ID TOP2A_HUMAN Reviewed; 1531 AA. AC P11388; B2RTS1; Q71UN1; Q71UQ5; Q9HB24; Q9HB25; Q9HB26; Q9UP44; Q9UQP9; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 04-MAY-2001, sequence version 3. DT 27-MAR-2024, entry version 261. DE RecName: Full=DNA topoisomerase 2-alpha; DE EC=5.6.2.2 {ECO:0000255|PROSITE-ProRule:PRU00995, ECO:0000269|PubMed:19222228, ECO:0000269|PubMed:19697956}; DE AltName: Full=DNA topoisomerase II, alpha isozyme; GN Name=TOP2A; Synonyms=TOP2; 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). RX PubMed=2845399; DOI=10.1073/pnas.85.19.7177; RA Tsai-Pflugfelder M., Liu L.F., Liu A.A., Tewey K.M., Whang-Peng J., RA Knutsen T., Huebner K., Croce C.M., Wang J.C.; RT "Cloning and sequencing of cDNA encoding human DNA topoisomerase II and RT localization of the gene to chromosome region 17q21-22."; RL Proc. Natl. Acad. Sci. U.S.A. 85:7177-7181(1988). RN [2] RP SEQUENCE REVISION TO 109-114. RX PubMed=8393377; RA Wasserman R.A., Austin C.A., Fisher L.M., Wang J.C.; RT "Use of yeast in the study of anticancer drugs targeting DNA RT topoisomerases: expression of a functional recombinant human DNA RT topoisomerase II alpha in yeast."; RL Cancer Res. 53:3591-3596(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=9795238; DOI=10.1016/s0378-1119(98)00468-5; RA Lang A.J., Mirski S.E., Cummings H.J., Yu Q., Gerlach J.H., Cole S.P.; RT "Structural organization of the human TOP2A and TOP2B genes."; RL Gene 221:255-266(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=10095062; DOI=10.1016/s0167-4781(99)00020-2; RA Sng J.H., Heaton V.J., Bell M., Mani P., Austin C.A., Fisher L.M.; RT "Molecular cloning and characterization of the human topoisomerase IIalpha RT and IIbeta genes: evidence for isoform evolution through gene RT duplication."; RL Biochim. Biophys. Acta 1444:395-406(1999). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-500 (ISOFORMS 2; 3 AND 4). RA Petruti-Mot A.S., Earnshaw W.C.; RT "Two differentially spliced forms of topoisomerase II alpha and beta mRNAs RT are conserved between birds and humans."; RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21 AND 48-72. RA Neri S., Govoni M., Perrotta L., Pozzi S., Pession A.; RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases. RN [10] RP PROTEIN SEQUENCE OF 1-17; 74-96; 124-131; 169-184; 243-251; 277-287; RP 325-336; 387-397; 467-478; 481-487; 500-519; 569-579; 702-713; 805-815; RP 828-835; 864-877; 937-958; 1021-1026 AND 1185-1196, ACETYLATION AT MET-1, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Ovarian carcinoma; RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.; RL Submitted (DEC-2008) to UniProtKB. RN [11] RP PROTEIN SEQUENCE OF 135-157; 228-241; 307-321; 325-336; 387-397; 401-416; RP 467-478; 536-550; 569-579; 640-655; 702-713; 805-815; 1011-1020; 1097-1114; RP 1169-1184; 1239-1259 AND 1374-1411, PHOSPHORYLATION AT SER-1106, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [12] RP SUBCELLULAR LOCATION. RX PubMed=8299728; DOI=10.1006/excr.1994.1046; RA Zini N., Santi S., Ognibene A., Bavelloni A., Neri L.M., Valmori A., RA Mariani E., Negri C., Astaldi-Ricotti G.C., Maraldi N.M.; RT "Discrete localization of different DNA topoisomerases in HeLa and K562 RT cell nuclei and subnuclear fractions."; RL Exp. Cell Res. 210:336-348(1994). RN [13] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=9155056; DOI=10.1038/bjc.1997.227; RA Turley H., Comley M., Houlbrook S., Nozaki N., Kikuchi A., Hickson I.D., RA Gatter K., Harris A.L.; RT "The distribution and expression of the two isoforms of DNA topoisomerase RT II in normal and neoplastic human tissues."; RL Br. J. Cancer 75:1340-1346(1997). RN [14] RP PHOSPHORYLATION AT SER-1469, AND MUTAGENESIS OF SER-1469. RX PubMed=10942766; DOI=10.1074/jbc.m005179200; RA Escargueil A.E., Plisov S.Y., Filhol O., Cochet C., Larsen A.K.; RT "Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase RT CK2 creates the MPM-2 phosphoepitope on Ser-1469."; RL J. Biol. Chem. 275:34710-34718(2000). RN [15] RP NUCLEAR EXPORT SIGNAL. RX PubMed=12821127; DOI=10.1016/s0006-291x(03)01077-5; RA Mirski S.E., Bielawski J.C., Cole S.P.; RT "Identification of functional nuclear export sequences in human RT topoisomerase IIalpha and beta."; RL Biochem. Biophys. Res. Commun. 306:905-911(2003). RN [16] RP INTERACTION WITH DHX9. RX PubMed=12711669; DOI=10.1093/nar/gkg328; RA Zhou K., Choe K.-T., Zaidi Z., Wang Q., Mathews M.B., Lee C.-G.; RT "RNA helicase A interacts with dsDNA and topoisomerase IIalpha."; RL Nucleic Acids Res. 31:2253-2260(2003). RN [17] RP INTERACTION WITH COPS5. RX PubMed=15126503; DOI=10.1074/jbc.m401411200; RA Yun J., Tomida A., Andoh T., Tsuruo T.; RT "Interaction between glucose-regulated destruction domain of DNA RT topoisomerase IIalpha and MPN domain of Jab1/CSN5."; RL J. Biol. Chem. 279:31296-31303(2004). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-1106; SER-1213; RP SER-1247; SER-1332; SER-1337; THR-1343; SER-1351; SER-1354; SER-1374; RP SER-1377 AND SER-1525, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1213; SER-1374; SER-1377 AND RP SER-1525, AND IDENTIFICATION BY 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1247, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17924679; DOI=10.1021/pr070152u; RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.; RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells RT and high confident phosphopeptide identification by cross-validation of RT MS/MS and MS/MS/MS spectra."; RL J. Proteome Res. 6:4150-4162(2007). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PLSCR1. RX PubMed=17567603; DOI=10.1093/nar/gkm434; RA Wyles J.P., Wu Z., Mirski S.E., Cole S.P.; RT "Nuclear interactions of topoisomerase II alpha and beta with phospholipid RT scramblase 1."; RL Nucleic Acids Res. 35:4076-4085(2007). RN [22] RP PHOSPHORYLATION AT THR-1343. RX PubMed=18062778; DOI=10.1042/bj20071394; RA Iida M., Matsuda M., Komatani H.; RT "Plk3 phosphorylates topoisomerase IIalpha at Thr(1342), a site that is not RT recognized by Plk1."; RL Biochem. J. 411:27-32(2008). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1504, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-1213; SER-1247; RP SER-1332; SER-1337 AND SER-1377, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [25] RP FUNCTION, AND INTERACTION WITH SETMAR. RX PubMed=18790802; DOI=10.1093/nar/gkn560; RA Williamson E.A., Rasila K.K., Corwin L.K., Wray J., Beck B.D., Severns V., RA Mobarak C., Lee S.H., Nickoloff J.A., Hromas R.; RT "The SET and transposase domain protein Metnase enhances chromosome RT decatenation: regulation by automethylation."; RL Nucleic Acids Res. 36:5822-5831(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1106; SER-1213; SER-1332; RP SER-1337; THR-1343; SER-1351; SER-1392; SER-1393; SER-1449; SER-1469; RP THR-1470; SER-1471; SER-1474 AND SER-1525, AND IDENTIFICATION BY MASS RP 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 [27] RP IDENTIFICATION BY MASS 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 [28] RP CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=19222228; DOI=10.1021/bi8023256; RA Deweese J.E., Burch A.M., Burgin A.B., Osheroff N.; RT "Use of divalent metal ions in the DNA cleavage reaction of human type II RT topoisomerases."; RL Biochemistry 48:1862-1869(2009). RN [29] RP MUTAGENESIS OF GLU-461; ASP-541; ASP-543 AND ASP-545, PUTATIVE RP METAL-BINDING SITES, CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=19697956; DOI=10.1021/bi900875c; RA Deweese J.E., Guengerich F.P., Burgin A.B., Osheroff N.; RT "Metal ion interactions in the DNA cleavage/ligation active site of human RT topoisomerase IIalpha."; RL Biochemistry 48:8940-8947(2009). RN [30] RP PHOSPHORYLATION AT SER-1106 BY CSNK1D/CK1. RX PubMed=19043076; DOI=10.1093/nar/gkn934; RA Grozav A.G., Chikamori K., Kozuki T., Grabowski D.R., Bukowski R.M., RA Willard B., Kinter M., Andersen A.H., Ganapathi R., Ganapathi M.K.; RT "Casein kinase I delta/epsilon phosphorylates topoisomerase IIalpha at RT serine-1106 and modulates DNA cleavage activity."; RL Nucleic Acids Res. 37:382-392(2009). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1247; SER-1374; SER-1387; RP SER-1393; SER-1504 AND SER-1525, AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [32] RP INTERACTION WITH SETMAR. RX PubMed=20457750; DOI=10.1093/nar/gkq339; RA De Haro L.P., Wray J., Williamson E.A., Durant S.T., Corwin L., RA Gentry A.C., Osheroff N., Lee S.H., Hromas R., Nickoloff J.A.; RT "Metnase promotes restart and repair of stalled and collapsed replication RT forks."; RL Nucleic Acids Res. 38:5681-5691(2010). RN [33] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-4; THR-282; SER-1106; THR-1205; SER-1213; SER-1247; RP SER-1332; SER-1337; THR-1343; SER-1351; SER-1354; SER-1374; SER-1377; RP SER-1471; SER-1474; SER-1495; SER-1504 AND SER-1525, AND IDENTIFICATION BY RP 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 [34] 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 [35] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-4; SER-1106; SER-1213; SER-1247; SER-1295; SER-1297; RP SER-1299; SER-1302; SER-1332; SER-1337; THR-1343; SER-1351; SER-1354; RP SER-1374; SER-1377; SER-1469; THR-1470; SER-1471; SER-1474; SER-1476 AND RP SER-1525, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [36] RP MUTAGENESIS OF 342-LYS--LYS-344. RX PubMed=23022727; DOI=10.1038/nsmb.2388; RA Schmidt B.H., Osheroff N., Berger J.M.; RT "Structure of a topoisomerase II-DNA-nucleotide complex reveals a new RT control mechanism for ATPase activity."; RL Nat. Struct. Mol. Biol. 19:1147-1154(2012). RN [37] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RECQL5. RX PubMed=22013166; DOI=10.1093/nar/gkr844; RA Ramamoorthy M., Tadokoro T., Rybanska I., Ghosh A.K., Wersto R., May A., RA Kulikowicz T., Sykora P., Croteau D.L., Bohr V.A.; RT "RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell RT cycle progression."; RL Nucleic Acids Res. 40:1621-1635(2012). RN [38] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [39] RP FUNCTION, MUTAGENESIS OF GLU-461; ASP-541 AND ASP-543, AND COFACTOR. RX PubMed=22323612; DOI=10.1073/pnas.1115704109; RA Lee S., Jung S.R., Heo K., Byl J.A., Deweese J.E., Osheroff N., Hohng S.; RT "DNA cleavage and opening reactions of human topoisomerase IIalpha are RT regulated via Mg2+-mediated dynamic bending of gate-DNA."; RL Proc. Natl. Acad. Sci. U.S.A. 109:2925-2930(2012). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-1106; SER-1213; RP THR-1244; SER-1247; SER-1374; SER-1377; SER-1391; SER-1449; SER-1469; RP SER-1471; SER-1474; SER-1495 AND SER-1504, AND IDENTIFICATION BY MASS RP 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 [41] RP INTERACTION WITH MCM3AP. RX PubMed=23652018; DOI=10.1038/ncomms2823; RA Singh S.K., Maeda K., Eid M.M., Almofty S.A., Ono M., Pham P., RA Goodman M.F., Sakaguchi N.; RT "GANP regulates recruitment of AID to immunoglobulin variable regions by RT modulating transcription and nucleosome occupancy."; RL Nat. Commun. 4:1830-1830(2013). RN [42] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1228; LYS-1240; LYS-1385 AND RP LYS-1492, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [43] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1240, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [44] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-639; LYS-662; LYS-676; LYS-1075; RP LYS-1196; LYS-1228; LYS-1240; LYS-1385 AND LYS-1442, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [45] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1228 AND LYS-1240, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [46] RP INTERACTION WITH ERCC6. RX PubMed=26030138; DOI=10.1371/journal.pone.0128558; RA Nicolai S., Filippi S., Caputo M., Cipak L., Gregan J., Ammerer G., RA Frontini M., Willems D., Prantera G., Balajee A.S., Proietti-De-Santis L.; RT "Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group RT B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin RT Dynamics."; RL PLoS ONE 10:E0128558-E0128558(2015). RN [47] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-17; LYS-156; LYS-157; LYS-261; RP LYS-352; LYS-386; LYS-397; LYS-416; LYS-418; LYS-425; LYS-440; LYS-466; RP LYS-480; LYS-529; LYS-584; LYS-599; LYS-614; LYS-622; LYS-625; LYS-632; RP LYS-639; LYS-655; LYS-662; LYS-676; LYS-1075; LYS-1114; LYS-1196; LYS-1204; RP LYS-1228; LYS-1240; LYS-1259; LYS-1276; LYS-1283; LYS-1286; LYS-1363; RP LYS-1367; LYS-1373; LYS-1385; LYS-1422; LYS-1442; LYS-1454; LYS-1459; RP LYS-1484 AND LYS-1492, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [48] RP DEUBIQUITINATION BY EPSTEIN-BARR VIRUS PROTEIN BPLF1 (MICROBIAL INFECTION), RP AND SUMOYLATION. RX PubMed=34543352; DOI=10.1371/journal.ppat.1009954; RA Li J., Nagy N., Liu J., Gupta S., Frisan T., Hennig T., Cameron D.P., RA Baranello L., Masucci M.G.; RT "The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the RT activity of topoisomerase II during productive infection."; RL PLoS Pathog. 17:e1009954-e1009954(2021). RN [49] RP SUBUNIT, AND INTERACTION WITH POLR1A AND UBTF. RX PubMed=36271492; DOI=10.26508/lsa.202201568; RA Daiss J.L., Pilsl M., Straub K., Bleckmann A., Hocherl M., Heiss F.B., RA Abascal-Palacios G., Ramsay E.P., Tluckova K., Mars J.C., Furtges T., RA Bruckmann A., Rudack T., Bernecky C., Lamour V., Panov K., Vannini A., RA Moss T., Engel C.; RT "The human RNA polymerase I structure reveals an HMG-like docking domain RT specific to metazoans."; RL Life. Sci Alliance 5:1-20(2022). RN [50] RP X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 29-428 IN COMPLEX WITH ADP, AND RP X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS) OF 29-428 IN COMPLEX WITH AMPPNP. RX PubMed=16100112; DOI=10.1074/jbc.m506520200; RA Wei H., Ruthenburg A.J., Bechis S.K., Verdine G.L.; RT "Nucleotide-dependent domain movement in the ATPase domain of a human type RT IIA DNA topoisomerase."; RL J. Biol. Chem. 280:37041-37047(2005). RN [51] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 431-1193 IN COMPLEX WITH DNA AND RP MAGNESIUM ION, SUBUNIT, AND COFACTOR. RX PubMed=22841979; DOI=10.1016/j.jmb.2012.07.014; RA Wendorff T.J., Schmidt B.H., Heslop P., Austin C.A., Berger J.M.; RT "The structure of DNA-bound human topoisomerase II alpha: conformational RT mechanisms for coordinating inter-subunit interactions with DNA cleavage."; RL J. Mol. Biol. 424:109-124(2012). RN [52] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 29-428 IN COMPLEX WITH ADP AND RP ATP ANALOGS, AND DOMAIN. RX PubMed=25202966; DOI=10.1371/journal.pone.0107289; RA Stanger F.V., Dehio C., Schirmer T.; RT "Structure of the N-terminal Gyrase B fragment in complex with ADPPi RT reveals rigid-body motion induced by ATP hydrolysis."; RL PLoS ONE 9:E107289-E107289(2014). RN [53] RP VARIANT AMSACRINE-RESISTANT LYS-487. RX PubMed=1651812; RA Hinds M., Deisseroth K., Mayes J., Altschuler E., Jansen R., Ledley F.D., RA Zwelling L.A.; RT "Identification of a point mutation in the topoisomerase II gene from a RT human leukemia cell line containing an amsacrine-resistant form of RT topoisomerase II."; RL Cancer Res. 51:4729-4731(1991). RN [54] RP VARIANT TENIPOSIDE-RESISTANT GLN-450. RX PubMed=1652758; DOI=10.1073/pnas.88.17.7654; RA Bugg B.Y., Danks M.K., Beck W.T., Suttle D.P.; RT "Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic RT cells selected for resistance to teniposide."; RL Proc. Natl. Acad. Sci. U.S.A. 88:7654-7658(1991). CC -!- FUNCTION: Key decatenating enzyme that alters DNA topology by binding CC to two double-stranded DNA molecules, generating a double-stranded CC break in one of the strands, passing the intact strand through the CC broken strand, and religating the broken strand (PubMed:17567603, CC PubMed:18790802, PubMed:22013166, PubMed:22323612). May play a role in CC regulating the period length of BMAL1 transcriptional oscillation (By CC similarity). {ECO:0000250|UniProtKB:Q01320, CC ECO:0000269|PubMed:17567603, ECO:0000269|PubMed:18790802, CC ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22323612}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP-dependent breakage, passage and rejoining of double- CC stranded DNA.; EC=5.6.2.2; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00995, ECO:0000269|PubMed:19222228, CC ECO:0000269|PubMed:19697956}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000305|PubMed:19222228, ECO:0000305|PubMed:19697956, CC ECO:0000305|PubMed:22323612, ECO:0000305|PubMed:22841979}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000305|PubMed:19222228, ECO:0000305|PubMed:19697956, CC ECO:0000305|PubMed:22323612, ECO:0000305|PubMed:22841979}; CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000305|PubMed:19222228, ECO:0000305|PubMed:19697956, CC ECO:0000305|PubMed:22323612, ECO:0000305|PubMed:22841979}; CC Note=Binds two Mg(2+) per subunit. The magnesium ions form salt bridges CC with both the protein and the DNA. Can also accept other divalent metal CC cations, such as Mn(2+) or Ca(2+). {ECO:0000305|PubMed:19222228, CC ECO:0000305|PubMed:19697956, ECO:0000305|PubMed:22323612, CC ECO:0000305|PubMed:22841979}; CC -!- ACTIVITY REGULATION: Specifically inhibited by the intercalating agent CC amsacrine. CC -!- SUBUNIT: Homodimer. Interacts with COPS5. Interacts with RECQL5; this CC stimulates DNA decatenation. Interacts with SETMAR; stimulates the CC topoisomerase activity (PubMed:18790802, PubMed:20457750). Interacts CC with DHX9; this interaction occurs in a E2 enzyme UBE2I- and RNA- CC dependent manner, negatively regulates DHX9-mediated double-stranded CC DNA and RNA duplex helicase activity and stimulates TOP2A-mediated CC supercoiled DNA relaxation activity (PubMed:12711669). Interacts with CC HNRNPU (via C-terminus); this interaction protects the topoisomerase CC TOP2A from degradation and positively regulates the relaxation of CC supercoiled DNA in a RNA-dependent manner (By similarity). Interacts CC with MCM3AP isoform GANP (PubMed:23652018). Interacts with ERCC6 CC (PubMed:26030138). Interacts with PLSCR1 (PubMed:17567603). Interacts CC with GCNA; this interaction allows the resolution of topoisomerase II CC (TOP2A) DNA-protein cross-links (By similarity). Interacts with CC POL1RA/RPA1 (via dock II) and UBTF in the context of Pol I complex; may CC assist Pol I transcription initiation by releasing supercoils occurring CC during DNA unwinding. {ECO:0000250|UniProtKB:P41516, CC ECO:0000250|UniProtKB:Q01320, ECO:0000269|PubMed:12711669, CC ECO:0000269|PubMed:15126503, ECO:0000269|PubMed:16100112, CC ECO:0000269|PubMed:17567603, ECO:0000269|PubMed:20457750, CC ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22841979, CC ECO:0000269|PubMed:23652018, ECO:0000269|PubMed:26030138, CC ECO:0000269|PubMed:36271492}. CC -!- INTERACTION: CC P11388; O14497-1: ARID1A; NbExp=2; IntAct=EBI-539628, EBI-15956509; CC P11388; P38398: BRCA1; NbExp=3; IntAct=EBI-539628, EBI-349905; CC P11388; P35222: CTNNB1; NbExp=5; IntAct=EBI-539628, EBI-491549; CC P11388; Q05655: PRKCD; NbExp=10; IntAct=EBI-539628, EBI-704279; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9155056}. Nucleus, CC nucleoplasm {ECO:0000269|PubMed:8299728}. Nucleus CC {ECO:0000269|PubMed:17567603, ECO:0000269|PubMed:22013166, CC ECO:0000269|PubMed:8299728, ECO:0000269|PubMed:9155056}. Nucleus, CC nucleolus {ECO:0000269|PubMed:9155056}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=P11388-1; Sequence=Displayed; CC Name=2; CC IsoId=P11388-2; Sequence=VSP_006531; CC Name=3; CC IsoId=P11388-3; Sequence=VSP_006529; CC Name=4; CC IsoId=P11388-4; Sequence=VSP_006530; CC -!- TISSUE SPECIFICITY: Expressed in the tonsil, spleen, lymph node, CC thymus, skin, pancreas, testis, colon, kidney, liver, brain and lung CC (PubMed:9155056). Also found in high-grade lymphomas, squamous cell CC lung tumors and seminomas (PubMed:9155056). CC {ECO:0000269|PubMed:9155056}. CC -!- DOMAIN: The N-terminus has several structural domains; the ATPase CC domain (about residues 1-265), the transducer domain (about 266-428) CC and the toprim domain (455-572) (PubMed:25202966). Comparing different CC structures shows ATP hydrolysis induces domain shifts in the N-terminus CC that are probably part of the mechanism of DNA cleavage and rejoining CC (PubMed:25202966). {ECO:0000250|UniProtKB:P0AES6, CC ECO:0000269|PubMed:25202966}. CC -!- PTM: Phosphorylation has no effect on catalytic activity. However, CC phosphorylation at Ser-1106 by CSNK1D/CK1 promotes DNA cleavable CC complex formation. {ECO:0000269|PubMed:10942766, CC ECO:0000269|PubMed:18062778, ECO:0000269|PubMed:19043076, CC ECO:0000269|Ref.11}. CC -!- PTM: (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1; CC leading to stabilized SUMOylated TOP2A trapped in cleavage complexes, CC which halts the DNA damage response to TOP2A-induced double-strand DNA CC breaks. {ECO:0000269|PubMed:34543352}. CC -!- PTM: SUMOylated. {ECO:0000269|PubMed:34543352}. CC -!- MISCELLANEOUS: Eukaryotic topoisomerase I and II can relax both CC negative and positive supercoils, whereas prokaryotic enzymes relax CC only negative supercoils. CC -!- SIMILARITY: Belongs to the type II topoisomerase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J04088; AAA61209.1; -; mRNA. DR EMBL; AF071747; AAC77388.1; -; Genomic_DNA. DR EMBL; AF071738; AAC77388.1; JOINED; Genomic_DNA. DR EMBL; AF071739; AAC77388.1; JOINED; Genomic_DNA. DR EMBL; AF071740; AAC77388.1; JOINED; Genomic_DNA. DR EMBL; AF071741; AAC77388.1; JOINED; Genomic_DNA. DR EMBL; AF071742; AAC77388.1; JOINED; Genomic_DNA. DR EMBL; AF071743; AAC77388.1; JOINED; Genomic_DNA. DR EMBL; AF071744; AAC77388.1; JOINED; Genomic_DNA. DR EMBL; AF071745; AAC77388.1; JOINED; Genomic_DNA. DR EMBL; AF071746; AAC77388.1; JOINED; Genomic_DNA. DR EMBL; AJ011741; CAA09762.1; -; Genomic_DNA. DR EMBL; AJ011742; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011743; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011744; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011745; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011746; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011747; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011748; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011749; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011750; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011751; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011752; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011753; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011754; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011755; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011756; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011757; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AJ011758; CAA09762.1; JOINED; Genomic_DNA. DR EMBL; AC080112; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF285157; AAG13403.1; -; mRNA. DR EMBL; AF285158; AAG13404.1; -; mRNA. DR EMBL; CH471152; EAW60663.1; -; Genomic_DNA. DR EMBL; BC140791; AAI40792.1; -; mRNA. DR EMBL; AF285159; AAG13405.1; -; mRNA. DR EMBL; AF069522; AAC23518.1; -; Genomic_DNA. DR EMBL; AF064590; AAC16736.1; -; Genomic_DNA. DR CCDS; CCDS45672.1; -. [P11388-1] DR PIR; A40493; A40493. DR RefSeq; NP_001058.2; NM_001067.3. [P11388-1] DR PDB; 1ZXM; X-ray; 1.87 A; A/B=29-428. DR PDB; 1ZXN; X-ray; 2.51 A; A/B/C/D=29-428. DR PDB; 4FM9; X-ray; 2.90 A; A=431-1193. DR PDB; 4R1F; X-ray; 2.51 A; A/B/C/D=29-428. DR PDB; 5GWK; X-ray; 3.15 A; A/B=429-1188. DR PDB; 5NNE; X-ray; 1.15 A; C=1198-1207. DR PDB; 6ZY5; EM; 3.60 A; A/B=1-1531. DR PDB; 6ZY6; EM; 4.10 A; A/B=1-1531. DR PDB; 6ZY7; EM; 4.64 A; A/B=1-1531. DR PDB; 6ZY8; EM; 7.40 A; A/B=1-1531. DR PDBsum; 1ZXM; -. DR PDBsum; 1ZXN; -. DR PDBsum; 4FM9; -. DR PDBsum; 4R1F; -. DR PDBsum; 5GWK; -. DR PDBsum; 5NNE; -. DR PDBsum; 6ZY5; -. DR PDBsum; 6ZY6; -. DR PDBsum; 6ZY7; -. DR PDBsum; 6ZY8; -. DR AlphaFoldDB; P11388; -. DR EMDB; EMD-11550; -. DR EMDB; EMD-11551; -. DR EMDB; EMD-11552; -. DR EMDB; EMD-11553; -. DR EMDB; EMD-11554; -. DR SMR; P11388; -. DR BioGRID; 113006; 491. DR CORUM; P11388; -. DR DIP; DIP-33887N; -. DR IntAct; P11388; 110. DR MINT; P11388; -. DR STRING; 9606.ENSP00000411532; -. DR BindingDB; P11388; -. DR ChEMBL; CHEMBL1806; -. DR DrugBank; DB05706; 13-deoxydoxorubicin. DR DrugBank; DB06013; Aldoxorubicin. DR DrugBank; DB05022; Amonafide. DR DrugBank; DB06263; Amrubicin. DR DrugBank; DB00276; Amsacrine. DR DrugBank; DB06420; Annamycin. DR DrugBank; DB04975; Banoxantrone. DR DrugBank; DB06362; Becatecarin. DR DrugBank; DB00537; Ciprofloxacin. DR DrugBank; DB00970; Dactinomycin. DR DrugBank; DB00694; Daunorubicin. DR DrugBank; DB06421; Declopramide. DR DrugBank; DB00380; Dexrazoxane. DR DrugBank; DB00997; Doxorubicin. DR DrugBank; DB05129; Elsamitrucin. DR DrugBank; DB00467; Enoxacin. DR DrugBank; DB00445; Epirubicin. DR DrugBank; DB00773; Etoposide. DR DrugBank; DB09047; Finafloxacin. DR DrugBank; DB04576; Fleroxacin. DR DrugBank; DB01645; Genistein. DR DrugBank; DB01177; Idarubicin. DR DrugBank; DB00978; Lomefloxacin. DR DrugBank; DB04967; Lucanthone. DR DrugBank; DB01204; Mitoxantrone. DR DrugBank; DB00218; Moxifloxacin. DR DrugBank; DB01059; Norfloxacin. DR DrugBank; DB01165; Ofloxacin. DR DrugBank; DB00487; Pefloxacin. DR DrugBank; DB01179; Podofilox. DR DrugBank; DB05920; RTA 744. DR DrugBank; DB04978; SP1049C. DR DrugBank; DB01208; Sparfloxacin. DR DrugBank; DB00444; Teniposide. DR DrugBank; DB00685; Trovafloxacin. DR DrugBank; DB00385; Valrubicin. DR DrugBank; DB06042; ZEN-012. DR DrugCentral; P11388; -. DR GuidetoPHARMACOLOGY; 2637; -. DR CarbonylDB; P11388; -. DR GlyGen; P11388; 16 sites, 1 O-linked glycan (16 sites). DR iPTMnet; P11388; -. DR MetOSite; P11388; -. DR PhosphoSitePlus; P11388; -. DR SwissPalm; P11388; -. DR BioMuta; TOP2A; -. DR DMDM; 13959709; -. DR CPTAC; CPTAC-1187; -. DR EPD; P11388; -. DR jPOST; P11388; -. DR MassIVE; P11388; -. DR MaxQB; P11388; -. DR PaxDb; 9606-ENSP00000411532; -. DR PeptideAtlas; P11388; -. DR ProteomicsDB; 52767; -. [P11388-1] DR ProteomicsDB; 52768; -. [P11388-2] DR ProteomicsDB; 52769; -. [P11388-3] DR ProteomicsDB; 52770; -. [P11388-4] DR Pumba; P11388; -. DR Antibodypedia; 1583; 1693 antibodies from 45 providers. DR DNASU; 7153; -. DR Ensembl; ENST00000423485.6; ENSP00000411532.1; ENSG00000131747.15. [P11388-1] DR GeneID; 7153; -. DR KEGG; hsa:7153; -. DR MANE-Select; ENST00000423485.6; ENSP00000411532.1; NM_001067.4; NP_001058.2. DR UCSC; uc002huq.4; human. [P11388-1] DR AGR; HGNC:11989; -. DR CTD; 7153; -. DR DisGeNET; 7153; -. DR GeneCards; TOP2A; -. DR HGNC; HGNC:11989; TOP2A. DR HPA; ENSG00000131747; Tissue enhanced (lymphoid tissue, testis). DR MalaCards; TOP2A; -. DR MIM; 126430; gene. DR neXtProt; NX_P11388; -. DR OpenTargets; ENSG00000131747; -. DR Orphanet; 635; Neuroblastoma. DR PharmGKB; PA354; -. DR VEuPathDB; HostDB:ENSG00000131747; -. DR eggNOG; KOG0355; Eukaryota. DR GeneTree; ENSGT00940000157539; -. DR HOGENOM; CLU_001935_1_0_1; -. DR InParanoid; P11388; -. DR OMA; NESMDYN; -. DR OrthoDB; 1944951at2759; -. DR PhylomeDB; P11388; -. DR TreeFam; TF105282; -. DR BRENDA; 5.6.2.2; 2681. DR BRENDA; 5.99.1.3; 2681. DR PathwayCommons; P11388; -. DR Reactome; R-HSA-1362277; Transcription of E2F targets under negative control by DREAM complex. DR Reactome; R-HSA-4615885; SUMOylation of DNA replication proteins. DR SignaLink; P11388; -. DR SIGNOR; P11388; -. DR BioGRID-ORCS; 7153; 841 hits in 1180 CRISPR screens. DR ChiTaRS; TOP2A; human. DR EvolutionaryTrace; P11388; -. DR GeneWiki; TOP2A; -. DR GenomeRNAi; 7153; -. DR Pharos; P11388; Tclin. DR PRO; PR:P11388; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P11388; Protein. DR Bgee; ENSG00000131747; Expressed in ventricular zone and 144 other cell types or tissues. DR ExpressionAtlas; P11388; baseline and differential. DR GO; GO:0000775; C:chromosome, centromeric region; IEA:Ensembl. DR GO; GO:0000793; C:condensed chromosome; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0009330; C:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex; IDA:UniProtKB. DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0008301; F:DNA binding, bending; IDA:UniProtKB. DR GO; GO:0003918; F:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity; IDA:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0043130; F:ubiquitin binding; IMP:UniProtKB. DR GO; GO:0030263; P:apoptotic chromosome condensation; IDA:UniProtKB. DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0006266; P:DNA ligation; IDA:UniProtKB. DR GO; GO:0006265; P:DNA topological change; IDA:UniProtKB. DR GO; GO:0040016; P:embryonic cleavage; IEA:Ensembl. DR GO; GO:0007143; P:female meiotic nuclear division; IEA:Ensembl. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl. DR GO; GO:1905463; P:negative regulation of DNA duplex unwinding; IMP:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0045870; P:positive regulation of single stranded viral RNA replication via double stranded DNA intermediate; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0000819; P:sister chromatid segregation; IBA:GO_Central. DR CDD; cd16930; HATPase_TopII-like; 1. DR CDD; cd00187; TOP4c; 1. DR CDD; cd03481; TopoIIA_Trans_ScTopoIIA; 1. DR CDD; cd03365; TOPRIM_TopoIIA; 1. DR Gene3D; 3.30.1360.40; -; 1. DR Gene3D; 3.30.1490.30; -; 1. DR Gene3D; 3.30.230.10; -; 1. DR Gene3D; 3.40.50.670; -; 1. DR Gene3D; 3.30.565.10; Histidine kinase-like ATPase, C-terminal domain; 1. DR Gene3D; 3.90.199.10; Topoisomerase II, domain 5; 1. DR Gene3D; 1.10.268.10; Topoisomerase, domain 3; 1. DR InterPro; IPR012542; DTHCT. DR InterPro; IPR003594; HATPase_C. DR InterPro; IPR036890; HATPase_C_sf. DR InterPro; IPR020568; Ribosomal_Su5_D2-typ_SF. DR InterPro; IPR014721; Ribsml_uS5_D2-typ_fold_subgr. DR InterPro; IPR001241; Topo_IIA. DR InterPro; IPR013760; Topo_IIA-like_dom_sf. DR InterPro; IPR013758; Topo_IIA_A/C_ab. DR InterPro; IPR013757; Topo_IIA_A_a_sf. DR InterPro; IPR013759; Topo_IIA_B_C. DR InterPro; IPR013506; Topo_IIA_bsu_dom2. DR InterPro; IPR002205; Topo_IIA_dom_A. DR InterPro; IPR001154; TopoII_euk. DR InterPro; IPR018522; TopoIIA_CS. DR InterPro; IPR031660; TOPRIM_C. DR InterPro; IPR006171; TOPRIM_domain. DR InterPro; IPR034157; TOPRIM_TopoII. DR PANTHER; PTHR10169:SF61; DNA TOPOISOMERASE 2-ALPHA; 1. DR PANTHER; PTHR10169; DNA TOPOISOMERASE/GYRASE; 1. DR Pfam; PF00204; DNA_gyraseB; 1. DR Pfam; PF00521; DNA_topoisoIV; 1. DR Pfam; PF08070; DTHCT; 1. DR Pfam; PF02518; HATPase_c; 1. DR Pfam; PF01751; Toprim; 1. DR Pfam; PF16898; TOPRIM_C; 1. DR PRINTS; PR01158; TOPISMRASEII. DR PRINTS; PR00418; TPI2FAMILY. DR SMART; SM00433; TOP2c; 1. DR SMART; SM00434; TOP4c; 1. DR SUPFAM; SSF55874; ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase; 1. DR SUPFAM; SSF54211; Ribosomal protein S5 domain 2-like; 1. DR SUPFAM; SSF56719; Type II DNA topoisomerase; 1. DR PROSITE; PS52040; TOPO_IIA; 1. DR PROSITE; PS00177; TOPOISOMERASE_II; 1. DR PROSITE; PS50880; TOPRIM; 1. DR UCD-2DPAGE; P11388; -. DR Genevisible; P11388; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Biological rhythms; Cytoplasm; Direct protein sequencing; DNA-binding; KW Isomerase; Isopeptide bond; Magnesium; Metal-binding; Nucleotide-binding; KW Nucleus; Phosphoprotein; Reference proteome; Topoisomerase; KW Ubl conjugation. FT CHAIN 1..1531 FT /note="DNA topoisomerase 2-alpha" FT /id="PRO_0000145363" FT DOMAIN 455..572 FT /note="Toprim" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995" FT DOMAIN 715..1171 FT /note="Topo IIA-type catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01384" FT REGION 342..344 FT /note="Interaction with DNA" FT /evidence="ECO:0000305|PubMed:23022727" FT REGION 990..999 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:22841979" FT REGION 1090..1123 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1184..1531 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1433..1439 FT /note="Interaction with PLSCR1" FT /evidence="ECO:0000269|PubMed:17567603" FT MOTIF 1018..1028 FT /note="Nuclear export signal" FT COMPBIAS 1225..1274 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1289..1332 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1333..1347 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1354..1372 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1408..1434 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1466..1504 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 805 FT /note="O-(5'-phospho-DNA)-tyrosine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01384" FT BINDING 91 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:16100112, FT ECO:0000269|PubMed:25202966" FT BINDING 120 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:16100112, FT ECO:0000269|PubMed:25202966" FT BINDING 148..150 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:16100112, FT ECO:0000269|PubMed:25202966" FT BINDING 161..168 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:16100112, FT ECO:0000269|PubMed:25202966" FT BINDING 376..378 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:16100112, FT ECO:0000305|PubMed:25202966" FT BINDING 461 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995" FT BINDING 541 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995" FT BINDING 541 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:22841979" FT BINDING 543 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:22841979" FT SITE 489 FT /note="Interaction with DNA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995" FT SITE 492 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:22841979" FT SITE 661 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:22841979" FT SITE 662 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:22841979" FT SITE 723 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:22841979" FT SITE 757 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:22841979" FT SITE 763 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:22841979" FT SITE 804 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250|UniProtKB:P06786" FT SITE 856 FT /note="Important for DNA bending; intercalates between base FT pairs of target DNA" FT /evidence="ECO:0000250|UniProtKB:P06786" FT SITE 931 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:22841979" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|Ref.10, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:22814378" FT MOD_RES 4 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 282 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1106 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000269|PubMed:19043076, ECO:0000269|Ref.11, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1205 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1213 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 1244 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1247 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 1295 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 1297 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 1299 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 1302 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 1327 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q01320" FT MOD_RES 1332 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 1337 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 1343 FT /note="Phosphothreonine; by PLK3" FT /evidence="ECO:0000269|PubMed:18062778, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 1351 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT MOD_RES 1354 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 1374 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1377 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1387 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1391 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1392 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1393 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 1422 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q01320" FT MOD_RES 1442 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q01320" FT MOD_RES 1449 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1469 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:10942766, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1470 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692" FT MOD_RES 1471 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1474 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1476 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 1495 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1504 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18220336, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1525 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT CROSSLNK 17 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 156 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 157 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 261 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 352 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 386 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 397 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 416 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 418 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 425 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 440 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 466 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 480 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 529 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 584 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 599 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 614 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 622 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 625 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 632 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 639 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 655 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 662 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 676 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 1075 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 1114 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1196 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 1204 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1228 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 1240 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 1240 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25114211, FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT CROSSLNK 1259 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1276 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1283 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1286 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1363 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1367 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1373 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1385 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT CROSSLNK 1422 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1442 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 1454 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1459 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1484 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1492 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT VAR_SEQ 321 FT /note="K -> KSSKYWSSRKSKQHILLNFFVLFKFINDAFFGICPFK (in FT isoform 3)" FT /evidence="ECO:0000303|Ref.8" FT /id="VSP_006529" FT VAR_SEQ 355 FT /note="Q -> QRELCNGAILAHCNLRLMGSSDSPASASRVAGIAGGCHHTQLIFVFL FT VETGFHHVGQAGLERLTSGDPPASASQSSGITDVK (in isoform 4)" FT /evidence="ECO:0000303|Ref.8" FT /id="VSP_006530" FT VAR_SEQ 401 FT /note="A -> AHLYSRFLIDPFFPNMIPNMIFSFSKA (in isoform 2)" FT /evidence="ECO:0000303|Ref.8" FT /id="VSP_006531" FT VARIANT 450 FT /note="R -> Q (in teniposide (VM-26) resistant cells; FT dbSNP:rs746765101)" FT /evidence="ECO:0000269|PubMed:1652758" FT /id="VAR_007532" FT VARIANT 487 FT /note="R -> K (in amsacrine resistant cells; FT dbSNP:rs267607133)" FT /evidence="ECO:0000269|PubMed:1651812" FT /id="VAR_007533" FT VARIANT 1324 FT /note="T -> K (in dbSNP:rs28969502)" FT /id="VAR_029245" FT VARIANT 1386 FT /note="G -> D (in dbSNP:rs34300454)" FT /id="VAR_052594" FT VARIANT 1515 FT /note="A -> S (in dbSNP:rs11540720)" FT /id="VAR_052595" FT MUTAGEN 342..344 FT /note="KKK->AAA: Reduced enzyme activity; abolishes FT stimulation of ATPase activity upon DNA binding." FT /evidence="ECO:0000269|PubMed:23022727" FT MUTAGEN 342..344 FT /note="KKK->EEE: Strongly reduced enzyme activity; FT abolishes stimulation of ATPase activity upon DNA binding." FT /evidence="ECO:0000269|PubMed:23022727" FT MUTAGEN 461 FT /note="E->A,C: Impairs bending of target DNA. Strongly FT reduced DNA cleavage." FT /evidence="ECO:0000269|PubMed:19697956, FT ECO:0000269|PubMed:22323612" FT MUTAGEN 541 FT /note="D->A,C: Impairs bending of target DNA. Strongly FT reduced DNA cleavage." FT /evidence="ECO:0000269|PubMed:19697956, FT ECO:0000269|PubMed:22323612" FT MUTAGEN 543 FT /note="D->A,C: Impairs bending of target DNA. Strongly FT reduced DNA cleavage." FT /evidence="ECO:0000269|PubMed:19697956, FT ECO:0000269|PubMed:22323612" FT MUTAGEN 545 FT /note="D->A,C: Strongly reduced DNA cleavage." FT /evidence="ECO:0000269|PubMed:19697956" FT MUTAGEN 1469 FT /note="S->A: Abolishes binding to the antibody MPM2." FT /evidence="ECO:0000269|PubMed:10942766" FT CONFLICT 152 FT /note="D -> H (in Ref. 4; CAA09762)" FT /evidence="ECO:0000305" FT CONFLICT 180 FT /note="E -> Q (in Ref. 4; CAA09762)" FT /evidence="ECO:0000305" FT CONFLICT 327 FT /note="D -> H (in Ref. 4; CAA09762)" FT /evidence="ECO:0000305" FT CONFLICT 1022 FT /note="F -> L (in Ref. 4; CAA09762)" FT /evidence="ECO:0000305" FT CONFLICT 1274 FT /note="T -> S (in Ref. 4; CAA09762)" FT /evidence="ECO:0000305" FT CONFLICT 1295 FT /note="S -> P (in Ref. 1; AAA61209)" FT /evidence="ECO:0000305" FT HELIX 30..33 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 34..36 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 39..45 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 48..51 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 57..65 FT /evidence="ECO:0007829|PDB:1ZXM" FT TURN 66..68 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 69..77 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 79..98 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 104..110 FT /evidence="ECO:0007829|PDB:1ZXM" FT TURN 111..114 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 115..123 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 128..130 FT /evidence="ECO:0007829|PDB:1ZXM" FT TURN 131..134 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 137..143 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 144..149 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 153..155 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 166..172 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 174..183 FT /evidence="ECO:0007829|PDB:1ZXM" FT TURN 184..187 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 188..195 FT /evidence="ECO:0007829|PDB:1ZXM" FT TURN 196..199 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 205..208 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 214..221 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 223..226 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 233..249 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 250..252 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 254..257 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 267..275 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 281..285 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 289..294 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 297..303 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 305..307 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 309..314 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 324..341 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 346..348 FT /evidence="ECO:0007829|PDB:1ZXN" FT HELIX 353..357 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 360..366 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 373..375 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 385..387 FT /evidence="ECO:0007829|PDB:1ZXM" FT STRAND 388..390 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 396..402 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 407..410 FT /evidence="ECO:0007829|PDB:1ZXM" FT HELIX 411..415 FT /evidence="ECO:0007829|PDB:1ZXN" FT STRAND 419..421 FT /evidence="ECO:0007829|PDB:1ZXN" FT STRAND 423..425 FT /evidence="ECO:0007829|PDB:1ZXN" FT TURN 445..448 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 452..454 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 456..462 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 463..476 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 478..486 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 498..503 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 505..514 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 518..520 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 525..530 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 534..539 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 544..560 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 562..566 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 570..573 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 577..581 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 586..590 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 592..601 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 607..612 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 616..618 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 621..629 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 631..634 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 635..639 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 644..653 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 658..678 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 685..688 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 691..694 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 695..701 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 703..714 FT /evidence="ECO:0007829|PDB:4FM9" FT TURN 718..720 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 724..735 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 744..754 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 762..772 FT /evidence="ECO:0007829|PDB:4FM9" FT TURN 793..799 FT /evidence="ECO:0007829|PDB:4FM9" FT TURN 803..805 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 812..817 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 822..824 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 831..833 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 834..839 FT /evidence="ECO:0007829|PDB:5GWK" FT TURN 848..850 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 853..856 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 861..864 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 869..881 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 897..903 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 906..910 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 912..915 FT /evidence="ECO:0007829|PDB:5GWK" FT STRAND 921..923 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 932..938 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 940..944 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 948..950 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 955..959 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 968..971 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 974..983 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 985..988 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 992..996 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 1000..1003 FT /evidence="ECO:0007829|PDB:4FM9" FT STRAND 1009..1011 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 1015..1059 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 1070..1080 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 1086..1091 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 1126..1129 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 1133..1136 FT /evidence="ECO:0007829|PDB:5GWK" FT HELIX 1138..1160 FT /evidence="ECO:0007829|PDB:4FM9" FT HELIX 1163..1189 FT /evidence="ECO:0007829|PDB:4FM9" SQ SEQUENCE 1531 AA; 174385 MW; 3DF40BC9E84789DC CRC64; MEVSPLQPVN ENMQVNKIKK NEDAKKRLSV ERIYQKKTQL EHILLRPDTY IGSVELVTQQ MWVYDEDVGI NYREVTFVPG LYKIFDEILV NAADNKQRDP KMSCIRVTID PENNLISIWN NGKGIPVVEH KVEKMYVPAL IFGQLLTSSN YDDDEKKVTG GRNGYGAKLC NIFSTKFTVE TASREYKKMF KQTWMDNMGR AGEMELKPFN GEDYTCITFQ PDLSKFKMQS LDKDIVALMV RRAYDIAGST KDVKVFLNGN KLPVKGFRSY VDMYLKDKLD ETGNSLKVIH EQVNHRWEVC LTMSEKGFQQ ISFVNSIATS KGGRHVDYVA DQIVTKLVDV VKKKNKGGVA VKAHQVKNHM WIFVNALIEN PTFDSQTKEN MTLQPKSFGS TCQLSEKFIK AAIGCGIVES ILNWVKFKAQ VQLNKKCSAV KHNRIKGIPK LDDANDAGGR NSTECTLILT EGDSAKTLAV SGLGVVGRDK YGVFPLRGKI LNVREASHKQ IMENAEINNI IKIVGLQYKK NYEDEDSLKT LRYGKIMIMT DQDQDGSHIK GLLINFIHHN WPSLLRHRFL EEFITPIVKV SKNKQEMAFY SLPEFEEWKS STPNHKKWKV KYYKGLGTST SKEAKEYFAD MKRHRIQFKY SGPEDDAAIS LAFSKKQIDD RKEWLTNFME DRRQRKLLGL PEDYLYGQTT TYLTYNDFIN KELILFSNSD NERSIPSMVD GLKPGQRKVL FTCFKRNDKR EVKVAQLAGS VAEMSSYHHG EMSLMMTIIN LAQNFVGSNN LNLLQPIGQF GTRLHGGKDS ASPRYIFTML SSLARLLFPP KDDHTLKFLY DDNQRVEPEW YIPIIPMVLI NGAEGIGTGW SCKIPNFDVR EIVNNIRRLM DGEEPLPMLP SYKNFKGTIE ELAPNQYVIS GEVAILNSTT IEISELPVRT WTQTYKEQVL EPMLNGTEKT PPLITDYREY HTDTTVKFVV KMTEEKLAEA ERVGLHKVFK LQTSLTCNSM VLFDHVGCLK KYDTVLDILR DFFELRLKYY GLRKEWLLGM LGAESAKLNN QARFILEKID GKIIIENKPK KELIKVLIQR GYDSDPVKAW KEAQQKVPDE EENEESDNEK ETEKSDSVTD SGPTFNYLLD MPLWYLTKEK KDELCRLRNE KEQELDTLKR KSPSDLWKED LATFIEELEA VEAKEKQDEQ VGLPGKGGKA KGKKTQMAEV LPSPRGQRVI PRITIEMKAE AEKKNKKKIK NENTEGSPQE DGVELEGLKQ RLEKKQKREP GTKTKKQTTL AFKPIKKGKK RNPWSDSESD RSSDESNFDV PPRETEPRRA ATKTKFTMDL DSDEDFSDFD EKTDDEDFVP SDASPPKTKT SPKLSNKELK PQKSVVSDLE ADDVKGSVPL SSSPPATHFP DETEITNPVP KKNVTVKKTA AKSQSSTSTT GAKKRAAPKG TKRDPALNSG VSQKPDPAKT KNRRKRKPST SDDSDSNFEK IVSKAVTSKK SKGESDDFHM DFDSAVAPRA KSVRAKKPIK YLEESDEDDL F //