TOP2B_HUMAN
ID TOP2B_HUMAN Reviewed; 1626 AA.
AC Q02880; Q13600; Q9UMG8; Q9UQP8;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2002, sequence version 3.
DT 03-AUG-2022, entry version 230.
DE RecName: Full=DNA topoisomerase 2-beta;
DE EC=5.6.2.2 {ECO:0000255|PROSITE-ProRule:PRU00995, ECO:0000269|PubMed:10684600};
DE AltName: Full=DNA topoisomerase II, beta isozyme;
GN Name=TOP2B;
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].
RX PubMed=1333583; DOI=10.1093/nar/20.21.5587;
RA Jenkins J.R., Ayton P., Jones T., Davies S.L., Simmons D.L., Harris A.L.,
RA Sheer D., Hickson I.D.;
RT "Isolation of cDNA clones encoding the beta isozyme of human DNA
RT topoisomerase II and localisation of the gene to chromosome 3p24.";
RL Nucleic Acids Res. 20:5587-5592(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8383537; DOI=10.1016/0167-4781(93)90215-y;
RA Austin C.A., Sng J.H., Patel S., Fisher L.M.;
RT "Novel HeLa topoisomerase II is the II beta isoform: complete coding
RT sequence and homology with other type II topoisomerases.";
RL Biochim. Biophys. Acta 1172:283-291(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 149-1034.
RX PubMed=2556712; DOI=10.1073/pnas.86.23.9431;
RA Chung T.D., Drake F.H., Tan K.B., Per S.R., Crooke S.T., Mirabelli C.K.;
RT "Characterization and immunological identification of cDNA clones encoding
RT two human DNA topoisomerase II isozymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:9431-9435(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 910-1626.
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 OF 1038-1271.
RX PubMed=2163884; DOI=10.1016/0014-5793(90)81520-x;
RA Austin C.A., Fisher L.M.;
RT "Isolation and characterization of a human cDNA clone encoding a novel DNA
RT topoisomerase II homologue from HeLa cells.";
RL FEBS Lett. 266:115-117(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE OF 1277-1626.
RX PubMed=9168988; DOI=10.1006/bbrc.1997.6539;
RA Yuwen H., Hsia C.C., Nakashima Y., Evangelista A., Tabor E.;
RT "Binding of wild-type p53 by topoisomerase II and overexpression of
RT topoisomerase II in human hepatocellular carcinoma.";
RL Biochem. Biophys. Res. Commun. 234:194-197(1997).
RN [7]
RP ALTERNATIVE SPLICING.
RX PubMed=8396237; DOI=10.1093/nar/21.16.3719;
RA Davies S.L., Jenkins J.R., Hickson I.D.;
RT "Human cells express two differentially spliced forms of topoisomerase II
RT beta mRNA.";
RL Nucleic Acids Res. 21:3719-3723(1993).
RN [8]
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 [9]
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 [10]
RP COFACTOR, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-482;
RP SER-485; ARG-508; LYS-510 AND ARG-515.
RX PubMed=10684600; DOI=10.1021/bi991328b;
RA West K.L., Meczes E.L., Thorn R., Turnbull R.M., Marshall R., Austin C.A.;
RT "Mutagenesis of E477 or K505 in the B' domain of human topoisomerase II
RT beta increases the requirement for magnesium ions during strand passage.";
RL Biochemistry 39:1223-1233(2000).
RN [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1336; SER-1340; SER-1400 AND
RP SER-1413, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE 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., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [13]
RP 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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Prostate cancer;
RX PubMed=17487921; DOI=10.1002/elps.200600782;
RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT "Toward a global characterization of the phosphoproteome in prostate cancer
RT cells: identification of phosphoproteins in the LNCaP cell line.";
RL Electrophoresis 28:2027-2034(2007).
RN [15]
RP 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1454, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1400; SER-1413 AND SER-1581,
RP AND IDENTIFICATION 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., 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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1336; SER-1340; SER-1342;
RP SER-1344; SER-1375; SER-1400; SER-1413; TYR-1421; SER-1424; SER-1466;
RP SER-1550; SER-1552; SER-1581; THR-1592; SER-1596; TYR-1609 AND SER-1613,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1236; THR-1292; SER-1342;
RP SER-1344; SER-1375; SER-1400; THR-1403; SER-1413; SER-1424; SER-1461;
RP SER-1466; SER-1473; SER-1476; SER-1522; SER-1524; THR-1575 AND SER-1581,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1236; SER-1336; SER-1340;
RP SER-1342; SER-1344; SER-1400; SER-1413; SER-1424; SER-1441; SER-1452;
RP SER-1454; SER-1466; SER-1476; SER-1522; SER-1524; SER-1526 AND SER-1613,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1336; SER-1340; SER-1342;
RP SER-1344; SER-1358; SER-1400; SER-1413; SER-1424; SER-1441; SER-1454;
RP SER-1466; SER-1522; SER-1524; SER-1550; SER-1581 AND SER-1613, AND
RP 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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1236; SER-1400; SER-1413;
RP SER-1424; SER-1452; SER-1454; SER-1466; SER-1522; SER-1524; SER-1550 AND
RP SER-1552, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1400; SER-1413; SER-1522;
RP SER-1524; SER-1550; SER-1552; THR-1575; SER-1576 AND SER-1581, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-34; LYS-1227; LYS-1271; LYS-1440
RP AND LYS-1456, SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-28 (ISOFORM
RP BETA-1), 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 [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-177; LYS-373; LYS-437; LYS-605;
RP LYS-643; LYS-1227; LYS-1440 AND LYS-1456, SUMOYLATION [LARGE SCALE
RP ANALYSIS] AT LYS-28 (ISOFORM BETA-1), AND IDENTIFICATION BY MASS
RP 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 [29]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1250, AND IDENTIFICATION BY MASS
RP 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 [30]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-33; LYS-177; LYS-178; LYS-228;
RP LYS-299; LYS-367; LYS-373; LYS-437; LYS-439; LYS-446; LYS-600; LYS-605;
RP LYS-635; LYS-643; LYS-646; LYS-676; LYS-712; LYS-1092; LYS-1214; LYS-1217;
RP LYS-1226; LYS-1227; LYS-1250; LYS-1262; LYS-1271; LYS-1323; LYS-1327;
RP LYS-1398; LYS-1440; LYS-1456 AND LYS-1490, SUMOYLATION [LARGE SCALE
RP ANALYSIS] AT LYS-28 AND LYS-29 (ISOFORM BETA-1), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE 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 [31]
RP INVOLVEMENT IN BILU, VARIANTS BILU LEU-488; GLU-593 DEL AND SER-638,
RP CHARACTERIZATION OF VARIANTS BILU LEU-488; GLU-593 DEL AND SER-638, AND
RP FUNCTION.
RX PubMed=31409799; DOI=10.1038/s41467-019-11570-6;
RA Broderick L., Yost S., Li D., McGeough M.D., Booshehri L.M., Guaderrama M.,
RA Brydges S.D., Kucharova K., Patel N.C., Harr M., Hakonarson H., Zackai E.,
RA Cowell I.G., Austin C.A., Huegle B., Gebauer C., Zhang J., Xu X., Wang J.,
RA Croker B.A., Frazer K.A., Putnam C.D., Hoffman H.M.;
RT "Mutations in topoisomerase IIbeta result in a B cell immunodeficiency.";
RL Nat. Commun. 10:3644-3644(2019).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.16 ANGSTROMS) OF 450-1206 IN COMPLEX WITH DNA;
RP MAGNESIUM AND ETOPOSIDE, ACTIVE SITE, COFACTOR, AND SUBUNIT.
RX PubMed=21778401; DOI=10.1126/science.1204117;
RA Wu C.C., Li T.K., Farh L., Lin L.Y., Lin T.S., Yu Y.J., Yen T.J.,
RA Chiang C.W., Chan N.L.;
RT "Structural basis of type II topoisomerase inhibition by the anticancer
RT drug etoposide.";
RL Science 333:459-462(2011).
RN [33]
RP VARIANT TYR-63, AND INVOLVEMENT IN DEVELOPMENTAL DELAY AND AUTISM SPECTRUM
RP DISORDER.
RX PubMed=28343847; DOI=10.1016/j.cca.2017.03.022;
RA Lam C.W., Yeung W.L., Law C.Y.;
RT "Global developmental delay and intellectual disability associated with a
RT de novo TOP2B mutation.";
RL Clin. Chim. Acta 469:63-68(2017).
RN [34]
RP VARIANT BILU PRO-490, CHARACTERIZATION OF VARIANT BILU PRO-490, AND
RP FUNCTION.
RX PubMed=32128574; DOI=10.1182/blood.2019003299;
RA Papapietro O., Chandra A., Eletto D., Inglott S., Plagnol V., Curtis J.,
RA Maes M., Alisaac A., Albuquerque A.S., Basseres E., Hermine O., Picard C.,
RA Fischer A., Durandy A., Kracker S., Burns S.O., Cuchet-Lourenco D.,
RA Okkenhaug K., Nejentsev S.;
RT "Topoisomerase 2beta mutation impairs early B-cell development.";
RL Blood 135:1497-1501(2020).
RN [35]
RP VARIANT TYR-63, AND INVOLVEMENT IN DEVELOPMENTAL DELAY AND AUTISM SPECTRUM
RP DISORDER.
RX PubMed=31953910; DOI=10.1002/mgg3.1145;
RA Hiraide T., Watanabe S., Matsubayashi T., Yanagi K., Nakashima M.,
RA Ogata T., Saitsu H.;
RT "A de novo TOP2B variant associated with global developmental delay and
RT autism spectrum disorder.";
RL Mol. Genet. Genomic Med. 8:e1145-e1145(2020).
RN [36]
RP VARIANT BILU GLU-593 DEL.
RX PubMed=33459963; DOI=10.1007/s10875-020-00963-8;
RA Erdos M., Lanyi A., Balazs G., Casanova J.L., Boisson B., Marodi L.;
RT "Inherited TOP2B Mutation: Possible Confirmation of Mutational Hotspots in
RT the TOPRIM Domain.";
RL J. Clin. Immunol. 41:817-819(2021).
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. Plays a role in B-cell
CC differentiation. {ECO:0000269|PubMed:10684600,
CC ECO:0000269|PubMed:31409799, ECO:0000269|PubMed:32128574}.
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:10684600};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00995,
CC ECO:0000269|PubMed:10684600, ECO:0000269|PubMed:21778401};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00995,
CC ECO:0000269|PubMed:10684600, ECO:0000269|PubMed:21778401};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00995,
CC ECO:0000269|PubMed:10684600, ECO:0000269|PubMed:21778401};
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:0000255|PROSITE-
CC ProRule:PRU00995, ECO:0000269|PubMed:10684600,
CC ECO:0000269|PubMed:21778401};
CC -!- SUBUNIT: Homodimer (PubMed:21778401). Interacts with KIAA1210 (By
CC similarity). Interacts with PLSCR1 (PubMed:19690332).
CC {ECO:0000250|UniProtKB:Q64511, ECO:0000269|PubMed:19690332,
CC ECO:0000269|PubMed:21778401}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:8299728,
CC ECO:0000269|PubMed:9155056}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:9155056}. Nucleus {ECO:0000269|PubMed:19690332}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Beta-2;
CC IsoId=Q02880-1; Sequence=Displayed;
CC Name=Beta-1;
CC IsoId=Q02880-2; Sequence=VSP_006532;
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 breast, colon and lung carcinomas,
CC Hodgkin's disease, large-cell non-Hodgkin's lymphoma, lymphocytic
CC lymphomas and seminomas (PubMed:9155056). {ECO:0000269|PubMed:9155056}.
CC -!- DISEASE: Note=Defects in TOP2B may be involved in global developmental
CC delay with autism spectrum disorder (ASD).
CC {ECO:0000269|PubMed:28343847, ECO:0000269|PubMed:31953910}.
CC -!- DISEASE: B-cell immunodeficiency, distal limb anomalies, and urogenital
CC malformations (BILU) [MIM:609296]: An autosomal dominant disorder
CC characterized by humoral immunodeficiency with undetectable B cells,
CC distal limb anomalies, dysmorphic facial features, and urogenital
CC malformations. {ECO:0000269|PubMed:31409799,
CC ECO:0000269|PubMed:32128574, ECO:0000269|PubMed:33459963}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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}.
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DR EMBL; X68060; CAA48197.1; -; mRNA.
DR EMBL; X71911; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z15111; CAA78815.1; -; mRNA.
DR EMBL; Z15115; CAA78821.1; -; mRNA.
DR EMBL; M27504; AAA61210.1; -; mRNA.
DR EMBL; AJ011721; CAA09753.1; -; Genomic_DNA.
DR EMBL; AJ011722; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; AJ011723; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; AJ011724; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; AJ011725; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; AJ011726; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; AJ011727; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; AJ011728; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; AJ011729; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; AJ011730; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; AJ011731; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; AJ011732; CAA09753.1; JOINED; Genomic_DNA.
DR EMBL; X53662; CAA37706.1; -; mRNA.
DR EMBL; U54831; AAB01982.1; -; mRNA.
DR CCDS; CCDS46776.1; -. [Q02880-2]
DR CCDS; CCDS82746.1; -. [Q02880-1]
DR PIR; S26730; A39242.
DR RefSeq; NP_001059.2; NM_001068.3. [Q02880-2]
DR RefSeq; NP_001317629.1; NM_001330700.1. [Q02880-1]
DR PDB; 3QX3; X-ray; 2.16 A; A/B=450-1206.
DR PDB; 4G0U; X-ray; 2.70 A; A/B=450-1206.
DR PDB; 4G0V; X-ray; 2.55 A; A/B=450-1206.
DR PDB; 4G0W; X-ray; 2.70 A; A/B=450-1206.
DR PDB; 4J3N; X-ray; 2.30 A; A/B=450-1206.
DR PDB; 5GWI; X-ray; 2.74 A; A/B=450-1206.
DR PDB; 5GWJ; X-ray; 2.57 A; A/B=450-1206.
DR PDB; 5ZAD; X-ray; 2.54 A; A/B=450-1206.
DR PDB; 5ZEN; X-ray; 2.75 A; A=450-1206.
DR PDB; 5ZQF; X-ray; 3.87 A; A=450-1206.
DR PDB; 5ZRF; X-ray; 2.30 A; A/B=450-1206.
DR PDBsum; 3QX3; -.
DR PDBsum; 4G0U; -.
DR PDBsum; 4G0V; -.
DR PDBsum; 4G0W; -.
DR PDBsum; 4J3N; -.
DR PDBsum; 5GWI; -.
DR PDBsum; 5GWJ; -.
DR PDBsum; 5ZAD; -.
DR PDBsum; 5ZEN; -.
DR PDBsum; 5ZQF; -.
DR PDBsum; 5ZRF; -.
DR AlphaFoldDB; Q02880; -.
DR SMR; Q02880; -.
DR BioGRID; 113008; 184.
DR CORUM; Q02880; -.
DR IntAct; Q02880; 44.
DR MINT; Q02880; -.
DR STRING; 9606.ENSP00000396704; -.
DR BindingDB; Q02880; -.
DR ChEMBL; CHEMBL3396; -.
DR DrugBank; DB08651; 3'-THIO-THYMIDINE-5'-PHOSPHATE.
DR DrugBank; DB05022; Amonafide.
DR DrugBank; DB06362; Becatecarin.
DR DrugBank; DB00970; Dactinomycin.
DR DrugBank; DB00694; Daunorubicin.
DR DrugBank; DB06421; Declopramide.
DR DrugBank; DB00380; Dexrazoxane.
DR DrugBank; DB00773; Etoposide.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR DrugBank; DB05488; Technetium Tc-99m ciprofloxacin.
DR DrugBank; DB06042; ZEN-012.
DR DrugCentral; Q02880; -.
DR GlyGen; Q02880; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q02880; -.
DR PhosphoSitePlus; Q02880; -.
DR SwissPalm; Q02880; -.
DR BioMuta; TOP2B; -.
DR DMDM; 20141946; -.
DR EPD; Q02880; -.
DR jPOST; Q02880; -.
DR MassIVE; Q02880; -.
DR MaxQB; Q02880; -.
DR PaxDb; Q02880; -.
DR PeptideAtlas; Q02880; -.
DR PRIDE; Q02880; -.
DR ProteomicsDB; 58133; -. [Q02880-1]
DR ProteomicsDB; 58134; -. [Q02880-2]
DR Antibodypedia; 3893; 301 antibodies from 36 providers.
DR DNASU; 7155; -.
DR Ensembl; ENST00000264331.9; ENSP00000264331.4; ENSG00000077097.16. [Q02880-1]
DR Ensembl; ENST00000435706.6; ENSP00000396704.2; ENSG00000077097.16. [Q02880-2]
DR GeneID; 7155; -.
DR KEGG; hsa:7155; -.
DR MANE-Select; ENST00000264331.9; ENSP00000264331.4; NM_001330700.2; NP_001317629.1.
DR UCSC; uc003cdj.4; human. [Q02880-1]
DR CTD; 7155; -.
DR DisGeNET; 7155; -.
DR GeneCards; TOP2B; -.
DR HGNC; HGNC:11990; TOP2B.
DR HPA; ENSG00000077097; Low tissue specificity.
DR MalaCards; TOP2B; -.
DR MIM; 126431; gene.
DR MIM; 609296; phenotype.
DR neXtProt; NX_Q02880; -.
DR OpenTargets; ENSG00000077097; -.
DR Orphanet; 567502; B-cell immunodeficiency-limb anomaly-urogenital malformation syndrome.
DR PharmGKB; PA36672; -.
DR VEuPathDB; HostDB:ENSG00000077097; -.
DR eggNOG; KOG0355; Eukaryota.
DR GeneTree; ENSGT00940000157921; -.
DR InParanoid; Q02880; -.
DR OMA; TWTQDFK; -.
DR OrthoDB; 117851at2759; -.
DR PhylomeDB; Q02880; -.
DR TreeFam; TF105282; -.
DR BRENDA; 5.6.2.2; 2681.
DR BRENDA; 5.99.1.3; 2681.
DR PathwayCommons; Q02880; -.
DR Reactome; R-HSA-4615885; SUMOylation of DNA replication proteins.
DR SignaLink; Q02880; -.
DR SIGNOR; Q02880; -.
DR BioGRID-ORCS; 7155; 18 hits in 1079 CRISPR screens.
DR ChiTaRS; TOP2B; human.
DR GeneWiki; TOP2B; -.
DR GenomeRNAi; 7155; -.
DR Pharos; Q02880; Tclin.
DR PRO; PR:Q02880; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q02880; protein.
DR Bgee; ENSG00000077097; Expressed in ganglionic eminence and 204 other tissues.
DR ExpressionAtlas; Q02880; baseline and differential.
DR Genevisible; Q02880; HS.
DR GO; GO:0005829; C:cytosol; 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:1990904; C:ribonucleoprotein complex; ISS: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; IEA:UniProtKB-KW.
DR GO; GO:0003918; F:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0006265; P:DNA topological change; IDA:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0045870; P:positive regulation of single stranded viral RNA replication via double stranded DNA intermediate; IMP:UniProtKB.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central.
DR GO; GO:0000819; P:sister chromatid segregation; IBA:GO_Central.
DR CDD; cd00187; TOP4c; 1.
DR CDD; cd03365; TOPRIM_TopoIIA; 1.
DR Gene3D; 1.10.268.10; -; 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 IDEAL; IID00462; -.
DR InterPro; IPR012542; DTHCT.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR InterPro; IPR028467; Top2b.
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; IPR018522; TopoIIA_CS.
DR InterPro; IPR031660; TOPRIM_C.
DR InterPro; IPR006171; TOPRIM_domain.
DR InterPro; IPR034157; TOPRIM_TopoII.
DR PANTHER; PTHR10169:SF36; PTHR10169:SF36; 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 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 Autism spectrum disorder; Disease variant; DNA-binding; Isomerase;
KW Isopeptide bond; Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Topoisomerase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q64511"
FT CHAIN 2..1626
FT /note="DNA topoisomerase 2-beta"
FT /id="PRO_0000145369"
FT DOMAIN 476..593
FT /note="Toprim"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT REGION 363..365
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 1011..1020
FT /note="Interaction with DNA"
FT REGION 1110..1140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1274..1604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1506..1512
FT /note="Interaction with PLSCR1"
FT /evidence="ECO:0000269|PubMed:17567603"
FT MOTIF 1034..1044
FT /note="Nuclear export signal"
FT COMPBIAS 1110..1129
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1300..1314
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1330..1374
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1375..1391
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1468..1485
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1501..1521
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 826
FT /note="O-(5'-phospho-DNA)-tyrosine intermediate"
FT /evidence="ECO:0000269|PubMed:21778401"
FT BINDING 112
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 141
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 169..171
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 182..189
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 397..399
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 482
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 562
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 562
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995,
FT ECO:0000269|PubMed:21778401"
FT BINDING 564
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995,
FT ECO:0000269|PubMed:21778401"
FT SITE 510
FT /note="Interaction with DNA"
FT SITE 513
FT /note="Interaction with DNA"
FT SITE 682
FT /note="Interaction with DNA"
FT SITE 683
FT /note="Interaction with DNA"
FT SITE 744
FT /note="Interaction with DNA"
FT SITE 778
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 825
FT /note="Transition state stabilizer"
FT SITE 877
FT /note="Important for DNA bending; intercalates between base
FT pairs of target DNA"
FT SITE 952
FT /note="Interaction with DNA"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q64511"
FT MOD_RES 3
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q64511"
FT MOD_RES 1236
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 1292
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1336
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 1340
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 1342
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 1344
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 1358
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1370
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q64511"
FT MOD_RES 1375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 1400
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1403
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1413
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1421
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1424
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 1441
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 1452
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1454
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1461
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1466
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 1473
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1476
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 1522
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1524
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1526
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1550
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1552
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1575
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1576
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1581
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT MOD_RES 1592
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1596
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1609
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT CROSSLNK 33
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 34
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 177
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 178
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 228
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 299
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 367
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 373
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 437
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 439
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 446
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 600
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 605
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 635
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 643
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 646
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="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:28112733"
FT CROSSLNK 712
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1092
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1214
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1217
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1226
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1227
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 1250
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 1262
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1271
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 CROSSLNK 1323
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1327
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1398
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1440
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 1456
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 1490
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 24..28
FT /note="Missing (in isoform Beta-1)"
FT /evidence="ECO:0000305"
FT /id="VSP_006532"
FT VARIANT 63
FT /note="H -> Y (probable disease-associated variant found in
FT patients with global developmental delay and autism
FT spectrum disorder; dbSNP:rs886039770)"
FT /evidence="ECO:0000269|PubMed:28343847,
FT ECO:0000269|PubMed:31953910"
FT /id="VAR_079273"
FT VARIANT 488
FT /note="S -> L (in BILU; loss-of-function variant in a yeast
FT complementation assay)"
FT /evidence="ECO:0000269|PubMed:31409799"
FT /id="VAR_086569"
FT VARIANT 490
FT /note="A -> P (in BILU; decreased protein abundance;
FT severely decreased DNA topoisomerase type II (double strand
FT cut, ATP-hydrolyzing) activity)"
FT /evidence="ECO:0000269|PubMed:32128574"
FT /id="VAR_086570"
FT VARIANT 593
FT /note="Missing (in BILU; loss-of-function variant in a
FT yeast complementation assay)"
FT /evidence="ECO:0000269|PubMed:31409799,
FT ECO:0000269|PubMed:33459963"
FT /id="VAR_086571"
FT VARIANT 638
FT /note="G -> S (in BILU; loss-of-function variant in a yeast
FT complementation assay)"
FT /evidence="ECO:0000269|PubMed:31409799"
FT /id="VAR_086572"
FT MUTAGEN 482
FT /note="E->Q: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:10684600"
FT MUTAGEN 485
FT /note="S->A: Slightly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:10684600"
FT MUTAGEN 508
FT /note="R->E: Slightly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:10684600"
FT MUTAGEN 510
FT /note="K->E: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:10684600"
FT MUTAGEN 515
FT /note="R->Q: Slightly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:10684600"
FT CONFLICT 1431
FT /note="T -> S (in Ref. 4; CAA78821/CAA09753)"
FT /evidence="ECO:0000305"
FT CONFLICT 1611
FT /note="A -> T (in Ref. 1; CAA48197)"
FT /evidence="ECO:0000305"
FT CONFLICT 1621
FT /note="D -> H (in Ref. 4; CAA09753)"
FT /evidence="ECO:0000305"
FT TURN 466..469
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:4G0U"
FT HELIX 473..475
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 477..482
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 483..491
FT /evidence="ECO:0007829|PDB:3QX3"
FT TURN 494..496
FT /evidence="ECO:0007829|PDB:5GWJ"
FT HELIX 497..499
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 502..507
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 514..516
FT /evidence="ECO:0007829|PDB:5ZAD"
FT HELIX 519..524
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 526..535
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 545..547
FT /evidence="ECO:0007829|PDB:4G0V"
FT HELIX 548..551
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 555..560
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 565..581
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 583..587
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 591..594
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 598..602
FT /evidence="ECO:0007829|PDB:5ZAD"
FT STRAND 607..612
FT /evidence="ECO:0007829|PDB:5ZAD"
FT HELIX 613..617
FT /evidence="ECO:0007829|PDB:5ZAD"
FT STRAND 630..633
FT /evidence="ECO:0007829|PDB:5ZAD"
FT HELIX 637..639
FT /evidence="ECO:0007829|PDB:5ZAD"
FT HELIX 644..650
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 652..655
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 656..660
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 664..674
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 676..678
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 679..698
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 706..710
FT /evidence="ECO:0007829|PDB:5ZAD"
FT STRAND 713..715
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 716..722
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 724..735
FT /evidence="ECO:0007829|PDB:3QX3"
FT TURN 739..741
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 745..757
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 765..776
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 782..793
FT /evidence="ECO:0007829|PDB:3QX3"
FT TURN 814..820
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 824..826
FT /evidence="ECO:0007829|PDB:4J3N"
FT HELIX 835..838
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 841..844
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 849..852
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 855..860
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 868..871
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 875..877
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 882..884
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 890..901
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 918..924
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 927..931
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 933..938
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 941..946
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 953..959
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 961..966
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 969..971
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 976..980
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 989..992
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 995..1004
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 1006..1009
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 1013..1017
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 1021..1024
FT /evidence="ECO:0007829|PDB:3QX3"
FT STRAND 1030..1034
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 1036..1080
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 1091..1100
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 1107..1114
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 1144..1147
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 1151..1154
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 1156..1177
FT /evidence="ECO:0007829|PDB:3QX3"
FT HELIX 1181..1205
FT /evidence="ECO:0007829|PDB:3QX3"
FT CROSSLNK Q02880-2:28
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 Q02880-2:29
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
SQ SEQUENCE 1626 AA; 183267 MW; E60E9262CC68B05D CRC64;
MAKSGGCGAG AGVGGGNGAL TWVTLFDQNN AAKKEESETA NKNDSSKKLS VERVYQKKTQ
LEHILLRPDT YIGSVEPLTQ FMWVYDEDVG MNCREVTFVP GLYKIFDEIL VNAADNKQRD
KNMTCIKVSI DPESNIISIW NNGKGIPVVE HKVEKVYVPA LIFGQLLTSS NYDDDEKKVT
GGRNGYGAKL CNIFSTKFTV ETACKEYKHS FKQTWMNNMM KTSEAKIKHF DGEDYTCITF
QPDLSKFKME KLDKDIVALM TRRAYDLAGS CRGVKVMFNG KKLPVNGFRS YVDLYVKDKL
DETGVALKVI HELANERWDV CLTLSEKGFQ QISFVNSIAT TKGGRHVDYV VDQVVGKLIE
VVKKKNKAGV SVKPFQVKNH IWVFINCLIE NPTFDSQTKE NMTLQPKSFG SKCQLSEKFF
KAASNCGIVE SILNWVKFKA QTQLNKKCSS VKYSKIKGIP KLDDANDAGG KHSLECTLIL
TEGDSAKSLA VSGLGVIGRD RYGVFPLRGK ILNVREASHK QIMENAEINN IIKIVGLQYK
KSYDDAESLK TLRYGKIMIM TDQDQDGSHI KGLLINFIHH NWPSLLKHGF LEEFITPIVK
ASKNKQELSF YSIPEFDEWK KHIENQKAWK IKYYKGLGTS TAKEAKEYFA DMERHRILFR
YAGPEDDAAI TLAFSKKKID DRKEWLTNFM EDRRQRRLHG LPEQFLYGTA TKHLTYNDFI
NKELILFSNS DNERSIPSLV DGFKPGQRKV LFTCFKRNDK REVKVAQLAG SVAEMSAYHH
GEQALMMTIV NLAQNFVGSN NINLLQPIGQ FGTRLHGGKD AASPRYIFTM LSTLARLLFP
AVDDNLLKFL YDDNQRVEPE WYIPIIPMVL INGAEGIGTG WACKLPNYDA REIVNNVRRM
LDGLDPHPML PNYKNFKGTI QELGQNQYAV SGEIFVVDRN TVEITELPVR TWTQVYKEQV
LEPMLNGTDK TPALISDYKE YHTDTTVKFV VKMTEEKLAQ AEAAGLHKVF KLQTTLTCNS
MVLFDHMGCL KKYETVQDIL KEFFDLRLSY YGLRKEWLVG MLGAESTKLN NQARFILEKI
QGKITIENRS KKDLIQMLVQ RGYESDPVKA WKEAQEKAAE EDETQNQHDD SSSDSGTPSG
PDFNYILNMS LWSLTKEKVE ELIKQRDAKG REVNDLKRKS PSDLWKEDLA AFVEELDKVE
SQEREDVLAG MSGKAIKGKV GKPKVKKLQL EETMPSPYGR RIIPEITAMK ADASKKLLKK
KKGDLDTAAV KVEFDEEFSG APVEGAGEEA LTPSVPINKG PKPKREKKEP GTRVRKTPTS
SGKPSAKKVK KRNPWSDDES KSESDLEETE PVVIPRDSLL RRAAAERPKY TFDFSEEEDD
DADDDDDDNN DLEELKVKAS PITNDGEDEF VPSDGLDKDE YTFSPGKSKA TPEKSLHDKK
SQDFGNLFSF PSYSQKSEDD SAKFDSNEED SASVFSPSFG LKQTDKVPSK TVAAKKGKPS
SDTVPKPKRA PKQKKVVEAV NSDSDSEFGI PKKTTTPKGK GRGAKKRKAS GSENEGDYNP
GRKTSKTTSK KPKKTSFDQD SDVDIFPSDF PTEPPSLPRT GRARKEVKYF AESDEEEDDV
DFAMFN
