MASCOT Search Results
Protein View: TOP2A_HUMAN
DNA topoisomerase 2-alpha OS=Homo sapiens GN=TOP2A PE=1 SV=3
AC Q9UQP9;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 04-MAY-2001, sequence version 3.
DT 29-OCT-2014, entry version 185.
DE RecName: Full=DNA topoisomerase 2-alpha;
DE EC=5.99.1.3;
DE AltName: Full=DNA topoisomerase II, alpha isozyme;
GN Name=TOP2A; Synonyms=TOP2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT and 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
RT IIalpha 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.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA 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
RT the 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT mRNAs 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;
RP 805-815; 828-835; 864-877; 937-958; 1021-1026 AND 1185-1196,
RP ACETYLATION AT MET-1, 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;
RP 401-416; 467-478; 536-550; 569-579; 640-655; 702-713; 805-815;
RP 1011-1020; 1097-1114; 1169-1184; 1239-1259 AND 1374-1411,
RP PHOSPHORYLATION AT SER-1106, AND 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 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
RT kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469.";
RL J. Biol. Chem. 275:34710-34718(2000).
RN [13]
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 [14]
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 [15]
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
RP SCALE 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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1213; SER-1374; SER-1377
RP AND SER-1525, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1247, AND IDENTIFICATION
RP BY 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
RT cells and high confident phosphopeptide identification by cross-
RT validation of MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [18]
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
RT is not recognized by Plk1.";
RL Biochem. J. 411:27-32(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1504, AND IDENTIFICATION
RP BY 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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-1213; SER-1247;
RP SER-1332; SER-1337 AND SER-1377, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [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
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1106; SER-1213;
RP SER-1332; SER-1337; THR-1343; SER-1351; SER-1392; SER-1393; SER-1449;
RP SER-1469; THR-1470; SER-1471; SER-1474 AND SER-1525, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [22]
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.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [23]
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
RT II topoisomerases.";
RL Biochemistry 48:1862-1869(2009).
RN [24]
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
RT human topoisomerase IIalpha.";
RL Biochemistry 48:8940-8947(2009).
RN [25]
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1247; SER-1374;
RP SER-1387; SER-1393; SER-1504 AND SER-1525, AND IDENTIFICATION BY MASS
RP 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 [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-4; THR-282; SER-1106; THR-1205; SER-1213;
RP SER-1247; SER-1332; SER-1337; THR-1343; SER-1351; SER-1354; SER-1374;
RP SER-1377; SER-1471; SER-1474; SER-1495; SER-1504 AND SER-1525, 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [28]
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.,
RA Buerckstuemmer T., 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 [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-4; SER-1106; SER-1213; SER-1247; SER-1295;
RP SER-1297; SER-1299; SER-1302; SER-1332; SER-1337; THR-1343; SER-1351;
RP SER-1354; SER-1374; SER-1377; SER-1469; THR-1470; SER-1471; SER-1474;
RP SER-1476 AND SER-1525, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
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 [31]
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.,
RA May A., Kulikowicz T., Sykora P., Croteau D.L., Bohr V.A.;
RT "RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and
RT cell cycle progression.";
RL Nucleic Acids Res. 40:1621-1635(2012).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY
RP MASS 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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [33]
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.,
RA 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 [34]
RP X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 29-428 IN COMPLEX WITH ADP,
RP AND X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS) OF 29-428 IN COMPLEX WITH
RP 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
RT type IIA DNA topoisomerase.";
RL J. Biol. Chem. 280:37041-37047(2005).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 431-1193 IN COMPLEX WITH DNA
RP AND 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:
RT conformational mechanisms for coordinating inter-subunit interactions
RT with DNA cleavage.";
RL J. Mol. Biol. 424:109-124(2012).
RN [36]
RP VARIANT AMSACRINE-RESISTANT LYS-487.
RX PubMed=1651812;
RA Hinds M., Deisseroth K., Mayes J., Altschuler E., Jansen R.,
RA Ledley F.D., Zwelling L.A.;
RT "Identification of a point mutation in the topoisomerase II gene from
RT a human leukemia cell line containing an amsacrine-resistant form of
RT topoisomerase II.";
RL Cancer Res. 51:4729-4731(1991).
RN [37]
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
RT leukemic cells selected for resistance to teniposide.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:7654-7658(1991).
CC -!- FUNCTION: Control of topological states of DNA by transient
CC breakage and subsequent rejoining of DNA strands. Topoisomerase II
CC makes double-strand breaks. Essential during mitosis and meiosis
CC for proper segregation of daughter chromosomes.
CC {ECO:0000269|PubMed:22013166, ECO:0000269|PubMed:22323612}.
CC -!- CATALYTIC ACTIVITY: ATP-dependent breakage, passage and rejoining
CC of double-stranded DNA. {ECO:0000255|PROSITE-ProRule:PRU00995,
CC ECO:0000269|PubMed:19222228, ECO:0000269|PubMed:19697956}.
CC -!- COFACTOR: Magnesium. Binds two Mg(2+) per subunit. The magnesium
CC ions form salt bridges with both the protein and the DNA. Can also
CC accept other divalent metal cations, such as Mn(2+) and Ca(2+)
CC (Probable). {ECO:0000305|PubMed:19222228,
CC ECO:0000305|PubMed:19697956, ECO:0000305|PubMed:22323612,
CC ECO:0000305|PubMed:22841979}.
CC -!- ENZYME REGULATION: Specifically inhibited by the intercalating
CC agent amsacrine.
CC -!- SUBUNIT: Homodimer. Interacts with COPS5. Interacts with RECQL5;
CC this stimulates DNA decatenation. {ECO:0000269|PubMed:15126503,
CC ECO:0000269|PubMed:16100112, ECO:0000269|PubMed:22013166,
CC ECO:0000269|PubMed:22841979}.
CC -!- INTERACTION:
CC P35222:CTNNB1; NbExp=5; IntAct=EBI-539628, EBI-491549;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22013166}.
CC Nucleus, nucleoplasm {ECO:0000269|PubMed:22013166}. Note=Generally
CC located in the nucleoplasm.
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 -!- 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:16964243, ECO:0000269|PubMed:17081983,
CC ECO:0000269|PubMed:17924679, ECO:0000269|PubMed:18062778,
CC ECO:0000269|PubMed:18220336, ECO:0000269|PubMed:18669648,
CC ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:19043076,
CC ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231,
CC ECO:0000269|PubMed:21406692, ECO:0000269|Ref.11}.
CC -!- MISCELLANEOUS: Eukaryotic topoisomerase I and II can relax both
CC negative and positive supercoils, whereas prokaryotic enzymes
CC relax only negative supercoils.
CC -!- SIMILARITY: Belongs to the type II topoisomerase family.
CC {ECO:0000305}.
CC -!- SIMILARITY: Contains 1 Toprim domain. {ECO:0000255|PROSITE-
CC ProRule:PRU00995}.
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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 UniGene; Hs.156346; -.
DR PDB; 1LWZ; Model; -; A=431-1200.
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 PDBsum; 1LWZ; -.
DR PDBsum; 1ZXM; -.
DR PDBsum; 1ZXN; -.
DR PDBsum; 4FM9; -.
DR ProteinModelPortal; P11388; -.
DR SMR; P11388; 29-1190.
DR BioGrid; 113006; 62.
DR DIP; DIP-33887N; -.
DR IntAct; P11388; 17.
DR MINT; MINT-98770; -.
DR BindingDB; P11388; -.
DR ChEMBL; CHEMBL1806; -.
DR DrugBank; DB00276; Amsacrine.
DR DrugBank; DB00537; Ciprofloxacin.
DR DrugBank; DB00970; Dactinomycin.
DR DrugBank; DB00694; Daunorubicin.
DR DrugBank; DB00380; Dexrazoxane.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB00467; Enoxacin.
DR DrugBank; DB00445; Epirubicin.
DR DrugBank; DB00773; Etoposide.
DR DrugBank; DB04576; Fleroxacin.
DR DrugBank; DB01177; Idarubicin.
DR DrugBank; DB01137; Levofloxacin.
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; DB01208; Sparfloxacin.
DR DrugBank; DB00444; Teniposide.
DR DrugBank; DB00685; Trovafloxacin.
DR DrugBank; DB00385; Valrubicin.
DR GuidetoPHARMACOLOGY; 2637; -.
DR PhosphoSite; P11388; -.
DR DMDM; 13959709; -.
DR UCD-2DPAGE; P11388; -.
DR MaxQB; P11388; -.
DR PaxDb; P11388; -.
DR PRIDE; P11388; -.
DR Ensembl; ENST00000423485; ENSP00000411532; ENSG00000131747. [P11388-1]
DR GeneID; 7153; -.
DR KEGG; hsa:7153; -.
DR UCSC; uc002huq.3; human. [P11388-1]
DR CTD; 7153; -.
DR GeneCards; GC17M038544; -.
DR H-InvDB; HIX0013797; -.
DR HGNC; HGNC:11989; TOP2A.
DR HPA; CAB002448; -.
DR HPA; HPA006458; -.
DR HPA; HPA026773; -.
DR MIM; 126430; gene.
DR neXtProt; NX_P11388; -.
DR Orphanet; 635; Neuroblastoma.
DR PharmGKB; PA354; -.
DR eggNOG; COG0187; -.
DR GeneTree; ENSGT00390000016222; -.
DR HOVERGEN; HBG052998; -.
DR InParanoid; P11388; -.
DR KO; K03164; -.
DR OMA; SRWEVCL; -.
DR OrthoDB; EOG73JKTM; -.
DR PhylomeDB; P11388; -.
DR TreeFam; TF105282; -.
DR BRENDA; 5.99.1.3; 2681.
DR Reactome; REACT_111214; G0 and Early G1.
DR SignaLink; P11388; -.
DR EvolutionaryTrace; P11388; -.
DR GeneWiki; TOP2A; -.
DR GenomeRNAi; 7153; -.
DR NextBio; 27992; -.
DR PRO; PR:P11388; -.
DR Bgee; P11388; -.
DR CleanEx; HS_TOP2A; -.
DR ExpressionAtlas; P11388; baseline and differential.
DR Genevestigator; P11388; -.
DR GO; GO:0000793; C:condensed chromosome; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0009330; C:DNA topoisomerase complex (ATP-hydrolyzing); IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0043234; C:protein complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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 (ATP-hydrolyzing) activity; IDA:UniProtKB.
DR GO; GO:0008094; F:DNA-dependent ATPase activity; IDA:UniProtKB.
DR GO; GO:0008144; F:drug binding; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI: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:0043130; F:ubiquitin binding; IMP:UniProtKB.
DR GO; GO:0030263; P:apoptotic chromosome condensation; IDA:UniProtKB.
DR GO; GO:0006200; P:ATP catabolic process; IDA:GOC.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0006266; P:DNA ligation; IDA:UniProtKB.
DR GO; GO:0006265; P:DNA topological change; IDA:UniProtKB.
DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IBA:RefGenome.
DR GO; GO:0040016; P:embryonic cleavage; IEA:Ensembl.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome.
DR GO; GO:0044774; P:mitotic DNA integrity checkpoint; IBA:RefGenome.
DR GO; GO:0006312; P:mitotic recombination; IBA:RefGenome.
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 from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:RefGenome.
DR GO; GO:0000819; P:sister chromatid segregation; IBA:RefGenome.
DR Gene3D; 1.10.268.10; -; 1.
DR Gene3D; 3.30.1360.40; -; 1.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR Gene3D; 3.40.50.670; -; 1.
DR Gene3D; 3.90.199.10; -; 1.
DR InterPro; IPR024946; Arg_repress_C-like.
DR InterPro; IPR012542; DTHCT.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR InterPro; IPR028466; Top2a.
DR InterPro; IPR001241; Topo_IIA.
DR InterPro; IPR002205; Topo_IIA_A/C.
DR InterPro; IPR013758; Topo_IIA_A/C_ab.
DR InterPro; IPR013757; Topo_IIA_A_a.
DR InterPro; IPR013506; Topo_IIA_bsu_dom2.
DR InterPro; IPR013759; Topo_IIA_cen_dom.
DR InterPro; IPR013760; Topo_IIA_like_dom.
DR InterPro; IPR018522; TopoIIA_CS.
DR InterPro; IPR006171; Toprim_domain.
DR PANTHER; PTHR10169:SF33; PTHR10169:SF33; 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 PRINTS; PR00418; TPI2FAMILY.
DR SMART; SM00387; HATPase_c; 1.
DR SMART; SM00433; TOP2c; 1.
DR SMART; SM00434; TOP4c; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR SUPFAM; SSF56719; SSF56719; 1.
DR PROSITE; PS00177; TOPOISOMERASE_II; 1.
DR PROSITE; PS50880; TOPRIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding;
KW Isomerase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Topoisomerase.
FT CHAIN 1 1531 DNA topoisomerase 2-alpha.
FT /FTId=PRO_0000145363.
FT DOMAIN 455 572 Toprim. {ECO:0000255|PROSITE-
FT ProRule:PRU00995}.
FT NP_BIND 148 150 ATP.
FT NP_BIND 161 168 ATP.
FT NP_BIND 376 378 ATP.
FT REGION 342 344 Interaction with DNA. {ECO:0000305}.
FT REGION 990 999 Interaction with DNA.
FT MOTIF 1018 1028 Nuclear export signal.
FT ACT_SITE 805 805 O-(5'-phospho-DNA)-tyrosine intermediate.
FT {ECO:0000250}.
FT METAL 461 461 Magnesium 1; catalytic.
FT {ECO:0000255|PROSITE-ProRule:PRU00995}.
FT METAL 541 541 Magnesium 1; catalytic.
FT {ECO:0000255|PROSITE-ProRule:PRU00995}.
FT METAL 541 541 Magnesium 2.
FT METAL 543 543 Magnesium 2.
FT BINDING 91 91 ATP.
FT BINDING 120 120 ATP.
FT SITE 489 489 Interaction with DNA.
FT {ECO:0000255|PROSITE-ProRule:PRU00995}.
FT SITE 492 492 Interaction with DNA.
FT SITE 661 661 Interaction with DNA.
FT SITE 662 662 Interaction with DNA.
FT SITE 723 723 Interaction with DNA.
FT SITE 757 757 Interaction with DNA.
FT SITE 763 763 Interaction with DNA.
FT SITE 804 804 Transition state stabilizer.
FT {ECO:0000250}.
FT SITE 856 856 Important for DNA bending; intercalates
FT between base pairs of target DNA.
FT {ECO:0000250}.
FT SITE 931 931 Interaction with DNA.
FT MOD_RES 1 1 N-acetylmethionine.
FT {ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692,
FT ECO:0000269|PubMed:22814378,
FT ECO:0000269|Ref.10}.
FT MOD_RES 4 4 Phosphoserine.
FT {ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:18691976,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 282 282 Phosphothreonine.
FT {ECO:0000269|PubMed:20068231}.
FT MOD_RES 1106 1106 Phosphoserine; by CK1.
FT {ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:19043076,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692,
FT ECO:0000269|Ref.11}.
FT MOD_RES 1205 1205 Phosphothreonine.
FT {ECO:0000269|PubMed:20068231}.
FT MOD_RES 1213 1213 Phosphoserine.
FT {ECO:0000269|PubMed:16964243,
FT ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:18691976,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1247 1247 Phosphoserine.
FT {ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:17924679,
FT ECO:0000269|PubMed:18691976,
FT ECO:0000269|PubMed:19690332,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1295 1295 Phosphoserine.
FT {ECO:0000269|PubMed:21406692}.
FT MOD_RES 1297 1297 Phosphoserine.
FT {ECO:0000269|PubMed:21406692}.
FT MOD_RES 1299 1299 Phosphoserine.
FT {ECO:0000269|PubMed:21406692}.
FT MOD_RES 1302 1302 Phosphoserine.
FT {ECO:0000269|PubMed:21406692}.
FT MOD_RES 1332 1332 Phosphoserine.
FT {ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:18691976,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1337 1337 Phosphoserine.
FT {ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:18691976,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1343 1343 Phosphothreonine; by PLK3.
FT {ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:18062778,
FT ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1351 1351 Phosphoserine.
FT {ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1354 1354 Phosphoserine.
FT {ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1374 1374 Phosphoserine.
FT {ECO:0000269|PubMed:16964243,
FT ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:19690332,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1377 1377 Phosphoserine.
FT {ECO:0000269|PubMed:16964243,
FT ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:18691976,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1387 1387 Phosphoserine.
FT {ECO:0000269|PubMed:19690332}.
FT MOD_RES 1392 1392 Phosphoserine.
FT {ECO:0000269|PubMed:18669648}.
FT MOD_RES 1393 1393 Phosphoserine.
FT {ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:19690332}.
FT MOD_RES 1422 1422 N6-acetyllysine. {ECO:0000250}.
FT MOD_RES 1442 1442 N6-acetyllysine. {ECO:0000250}.
FT MOD_RES 1449 1449 Phosphoserine.
FT {ECO:0000269|PubMed:18669648}.
FT MOD_RES 1469 1469 Phosphoserine; by CK2.
FT {ECO:0000269|PubMed:10942766,
FT ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1470 1470 Phosphothreonine.
FT {ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1471 1471 Phosphoserine.
FT {ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1474 1474 Phosphoserine.
FT {ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT MOD_RES 1476 1476 Phosphoserine.
FT {ECO:0000269|PubMed:21406692}.
FT MOD_RES 1495 1495 Phosphoserine.
FT {ECO:0000269|PubMed:20068231}.
FT MOD_RES 1504 1504 Phosphoserine.
FT {ECO:0000269|PubMed:18220336,
FT ECO:0000269|PubMed:19690332,
FT ECO:0000269|PubMed:20068231}.
FT MOD_RES 1525 1525 Phosphoserine.
FT {ECO:0000269|PubMed:16964243,
FT ECO:0000269|PubMed:17081983,
FT ECO:0000269|PubMed:18669648,
FT ECO:0000269|PubMed:19690332,
FT ECO:0000269|PubMed:20068231,
FT ECO:0000269|PubMed:21406692}.
FT VAR_SEQ 321 321 K -> KSSKYWSSRKSKQHILLNFFVLFKFINDAFFGICPF
FT K (in isoform 3). {ECO:0000303|Ref.8}.
FT /FTId=VSP_006529.
FT VAR_SEQ 355 355 Q -> QRELCNGAILAHCNLRLMGSSDSPASASRVAGIAGG
FT CHHTQLIFVFLVETGFHHVGQAGLERLTSGDPPASASQSSG
FT ITDVK (in isoform 4).
FT {ECO:0000303|Ref.8}.
FT /FTId=VSP_006530.
FT VAR_SEQ 401 401 A -> AHLYSRFLIDPFFPNMIPNMIFSFSKA (in
FT isoform 2). {ECO:0000303|Ref.8}.
FT /FTId=VSP_006531.
FT VARIANT 450 450 R -> Q (in teniposide (VM-26) resistant
FT cells). {ECO:0000269|PubMed:1652758}.
FT /FTId=VAR_007532.
FT VARIANT 487 487 R -> K (in amsacrine resistant cells).
FT {ECO:0000269|PubMed:1651812}.
FT /FTId=VAR_007533.
FT VARIANT 1324 1324 T -> K (in dbSNP:rs28969502).
FT /FTId=VAR_029245.
FT VARIANT 1386 1386 G -> D (in dbSNP:rs34300454).
FT /FTId=VAR_052594.
FT VARIANT 1515 1515 A -> S (in dbSNP:rs11540720).
FT /FTId=VAR_052595.
FT MUTAGEN 342 344 KKK->AAA: Reduced enzyme activity;
FT abolishes stimulation of ATPase activity
FT upon DNA binding.
FT {ECO:0000269|PubMed:23022727}.
FT MUTAGEN 342 344 KKK->EEE: Strongly reduced enzyme
FT activity; abolishes stimulation of ATPase
FT activity upon DNA binding.
FT {ECO:0000269|PubMed:23022727}.
FT MUTAGEN 461 461 E->A,C: Impairs bending of target DNA.
FT Strongly reduced DNA cleavage.
FT {ECO:0000269|PubMed:19697956,
FT ECO:0000269|PubMed:22323612}.
FT MUTAGEN 541 541 D->A,C: Impairs bending of target DNA.
FT Strongly reduced DNA cleavage.
FT {ECO:0000269|PubMed:19697956,
FT ECO:0000269|PubMed:22323612}.
FT MUTAGEN 543 543 D->A,C: Impairs bending of target DNA.
FT Strongly reduced DNA cleavage.
FT {ECO:0000269|PubMed:19697956,
FT ECO:0000269|PubMed:22323612}.
FT MUTAGEN 545 545 D->A,C: Strongly reduced DNA cleavage.
FT {ECO:0000269|PubMed:19697956}.
FT MUTAGEN 1469 1469 S->A: Abolishes binding to the antibody
FT MPM2. {ECO:0000269|PubMed:10942766}.
FT CONFLICT 152 152 D -> H (in Ref. 4; CAA09762).
FT {ECO:0000305}.
FT CONFLICT 180 180 E -> Q (in Ref. 4; CAA09762).
FT {ECO:0000305}.
FT CONFLICT 327 327 D -> H (in Ref. 4; CAA09762).
FT {ECO:0000305}.
FT CONFLICT 1022 1022 F -> L (in Ref. 4; CAA09762).
FT {ECO:0000305}.
FT CONFLICT 1274 1274 T -> S (in Ref. 4; CAA09762).
FT {ECO:0000305}.
FT CONFLICT 1295 1295 S -> P (in Ref. 1; AAA61209).
FT {ECO:0000305}.
FT HELIX 30 33
FT STRAND 34 36
FT HELIX 39 45
FT HELIX 48 51
FT STRAND 57 65
FT TURN 66 68
FT STRAND 69 77
FT HELIX 79 98
FT STRAND 104 110
FT TURN 111 114
FT STRAND 115 123
FT STRAND 128 130
FT TURN 131 134
FT HELIX 137 143
FT STRAND 144 149
FT HELIX 153 155
FT HELIX 166 172
FT STRAND 174 183
FT TURN 184 187
FT STRAND 188 195
FT TURN 196 199
FT STRAND 205 208
FT STRAND 214 221
FT HELIX 223 226
FT HELIX 233 249
FT STRAND 250 252
FT STRAND 254 257
FT HELIX 267 275
FT STRAND 281 285
FT STRAND 289 294
FT STRAND 297 303
FT STRAND 305 307
FT STRAND 309 314
FT HELIX 324 341
FT HELIX 353 357
FT STRAND 360 366
FT STRAND 373 375
FT HELIX 385 387
FT STRAND 388 390
FT HELIX 396 402
FT HELIX 411 415
FT STRAND 419 421
FT TURN 445 448
FT HELIX 452 454
FT STRAND 456 462
FT HELIX 463 476
FT STRAND 478 486
FT HELIX 498 503
FT HELIX 505 514
FT STRAND 518 520
FT HELIX 525 530
FT STRAND 534 539
FT HELIX 544 560
FT HELIX 562 566
FT STRAND 570 573
FT STRAND 577 581
FT STRAND 586 590
FT HELIX 592 601
FT STRAND 607 612
FT HELIX 616 618
FT HELIX 621 629
FT HELIX 631 634
FT STRAND 635 639
FT HELIX 644 653
FT HELIX 658 678
FT STRAND 685 688
FT STRAND 691 694
FT HELIX 695 701
FT HELIX 703 714
FT TURN 718 720
FT HELIX 724 735
FT HELIX 744 754
FT HELIX 762 772
FT TURN 793 799
FT TURN 803 805
FT HELIX 812 817
FT HELIX 822 824
FT HELIX 831 833
FT TURN 848 850
FT STRAND 853 856
FT STRAND 861 864
FT HELIX 869 881
FT STRAND 897 903
FT STRAND 906 910
FT STRAND 921 923
FT HELIX 932 938
FT HELIX 940 944
FT STRAND 948 950
FT STRAND 955 959
FT STRAND 968 971
FT HELIX 974 983
FT HELIX 985 988
FT STRAND 992 996
FT STRAND 1000 1003
FT STRAND 1009 1011
FT HELIX 1015 1059
FT HELIX 1070 1080
FT HELIX 1086 1091
FT HELIX 1126 1129
FT HELIX 1138 1160
FT HELIX 1163 1189
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