RFA2_PONAB
ID RFA2_PONAB Reviewed; 270 AA.
AC Q5RC43;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 93.
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;
GN Name=RPA2;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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).
CC Interacts with SERTAD3. Interacts with TIPIN. Interacts with TIMELESS.
CC Interacts with PPP4R2; the interaction is direct, DNA damage-dependent
CC and mediates the recruitment of the PP4 catalytic subunit PPP4C.
CC Interacts (hyperphosphorylated) with RAD51. Interacts with SMARCAL1;
CC the interaction is direct and mediates the recruitment to the RPA
CC complex of SMARCAL1. Interacts with RAD52 and XPA; those interactions
CC are direct and associate RAD52 and XPA to the RPA complex. Interacts
CC with FBH1. Interacts with ETAA1; the interaction is direct and promotes
CC ETAA1 recruitment at stalled replication forks. Interacts with DDI2 (By
CC similarity). {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}.
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; CR858438; CAH90667.1; -; mRNA.
DR RefSeq; NP_001125362.2; NM_001131890.2.
DR AlphaFoldDB; Q5RC43; -.
DR BMRB; Q5RC43; -.
DR SMR; Q5RC43; -.
DR STRING; 9601.ENSPPYP00000001907; -.
DR GeneID; 100172265; -.
DR KEGG; pon:100172265; -.
DR CTD; 6118; -.
DR eggNOG; KOG3108; Eukaryota.
DR InParanoid; Q5RC43; -.
DR OrthoDB; 924826at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005662; C:DNA replication factor A complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; ISS:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; ISS:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
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: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 2: Evidence at transcript 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_0000097272"
FT DNA_BIND 74..148
FT /note="OB"
FT REGION 21..40
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 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; 29235 MW; 4CCFB8F7D317D13B CRC64;
MWNSGFESYG SSSYGGAGGY TQSPGGFGSP APSQAEKKSR ARAQHIVPCT ISQLLSATLV
DEVFRIGNVE ISQVTIVGII RHAEKAPTNI VYKIDDMTAA PMDVRQWVDT DDASSENTVV
PPETYVKVAG HLRSFQNKKS LVAFKIMPLE DMNEFTTHIL EVINAHMVLS KANSQPSAGR
APISNPGMSE AGNFGGNSFM PANGLTVAQN QVLNLIKACP RPEGLNFQDL KNQLKHMSVS
SVKQAMDFLS NEGHIYSTVD DDHFKSTDAE
