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 UCD-2DPAGE; P11388; -.
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 Genevisible; P11388; HS.
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.
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
//
