RFA2_HUMAN
ID RFA2_HUMAN Reviewed; 270 AA.
AC P15927; Q52II0; Q5TEI9; Q5TEJ5;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 225.
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=REPA2, RPA32, RPA34;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, FUNCTION
RP IN DNA REPLICATION, AND IDENTIFICATION IN RPA COMPLEX.
RX PubMed=2406247; DOI=10.1016/s0021-9258(19)39750-9;
RA Erdile L.F., Wold M.S., Kelly T.J.;
RT "The primary structure of the 32-kDa subunit of human replication protein
RT A.";
RL J. Biol. Chem. 265:3177-3182(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-14; ARG-15 AND SER-203.
RG NIEHS SNPs program;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney, Lung, and Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP CELL CYCLE-DEPENDENT PHOSPHORYLATION.
RX PubMed=2200738; DOI=10.1101/gad.4.6.968;
RA Din S., Brill S.J., Fairman M.P., Stillman B.;
RT "Cell-cycle-regulated phosphorylation of DNA replication factor A from
RT human and yeast cells.";
RL Genes Dev. 4:968-977(1990).
RN [7]
RP DNA DAMAGE-INDUCED PHOSPHORYLATION, AND PHOSPHORYLATION AT SER-23 AND
RP SER-29.
RX PubMed=1318195; DOI=10.1002/j.1460-2075.1992.tb05278.x;
RA Dutta A., Stillman B.;
RT "cdc2 family kinases phosphorylate a human cell DNA replication factor,
RT RPA, and activate DNA replication.";
RL EMBO J. 11:2189-2199(1992).
RN [8]
RP PHOSPHORYLATION AT SER-23 AND SER-29.
RX PubMed=8246944; DOI=10.1128/mcb.13.12.7222-7231.1993;
RA Liu V.F., Weaver D.T.;
RT "The ionizing radiation-induced replication protein A phosphorylation
RT response differs between ataxia telangiectasia and normal human cells.";
RL Mol. Cell. Biol. 13:7222-7231(1993).
RN [9]
RP FUNCTION IN NUCLEOTIDE EXCISION REPAIR.
RX PubMed=7697716; DOI=10.1016/0092-8674(95)90289-9;
RA Aboussekhra A., Biggerstaff M., Shivji M.K., Vilpo J.A., Moncollin V.,
RA Podust V.N., Protic M., Huebscher U., Egly J.M., Wood R.D.;
RT "Mammalian DNA nucleotide excision repair reconstituted with purified
RT protein components.";
RL Cell 80:859-868(1995).
RN [10]
RP FUNCTION IN NUCLEOTIDE EXCISION REPAIR, AND INTERACTION WITH XPA.
RX PubMed=7700386; DOI=10.1038/374566a0;
RA He Z., Henricksen L.A., Wold M.S., Ingles C.J.;
RT "RPA involvement in the damage-recognition and incision steps of nucleotide
RT excision repair.";
RL Nature 374:566-569(1995).
RN [11]
RP FUNCTION IN HOMOLOGOUS RECOMBINATION, AND INTERACTION WITH RAD52.
RX PubMed=8702565; DOI=10.1074/jbc.271.31.18996;
RA Park M.S., Ludwig D.L., Stigger E., Lee S.H.;
RT "Physical interaction between human RAD52 and RPA is required for
RT homologous recombination in mammalian cells.";
RL J. Biol. Chem. 271:18996-19000(1996).
RN [12]
RP ACETYLATION AT MET-1, PHOSPHORYLATION AT THR-21; SER-29 AND SER-33,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF SER-29.
RX PubMed=9139719; DOI=10.1074/jbc.272.19.12634;
RA Niu H., Erdjument-Bromage H., Pan Z.-Q., Lee S.-H., Tempst P., Hurwitz J.;
RT "Mapping of amino acid residues in the p34 subunit of human single-stranded
RT DNA-binding protein phosphorylated by DNA-dependent protein kinase and Cdc2
RT kinase in vitro.";
RL J. Biol. Chem. 272:12634-12641(1997).
RN [13]
RP PHOSPHORYLATION AT THR-21; SER-23; SER-29 AND SER-33.
RX PubMed=9295339; DOI=10.1074/jbc.272.38.23896;
RA Zernik-Kobak M., Vasunia K., Connelly M., Anderson C.W., Dixon K.;
RT "Sites of UV-induced phosphorylation of the p34 subunit of replication
RT protein A from HeLa cells.";
RL J. Biol. Chem. 272:23896-23904(1997).
RN [14]
RP FUNCTION IN DNA REPLICATION, FUNCTION IN DNA MISMATCH REPAIR, AND FUNCTION
RP IN NUCLEOTIDE EXCISION REPAIR.
RX PubMed=9430682; DOI=10.1074/jbc.273.3.1453;
RA Lin Y.L., Shivji M.K., Chen C., Kolodner R., Wood R.D., Dutta A.;
RT "The evolutionarily conserved zinc finger motif in the largest subunit of
RT human replication protein A is required for DNA replication and mismatch
RT repair but not for nucleotide excision repair.";
RL J. Biol. Chem. 273:1453-1461(1998).
RN [15]
RP FUNCTION IN BASE EXCISION REPAIR.
RX PubMed=9765279; DOI=10.1074/jbc.273.42.27492;
RA DeMott M.S., Zigman S., Bambara R.A.;
RT "Replication protein A stimulates long patch DNA base excision repair.";
RL J. Biol. Chem. 273:27492-27498(1998).
RN [16]
RP INTERACTION WITH SERTAD3, AND SUBCELLULAR LOCATION.
RX PubMed=10982866; DOI=10.1093/nar/28.18.3478;
RA Cho J.M., Song D.J., Bergeron J., Benlimame N., Wold M.S.,
RA Alaoui-Jamali M.A.;
RT "RBT1, a novel transcriptional co-activator, binds the second subunit of
RT replication protein A.";
RL Nucleic Acids Res. 28:3478-3485(2000).
RN [17]
RP PHOSPHORYLATION BY ATR, AND SUBCELLULAR LOCATION.
RX PubMed=12814551; DOI=10.1016/s0960-9822(03)00376-2;
RA Barr S.M., Leung C.G., Chang E.E., Cimprich K.A.;
RT "ATR kinase activity regulates the intranuclear translocation of ATR and
RT RPA following ionizing radiation.";
RL Curr. Biol. 13:1047-1051(2003).
RN [18]
RP FUNCTION IN DNA REPLICATION.
RX PubMed=15205463; DOI=10.1074/jbc.m403825200;
RA Weisshart K., Pestryakov P., Smith R.W.P., Hartmann H., Kremmer E.,
RA Lavrik O., Nasheuer H.-P.;
RT "Coordinated regulation of replication protein A activities by its subunits
RT p14 and p32.";
RL J. Biol. Chem. 279:35368-35376(2004).
RN [19]
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 [20]
RP FUNCTION IN HOMOLOGOUS RECOMBINATION REPAIR, AND INTERACTION WITH RAD52.
RX PubMed=17765923; DOI=10.1016/j.jmb.2007.07.068;
RA Sleeth K.M., Sorensen C.S., Issaeva N., Dziegielewski J., Bartek J.,
RA Helleday T.;
RT "RPA mediates recombination repair during replication stress and is
RT displaced from DNA by checkpoint signalling in human cells.";
RL J. Mol. Biol. 373:38-47(2007).
RN [21]
RP INTERACTION WITH TIPIN.
RX PubMed=17296725; DOI=10.1128/mcb.02190-06;
RA Uensal-Kacmaz K., Chastain P.D., Qu P.-P., Minoo P., Cordeiro-Stone M.,
RA Sancar A., Kaufmann W.K.;
RT "The human Tim/Tipin complex coordinates an Intra-S checkpoint response to
RT UV that slows replication fork displacement.";
RL Mol. Cell. Biol. 27:3131-3142(2007).
RN [22]
RP FUNCTION IN TELOMERE MAINTENANCE, AND SUBCELLULAR LOCATION.
RX PubMed=17959650; DOI=10.1093/nar/gkm738;
RA Grudic A., Jul-Larsen A., Haring S.J., Wold M.S., Loenning P.E.,
RA Bjerkvig R., Boee S.O.;
RT "Replication protein A prevents accumulation of single-stranded telomeric
RT DNA in cells that use alternative lengthening of telomeres.";
RL Nucleic Acids Res. 35:7267-7278(2007).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [25]
RP INTERACTION WITH SMARCAL1.
RX PubMed=19793863; DOI=10.1101/gad.1831509;
RA Yusufzai T., Kong X., Yokomori K., Kadonaga J.T.;
RT "The annealing helicase HARP is recruited to DNA repair sites via an
RT interaction with RPA.";
RL Genes Dev. 23:2400-2404(2009).
RN [26]
RP INTERACTION WITH SMARCAL1.
RX PubMed=19793861; DOI=10.1101/gad.1839909;
RA Bansbach C.E., Betous R., Lovejoy C.A., Glick G.G., Cortez D.;
RT "The annealing helicase SMARCAL1 maintains genome integrity at stalled
RT replication forks.";
RL Genes Dev. 23:2405-2414(2009).
RN [27]
RP INTERACTION WITH SMARCAL1.
RX PubMed=19793862; DOI=10.1101/gad.1832309;
RA Ciccia A., Bredemeyer A.L., Sowa M.E., Terret M.E., Jallepalli P.V.,
RA Harper J.W., Elledge S.J.;
RT "The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved
RT in replication fork restart.";
RL Genes Dev. 23:2415-2425(2009).
RN [28]
RP FUNCTION AS PART OF THE RPA COMPLEX.
RX PubMed=19116208; DOI=10.1074/jbc.m808963200;
RA Mason A.C., Haring S.J., Pryor J.M., Staloch C.A., Gan T.F., Wold M.S.;
RT "An alternative form of replication protein a prevents viral replication in
RT vitro.";
RL J. Biol. Chem. 284:5324-5331(2009).
RN [29]
RP TISSUE SPECIFICITY.
RX PubMed=19996105; DOI=10.1074/jbc.m109.079418;
RA Kemp M.G., Mason A.C., Carreira A., Reardon J.T., Haring S.J.,
RA Borgstahl G.E., Kowalczykowski S.C., Sancar A., Wold M.S.;
RT "An alternative form of replication protein a expressed in normal human
RT tissues supports DNA repair.";
RL J. Biol. Chem. 285:4788-4797(2010).
RN [30]
RP FUNCTION IN DNA REPAIR, PHOSPHORYLATION, DEPHOSPHORYLATION BY PP4,
RP INTERACTION WITH PPP4C; PPP4R2 AND RAD51, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF SER-8; SER-23; SER-29 AND SER-33.
RX PubMed=20154705; DOI=10.1038/nsmb.1769;
RA Lee D.H., Pan Y., Kanner S., Sung P., Borowiec J.A., Chowdhury D.;
RT "A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair
RT via homologous recombination.";
RL Nat. Struct. Mol. Biol. 17:365-372(2010).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-23 AND SER-29, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [32]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [33]
RP FUNCTION IN REPLICATION CHECKPOINT, INTERACTION WITH RFWD3, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21504906; DOI=10.1074/jbc.m111.222869;
RA Gong Z., Chen J.;
RT "E3 ligase RFWD3 participates in replication checkpoint control.";
RL J. Biol. Chem. 286:22308-22313(2011).
RN [34]
RP INTERACTION WITH RFWD3, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT
RP THR-21.
RX PubMed=21558276; DOI=10.1074/jbc.m111.222802;
RA Liu S., Chu J., Yucer N., Leng M., Wang S.Y., Chen B.P., Hittelman W.N.,
RA Wang Y.;
RT "RING finger and WD repeat domain 3 (RFWD3) associates with replication
RT protein A (RPA) and facilitates RPA-mediated DNA damage response.";
RL J. Biol. Chem. 286:22314-22322(2011).
RN [35]
RP PHOSPHORYLATION AT SER-4 AND SER-8 BY PRKDC, AND MUTAGENESIS OF SER-4 AND
RP SER-8.
RX PubMed=21731742; DOI=10.1371/journal.pone.0021424;
RA Liaw H., Lee D., Myung K.;
RT "DNA-PK-dependent RPA2 hyperphosphorylation facilitates DNA repair and
RT suppresses sister chromatid exchange.";
RL PLoS ONE 6:E21424-E21424(2011).
RN [36]
RP INDUCTION BY DNA DAMAGE.
RX PubMed=23393223; DOI=10.1093/carcin/bgt052;
RA Yin J.Y., Dong Z.Z., Liu R.Y., Chen J., Liu Z.Q., Zhang J.T.;
RT "Translational regulation of RPA2 via internal ribosomal entry site and by
RT eIF3a.";
RL Carcinogenesis 34:1224-1231(2013).
RN [37]
RP INTERACTION WITH FBH1.
RX PubMed=23319600; DOI=10.1083/jcb.201209002;
RA Jeong Y.T., Rossi M., Cermak L., Saraf A., Florens L., Washburn M.P.,
RA Sung P., Schildkraut C.L., Schildkraut C., Pagano M.;
RT "FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA
RT replication stress.";
RL J. Cell Biol. 200:141-149(2013).
RN [38]
RP FUNCTION, INTERACTION WITH PRPF19, AND UBIQUITINATION BY PRPF19.
RX PubMed=24332808; DOI=10.1016/j.molcel.2013.11.002;
RA Marechal A., Li J.M., Ji X.Y., Wu C.S., Yazinski S.A., Nguyen H.D., Liu S.,
RA Jimenez A.E., Jin J., Zou L.;
RT "PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives
RT ATR activation via a ubiquitin-mediated circuitry.";
RL Mol. Cell 53:235-246(2014).
RN [39]
RP UBIQUITINATION AT LYS-37 AND LYS-38, PHOSPHORYLATION AT SER-4; SER-8;
RP THR-21 AND SER-33, AND MUTAGENESIS OF 37-LYS-LYS-38.
RX PubMed=26474068; DOI=10.1016/j.molcel.2015.09.011;
RA Elia A.E., Wang D.C., Willis N.A., Boardman A.P., Hajdu I., Adeyemi R.O.,
RA Lowry E., Gygi S.P., Scully R., Elledge S.J.;
RT "RFWD3-dependent ubiquitination of RPA regulates repair at stalled
RT replication forks.";
RL Mol. Cell 60:280-293(2015).
RN [40]
RP INTERACTION WITH ETAA1.
RX PubMed=27601467; DOI=10.1074/jbc.c116.747758;
RA Feng S., Zhao Y., Xu Y., Ning S., Huo W., Hou M., Gao G., Ji J., Guo R.,
RA Xu D.;
RT "Ewing Tumor-associated Antigen 1 interacts with replication protein A to
RT promote restart of stalled replication forks.";
RL J. Biol. Chem. 291:21956-21962(2016).
RN [41]
RP FUNCTION, AND INTERACTION WITH ETAA1.
RX PubMed=27723720; DOI=10.1038/ncb3415;
RA Bass T.E., Luzwick J.W., Kavanaugh G., Carroll C., Dungrawala H.,
RA Glick G.G., Feldkamp M.D., Putney R., Chazin W.J., Cortez D.;
RT "ETAA1 acts at stalled replication forks to maintain genome integrity.";
RL Nat. Cell Biol. 18:1185-1195(2016).
RN [42]
RP FUNCTION, AND INTERACTION WITH ETAA1.
RX PubMed=27723717; DOI=10.1038/ncb3422;
RA Haahr P., Hoffmann S., Tollenaere M.A., Ho T., Toledo L.I., Mann M.,
RA Bekker-Jensen S., Raeschle M., Mailand N.;
RT "Activation of the ATR kinase by the RPA-binding protein ETAA1.";
RL Nat. Cell Biol. 18:1196-1207(2016).
RN [43]
RP INTERACTION WITH RFWD3, AND MUTAGENESIS OF PHE-248; GLU-252; GLY-253 AND
RP HIS-254.
RX PubMed=28575657; DOI=10.1016/j.molcel.2017.04.021;
RA Feeney L., Munoz I.M., Lachaud C., Toth R., Appleton P.L., Schindler D.,
RA Rouse J.;
RT "RPA-mediated recruitment of the E3 ligase RFWD3 is vital for interstrand
RT crosslink repair and human health.";
RL Mol. Cell 66:610-621(2017).
RN [44]
RP INTERACTION WITH DDI2.
RX PubMed=29290612; DOI=10.1016/j.molcel.2017.11.035;
RA Kottemann M.C., Conti B.A., Lach F.P., Smogorzewska A.;
RT "Removal of RTF2 from Stalled Replisomes Promotes Maintenance of Genome
RT Integrity.";
RL Mol. Cell 69:24-35.E5(2018).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 43-171 IN COMPLEX WITH RPA1 AND
RP RPA3.
RX PubMed=10449415; DOI=10.1093/emboj/18.16.4498;
RA Bochkarev A., Bochkareva E., Frappier L., Edwards A.M.;
RT "The crystal structure of the complex of replication protein A subunits
RT RPA32 and RPA14 reveals a mechanism for single-stranded DNA binding.";
RL EMBO J. 18:4498-4504(1999).
RN [46]
RP STRUCTURE BY NMR OF 172-270, INTERACTION WITH RAD52; UNG AND XPA, AND
RP REGION.
RX PubMed=11081631; DOI=10.1016/s0092-8674(00)00136-7;
RA Mer G., Bochkarev A., Gupta R., Bochkareva E., Frappier L., Ingles C.J.,
RA Edwards A.M., Chazin W.J.;
RT "Structural basis for the recognition of DNA repair proteins UNG2, XPA, and
RT RAD52 by replication factor RPA.";
RL Cell 103:449-456(2000).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 44-171.
RX PubMed=11927569; DOI=10.1093/emboj/21.7.1855;
RA Bochkareva E., Korolev S., Lees-Miller S.P., Bochkarev A.;
RT "Structure of the RPA trimerization core and its role in the multistep DNA-
RT binding mechanism of RPA.";
RL EMBO J. 21:1855-1863(2002).
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:0000269|PubMed:15205463, ECO:0000269|PubMed:17765923,
CC ECO:0000269|PubMed:17959650, ECO:0000269|PubMed:19116208,
CC ECO:0000269|PubMed:20154705, ECO:0000269|PubMed:21504906,
CC ECO:0000269|PubMed:2406247, ECO:0000269|PubMed:24332808,
CC ECO:0000269|PubMed:7697716, ECO:0000269|PubMed:7700386,
CC ECO:0000269|PubMed:8702565, ECO:0000269|PubMed:9430682,
CC ECO:0000269|PubMed:9765279}.
CC -!- SUBUNIT: Component of the replication protein A complex (RPA/RP-A), a
CC heterotrimeric complex composed of RPA1, RPA2 and RPA3 (PubMed:2406247,
CC PubMed:19116208, PubMed:10449415). Interacts with PRPF19; the PRP19-
CC CDC5L complex is recruited to the sites of DNA repair where it
CC ubiquitinates the replication protein A complex (RPA)
CC (PubMed:24332808). Interacts with SERTAD3 (PubMed:10982866). Interacts
CC with TIPIN (PubMed:17141802, PubMed:17296725). Interacts with TIMELESS
CC (PubMed:17141802). Interacts with PPP4R2; the interaction is direct,
CC DNA damage-dependent and mediates the recruitment of the PP4 catalytic
CC subunit PPP4C (PubMed:20154705). Interacts (hyperphosphorylated) with
CC RAD51 (PubMed:20154705). Interacts with SMARCAL1; the interaction is
CC direct and mediates the recruitment to the RPA complex of SMARCAL1
CC (PubMed:19793861, PubMed:19793862, PubMed:19793863). Interacts with
CC RAD52 and XPA; those interactions are direct and associate RAD52 and
CC XPA to the RPA complex (PubMed:7700386, PubMed:8702565,
CC PubMed:17765923, PubMed:11081631). Interacts with FBH1
CC (PubMed:23319600). Interacts with ETAA1; the interaction is direct and
CC promotes ETAA1 recruitment at stalled replication forks
CC (PubMed:27601467, PubMed:27723720, PubMed:27723717). Interacts with
CC RFWD3 (PubMed:21504906, PubMed:21558276, PubMed:26474068,
CC PubMed:28575657). Interacts with DDI2 (PubMed:29290612).
CC {ECO:0000269|PubMed:10449415, ECO:0000269|PubMed:10982866,
CC ECO:0000269|PubMed:11081631, ECO:0000269|PubMed:17141802,
CC ECO:0000269|PubMed:17296725, ECO:0000269|PubMed:17765923,
CC ECO:0000269|PubMed:19793861, ECO:0000269|PubMed:19793862,
CC ECO:0000269|PubMed:19793863, ECO:0000269|PubMed:20154705,
CC ECO:0000269|PubMed:21504906, ECO:0000269|PubMed:21558276,
CC ECO:0000269|PubMed:23319600, ECO:0000269|PubMed:2406247,
CC ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:26474068,
CC ECO:0000269|PubMed:27601467, ECO:0000269|PubMed:27723717,
CC ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:28575657,
CC ECO:0000269|PubMed:29290612, ECO:0000269|PubMed:7700386,
CC ECO:0000269|PubMed:8702565}.
CC -!- INTERACTION:
CC P15927; P24863: CCNC; NbExp=3; IntAct=EBI-621404, EBI-395261;
CC P15927; O75419: CDC45; NbExp=4; IntAct=EBI-621404, EBI-374969;
CC P15927; O60516: EIF4EBP3; NbExp=3; IntAct=EBI-621404, EBI-746950;
CC P15927; P04406: GAPDH; NbExp=2; IntAct=EBI-621404, EBI-354056;
CC P15927; P49643-1: PRIM2; NbExp=3; IntAct=EBI-621404, EBI-15866483;
CC P15927; Q6PCD5: RFWD3; NbExp=3; IntAct=EBI-621404, EBI-2129159;
CC P15927; P27694: RPA1; NbExp=15; IntAct=EBI-621404, EBI-621389;
CC P15927; P35244: RPA3; NbExp=9; IntAct=EBI-621404, EBI-621428;
CC P15927; Q9UJW9: SERTAD3; NbExp=5; IntAct=EBI-621404, EBI-748621;
CC P15927; Q9NZC9: SMARCAL1; NbExp=14; IntAct=EBI-621404, EBI-5457961;
CC P15927; Q9BVW5: TIPIN; NbExp=4; IntAct=EBI-621404, EBI-2515360;
CC P15927; P13051: UNG; NbExp=6; IntAct=EBI-621404, EBI-1025947;
CC P15927; P23025: XPA; NbExp=8; IntAct=EBI-621404, EBI-295222;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10982866,
CC ECO:0000269|PubMed:12814551, ECO:0000269|PubMed:20154705,
CC ECO:0000269|PubMed:21504906}. Nucleus, PML body
CC {ECO:0000269|PubMed:12814551}. Note=Redistributes to discrete nuclear
CC foci upon DNA damage in an ATR-dependent manner.
CC {ECO:0000269|PubMed:12814551}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P15927-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P15927-2; Sequence=VSP_017201;
CC Name=3;
CC IsoId=P15927-3; Sequence=VSP_017202;
CC -!- INDUCTION: Translationally up-regulated in response to DNA damage (at
CC protein level). {ECO:0000269|PubMed:23393223}.
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:0000269|PubMed:12814551, ECO:0000269|PubMed:1318195,
CC ECO:0000269|PubMed:20154705, ECO:0000269|PubMed:21558276,
CC ECO:0000269|PubMed:21731742, ECO:0000269|PubMed:26474068,
CC ECO:0000269|PubMed:8246944, ECO:0000269|PubMed:9139719,
CC ECO:0000269|PubMed:9295339}.
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 (PubMed:24332808). Ubiquitinated by RFWD3 at
CC stalled replication forks in response to DNA damage: ubiquitination by
CC RFWD3 does not lead to degradation by the proteasome and promotes
CC removal of the RPA complex from stalled replication forks, promoting
CC homologous recombination (PubMed:26474068).
CC {ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:26474068}.
CC -!- SIMILARITY: Belongs to the replication factor A protein 2 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/rpa2/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RPA2ID42146ch1p35.html";
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; J05249; AAA36560.1; -; mRNA.
DR EMBL; CR450348; CAG29344.1; -; mRNA.
DR EMBL; DQ001128; AAX84514.1; -; Genomic_DNA.
DR EMBL; AL109927; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001630; AAH01630.1; -; mRNA.
DR EMBL; BC012157; AAH12157.1; -; mRNA.
DR EMBL; BC021257; AAH21257.1; -; mRNA.
DR CCDS; CCDS314.1; -. [P15927-1]
DR CCDS; CCDS72740.1; -. [P15927-2]
DR PIR; A43711; A43711.
DR RefSeq; NP_001273005.1; NM_001286076.1.
DR RefSeq; NP_001284487.1; NM_001297558.1. [P15927-2]
DR RefSeq; NP_002937.1; NM_002946.4. [P15927-1]
DR PDB; 1DPU; NMR; -; A=172-270.
DR PDB; 1L1O; X-ray; 2.80 A; B/E=44-171.
DR PDB; 1QUQ; X-ray; 2.50 A; A/C=43-171.
DR PDB; 1Z1D; NMR; -; A=172-270.
DR PDB; 2PI2; X-ray; 2.00 A; A/B/C/D=1-270.
DR PDB; 2PQA; X-ray; 2.50 A; A/C=42-172.
DR PDB; 2Z6K; X-ray; 3.00 A; A/B=1-270.
DR PDB; 3KDF; X-ray; 1.98 A; B/D=41-172.
DR PDB; 4MQV; X-ray; 1.95 A; A/C=202-270.
DR PDB; 4OU0; X-ray; 1.40 A; A=202-270.
DR PDBsum; 1DPU; -.
DR PDBsum; 1L1O; -.
DR PDBsum; 1QUQ; -.
DR PDBsum; 1Z1D; -.
DR PDBsum; 2PI2; -.
DR PDBsum; 2PQA; -.
DR PDBsum; 2Z6K; -.
DR PDBsum; 3KDF; -.
DR PDBsum; 4MQV; -.
DR PDBsum; 4OU0; -.
DR AlphaFoldDB; P15927; -.
DR BMRB; P15927; -.
DR SMR; P15927; -.
DR BioGRID; 112038; 568.
DR ComplexPortal; CPX-1878; Replication protein A complex, RPA2 variant.
DR CORUM; P15927; -.
DR DIP; DIP-24187N; -.
DR IntAct; P15927; 113.
DR MINT; P15927; -.
DR STRING; 9606.ENSP00000363017; -.
DR GlyGen; P15927; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P15927; -.
DR MetOSite; P15927; -.
DR PhosphoSitePlus; P15927; -.
DR SwissPalm; P15927; -.
DR BioMuta; RPA2; -.
DR DMDM; 132474; -.
DR EPD; P15927; -.
DR jPOST; P15927; -.
DR MassIVE; P15927; -.
DR MaxQB; P15927; -.
DR PaxDb; P15927; -.
DR PeptideAtlas; P15927; -.
DR PRIDE; P15927; -.
DR ProteomicsDB; 53246; -. [P15927-1]
DR ProteomicsDB; 53247; -. [P15927-2]
DR ProteomicsDB; 53248; -. [P15927-3]
DR Antibodypedia; 4296; 905 antibodies from 43 providers.
DR DNASU; 6118; -.
DR Ensembl; ENST00000313433.11; ENSP00000363015.3; ENSG00000117748.10. [P15927-3]
DR Ensembl; ENST00000373909.7; ENSP00000363017.3; ENSG00000117748.10. [P15927-2]
DR Ensembl; ENST00000373912.8; ENSP00000363021.3; ENSG00000117748.10. [P15927-1]
DR GeneID; 6118; -.
DR KEGG; hsa:6118; -.
DR MANE-Select; ENST00000373912.8; ENSP00000363021.3; NM_002946.5; NP_002937.1.
DR UCSC; uc001bpe.3; human. [P15927-1]
DR CTD; 6118; -.
DR DisGeNET; 6118; -.
DR GeneCards; RPA2; -.
DR HGNC; HGNC:10290; RPA2.
DR HPA; ENSG00000117748; Low tissue specificity.
DR MIM; 179836; gene.
DR neXtProt; NX_P15927; -.
DR OpenTargets; ENSG00000117748; -.
DR PharmGKB; PA34652; -.
DR VEuPathDB; HostDB:ENSG00000117748; -.
DR eggNOG; KOG3108; Eukaryota.
DR GeneTree; ENSGT00390000010045; -.
DR HOGENOM; CLU_051033_1_0_1; -.
DR InParanoid; P15927; -.
DR OMA; TYKIDDG; -.
DR OrthoDB; 924826at2759; -.
DR PhylomeDB; P15927; -.
DR TreeFam; TF105242; -.
DR PathwayCommons; P15927; -.
DR Reactome; R-HSA-110312; Translesion synthesis by REV1.
DR Reactome; R-HSA-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-HSA-110320; Translesion Synthesis by POLH.
DR Reactome; R-HSA-174437; Removal of the Flap Intermediate from the C-strand.
DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-HSA-3371511; HSF1 activation.
DR Reactome; R-HSA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-HSA-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR Reactome; R-HSA-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-HSA-5655862; Translesion synthesis by POLK.
DR Reactome; R-HSA-5656121; Translesion synthesis by POLI.
DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-HSA-5696397; Gap-filling DNA repair synthesis and ligation in GG-NER.
DR Reactome; R-HSA-5696400; Dual Incision in GG-NER.
DR Reactome; R-HSA-6782135; Dual incision in TC-NER.
DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-68962; Activation of the pre-replicative complex.
DR Reactome; R-HSA-69166; Removal of the Flap Intermediate.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-912446; Meiotic recombination.
DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51.
DR SignaLink; P15927; -.
DR SIGNOR; P15927; -.
DR BioGRID-ORCS; 6118; 787 hits in 1089 CRISPR screens.
DR ChiTaRS; RPA2; human.
DR EvolutionaryTrace; P15927; -.
DR GeneWiki; RPA2; -.
DR GenomeRNAi; 6118; -.
DR Pharos; P15927; Tbio.
DR PRO; PR:P15927; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P15927; protein.
DR Bgee; ENSG00000117748; Expressed in ventricular zone and 202 other tissues.
DR ExpressionAtlas; P15927; baseline and differential.
DR Genevisible; P15927; HS.
DR GO; GO:0000785; C:chromatin; IDA:CACAO.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0005662; C:DNA replication factor A complex; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0098505; F:G-rich strand telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0006284; P:base-excision repair; IDA:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IDA:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0006298; P:mismatch repair; IMP:UniProtKB.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; IMP:UniProtKB.
DR GO; GO:0034502; P:protein localization to chromosome; IDA:UniProtKB.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IMP:UniProtKB.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0000723; P:telomere maintenance; IMP:UniProtKB.
DR DisProt; DP01361; -.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR IDEAL; IID00026; -.
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 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW DNA damage; DNA recombination; DNA repair; DNA replication; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..270
FT /note="Replication protein A 32 kDa subunit"
FT /id="PRO_0000097270"
FT DNA_BIND 74..148
FT /note="OB"
FT REGION 21..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:0000269|PubMed:11081631"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:9139719,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:20068231"
FT MOD_RES 4
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:21731742,
FT ECO:0000269|PubMed:26474068"
FT MOD_RES 8
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:21731742,
FT ECO:0000269|PubMed:26474068"
FT MOD_RES 21
FT /note="Phosphothreonine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:21558276,
FT ECO:0000269|PubMed:26474068, ECO:0000269|PubMed:9139719,
FT ECO:0000269|PubMed:9295339"
FT MOD_RES 23
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000269|PubMed:1318195,
FT ECO:0000269|PubMed:8246944, ECO:0000269|PubMed:9295339,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 29
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:1318195,
FT ECO:0000269|PubMed:8246944, ECO:0000269|PubMed:9139719,
FT ECO:0000269|PubMed:9295339, ECO:0007744|PubMed:20068231"
FT MOD_RES 33
FT /note="Phosphoserine; by PRKDC"
FT /evidence="ECO:0000269|PubMed:26474068,
FT ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9295339"
FT CROSSLNK 37
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:26474068"
FT CROSSLNK 38
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:26474068"
FT VAR_SEQ 1..4
FT /note="MWNS -> MGRGDRNKRSIR (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_017201"
FT VAR_SEQ 1..4
FT /note="MWNS -> MWNSNDGGAGWRRKRIAGGFSKRASLGSERRVVAGEEGRERSWG
FT VWGSPAGRRRGRLGRLGQCLKGRSLREPAGFSEAWDVAQALILLFKTG (in
FT isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_017202"
FT VARIANT 14
FT /note="Y -> S (in dbSNP:rs28988896)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_023300"
FT VARIANT 15
FT /note="G -> R (in dbSNP:rs28988897)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_023301"
FT VARIANT 203
FT /note="N -> S (in dbSNP:rs28904899)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_023302"
FT MUTAGEN 4
FT /note="S->A: Increased RAD51 foci formation and homologous
FT recombination efficiency at DNA double-strand breaks; when
FT associated with A-8."
FT /evidence="ECO:0000269|PubMed:21731742"
FT MUTAGEN 8
FT /note="S->A: Increased RAD51 foci formation and homologous
FT recombination efficiency at DNA double-strand breaks; when
FT associated with A-4."
FT /evidence="ECO:0000269|PubMed:20154705,
FT ECO:0000269|PubMed:21731742"
FT MUTAGEN 8
FT /note="S->D: Lower homologous recombination efficiency
FT following DNA double strand break. Impaired DNA synthesis
FT following DNA damage; when associated with D-33. No effect
FT on cell-cycle progression, nor DNA synthesis in undamaged
FT cells; when associated with D-23; D-29 and D-33. Impaired
FT DNA double strand breaks repair; when associated with D-23;
FT D-29 and D-33. Extended DNA damage-induced G2-M checkpoint;
FT when associated with D-23; D-29 and D-33. Preferentially
FT interacts with RAD51; when associated with D-23; D-29 and
FT D-33."
FT /evidence="ECO:0000269|PubMed:20154705,
FT ECO:0000269|PubMed:21731742"
FT MUTAGEN 23
FT /note="S->D: No effect on DNA synthesis following DNA
FT damage; when associated with D-29. No effect on cell-cycle
FT progression, nor DNA synthesis in undamaged cells; when
FT associated with D-8; D-29 and D-33. Impaired DNA double
FT strand breaks repair; when associated with D-8; D-29 and D-
FT 33. Extended DNA damage-induced G2-M checkpoint; when
FT associated with D-8; D-29 and D-33. Preferentially
FT interacts with RAD51; when associated with D-8; D-29 and D-
FT 33."
FT /evidence="ECO:0000269|PubMed:20154705"
FT MUTAGEN 29
FT /note="S->A: Reduces phosphorylation by CDK1."
FT /evidence="ECO:0000269|PubMed:20154705,
FT ECO:0000269|PubMed:9139719"
FT MUTAGEN 29
FT /note="S->D: No effect on DNA synthesis following DNA
FT damage; when associated with D-23. No effect on cell-cycle
FT progression, nor DNA synthesis in undamaged cells; when
FT associated with D-8; D-23 and D-33. Impaired DNA double
FT strand breaks repair; when associated with D-8; D-23 and D-
FT 33. Extended DNA damage-induced G2-M checkpoint; when
FT associated with D-8; D-23 and D-33. Preferentially
FT interacts with RAD51; when associated with D-8; D-23 and D-
FT 33."
FT /evidence="ECO:0000269|PubMed:20154705,
FT ECO:0000269|PubMed:9139719"
FT MUTAGEN 33
FT /note="S->D: Lower homologous recombination efficiency
FT following DNA double strand break. Impaired DNA synthesis
FT following DNA damage; when associated with D-8. No effect
FT on cell-cycle progression, nor DNA synthesis in undamaged
FT cells; when associated with D-8; D-23 and D-29. Impaired
FT DNA double strand breaks repair; when associated with D-8;
FT D-23 and D-29. Extended DNA damage-induced G2-M checkpoint;
FT when associated with D-8; D-23 and D-29. Preferentially
FT interacts with RAD51; when associated with D-8; D-23 and D-
FT 29."
FT /evidence="ECO:0000269|PubMed:20154705"
FT MUTAGEN 37..38
FT /note="KK->RR: Impaired ubiquitination without affecting
FT homologous recombination."
FT /evidence="ECO:0000269|PubMed:26474068"
FT MUTAGEN 248
FT /note="F->A: Abolishes interaction with RFWD3, leading to
FT impair DNA interstrand cross-links (ICL) repair."
FT /evidence="ECO:0000269|PubMed:28575657"
FT MUTAGEN 252
FT /note="E->A: Abolishes interaction with RFWD3, leading to
FT impair DNA interstrand cross-links (ICL) repair."
FT /evidence="ECO:0000269|PubMed:28575657"
FT MUTAGEN 253
FT /note="G->A: Does not affect interaction with RFWD3."
FT /evidence="ECO:0000269|PubMed:28575657"
FT MUTAGEN 254
FT /note="H->A: Abolishes interaction with RFWD3, leading to
FT impair DNA interstrand cross-links (ICL) repair."
FT /evidence="ECO:0000269|PubMed:28575657"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:1L1O"
FT HELIX 51..55
FT /evidence="ECO:0007829|PDB:3KDF"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:3KDF"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:3KDF"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:1QUQ"
FT STRAND 73..85
FT /evidence="ECO:0007829|PDB:3KDF"
FT STRAND 87..95
FT /evidence="ECO:0007829|PDB:3KDF"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:3KDF"
FT STRAND 102..107
FT /evidence="ECO:0007829|PDB:3KDF"
FT STRAND 125..135
FT /evidence="ECO:0007829|PDB:3KDF"
FT STRAND 138..148
FT /evidence="ECO:0007829|PDB:3KDF"
FT HELIX 153..171
FT /evidence="ECO:0007829|PDB:3KDF"
FT HELIX 207..218
FT /evidence="ECO:0007829|PDB:4OU0"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:1DPU"
FT HELIX 227..233
FT /evidence="ECO:0007829|PDB:4OU0"
FT HELIX 239..252
FT /evidence="ECO:0007829|PDB:4OU0"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:4OU0"
FT STRAND 263..266
FT /evidence="ECO:0007829|PDB:4OU0"
SQ SEQUENCE 270 AA; 29247 MW; 61A563EA7B34A9B1 CRC64;
MWNSGFESYG SSSYGGAGGY TQSPGGFGSP APSQAEKKSR ARAQHIVPCT ISQLLSATLV
DEVFRIGNVE ISQVTIVGII RHAEKAPTNI VYKIDDMTAA PMDVRQWVDT DDTSSENTVV
PPETYVKVAG HLRSFQNKKS LVAFKIMPLE DMNEFTTHIL EVINAHMVLS KANSQPSAGR
APISNPGMSE AGNFGGNSFM PANGLTVAQN QVLNLIKACP RPEGLNFQDL KNQLKHMSVS
SIKQAVDFLS NEGHIYSTVD DDHFKSTDAE
