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 24-JAN-2024, entry version 238. 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 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 [33] 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 [34] 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 [35] 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 [36] 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 [37] 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 -!- 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 -!- 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}. 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; 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 PDB; 7QFN; X-ray; 2.62 A; A=50-449. DR PDB; 7QFO; X-ray; 1.90 A; A=50-449. DR PDB; 7ZBG; X-ray; 2.30 A; A=50-449. 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 PDBsum; 7QFN; -. DR PDBsum; 7QFO; -. DR PDBsum; 7ZBG; -. DR AlphaFoldDB; Q02880; -. DR SMR; Q02880; -. DR BioGRID; 113008; 243. DR CORUM; Q02880; -. DR IntAct; Q02880; 47. DR MINT; Q02880; -. DR STRING; 9606.ENSP00000264331; -. 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; DB00997; Doxorubicin. DR DrugBank; DB00773; Etoposide. DR DrugBank; DB01059; Norfloxacin. 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; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000396704; -. DR PeptideAtlas; Q02880; -. DR ProteomicsDB; 58133; -. [Q02880-1] DR ProteomicsDB; 58134; -. [Q02880-2] DR Pumba; Q02880; -. DR Antibodypedia; 3893; 331 antibodies from 36 providers. DR DNASU; 7155; -. DR Ensembl; ENST00000264331.9; ENSP00000264331.4; ENSG00000077097.17. [Q02880-1] DR Ensembl; ENST00000435706.6; ENSP00000396704.2; ENSG00000077097.17. [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 AGR; HGNC:11990; -. 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; 1944951at2759; -. 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; 20 hits in 1166 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 206 other cell types or 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:HPA. 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:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0043021; F:ribonucleoprotein complex binding; IEA:Ensembl. DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl. DR GO; GO:0030183; P:B cell differentiation; IMP:UniProtKB. DR GO; GO:0071318; P:cellular response to ATP; IEA:Ensembl. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0090398; P:cellular senescence; 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:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; 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; 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 IDEAL; IID00462; -. 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:SF36; DNA TOPOISOMERASE 2-BETA; 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 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 DOMAIN 736..1189 FT /note="Topo IIA-type catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01384" 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:0000255|PROSITE-ProRule:PRU01384, FT 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 (found in patients with global developmental FT delay and autism spectrum disorder; likely pathogenic; FT 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 52..54 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 60..66 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 69..72 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 78..86 FT /evidence="ECO:0007829|PDB:7QFO" FT TURN 87..89 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 90..98 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 100..119 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 125..131 FT /evidence="ECO:0007829|PDB:7QFO" FT TURN 132..135 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 136..141 FT /evidence="ECO:0007829|PDB:7QFO" FT TURN 152..154 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 158..164 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 165..167 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 174..176 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 187..193 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 195..204 FT /evidence="ECO:0007829|PDB:7QFO" FT TURN 205..208 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 209..216 FT /evidence="ECO:0007829|PDB:7QFO" FT TURN 217..220 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 226..229 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 235..242 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 244..247 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 254..270 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 275..278 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 288..296 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 310..315 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 318..324 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 326..328 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 330..335 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 341..344 FT /evidence="ECO:0007829|PDB:7ZBG" FT HELIX 345..363 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 374..378 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 381..387 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 394..396 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 406..408 FT /evidence="ECO:0007829|PDB:7QFO" FT STRAND 409..411 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 417..424 FT /evidence="ECO:0007829|PDB:7QFO" FT TURN 425..427 FT /evidence="ECO:0007829|PDB:7QFO" FT HELIX 428..433 FT /evidence="ECO:0007829|PDB:7QFO" 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 //