RFA2_MOUSE
ID RFA2_MOUSE Reviewed; 270 AA.
AC Q62193;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Replication protein A 32 kDa subunit;
DE Short=RP-A p32;
DE AltName: Full=Replication factor A protein 2;
DE Short=RF-A protein 2;
DE AltName: Full=Replication protein A 34 kDa subunit;
DE Short=RP-A p34;
GN Name=Rpa2; Synonyms=Rpa34;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1908076; DOI=10.1093/nar/19.15.4292;
RA Nakagawa M., Tsukada S., Soma T., Shimizu Y.K., Miyake S., Iwamatsu A.,
RA Sugiyama H.;
RT "cDNA cloning of the murine 30-kDa protein homologous to the 32-kDa subunit
RT of human replication protein A.";
RL Nucleic Acids Res. 19:4292-4292(1991).
RN [2]
RP INTERACTION WITH TIMELESS AND TIPIN.
RX PubMed=17141802; DOI=10.1016/j.jmb.2006.10.097;
RA Gotter A.L., Suppa C., Emanuel B.S.;
RT "Mammalian TIMELESS and Tipin are evolutionarily conserved replication
RT fork-associated factors.";
RL J. Mol. Biol. 366:36-52(2007).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Liver, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: As part of the heterotrimeric replication protein A complex
CC (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates,
CC that form during DNA replication or upon DNA stress. It prevents their
CC reannealing and in parallel, recruits and activates different proteins
CC and complexes involved in DNA metabolism. Thereby, it plays an
CC essential role both in DNA replication and the cellular response to DNA
CC damage. In the cellular response to DNA damage, the RPA complex
CC controls DNA repair and DNA damage checkpoint activation. Through
CC recruitment of ATRIP activates the ATR kinase a master regulator of the
CC DNA damage response. It is required for the recruitment of the DNA
CC double-strand break repair factors RAD51 and RAD52 to chromatin in
CC response to DNA damage. Also recruits to sites of DNA damage proteins
CC like XPA and XPG that are involved in nucleotide excision repair and is
CC required for this mechanism of DNA repair. Also plays a role in base
CC excision repair (BER) probably through interaction with UNG. Also
CC recruits SMARCAL1/HARP, which is involved in replication fork restart,
CC to sites of DNA damage. May also play a role in telomere maintenance.
CC {ECO:0000250|UniProtKB:P15927}.
CC -!- SUBUNIT: Component of the replication protein A complex (RPA/RP-A), a
CC heterotrimeric complex composed of RPA1, RPA2 and RPA3. Interacts with
CC PRPF19; the PRP19-CDC5L complex is recruited to the sites of DNA repair
CC where it ubiquitinates the replication protein A complex (RPA) (By
CC similarity). Interacts with SERTAD3. Interacts with TIPIN
CC (PubMed:17141802). Interacts with TIMELESS (PubMed:17141802). Interacts
CC with PPP4R2; the interaction is direct, DNA damage-dependent and
CC mediates the recruitment of the PP4 catalytic subunit PPP4C (By
CC similarity). Interacts (hyperphosphorylated) with RAD51 (By
CC similarity). Interacts with SMARCAL1; the interaction is direct and
CC mediates the recruitment to the RPA complex of SMARCAL1 (By
CC similarity). Interacts with RAD52 and XPA; those interactions are
CC direct and associate RAD52 and XPA to the RPA complex (By similarity).
CC Interacts with FBH1 (By similarity). Interacts with ETAA1; the
CC interaction is direct and promotes ETAA1 recruitment at stalled
CC replication forks (By similarity). Interacts with DDI2 (By similarity).
CC {ECO:0000250|UniProtKB:P15927}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P15927}. Nucleus,
CC PML body {ECO:0000250|UniProtKB:P15927}. Note=Redistributes to discrete
CC nuclear foci upon DNA damage in an ATR-dependent manner.
CC {ECO:0000250|UniProtKB:P15927, ECO:0000269|PubMed:17141802}.
CC -!- PTM: Differentially phosphorylated throughout the cell cycle, becoming
CC phosphorylated at the G1-S transition and dephosphorylated in late
CC mitosis. Mainly phosphorylated at Ser-23 and Ser-29, by cyclin A-CDK2
CC and cyclin B-CDK1, respectively during DNA replication and mitosis.
CC Dephosphorylation may require the serine/threonine-protein phosphatase
CC 4. Phosphorylation at Ser-23 and Ser-29 is a prerequisite for further
CC phosphorylation. Becomes hyperphosphorylated on additional residues
CC including Ser-4, Ser-8, Thr-21 and Ser-33 in response to DNA damage.
CC Hyperphosphorylation is mediated by ATM, ATR and PRKDC. Primarily
CC recruited to DNA repair nuclear foci as a hypophosphorylated form it
CC undergoes subsequent hyperphosphorylation, catalyzed by ATR.
CC Hyperphosphorylation is required for RAD51 recruitment to chromatin and
CC efficient DNA repair. Phosphorylation at Thr-21 depends upon RFWD3
CC presence. {ECO:0000250|UniProtKB:P15927}.
CC -!- PTM: DNA damage-induced 'Lys-63'-linked polyubiquitination by PRPF19
CC mediates ATRIP recruitment to the RPA complex at sites of DNA damage
CC and activation of ATR. Ubiquitinated by RFWD3 at stalled replication
CC forks in response to DNA damage: ubiquitination by RFWD3 does not lead
CC to degradation by the proteasome and promotes removal of the RPA
CC complex from stalled replication forks, promoting homologous
CC recombination. {ECO:0000250|UniProtKB:P15927}.
CC -!- SIMILARITY: Belongs to the replication factor A protein 2 family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D00812; BAA00693.1; -; mRNA.
DR CCDS; CCDS18734.1; -.
DR PIR; S28682; S28682.
DR AlphaFoldDB; Q62193; -.
DR SMR; Q62193; -.
DR CORUM; Q62193; -.
DR DIP; DIP-48715N; -.
DR IntAct; Q62193; 2.
DR STRING; 10090.ENSMUSP00000099621; -.
DR iPTMnet; Q62193; -.
DR PhosphoSitePlus; Q62193; -.
DR EPD; Q62193; -.
DR jPOST; Q62193; -.
DR MaxQB; Q62193; -.
DR PaxDb; Q62193; -.
DR PeptideAtlas; Q62193; -.
DR PRIDE; Q62193; -.
DR ProteomicsDB; 253119; -.
DR MGI; MGI:1339939; Rpa2.
DR eggNOG; KOG3108; Eukaryota.
DR InParanoid; Q62193; -.
DR PhylomeDB; Q62193; -.
DR Reactome; R-MMU-110312; Translesion synthesis by REV1.
DR Reactome; R-MMU-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-MMU-110320; Translesion Synthesis by POLH.
DR Reactome; R-MMU-174437; Removal of the Flap Intermediate from the C-strand.
DR Reactome; R-MMU-176187; Activation of ATR in response to replication stress.
DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-MMU-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-MMU-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR Reactome; R-MMU-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-MMU-5655862; Translesion synthesis by POLK.
DR Reactome; R-MMU-5656121; Translesion synthesis by POLI.
DR Reactome; R-MMU-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-MMU-5696397; Gap-filling DNA repair synthesis and ligation in GG-NER.
DR Reactome; R-MMU-5696400; Dual Incision in GG-NER.
DR Reactome; R-MMU-6782135; Dual incision in TC-NER.
DR Reactome; R-MMU-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-MMU-6783310; Fanconi Anemia Pathway.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-MMU-68962; Activation of the pre-replicative complex.
DR Reactome; R-MMU-69166; Removal of the Flap Intermediate.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR ChiTaRS; Rpa2; mouse.
DR PRO; PR:Q62193; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q62193; protein.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR GO; GO:0005662; C:DNA replication factor A complex; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISO:MGI.
DR GO; GO:0003684; F:damaged DNA binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0098505; F:G-rich strand telomeric DNA binding; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006284; P:base-excision repair; ISS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; ISS:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0006298; P:mismatch repair; ISS:UniProtKB.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; ISO:MGI.
DR GO; GO:0006289; P:nucleotide-excision repair; ISS:UniProtKB.
DR GO; GO:0034502; P:protein localization to chromosome; ISS:UniProtKB.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; ISS:UniProtKB.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0000723; P:telomere maintenance; ISS:UniProtKB.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR040260; RFA2-like.
DR InterPro; IPR014646; Rfa2/RPA32.
DR InterPro; IPR014892; RPA_C.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR13989; PTHR13989; 1.
DR Pfam; PF08784; RPA_C; 1.
DR PIRSF; PIRSF036949; RPA32; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
PE 1: Evidence at protein level;
KW Acetylation; DNA damage; DNA recombination; DNA repair; DNA replication;
KW DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..270
FT /note="Replication protein A 32 kDa subunit"
FT /id="PRO_0000097271"
FT DNA_BIND 74..148
FT /note="OB"
FT REGION 1..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 187..270
FT /note="Interaction with RAD52, TIPIN, UNG and XPA"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..37
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P15927"
FT MOD_RES 4
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000250|UniProtKB:P15927"
FT MOD_RES 8
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000250|UniProtKB:P15927"
FT MOD_RES 21
FT /note="Phosphothreonine; by PRKDC"
FT /evidence="ECO:0000250|UniProtKB:P15927"
FT MOD_RES 23
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000250|UniProtKB:P15927"
FT MOD_RES 29
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:P15927"
FT MOD_RES 33
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000250|UniProtKB:P15927"
FT CROSSLNK 37
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P15927"
FT CROSSLNK 38
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P15927"
SQ SEQUENCE 270 AA; 29718 MW; BF0EF86612A48011 CRC64;
MWNSGFESFT SSTYGGRGGY TQSPGGFGSP TPSQAEKKSR VRAQHIVPCT ISQLLSATLT
DEVFRIGDVE ISQVTIVGII RHAEKAPTNI VYKIDDMTAP PMDVRQWVDT DDASGENAVV
PPETYVKVAG HLRSFQNKKS LVAFKIIPLE DMNEFTAHIL EVVNSHMMLS KPNSQASAGR
PSMSNPGMSE SFNFSGNNFM PANRLTVVQN QVLNLIKACP RPEGLNFQDL RSQLQHMPVP
SIKQAVDFLC NEGHIYSTVD DDHFKSTDAE
