neXtProti | NX_P35244 |
VEuPathDBi | HostDB:ENSG00000106399 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Nucleus
- DNA replication factor A complex Source: UniProtKB
- nucleoplasm Source: Reactome
Other locations
- site of double-strand break Source: GO_Central
Keywords - Cellular componenti
NucleusPathology & Biotechi
Organism-specific databases
DisGeNETi | 6119 |
OpenTargetsi | ENSG00000106399 |
PharmGKBi | PA34653 |
Miscellaneous databases
Pharosi | P35244, Tbio |
Genetic variation databases
BioMutai | RPA3 |
DMDMi | 464608 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000097276 | 2 – 121 | Replication protein A 14 kDa subunitAdd BLAST | 120 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylvalineCombined sources | 1 | |
Cross-linki | 23 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 39 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 88 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication |
Post-translational modificationi
Keywords - PTMi
Acetylation, Isopeptide bond, Ubl conjugationProteomic databases
EPDi | P35244 |
jPOSTi | P35244 |
MassIVEi | P35244 |
MaxQBi | P35244 |
PaxDbi | P35244 |
PeptideAtlasi | P35244 |
PRIDEi | P35244 |
ProteomicsDBi | 55011 |
TopDownProteomicsi | P35244 |
PTM databases
iPTMneti | P35244 |
MetOSitei | P35244 |
PhosphoSitePlusi | P35244 |
Expressioni
Gene expression databases
Bgeei | ENSG00000106399, Expressed in bronchial epithelial cell and 237 other tissues |
ExpressionAtlasi | P35244, baseline and differential |
Genevisiblei | P35244, HS |
Organism-specific databases
HPAi | ENSG00000106399, Low tissue specificity |
Interactioni
Subunit structurei
Component of the canonical replication protein A complex (RPA), a heterotrimer composed of RPA1, RPA2 and RPA3. Also component of the aRPA, the alternative replication protein A complex, a trimeric complex similar to the replication protein A complex/RPA but where RPA1 and RPA3 are associated with RPA4 instead of RPA2.
2 PublicationsBinary interactionsi
P35244
With | #Exp. | IntAct |
---|---|---|
RAD52 [P43351] | 3 | EBI-621428,EBI-706448 |
RPA1 [P27694] | 11 | EBI-621428,EBI-621389 |
RPA2 [P15927] | 9 | EBI-621428,EBI-621404 |
Protein-protein interaction databases
BioGRIDi | 112039, 465 interactors |
ComplexPortali | CPX-1878, Replication protein A complex, RPA2 variant CPX-1879, Replication protein A complex, RPA4 variant |
CORUMi | P35244 |
DIPi | DIP-24190N |
IntActi | P35244, 72 interactors |
MINTi | P35244 |
STRINGi | 9606.ENSP00000223129 |
Miscellaneous databases
RNActi | P35244, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P35244 |
SMRi | P35244 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P35244 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502S203, Eukaryota |
GeneTreei | ENSGT00390000008029 |
InParanoidi | P35244 |
OMAi | INRPVCF |
OrthoDBi | 1594928at2759 |
PhylomeDBi | P35244 |
TreeFami | TF105243 |
Family and domain databases
Gene3Di | 2.40.50.140, 1 hit |
IDEALi | IID00040 |
InterProi | View protein in InterPro IPR012340, NA-bd_OB-fold IPR013970, Rfa2 |
Pfami | View protein in Pfam PF08661, Rep_fac-A_3, 1 hit |
SUPFAMi | SSF50249, SSF50249, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MVDMMDLPRS RINAGMLAQF IDKPVCFVGR LEKIHPTGKM FILSDGEGKN
60 70 80 90 100
GTIELMEPLD EEISGIVEVV GRVTAKATIL CTSYVQFKED SHPFDLGLYN
110 120
EAVKIIHDFP QFYPLGIVQH D
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketB5MC59 | B5MC59_HUMAN | Replication protein A 14 kDa subuni... | RPA3 hCG_17407 | 82 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L07493 mRNA Translation: AAA58350.1 BT007320 mRNA Translation: AAP35984.1 DQ003136 Genomic DNA Translation: AAX84517.1 AC004948 Genomic DNA Translation: AAQ96878.1 BC005264 mRNA Translation: AAH05264.1 BC009868 mRNA Translation: AAH09868.1 |
CCDSi | CCDS5356.1 |
PIRi | A46008 |
RefSeqi | NP_002938.1, NM_002947.4 |
Genome annotation databases
Ensembli | ENST00000223129.8; ENSP00000223129.4; ENSG00000106399.11 ENST00000396682.6; ENSP00000379914.2; ENSG00000106399.11 |
GeneIDi | 6119 |
KEGGi | hsa:6119 |
MANE-Selecti | ENST00000223129.8; ENSP00000223129.4; NM_002947.5; NP_002938.1 |
UCSCi | uc003sri.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L07493 mRNA Translation: AAA58350.1 BT007320 mRNA Translation: AAP35984.1 DQ003136 Genomic DNA Translation: AAX84517.1 AC004948 Genomic DNA Translation: AAQ96878.1 BC005264 mRNA Translation: AAH05264.1 BC009868 mRNA Translation: AAH09868.1 |
CCDSi | CCDS5356.1 |
PIRi | A46008 |
RefSeqi | NP_002938.1, NM_002947.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1L1O | X-ray | 2.80 | A/D | 1-121 | [»] | |
1QUQ | X-ray | 2.50 | B/D | 1-121 | [»] | |
2PI2 | X-ray | 2.00 | E/F/G/H | 1-121 | [»] | |
2PQA | X-ray | 2.50 | B/D | 1-121 | [»] | |
2Z6K | X-ray | 3.00 | C/D | 1-121 | [»] | |
3KDF | X-ray | 1.98 | A/C | 1-121 | [»] | |
AlphaFoldDBi | P35244 | |||||
SMRi | P35244 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112039, 465 interactors |
ComplexPortali | CPX-1878, Replication protein A complex, RPA2 variant CPX-1879, Replication protein A complex, RPA4 variant |
CORUMi | P35244 |
DIPi | DIP-24190N |
IntActi | P35244, 72 interactors |
MINTi | P35244 |
STRINGi | 9606.ENSP00000223129 |
PTM databases
iPTMneti | P35244 |
MetOSitei | P35244 |
PhosphoSitePlusi | P35244 |
Genetic variation databases
BioMutai | RPA3 |
DMDMi | 464608 |
Proteomic databases
EPDi | P35244 |
jPOSTi | P35244 |
MassIVEi | P35244 |
MaxQBi | P35244 |
PaxDbi | P35244 |
PeptideAtlasi | P35244 |
PRIDEi | P35244 |
ProteomicsDBi | 55011 |
TopDownProteomicsi | P35244 |
Protocols and materials databases
Antibodypediai | 1308, 301 antibodies from 30 providers |
DNASUi | 6119 |
Genome annotation databases
Ensembli | ENST00000223129.8; ENSP00000223129.4; ENSG00000106399.11 ENST00000396682.6; ENSP00000379914.2; ENSG00000106399.11 |
GeneIDi | 6119 |
KEGGi | hsa:6119 |
MANE-Selecti | ENST00000223129.8; ENSP00000223129.4; NM_002947.5; NP_002938.1 |
UCSCi | uc003sri.4, human |
Organism-specific databases
CTDi | 6119 |
DisGeNETi | 6119 |
GeneCardsi | RPA3 |
HGNCi | HGNC:10291, RPA3 |
HPAi | ENSG00000106399, Low tissue specificity |
MIMi | 179837, gene |
neXtProti | NX_P35244 |
OpenTargetsi | ENSG00000106399 |
PharmGKBi | PA34653 |
VEuPathDBi | HostDB:ENSG00000106399 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S203, Eukaryota |
GeneTreei | ENSGT00390000008029 |
InParanoidi | P35244 |
OMAi | INRPVCF |
OrthoDBi | 1594928at2759 |
PhylomeDBi | P35244 |
TreeFami | TF105243 |
Enzyme and pathway databases
PathwayCommonsi | P35244 |
Reactomei | R-HSA-110312, Translesion synthesis by REV1 R-HSA-110314, Recognition of DNA damage by PCNA-containing replication complex R-HSA-110320, Translesion Synthesis by POLH R-HSA-174437, Removal of the Flap Intermediate from the C-strand R-HSA-176187, Activation of ATR in response to replication stress R-HSA-3371453, Regulation of HSF1-mediated heat shock response R-HSA-3371511, HSF1 activation R-HSA-5358565, Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) R-HSA-5358606, Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) R-HSA-5651801, PCNA-Dependent Long Patch Base Excision Repair R-HSA-5655862, Translesion synthesis by POLK R-HSA-5656121, Translesion synthesis by POLI R-HSA-5656169, Termination of translesion DNA synthesis R-HSA-5685938, HDR through Single Strand Annealing (SSA) R-HSA-5685942, HDR through Homologous Recombination (HRR) R-HSA-5693607, Processing of DNA double-strand break ends R-HSA-5693616, Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-5696395, Formation of Incision Complex in GG-NER R-HSA-5696397, Gap-filling DNA repair synthesis and ligation in GG-NER R-HSA-5696400, Dual Incision in GG-NER R-HSA-6782135, Dual incision in TC-NER R-HSA-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-6783310, Fanconi Anemia Pathway R-HSA-6804756, Regulation of TP53 Activity through Phosphorylation R-HSA-68962, Activation of the pre-replicative complex R-HSA-69166, Removal of the Flap Intermediate R-HSA-69473, G2/M DNA damage checkpoint R-HSA-912446, Meiotic recombination |
SignaLinki | P35244 |
SIGNORi | P35244 |
Miscellaneous databases
BioGRID-ORCSi | 6119, 807 hits in 1034 CRISPR screens |
ChiTaRSi | RPA3, human |
EvolutionaryTracei | P35244 |
GeneWikii | RPA3 |
GenomeRNAii | 6119 |
Pharosi | P35244, Tbio |
PROi | PR:P35244 |
RNActi | P35244, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000106399, Expressed in bronchial epithelial cell and 237 other tissues |
ExpressionAtlasi | P35244, baseline and differential |
Genevisiblei | P35244, HS |
Family and domain databases
Gene3Di | 2.40.50.140, 1 hit |
IDEALi | IID00040 |
InterProi | View protein in InterPro IPR012340, NA-bd_OB-fold IPR013970, Rfa2 |
Pfami | View protein in Pfam PF08661, Rep_fac-A_3, 1 hit |
SUPFAMi | SSF50249, SSF50249, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | RFA3_HUMAN | |
Accessioni | P35244Primary (citable) accession number: P35244 Secondary accession number(s): Q549U6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1994 |
Last sequence update: | February 1, 1994 | |
Last modified: | May 25, 2022 | |
This is version 195 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families