ID TOPB1_HUMAN Reviewed; 1522 AA.
AC Q92547; B7Z7W8; Q7LGC1; Q9UEB9;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 27-MAR-2024, entry version 205.
DE RecName: Full=DNA topoisomerase 2-binding protein 1 {ECO:0000305};
DE AltName: Full=DNA topoisomerase II-beta-binding protein 1 {ECO:0000303|PubMed:9461304};
DE Short=TopBP1 {ECO:0000303|PubMed:9461304};
DE AltName: Full=DNA topoisomerase II-binding protein 1 {ECO:0000303|PubMed:9461304};
GN Name=TOPBP1 {ECO:0000303|PubMed:9461304, ECO:0000312|HGNC:HGNC:17008};
GN Synonyms=KIAA0259 {ECO:0000303|PubMed:9039502};
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], INTERACTION WITH TOP2B, AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=9461304; DOI=10.1111/j.1432-1033.1997.00794.x;
RA Yamane K., Kawabata M., Tsuruo T.;
RT "A DNA topoisomerase II binding protein with eight repeating regions
RT similar to DNA repair enzymes and to a cell cycle regulator.";
RL Eur. J. Biochem. 250:794-799(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10498869; DOI=10.1038/sj.onc.1202922;
RA Yamane K., Tsuruo T.;
RT "Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind
RT strand breaks and termini of DNA.";
RL Oncogene 18:5194-5203(1999).
RN [6]
RP FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND INTERACTION WITH POLE
RP AND RAD9A.
RX PubMed=11395493; DOI=10.1074/jbc.m102245200;
RA Maekiniemi M., Hillukkala T., Tuusa J., Reini K., Vaara M., Huang D.,
RA Pospiech H., Majuri I., Westerling T., Maekelae T.P., Syvaeoja J.E.;
RT "BRCT domain-containing protein TopBP1 functions in DNA replication and
RT damage response.";
RL J. Biol. Chem. 276:30399-30406(2001).
RN [7]
RP FUNCTION, PHOSPHORYLATION, INTERACTION WITH UBR5, UBIQUITINATION,
RP PROTEASOME-MEDIATED DEGRADATION, AND SUBCELLULAR LOCATION.
RX PubMed=11714696; DOI=10.1074/jbc.m104347200;
RA Honda Y., Tojo M., Matsuzaki K., Anan T., Matsumoto M., Ando M., Saya H.,
RA Nakao M.;
RT "Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-
RT binding protein for DNA damage response.";
RL J. Biol. Chem. 277:3599-3605(2002).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH E2F1.
RX PubMed=12697828; DOI=10.1128/mcb.23.9.3287-3304.2003;
RA Liu K., Lin F.-T., Ruppert J.M., Lin W.-C.;
RT "Regulation of E2F1 by BRCT domain-containing protein TopBP1.";
RL Mol. Cell. Biol. 23:3287-3304(2003).
RN [9]
RP INDUCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PML.
RX PubMed=12773567; DOI=10.1128/mcb.23.12.4247-4256.2003;
RA Xu Z.-X., Timanova-Atanasova A., Zhao R.-X., Chang K.-S.;
RT "PML colocalizes with and stabilizes the DNA damage response protein
RT TopBP1.";
RL Mol. Cell. Biol. 23:4247-4256(2003).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=15138768; DOI=10.1007/s00412-004-0277-5;
RA Reini K., Uitto L., Perera D., Moens P.B., Freire R., Syvaeoja J.E.;
RT "TopBP1 localises to centrosomes in mitosis and to chromosome cores in
RT meiosis.";
RL Chromosoma 112:323-330(2004).
RN [11]
RP FUNCTION, AND INTERACTION WITH E2F1; SMARCA2; SMARCA4 AND THE SWI/SNF
RP CHROMATIN REMODELING COMPLEX.
RX PubMed=15075294; DOI=10.1101/gad.1180204;
RA Liu K., Luo Y., Lin F.-T., Lin W.-C.;
RT "TopBP1 recruits Brg1/Brm to repress E2F1-induced apoptosis, a novel pRb-
RT independent and E2F1-specific control for cell survival.";
RL Genes Dev. 18:673-686(2004).
RN [12]
RP FUNCTION.
RX PubMed=16530042; DOI=10.1016/j.cell.2005.12.041;
RA Kumagai A., Lee J., Yoo H.Y., Dunphy W.G.;
RT "TopBP1 activates the ATR-ATRIP complex.";
RL Cell 124:943-955(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-888, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [14]
RP FUNCTION, INTERACTION WITH RAD9A, AND DOMAIN.
RX PubMed=17575048; DOI=10.1101/gad.1547007;
RA Delacroix S., Wagner J.M., Kobayashi M., Yamamoto K., Karnitz L.M.;
RT "The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via
RT TopBP1.";
RL Genes Dev. 21:1472-1477(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-779; THR-848; SER-888 AND
RP SER-1002, AND 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-888, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP FUNCTION, AND INTERACTION WITH RAD9A.
RX PubMed=20545769; DOI=10.1111/j.1365-2443.2010.01418.x;
RA Takeishi Y., Ohashi E., Ogawa K., Masai H., Obuse C., Tsurimoto T.;
RT "Casein kinase 2-dependent phosphorylation of human Rad9 mediates the
RT interaction between human Rad9-Hus1-Rad1 complex and TopBP1.";
RL Genes Cells 15:761-771(2010).
RN [19]
RP INTERACTION WITH TICRR.
RX PubMed=20080954; DOI=10.1101/gad.1860310;
RA Sansam C.L., Cruz N.M., Danielian P.S., Amsterdam A., Lau M.L., Hopkins N.,
RA Lees J.A.;
RT "A vertebrate gene, ticrr, is an essential checkpoint and replication
RT regulator.";
RL Genes Dev. 24:183-194(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-886 AND SER-888, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [21]
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 [22]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MDC1.
RX PubMed=21482717; DOI=10.1083/jcb.201010026;
RA Wang J., Gong Z., Chen J.;
RT "MDC1 collaborates with TopBP1 in DNA replication checkpoint control.";
RL J. Cell Biol. 193:267-273(2011).
RN [23]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ATR, PHOSPHORYLATION AT
RP THR-1062, AND MUTAGENESIS OF SER-1273; ARG-1280 AND LYS-1317.
RX PubMed=21777809; DOI=10.1016/j.molcel.2011.06.019;
RA Liu S., Shiotani B., Lahiri M., Marechal A., Tse A., Leung C.C.,
RA Glover J.N., Yang X.H., Zou L.;
RT "ATR autophosphorylation as a molecular switch for checkpoint activation.";
RL Mol. Cell 43:192-202(2011).
RN [24]
RP SUBCELLULAR LOCATION, INTERACTION WITH RHNO1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=21659603; DOI=10.1126/science.1203430;
RA Cotta-Ramusino C., McDonald E.R. III, Hurov K., Sowa M.E., Harper J.W.,
RA Elledge S.J.;
RT "A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1
RT interacting protein required for ATR signaling.";
RL Science 332:1313-1317(2011).
RN [25]
RP INTERACTION WITH RECQ4.
RX PubMed=22730300; DOI=10.1093/nar/gks591;
RA Ohlenschlager O., Kuhnert A., Schneider A., Haumann S., Bellstedt P.,
RA Keller H., Saluz H.P., Hortschansky P., Hanel F., Grosse F., Gorlach M.,
RA Pospiech H.;
RT "The N-terminus of the human RecQL4 helicase is a homeodomain-like DNA
RT interaction motif.";
RL Nucleic Acids Res. 40:8309-8324(2012).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-298; THR-779; SER-860;
RP THR-861; SER-864; SER-888; THR-1064 AND SER-1504, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [27]
RP INTERACTION WITH RHNO1.
RX PubMed=25602520; DOI=10.4161/15384101.2014.967076;
RA Lindsey-Boltz L.A., Kemp M.G., Capp C., Sancar A.;
RT "RHINO forms a stoichiometric complex with the 9-1-1 checkpoint clamp and
RT mediates ATR-Chk1 signaling.";
RL Cell Cycle 14:99-108(2015).
RN [28]
RP INTERACTION WITH HELB.
RX PubMed=25933514; DOI=10.1016/j.yexcr.2015.04.014;
RA Gerhardt J., Guler G.D., Fanning E.;
RT "Human DNA helicase B interacts with the replication initiation protein
RT Cdc45 and facilitates Cdc45 binding onto chromatin.";
RL Exp. Cell Res. 334:283-293(2015).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RAD51.
RX PubMed=26811421; DOI=10.1083/jcb.201507042;
RA Moudry P., Watanabe K., Wolanin K.M., Bartkova J., Wassing I.E.,
RA Watanabe S., Strauss R., Troelsgaard Pedersen R., Oestergaard V.H.,
RA Lisby M., Andujar-Sanchez M., Maya-Mendoza A., Esashi F., Lukas J.,
RA Bartek J.;
RT "TOPBP1 regulates RAD51 phosphorylation and chromatin loading and
RT determines PARP inhibitor sensitivity.";
RL J. Cell Biol. 212:281-288(2016).
RN [30]
RP FUNCTION, INTERACTION WITH MDC1, SUBCELLULAR LOCATION, DOMAIN, AND
RP MUTAGENESIS OF LYS-155.
RX PubMed=30898438; DOI=10.1016/j.molcel.2019.02.014;
RA Leimbacher P.A., Jones S.E., Shorrocks A.K., de Marco Zompit M., Day M.,
RA Blaauwendraad J., Bundschuh D., Bonham S., Fischer R., Fink D.,
RA Kessler B.M., Oliver A.W., Pearl L.H., Blackford A.N., Stucki M.;
RT "MDC1 interacts with TOPBP1 to maintain chromosomal stability during
RT mitosis.";
RL Mol. Cell 74:571-583(2019).
RN [31]
RP FUNCTION, AND DEUBIQUITINATION BY USP13.
RX PubMed=33592542; DOI=10.1016/j.dnarep.2021.103063;
RA Kim W., Zhao F., Gao H., Qin S., Hou J., Deng M., Kloeber J.A., Huang J.,
RA Zhou Q., Guo G., Gao M., Zeng X., Zhu S., Tu X., Wu Z., Zhang Y., Yin P.,
RA Kaufmann S.H., Luo K., Lou Z.;
RT "USP13 regulates the replication stress response by deubiquitinating
RT TopBP1.";
RL DNA Repair 100:103063-103063(2021).
RN [32]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CIP2A, AND MUTAGENESIS OF
RP 837-PHE--VAL-839.
RX PubMed=35121901; DOI=10.1038/s43018-021-00266-w;
RA Adam S., Rossi S.E., Moatti N., De Marco Zompit M., Xue Y., Ng T.F.,
RA Alvarez-Quilon A., Desjardins J., Bhaskaran V., Martino G., Setiaputra D.,
RA Noordermeer S.M., Ohsumi T.K., Hustedt N., Szilard R.K., Chaudhary N.,
RA Munro M., Veloso A., Melo H., Yin S.Y., Papp R., Young J.T.F., Zinda M.,
RA Stucki M., Durocher D.;
RT "The CIP2A-TOPBP1 axis safeguards chromosome stability and is a synthetic
RT lethal target for BRCA-mutated cancer.";
RL Nat. Cancer 2:1357-1371(2021).
RN [33]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CIP2A.
RX PubMed=35842428; DOI=10.1038/s41467-022-31865-5;
RA De Marco Zompit M., Esteban M.T., Mooser C., Adam S., Rossi S.E.,
RA Jeanrenaud A., Leimbacher P.A., Fink D., Shorrocks A.K., Blackford A.N.,
RA Durocher D., Stucki M.;
RT "The CIP2A-TOPBP1 complex safeguards chromosomal stability during
RT mitosis.";
RL Nat. Commun. 13:4143-4143(2022).
RN [34]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HTATSF1, AND MUTAGENESIS
RP OF LYS-250; LYS-704 AND LYS-1317.
RX PubMed=35597237; DOI=10.1016/j.molcel.2022.04.031;
RA Zhao J., Tian S., Guo Q., Bao K., Yu G., Wang X., Shen X., Zhang J.,
RA Chen J., Yang Y., Liu L., Li X., Hao J., Yang N., Liu Z., Ai D., Yang J.,
RA Zhu Y., Yao Z., Ma S., Zhang K., Shi L.;
RT "A PARylation-phosphorylation cascade promotes TOPBP1 loading and RPA-RAD51
RT exchange in homologous recombination.";
RL Mol. Cell 82:2571-2587(2022).
RN [35]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CIP2A.
RX PubMed=37165191; DOI=10.1038/s41586-023-05974-0;
RA Lin Y.F., Hu Q., Mazzagatti A., Valle-Inclan J.E., Maurais E.G., Dahiya R.,
RA Guyer A., Sanders J.T., Engel J.L., Nguyen G., Bronder D., Bakhoum S.F.,
RA Cortes-Ciriano I., Ly P.;
RT "Mitotic clustering of pulverized chromosomes from micronuclei.";
RL Nature 618:1041-1048(2023).
RN [36]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CIP2A.
RX PubMed=37316668; DOI=10.1038/s41586-023-06216-z;
RA Trivedi P., Steele C.D., Au F.K.C., Alexandrov L.B., Cleveland D.W.;
RT "Mitotic tethering enables inheritance of shattered micronuclear
RT chromosomes.";
RL Nature 618:1049-1056(2023).
RN [37]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH POLQ, AND DOMAIN.
RX PubMed=37674080; DOI=10.1038/s41586-023-06506-6;
RA Gelot C., Kovacs M.T., Miron S., Mylne E., Haan A., Boeffard-Dosierre L.,
RA Ghouil R., Popova T., Dingli F., Loew D., Guirouilh-Barbat J., Del Nery E.,
RA Zinn-Justin S., Ceccaldi R.;
RT "Poltheta is phosphorylated by PLK1 to repair double-strand breaks in
RT mitosis.";
RL Nature 621:415-422(2023).
RN [38]
RP STRUCTURE BY NMR OF 327-444.
RG RIKEN structural genomics initiative (RSGI);
RT "The third BRCA1 C-terminus (BRCT) domain of topoisomerase II binding
RT protein.";
RL Submitted (NOV-2004) to the PDB data bank.
RN [39]
RP X-RAY CRYSTALLOGRAPHY (1.34 ANGSTROMS) OF 893-996.
RX PubMed=19937654; DOI=10.1002/pro.290;
RA Leung C.C., Kellogg E., Kuhnert A., Hanel F., Baker D., Glover J.N.;
RT "Insights from the crystal structure of the sixth BRCT domain of
RT topoisomerase IIbeta binding protein 1.";
RL Protein Sci. 19:162-167(2010).
RN [40] {ECO:0007744|PDB:3UEN, ECO:0007744|PDB:3UEO}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 549-746 IN COMPLEX WITH MDC1, AND
RP MUTAGENESIS OF SER-564; 681-ARG-LYS-682 AND LYS-704.
RX PubMed=23891287; DOI=10.1016/j.str.2013.06.015;
RA Leung C.C., Sun L., Gong Z., Burkat M., Edwards R., Assmus M., Chen J.,
RA Glover J.N.;
RT "Structural insights into recognition of MDC1 by TopBP1 in DNA replication
RT checkpoint control.";
RL Structure 21:1450-1459(2013).
RN [41] {ECO:0007744|PDB:6RML, ECO:0007744|PDB:6RMM}
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 1-290 IN COMPLEX WITH TP53BP1,
RP FUNCTION, DOMAIN, AND MUTAGENESIS OF LYS-155 AND LYS-250.
RX PubMed=31135337; DOI=10.7554/elife.44353;
RA Bigot N., Day M., Baldock R.A., Watts F.Z., Oliver A.W., Pearl L.H.;
RT "Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1
RT to control the G1 DNA damage checkpoint.";
RL Elife 8:e44353-e44353(2019).
CC -!- FUNCTION: Scaffold protein that acts as a key protein-protein adapter
CC in DNA replication and DNA repair (PubMed:10498869, PubMed:11395493,
CC PubMed:11714696, PubMed:17575048, PubMed:20545769, PubMed:21777809,
CC PubMed:26811421, PubMed:30898438, PubMed:33592542, PubMed:35597237,
CC PubMed:37674080, PubMed:31135337). Composed of multiple BRCT domains,
CC which specifically recognize and bind phosphorylated proteins, bringing
CC proteins together into functional combinations (PubMed:17575048,
CC PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438,
CC PubMed:35597237, PubMed:37674080, PubMed:31135337). Required for DNA
CC replication initiation but not for the formation of pre-replicative
CC complexes or the elongation stages (By similarity). Necessary for the
CC loading of replication factors onto chromatin, including GMNC, CDC45,
CC DNA polymerases and components of the GINS complex (By similarity).
CC Plays a central role in DNA repair by bridging proteins and promoting
CC recruitment of proteins to DNA damage sites (PubMed:30898438,
CC PubMed:35597237, PubMed:37674080). Involved in double-strand break
CC (DSB) repair via homologous recombination in S-phase by promoting the
CC exchange between the DNA replication factor A (RPA) complex and RAD51
CC (PubMed:26811421, PubMed:35597237). Mechanistically, TOPBP1 is
CC recruited to DNA damage sites in S-phase via interaction with
CC phosphorylated HTATSF1, and promotes the loading of RAD51, thereby
CC facilitating RAD51 nucleofilaments formation and RPA displacement,
CC followed by homologous recombination (PubMed:35597237). Involved in
CC microhomology-mediated end-joining (MMEJ) DNA repair by promoting
CC recruitment of polymerase theta (POLQ) to DNA damage sites during
CC mitosis (PubMed:37674080). MMEJ is an alternative non-homologous end-
CC joining (NHEJ) machinery that takes place during mitosis to repair DSBs
CC in DNA that originate in S-phase (PubMed:37674080). Recognizes and
CC binds POLQ phosphorylated by PLK1, enabling its recruitment to DSBs for
CC subsequent repair (PubMed:37674080). Involved in G1 DNA damage
CC checkpoint by acting as a molecular adapter that couples TP53BP1 and
CC the 9-1-1 complex (PubMed:31135337). In response to DNA damage,
CC triggers the recruitment of checkpoint signaling proteins on chromatin,
CC which activate the CHEK1 signaling pathway and block S-phase
CC progression (PubMed:16530042, PubMed:21777809). Acts as an activator of
CC the kinase activity of ATR (PubMed:16530042, PubMed:21777809). Also
CC required for chromosomal stability when DSBs occur during mitosis by
CC forming filamentous assemblies that bridge MDC1 and tether broken
CC chromosomes during mitosis (PubMed:30898438). Together with CIP2A,
CC plays an essential role in the response to genome instability generated
CC by the presence of acentric chromosome fragments derived from shattered
CC chromosomes within micronuclei (PubMed:35121901, PubMed:35842428,
CC PubMed:37165191, PubMed:37316668). Micronuclei, which are frequently
CC found in cancer cells, consist of chromatin surrounded by their own
CC nuclear membrane: following breakdown of the micronuclear envelope, a
CC process associated with chromothripsis, the CIP2A-TOPBP1 complex
CC tethers chromosome fragments during mitosis to ensure clustered
CC segregation of the fragments to a single daughter cell nucleus,
CC facilitating re-ligation with limited chromosome scattering and loss
CC (PubMed:37165191, PubMed:37316668). Recruits the SWI/SNF chromatin
CC remodeling complex to E2F1-responsive promoters, thereby down-
CC regulating E2F1 activity and inhibiting E2F1-dependent apoptosis during
CC G1/S transition and after DNA damage (PubMed:12697828,
CC PubMed:15075294). {ECO:0000250|UniProtKB:Q800K6,
CC ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493,
CC ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:12697828,
CC ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:16530042,
CC ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769,
CC ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:26811421,
CC ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31135337,
CC ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:35121901,
CC ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428,
CC ECO:0000269|PubMed:37165191, ECO:0000269|PubMed:37316668,
CC ECO:0000269|PubMed:37674080}.
CC -!- SUBUNIT: Interacts (via BRCT domains 1 and 2) with (phosphorylated)
CC MDC1; promoting TOPBP1 recruitment to DNA damage sites during mitosis
CC (PubMed:21482717, PubMed:30898438, PubMed:23891287). Interacts (via
CC BRCT domains 7 and 8) with (autophosphorylated) ATR; promoting
CC activation of ATR (PubMed:21777809). Interacts (via BRCT domains 7 and
CC 8) with (phosphorylated) POLQ; specifically binds POLQ phosphorylated
CC by PLK1, promoting POLQ recruitment to DNA damage sites
CC (PubMed:37674080). Interacts (via BRCT domains 1 and 2) with
CC (phosphorylated) RAD9A (PubMed:11395493, PubMed:17575048,
CC PubMed:20545769). Interacts (via BRCT domain 2) with (phosphorylated)
CC TP53BP1 (PubMed:31135337). Interacts (via BRCT domain 2) with
CC (phosphorylated) HTATSF1 (PubMed:35597237). Interacts (via BRCT domains
CC 7 and 8) with (phosphorylated) RAD51; promoting RAD51 recruitment to
CC damaged chromatin (PubMed:26811421). Interacts with CIP2A; forming the
CC CIP2A-TOPBP1 complex (PubMed:35121901, PubMed:35842428,
CC PubMed:37165191, PubMed:37316668). Interacts with POLE
CC (PubMed:11395493). Interacts with UBR5 (PubMed:11714696). Interacts
CC with E2F1 (PubMed:12697828, PubMed:15075294). Interacts with PML
CC (PubMed:12773567). Interacts with SMARCA2 (PubMed:15075294). Interacts
CC with SMARCA4 (PubMed:15075294). Interacts with RHNO1 (PubMed:21659603,
CC PubMed:25602520). May interact with TOP2B (PubMed:9461304). Interacts
CC with TICRR (PubMed:20080954). Interacts with HELB (PubMed:25933514).
CC Interacts (via residues 1233-1522) with RECQL4 (PubMed:22730300).
CC {ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696,
CC ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:12773567,
CC ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:17575048,
CC ECO:0000269|PubMed:20080954, ECO:0000269|PubMed:20545769,
CC ECO:0000269|PubMed:21482717, ECO:0000269|PubMed:21659603,
CC ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:22730300,
CC ECO:0000269|PubMed:23891287, ECO:0000269|PubMed:25602520,
CC ECO:0000269|PubMed:25933514, ECO:0000269|PubMed:26811421,
CC ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31135337,
CC ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237,
CC ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37165191,
CC ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080,
CC ECO:0000269|PubMed:9461304}.
CC -!- INTERACTION:
CC Q92547; P31749: AKT1; NbExp=2; IntAct=EBI-308302, EBI-296087;
CC Q92547; O75419: CDC45; NbExp=6; IntAct=EBI-308302, EBI-374969;
CC Q92547; Q01094: E2F1; NbExp=3; IntAct=EBI-308302, EBI-448924;
CC Q92547; Q9UGU0: TCF20; NbExp=8; IntAct=EBI-308302, EBI-3444158;
CC Q92547; Q92547: TOPBP1; NbExp=5; IntAct=EBI-308302, EBI-308302;
CC Q92547; Q13105: ZBTB17; NbExp=2; IntAct=EBI-308302, EBI-372156;
CC Q92547; P03120: E2; Xeno; NbExp=2; IntAct=EBI-308302, EBI-1779322;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11395493,
CC ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:12773567}. Chromosome
CC {ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493,
CC ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:15138768,
CC ECO:0000269|PubMed:21482717, ECO:0000269|PubMed:21659603,
CC ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:26811421,
CC ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:35121901,
CC ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428,
CC ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:15138768}. Cytoplasm, cytoskeleton, spindle pole
CC {ECO:0000269|PubMed:15138768}. Note=Localizes to sites of DNA damage,
CC such as double-stranded breaks (DSBs) (PubMed:10498869,
CC PubMed:21482717, PubMed:21659603, PubMed:30898438, PubMed:35842428,
CC PubMed:37674080, PubMed:21777809). Recruited to DNA double-strand break
CC (DSBs) during S-phase following interaction with phosphorylated HTATSF1
CC (PubMed:35597237). Recruited to DSBs during mitosis following
CC interaction with phosphorylated MDC1 (PubMed:30898438). Has a uniform
CC nuclear distribution during G phase (PubMed:11395493). Colocalizes with
CC BRCA1 at stalled replication forks during S phase (PubMed:11395493). In
CC mitotic cells it colocalizes with BRCA1 at spindle poles and
CC centrosomes during metaphase and anaphase (PubMed:11395493). Detected
CC in discrete foci together with PML and numerous DNA repair enzymes
CC after DNA damage by alkylating agents, UV or gamma irradiation
CC (PubMed:12773567). Detected on unpaired autosomes in meiotic prophase
CC cells (By similarity). Detected on X and Y chromosomes during later
CC stages of prophase (By similarity). Colocalizes with ATR and H2AX at
CC unsynapsed chromosome cores during prophase (By similarity). Localizes
CC to broken chromosomes within micronuclei during interphase and
CC following chromothripsis (PubMed:37165191, PubMed:37316668).
CC Localization to broken chromosomes is mainly independent of MDC1
CC (PubMed:35121901, PubMed:37165191). {ECO:0000250|UniProtKB:Q6ZQF0,
CC ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493,
CC ECO:0000269|PubMed:12773567, ECO:0000269|PubMed:21482717,
CC ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21777809,
CC ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:35121901,
CC ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428,
CC ECO:0000269|PubMed:37165191, ECO:0000269|PubMed:37316668,
CC ECO:0000269|PubMed:37674080}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, brain, placenta, lung
CC and kidney. {ECO:0000269|PubMed:9461304}.
CC -!- INDUCTION: Up-regulated during the S phase of the cell cycle. Up-
CC regulated by E2F1 and interferon. {ECO:0000269|PubMed:12773567}.
CC -!- DOMAIN: Some BRCT domains specifically recognize and bind
CC phosphoserine/phosphothreonine marks on proteins (PubMed:17575048,
CC PubMed:20545769, PubMed:21777809, PubMed:30898438, PubMed:35597237,
CC PubMed:37674080, PubMed:23891287, PubMed:31135337). BRCT domains 1 and
CC 2 bind phosphorylated MDC1 and RAD9A (PubMed:17575048, PubMed:20545769,
CC PubMed:30898438). BRCT domain 2 binds phosphorylated HTATSF1 and
CC TP53BP1 (PubMed:35597237, PubMed:31135337). BRCT domains 7 and 8 bind
CC phosphorylated ATR, POLQ and RAD51 (PubMed:21777809, PubMed:37674080,
CC PubMed:26811421). {ECO:0000269|PubMed:17575048,
CC ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21777809,
CC ECO:0000269|PubMed:23891287, ECO:0000269|PubMed:26811421,
CC ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31135337,
CC ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:37674080}.
CC -!- PTM: Phosphorylated on serine and threonine residues in response to X-
CC ray irradiation. {ECO:0000269|PubMed:11395493,
CC ECO:0000269|PubMed:11714696}.
CC -!- PTM: Ubiquitinated and degraded by the proteasome. X-ray irradiation
CC reduces ubiquitination (PubMed:11714696). Deubiquitinated by USP13;
CC leading to TOPBP1 stabilizion and activation of the ATR-TOPBP1 axis
CC pathway (PubMed:33592542). {ECO:0000269|PubMed:11714696,
CC ECO:0000269|PubMed:33592542}.
CC -!- SIMILARITY: Belongs to the TOPBP1 family. {ECO:0000305}.
CC -!- CAUTION: Interaction with phosphorylated MDC1 was initially thought to
CC be mediated by BRCT domains 4 and 5 (PubMed:23891287). However, it was
CC later shown to be mainly mediated by BRCT domains 1 and 2
CC (PubMed:30898438). {ECO:0000269|PubMed:23891287,
CC ECO:0000269|PubMed:30898438}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA13389.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA34202.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AB019397; BAA34202.1; ALT_INIT; mRNA.
DR EMBL; D87448; BAA13389.1; ALT_INIT; mRNA.
DR EMBL; AK302584; BAH13754.1; -; mRNA.
DR EMBL; AC016255; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC083905; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS46919.1; -.
DR RefSeq; NP_008958.2; NM_007027.3.
DR RefSeq; XP_016861125.1; XM_017005636.1.
DR PDB; 1WF6; NMR; -; A=326-444.
DR PDB; 2XNH; X-ray; 2.80 A; A=1-287.
DR PDB; 2XNK; X-ray; 2.60 A; A/B/C/D=1-290.
DR PDB; 3AL2; X-ray; 2.00 A; A=1264-1493.
DR PDB; 3AL3; X-ray; 2.15 A; A=1264-1493.
DR PDB; 3JVE; X-ray; 1.34 A; A=893-996.
DR PDB; 3OLC; X-ray; 2.40 A; X=1-290.
DR PDB; 3PD7; X-ray; 1.26 A; A/B=893-994.
DR PDB; 3UEN; X-ray; 1.90 A; A=549-746.
DR PDB; 3UEO; X-ray; 2.60 A; A/B/C/D=549-746.
DR PDB; 6RML; X-ray; 2.81 A; A/B=1-290.
DR PDB; 6RMM; X-ray; 3.53 A; A/B/C/D=548-741.
DR PDB; 7CMZ; X-ray; 1.70 A; A=1264-1493.
DR PDBsum; 1WF6; -.
DR PDBsum; 2XNH; -.
DR PDBsum; 2XNK; -.
DR PDBsum; 3AL2; -.
DR PDBsum; 3AL3; -.
DR PDBsum; 3JVE; -.
DR PDBsum; 3OLC; -.
DR PDBsum; 3PD7; -.
DR PDBsum; 3UEN; -.
DR PDBsum; 3UEO; -.
DR PDBsum; 6RML; -.
DR PDBsum; 6RMM; -.
DR PDBsum; 7CMZ; -.
DR AlphaFoldDB; Q92547; -.
DR SMR; Q92547; -.
DR BioGRID; 116256; 112.
DR ComplexPortal; CPX-4426; BRCA1-B complex.
DR CORUM; Q92547; -.
DR DIP; DIP-24263N; -.
DR IntAct; Q92547; 34.
DR MINT; Q92547; -.
DR STRING; 9606.ENSP00000260810; -.
DR BindingDB; Q92547; -.
DR ChEMBL; CHEMBL3175; -.
DR GlyGen; Q92547; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q92547; -.
DR PhosphoSitePlus; Q92547; -.
DR BioMuta; TOPBP1; -.
DR DMDM; 296453012; -.
DR CPTAC; CPTAC-3258; -.
DR CPTAC; CPTAC-3290; -.
DR CPTAC; CPTAC-3291; -.
DR CPTAC; CPTAC-950; -.
DR EPD; Q92547; -.
DR jPOST; Q92547; -.
DR MassIVE; Q92547; -.
DR MaxQB; Q92547; -.
DR PaxDb; 9606-ENSP00000260810; -.
DR PeptideAtlas; Q92547; -.
DR ProteomicsDB; 75308; -.
DR Pumba; Q92547; -.
DR Antibodypedia; 8745; 357 antibodies from 32 providers.
DR DNASU; 11073; -.
DR Ensembl; ENST00000260810.10; ENSP00000260810.5; ENSG00000163781.14.
DR GeneID; 11073; -.
DR KEGG; hsa:11073; -.
DR MANE-Select; ENST00000260810.10; ENSP00000260810.5; NM_007027.4; NP_008958.2.
DR UCSC; uc003eps.4; human.
DR AGR; HGNC:17008; -.
DR CTD; 11073; -.
DR DisGeNET; 11073; -.
DR GeneCards; TOPBP1; -.
DR HGNC; HGNC:17008; TOPBP1.
DR HPA; ENSG00000163781; Low tissue specificity.
DR MIM; 607760; gene.
DR neXtProt; NX_Q92547; -.
DR OpenTargets; ENSG00000163781; -.
DR PharmGKB; PA134934073; -.
DR VEuPathDB; HostDB:ENSG00000163781; -.
DR eggNOG; KOG1929; Eukaryota.
DR GeneTree; ENSGT00940000157001; -.
DR HOGENOM; CLU_004165_1_0_1; -.
DR InParanoid; Q92547; -.
DR OMA; NVHCLKT; -.
DR OrthoDB; 449768at2759; -.
DR PhylomeDB; Q92547; -.
DR TreeFam; TF326403; -.
DR PathwayCommons; Q92547; -.
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
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-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51.
DR SignaLink; Q92547; -.
DR SIGNOR; Q92547; -.
DR BioGRID-ORCS; 11073; 764 hits in 1170 CRISPR screens.
DR ChiTaRS; TOPBP1; human.
DR EvolutionaryTrace; Q92547; -.
DR GeneWiki; TOPBP1; -.
DR GenomeRNAi; 11073; -.
DR Pharos; Q92547; Tbio.
DR PRO; PR:Q92547; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q92547; Protein.
DR Bgee; ENSG00000163781; Expressed in sperm and 204 other cell types or tissues.
DR ExpressionAtlas; Q92547; baseline and differential.
DR Genevisible; Q92547; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0070532; C:BRCA1-B complex; IPI:ComplexPortal.
DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005694; C:chromosome; IDA:UniProtKB.
DR GO; GO:0000794; C:condensed nuclear chromosome; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0090734; C:site of DNA damage; IDA:UniProt.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0140463; F:chromatin-protein adaptor activity; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0140031; F:phosphorylation-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:UniProtKB.
DR GO; GO:0051276; P:chromosome organization; IDA:UniProtKB.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB.
DR GO; GO:0006259; P:DNA metabolic process; TAS:ProtInc.
DR GO; GO:0006281; P:DNA repair; NAS:UniProtKB.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0006270; P:DNA replication initiation; IBA:GO_Central.
DR GO; GO:0097681; P:double-strand break repair via alternative nonhomologous end joining; IDA:UniProtKB.
DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; IDA:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0035825; P:homologous recombination; NAS:ComplexPortal.
DR GO; GO:0033314; P:mitotic DNA replication checkpoint signaling; IBA:GO_Central.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:1990166; P:protein localization to site of double-strand break; IDA:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
DR CDD; cd17737; BRCT_TopBP1_rpt1; 1.
DR CDD; cd17731; BRCT_TopBP1_rpt2_like; 1.
DR CDD; cd17718; BRCT_TopBP1_rpt3; 1.
DR CDD; cd17749; BRCT_TopBP1_rpt4; 1.
DR CDD; cd18434; BRCT_TopBP1_rpt5; 1.
DR CDD; cd17727; BRCT_TopBP1_rpt6; 1.
DR CDD; cd17738; BRCT_TopBP1_rpt7; 1.
DR CDD; cd17728; BRCT_TopBP1_rpt8; 1.
DR Gene3D; 3.40.50.10190; BRCT domain; 9.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR035960; Secretoglobin_sf.
DR InterPro; IPR049542; TopBP1-like_BRCT0.
DR InterPro; IPR044737; TopBP1_BRCT_1.
DR PANTHER; PTHR13561; DNA REPLICATION REGULATOR DPB11-RELATED; 1.
DR PANTHER; PTHR13561:SF20; DNA TOPOISOMERASE 2-BINDING PROTEIN 1; 1.
DR Pfam; PF00533; BRCT; 6.
DR Pfam; PF12738; PTCB-BRCT; 1.
DR Pfam; PF21298; TopBP1_BRCT0; 1.
DR SMART; SM00292; BRCT; 7.
DR SUPFAM; SSF52113; BRCT domain; 6.
DR SUPFAM; SSF48201; Uteroglobin-like; 1.
DR PROSITE; PS50172; BRCT; 7.
PE 1: Evidence at protein level;
KW 3D-structure; Chromosome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair;
KW DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ubl conjugation.
FT CHAIN 1..1522
FT /note="DNA topoisomerase 2-binding protein 1"
FT /id="PRO_0000072631"
FT DOMAIN 101..189
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 195..284
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 354..444
FT /note="BRCT 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 548..633
FT /note="BRCT 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 641..738
FT /note="BRCT 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 900..991
FT /note="BRCT 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 1259..1351
FT /note="BRCT 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 1389..1486
FT /note="BRCT 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT REGION 756..891
FT /note="Interaction with CIP2A"
FT /evidence="ECO:0000269|PubMed:35121901,
FT ECO:0000269|PubMed:35842428"
FT REGION 1018..1058
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1083..1118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1501..1522
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 852..858
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 1517..1520
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 1036..1058
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 298
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 779
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 848
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 860
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 861
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 864
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 886
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 888
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1002
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1062
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21777809"
FT MOD_RES 1064
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1504
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 817
FT /note="S -> L (in dbSNP:rs17301766)"
FT /id="VAR_059733"
FT VARIANT 955
FT /note="N -> S (in dbSNP:rs10935070)"
FT /id="VAR_057007"
FT VARIANT 1042
FT /note="N -> S (in dbSNP:rs10935070)"
FT /id="VAR_059734"
FT MUTAGEN 155
FT /note="K->E: Impaired interaction with phosphorylated MDC1.
FT Does not affect interaction with phosphorylated TP53BP1."
FT /evidence="ECO:0000269|PubMed:30898438,
FT ECO:0000269|PubMed:31135337"
FT MUTAGEN 250
FT /note="K->A: Abolished interaction with phosphorylated
FT HTATSF1."
FT /evidence="ECO:0000269|PubMed:35597237"
FT MUTAGEN 250
FT /note="K->E: Abolished interaction with phosphorylated
FT TP53BP1."
FT /evidence="ECO:0000269|PubMed:31135337"
FT MUTAGEN 564
FT /note="S->A: Does not affect interaction with MDC1."
FT /evidence="ECO:0000269|PubMed:23891287"
FT MUTAGEN 681..682
FT /note="RK->EE: Decreased interaction with MDC1."
FT /evidence="ECO:0000269|PubMed:23891287"
FT MUTAGEN 704
FT /note="K->A: Decreased interaction with MDC1. Does not
FT affect interaction with phosphorylated HTATSF1."
FT /evidence="ECO:0000269|PubMed:23891287,
FT ECO:0000269|PubMed:35597237"
FT MUTAGEN 837..839
FT /note="FDV->AAA: Decreased interaction with CIP2A."
FT /evidence="ECO:0000269|PubMed:35121901"
FT MUTAGEN 1273
FT /note="S->A: Decreased interaction with autophosphorylated
FT ATR."
FT /evidence="ECO:0000269|PubMed:21777809"
FT MUTAGEN 1280
FT /note="R->Q: Decreased interaction with autophosphorylated
FT ATR."
FT /evidence="ECO:0000269|PubMed:21777809"
FT MUTAGEN 1317
FT /note="K->A: Does not affect interaction with
FT phosphorylated HTATSF1."
FT /evidence="ECO:0000269|PubMed:35597237"
FT MUTAGEN 1317
FT /note="K->M: Decreased interaction with autophosphorylated
FT ATR."
FT /evidence="ECO:0000269|PubMed:21777809"
FT CONFLICT 457
FT /note="K -> Q (in Ref. 1; BAA34202 and 2; BAA13389)"
FT /evidence="ECO:0000305"
FT CONFLICT 911
FT /note="C -> R (in Ref. 3; BAH13754)"
FT /evidence="ECO:0000305"
FT STRAND 11..15
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 21..33
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 66..74
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 81..89
FT /evidence="ECO:0007829|PDB:3OLC"
FT TURN 105..108
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 110..115
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 118..130
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 145..151
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 154..161
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 169..180
FT /evidence="ECO:0007829|PDB:3OLC"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:2XNH"
FT HELIX 187..189
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 192..195
FT /evidence="ECO:0007829|PDB:3OLC"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 204..207
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 212..224
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 231..234
FT /evidence="ECO:0007829|PDB:6RML"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 244..246
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 249..256
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:3OLC"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:3OLC"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:1WF6"
FT HELIX 341..343
FT /evidence="ECO:0007829|PDB:1WF6"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:1WF6"
FT TURN 356..361
FT /evidence="ECO:0007829|PDB:1WF6"
FT STRAND 363..368
FT /evidence="ECO:0007829|PDB:1WF6"
FT HELIX 372..383
FT /evidence="ECO:0007829|PDB:1WF6"
FT STRAND 387..391
FT /evidence="ECO:0007829|PDB:1WF6"
FT STRAND 398..403
FT /evidence="ECO:0007829|PDB:1WF6"
FT HELIX 407..414
FT /evidence="ECO:0007829|PDB:1WF6"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:1WF6"
FT HELIX 424..433
FT /evidence="ECO:0007829|PDB:1WF6"
FT HELIX 440..442
FT /evidence="ECO:0007829|PDB:1WF6"
FT TURN 552..555
FT /evidence="ECO:0007829|PDB:3UEN"
FT STRAND 557..560
FT /evidence="ECO:0007829|PDB:3UEN"
FT HELIX 565..577
FT /evidence="ECO:0007829|PDB:3UEN"
FT STRAND 591..596
FT /evidence="ECO:0007829|PDB:3UEN"
FT STRAND 607..612
FT /evidence="ECO:0007829|PDB:3UEN"
FT HELIX 613..621
FT /evidence="ECO:0007829|PDB:3UEN"
FT HELIX 628..630
FT /evidence="ECO:0007829|PDB:3UEN"
FT HELIX 632..634
FT /evidence="ECO:0007829|PDB:3UEN"
FT TURN 645..648
FT /evidence="ECO:0007829|PDB:3UEN"
FT STRAND 650..653
FT /evidence="ECO:0007829|PDB:3UEN"
FT HELIX 658..670
FT /evidence="ECO:0007829|PDB:3UEN"
FT TURN 685..688
FT /evidence="ECO:0007829|PDB:3UEN"
FT STRAND 693..696
FT /evidence="ECO:0007829|PDB:3UEN"
FT STRAND 698..700
FT /evidence="ECO:0007829|PDB:3UEN"
FT HELIX 703..710
FT /evidence="ECO:0007829|PDB:3UEN"
FT HELIX 718..727
FT /evidence="ECO:0007829|PDB:3UEN"
FT HELIX 733..735
FT /evidence="ECO:0007829|PDB:3UEN"
FT HELIX 738..740
FT /evidence="ECO:0007829|PDB:3UEN"
FT TURN 904..907
FT /evidence="ECO:0007829|PDB:3PD7"
FT STRAND 909..912
FT /evidence="ECO:0007829|PDB:3PD7"
FT HELIX 914..919
FT /evidence="ECO:0007829|PDB:3PD7"
FT HELIX 920..929
FT /evidence="ECO:0007829|PDB:3PD7"
FT STRAND 933..937
FT /evidence="ECO:0007829|PDB:3PD7"
FT STRAND 943..946
FT /evidence="ECO:0007829|PDB:3PD7"
FT HELIX 956..963
FT /evidence="ECO:0007829|PDB:3PD7"
FT STRAND 967..969
FT /evidence="ECO:0007829|PDB:3PD7"
FT HELIX 971..980
FT /evidence="ECO:0007829|PDB:3PD7"
FT HELIX 986..988
FT /evidence="ECO:0007829|PDB:3PD7"
FT STRAND 1269..1274
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1277..1289
FT /evidence="ECO:0007829|PDB:7CMZ"
FT STRAND 1297..1299
FT /evidence="ECO:0007829|PDB:7CMZ"
FT STRAND 1305..1311
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1316..1323
FT /evidence="ECO:0007829|PDB:7CMZ"
FT STRAND 1327..1329
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1332..1340
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1347..1349
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1354..1359
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1365..1386
FT /evidence="ECO:0007829|PDB:7CMZ"
FT TURN 1393..1396
FT /evidence="ECO:0007829|PDB:7CMZ"
FT STRAND 1398..1402
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1405..1417
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1428..1431
FT /evidence="ECO:0007829|PDB:7CMZ"
FT STRAND 1435..1439
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1453..1458
FT /evidence="ECO:0007829|PDB:7CMZ"
FT STRAND 1462..1465
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1467..1474
FT /evidence="ECO:0007829|PDB:7CMZ"
FT STRAND 1475..1477
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1481..1483
FT /evidence="ECO:0007829|PDB:7CMZ"
FT HELIX 1487..1489
FT /evidence="ECO:0007829|PDB:7CMZ"
SQ SEQUENCE 1522 AA; 170679 MW; 02C25880EDCD6AC7 CRC64;
MSRNDKEPFF VKFLKSSDNS KCFFKALESI KEFQSEEYLQ IITEEEALKI KENDRSLYIC
DPFSGVVFDH LKKLGCRIVG PQVVIFCMHH QRCVPRAEHP VYNMVMSDVT ISCTSLEKEK
REEVHKYVQM MGGRVYRDLN VSVTHLIAGE VGSKKYLVAA NLKKPILLPS WIKTLWEKSQ
EKKITRYTDI NMEDFKCPIF LGCIICVTGL CGLDRKEVQQ LTVKHGGQYM GQLKMNECTH
LIVQEPKGQK YECAKRWNVH CVTTQWFFDS IEKGFCQDES IYKTEPRPEA KTMPNSSTPT
SQINTIDSRT LSDVSNISNI NASCVSESIC NSLNSKLEPT LENLENLDVS AFQAPEDLLD
GCRIYLCGFS GRKLDKLRRL INSGGGVRFN QLNEDVTHVI VGDYDDELKQ FWNKSAHRPH
VVGAKWLLEC FSKGYMLSEE PYIHANYQPV EIPVSHKPES KAALLKKKNS SFSKKDFAPS
EKHEQADEDL LSQYENGSST VVEAKTSEAR PFNDSTHAEP LNDSTHISLQ EENQSSVSHC
VPDVSTITEE GLFSQKSFLV LGFSNENESN IANIIKENAG KIMSLLSRTV ADYAVVPLLG
CEVEATVGEV VTNTWLVTCI DYQTLFDPKS NPLFTPVPVM TGMTPLEDCV ISFSQCAGAE
KESLTFLANL LGASVQEYFV RKSNAKKGMF ASTHLILKER GGSKYEAAKK WNLPAVTIAW
LLETARTGKR ADESHFLIEN STKEERSLET EITNGINLNS DTAEHPGTRL QTHRKTVVTP
LDMNRFQSKA FRAVVSQHAR QVAASPAVGQ PLQKEPSLHL DTPSKFLSKD KLFKPSFDVK
DALAALETPG RPSQQKRKPS TPLSEVIVKN LQLALANSSR NAVALSASPQ LKEAQSEKEE
APKPLHKVVV CVSKKLSKKQ SELNGIAASL GADYRWSFDE TVTHFIYQGR PNDTNREYKS
VKERGVHIVS EHWLLDCAQE CKHLPESLYP HTYNPKMSLD ISAVQDGRLC NSRLLSAVSS
TKDDEPDPLI LEENDVDNMA TNNKESAPSN GSGKNDSKGV LTQTLEMREN FQKQLQEIMS
ATSIVKPQGQ RTSLSRSGCN SASSTPDSTR SARSGRSRVL EALRQSRQTV PDVNTEPSQN
EQIIWDDPTA REERARLASN LQWPSCPTQY SELQVDIQNL EDSPFQKPLH DSEIAKQAVC
DPGNIRVTEA PKHPISEELE TPIKDSHLIP TPQAPSIAFP LANPPVAPHP REKIITIEET
HEELKKQYIF QLSSLNPQER IDYCHLIEKL GGLVIEKQCF DPTCTHIVVG HPLRNEKYLA
SVAAGKWVLH RSYLEACRTA GHFVQEEDYE WGSSSILDVL TGINVQQRRL ALAAMRWRKK
IQQRQESGIV EGAFSGWKVI LHVDQSREAG FKRLLQSGGA KVLPGHSVPL FKEATHLFSD
LNKLKPDDSG VNIAEAAAQN VYCLRTEYIA DYLMQESPPH VENYCLPEAI SFIQNNKELG
TGLSQKRKAP TEKNKIKRPR VH
//
