RFA1_PONAB
ID RFA1_PONAB Reviewed; 616 AA.
AC Q5R7Q4;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Replication protein A 70 kDa DNA-binding subunit;
DE Short=RP-A p70;
DE AltName: Full=Replication factor A protein 1;
DE Short=RF-A protein 1;
GN Name=RPA1;
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=Kidney;
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:P27694}.
CC -!- SUBUNIT: Component of the canonical replication protein A complex
CC (RPA), a heterotrimer composed of RPA1, RPA2 and RPA3. The DNA-binding
CC activity may reside exclusively on the RPA1 subunit. 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 RIPK1. Interacts with the polymerase alpha subunit
CC POLA1/p180; this interaction stabilizes the replicative complex and
CC reduces the misincorporation rate of DNA polymerase alpha by acting as
CC a fidelity clamp. Interacts with RAD51 and SENP6 to regulate DNA
CC repair. Interacts with HELB; this interaction promotes HELB recruitment
CC to chromatin following DNA damage. Interacts with PRIMPOL; leading to
CC recruit PRIMPOL on chromatin and stimulate its DNA primase activity.
CC Interacts with XPA; the interaction is direct and associates XPA with
CC the RPA complex. Interacts with ETAA1; the interaction is direct and
CC promotes ETAA1 recruitment at stalled replication forks. Interacts with
CC RPA1; this interaction associates HROB with the RPA complex (By
CC similarity). {ECO:0000250|UniProtKB:P27694,
CC ECO:0000250|UniProtKB:Q8VEE4}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P27694}. Nucleus,
CC PML body {ECO:0000250|UniProtKB:P27694}.
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:P27694}.
CC -!- PTM: Sumoylated on lysine residues Lys-449 and Lys-577, with Lys-449
CC being the major site. Sumoylation promotes recruitment of RAD51 to the
CC DNA damage foci to initiate DNA repair through homologous
CC recombination. Desumoylated by SENP6 (By similarity).
CC {ECO:0000250|UniProtKB:P27694}.
CC -!- SIMILARITY: Belongs to the replication factor A protein 1 family.
CC {ECO:0000305}.
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DR EMBL; CR860058; CAH92206.1; -; mRNA.
DR RefSeq; NP_001126290.1; NM_001132818.1.
DR AlphaFoldDB; Q5R7Q4; -.
DR BMRB; Q5R7Q4; -.
DR SMR; Q5R7Q4; -.
DR GeneID; 100173266; -.
DR KEGG; pon:100173266; -.
DR CTD; 6117; -.
DR InParanoid; Q5R7Q4; -.
DR OrthoDB; 1189265at2759; -.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0090734; C:site of DNA damage; ISS:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0006284; P:base-excision repair; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; 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 CDD; cd04476; RPA1_DBD_C; 1.
DR CDD; cd04477; RPA1N; 1.
DR Gene3D; 2.40.50.140; -; 4.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR004365; NA-bd_OB_tRNA.
DR InterPro; IPR013955; Rep_factor-A_C.
DR InterPro; IPR007199; Rep_factor-A_N.
DR InterPro; IPR031657; REPA_OB_2.
DR InterPro; IPR004591; Rfa1.
DR PANTHER; PTHR23273; PTHR23273; 1.
DR Pfam; PF04057; Rep-A_N; 1.
DR Pfam; PF08646; Rep_fac-A_C; 1.
DR Pfam; PF16900; REPA_OB_2; 1.
DR Pfam; PF01336; tRNA_anti-codon; 1.
DR SUPFAM; SSF50249; SSF50249; 4.
DR TIGRFAMs; TIGR00617; rpa1; 1.
PE 2: Evidence at transcript level;
KW Acetylation; DNA damage; DNA recombination; DNA repair; DNA replication;
KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..616
FT /note="Replication protein A 70 kDa DNA-binding subunit"
FT /id="PRO_0000097262"
FT DNA_BIND 197..281
FT /note="OB"
FT ZN_FING 481..503
FT /note="C4-type"
FT /evidence="ECO:0000255"
FT REGION 121..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 138..155
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT MOD_RES 163
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT MOD_RES 167
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT MOD_RES 180
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT MOD_RES 191
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT MOD_RES 259
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 22
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 88
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 163
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 167
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 183
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 220
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 244
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 259
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 267
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 331
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 410
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 431
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 449
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 458
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 553
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
FT CROSSLNK 577
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P27694"
SQ SEQUENCE 616 AA; 68125 MW; 4A5A3A20AB66E994 CRC64;
MVGQLSEGAI AAIMQKGDTN IKPILQVINI RPITTGNSPP RYRLLMSDGL NTLSSFMSAT
QLNPLVEQEQ LSSNCVCQIN RFIVNTLKDG RRVVILMELE VLKSAEVVGV KIGNPVPYNE
GLGQPQVAPP APAASPAASS RPQPQNGTSG AGSTVSKAYG ASKTFGKAAG PSLSHNSGGT
QSKVVPIASL TPYQSKWTIC ARVTNKSQIR TWSNSRGEEK LFSLELVDES GEIRATAFNE
QVDKFFPLIE VNKVYYFSKG TLKIANKQFT AVKNDYEMTF NNETSVMPCE DDHHLPTVQF
DFTGIDDLEN KSKDSLVDII GICKSYEDAT KITVRSNNRE VAKRNIYLMD TSGKVVTATL
WGEDADKFDG SRQPVLAIKG ARVSDFGGRS LSVLSSSTII ANPDIPEAYK LRGWFDAEGQ
ALDGVSISDL KSGGVGGGNT NWKTLYEVKS ENLGQGDKPD YFSSVATVVY LRKENCMYQA
CPTQDCNKKV IDQQNGLYRC EKCDTEFPNF KYRMILSVNI ADFQENQWVT CFQESAEAIL
GQNAAYLGEL KDKNEQAFEE VFQNANFRSF IFRVRVKVET YNDESRIKAT VMDVKPVDYR
EYGRRLVMSI RRSALM
