TOP2_DROME
ID TOP2_DROME Reviewed; 1447 AA.
AC P15348; M9PDQ1; Q6NR40; Q9VIW2;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=DNA topoisomerase 2 {ECO:0000305};
DE EC=5.6.2.2 {ECO:0000269|PubMed:10751154, ECO:0000269|PubMed:10786800, ECO:0000269|PubMed:1328202, ECO:0000269|PubMed:2547764, ECO:0000269|PubMed:6308011, ECO:0000269|PubMed:8978614, ECO:0000269|PubMed:9545289};
DE AltName: Full=DNA topoisomerase II {ECO:0000305};
GN Name=Top2 {ECO:0000303|PubMed:25340780, ECO:0000312|FlyBase:FBgn0284220};
GN ORFNames=CG10223 {ECO:0000312|FlyBase:FBgn0284220};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2538621; DOI=10.1016/0022-2836(89)90361-6;
RA Wyckoff E., Natalie D., Nolan J.M., Lee M., Hsieh T.-S.;
RT "Structure of the Drosophila DNA topoisomerase II gene. Nucleotide sequence
RT and homology among topoisomerases II.";
RL J. Mol. Biol. 205:1-13(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAQ23558.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (FEB-2015) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=6308011; DOI=10.1016/s0021-9258(17)44700-4;
RA Osheroff N., Shelton E.R., Brutlag D.L.;
RT "DNA topoisomerase II from Drosophila melanogaster. Relaxation of
RT supercoiled DNA.";
RL J. Biol. Chem. 258:9536-9543(1983).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=2547764; DOI=10.1016/s0021-9258(18)80026-6;
RA Lee M.P., Sander M., Hsieh T.S.;
RT "Single strand DNA cleavage reaction of duplex DNA by Drosophila
RT topoisomerase II.";
RL J. Biol. Chem. 264:13510-13518(1989).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND PHOSPHORYLATION.
RX PubMed=1328202; DOI=10.1016/s0021-9258(19)88732-x;
RA Corbett A.H., DeVore R.F., Osheroff N.;
RT "Effect of casein kinase II-mediated phosphorylation on the catalytic cycle
RT of topoisomerase II. Regulation of enzyme activity by enhancement of ATP
RT hydrolysis.";
RL J. Biol. Chem. 267:20513-20518(1992).
RN [9]
RP FUNCTION, COFACTOR, AND PHOSPHORYLATION.
RX PubMed=8383533; DOI=10.1021/bi00059a029;
RA Corbett A.H., Fernald A.W., Osheroff N.;
RT "Protein kinase C modulates the catalytic activity of topoisomerase II by
RT enhancing the rate of ATP hydrolysis: evidence for a common mechanism of
RT regulation by phosphorylation.";
RL Biochemistry 32:2090-2097(1993).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH BARR, AND SUBCELLULAR
RP LOCATION.
RX PubMed=8978614; DOI=10.1016/s0092-8674(00)81804-8;
RA Bhat M.A., Philp A.V., Glover D.M., Bellen H.J.;
RT "Chromatid segregation at anaphase requires the barren product, a novel
RT chromosome-associated protein that interacts with Topoisomerase II.";
RL Cell 87:1103-1114(1996).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-359.
RX PubMed=9545289; DOI=10.1074/jbc.273.16.9586;
RA Hu T., Chang S., Hsieh T.;
RT "Identifying Lys359 as a critical residue for the ATP-dependent reactions
RT of Drosophila DNA topoisomerase II.";
RL J. Biol. Chem. 273:9586-9592(1998).
RN [12]
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=10885744; DOI=10.1006/dbio.2000.9704;
RA Zhang C.X., Chen A.D., Gettel N.J., Hsieh T.S.;
RT "Essential functions of DNA topoisomerase I in Drosophila melanogaster.";
RL Dev. Biol. 222:27-40(2000).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=10751154; DOI=10.1242/jcs.113.9.1635;
RA Rzepecki R., Fisher P.A.;
RT "During both interphase and mitosis, DNA topoisomerase II interacts with
RT DNA as well as RNA through the protein's C-terminal domain.";
RL J. Cell Sci. 113:1635-1647(2000).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10786800; DOI=10.1038/35009144;
RA Strick T.R., Croquette V., Bensimon D.;
RT "Single-molecule analysis of DNA uncoiling by a type II topoisomerase.";
RL Nature 404:901-904(2000).
RN [15]
RP INTERACTION WITH BARR AND PH-P, AND SUBCELLULAR LOCATION.
RX PubMed=11172718; DOI=10.1016/s1097-2765(01)00161-7;
RA Lupo R., Breiling A., Bianchi M.E., Orlando V.;
RT "Drosophila chromosome condensation proteins Topoisomerase II and Barren
RT colocalize with Polycomb and maintain Fab-7 PRE silencing.";
RL Mol. Cell 7:127-136(2001).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14600258; DOI=10.1242/jcs.00797;
RA Chang C.J., Goulding S., Earnshaw W.C., Carmena M.;
RT "RNAi analysis reveals an unexpected role for topoisomerase II in
RT chromosome arm congression to a metaphase plate.";
RL J. Cell Sci. 116:4715-4726(2003).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1284; SER-1344; THR-1352;
RP SER-1374; SER-1385; SER-1392 AND SER-1396, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18752348; DOI=10.1371/journal.pbio.0060207;
RA Coelho P.A., Queiroz-Machado J., Carmo A.M., Moutinho-Pereira S.,
RA Maiato H., Sunkel C.E.;
RT "Dual role of topoisomerase II in centromere resolution and aurora B
RT activity.";
RL PLoS Biol. 6:E207-E207(2008).
RN [19]
RP FUNCTION, INTERACTION WITH MOD(MDG4), SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=21304601; DOI=10.1371/journal.pone.0016562;
RA Ramos E., Torre E.A., Bushey A.M., Gurudatta B.V., Corces V.G.;
RT "DNA topoisomerase II modulates insulator function in Drosophila.";
RL PLoS ONE 6:E16562-E16562(2011).
RN [20]
RP FUNCTION, INTERACTION WITH MLE, AND ASSOCIATION WITH THE MSL COMPLEX.
RX PubMed=23989663; DOI=10.4161/trns.26185;
RA Cugusi S., Ramos E., Ling H., Yokoyama R., Luk K.M., Lucchesi J.C.;
RT "Topoisomerase II plays a role in dosage compensation in Drosophila.";
RL Transcription 4:238-250(2013).
RN [21]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25340780; DOI=10.1371/journal.pgen.1004650;
RA Hughes S.E., Hawley R.S.;
RT "Topoisomerase II is required for the proper separation of heterochromatic
RT regions during Drosophila melanogaster female meiosis.";
RL PLoS Genet. 10:E1004650-E1004650(2014).
CC -!- FUNCTION: Control of topological states of DNA by transient breakage
CC and subsequent rejoining of DNA strands (PubMed:6308011,
CC PubMed:2547764, PubMed:1328202, PubMed:8383533, PubMed:10786800,
CC PubMed:8978614). Topoisomerase II makes double-strand breaks
CC (PubMed:6308011, PubMed:2547764, PubMed:1328202, PubMed:8383533,
CC PubMed:10786800, PubMed:9545289). Essential during mitosis and meiosis
CC for proper segregation of daughter chromosomes (PubMed:10751154,
CC PubMed:14600258, PubMed:18752348, PubMed:25340780). During meiosis, it
CC disrupts heterochromatic connections between achiasmate and chiasmate
CC homologs after spindle assembly so that chromosomes can separate at
CC prometaphase I (PubMed:25340780). During mitosis, it functions in the
CC separation of sister chromatids by establishing amphitelic kinetochore
CC attachments in mitotic spindles (PubMed:18752348). May have a role in
CC chromatin condensation and chromosome structure (PubMed:14600258,
CC PubMed:18752348, PubMed:25340780). May be involved in X-chromosome
CC dosage compensation, perhaps by modifying the topological state of
CC compensated genes (PubMed:23989663). Regulates activity of the gypsy
CC chromatin insulator complex by binding to mod(mdg4) and preventing its
CC degradation (PubMed:21304601). {ECO:0000269|PubMed:10751154,
CC ECO:0000269|PubMed:10786800, ECO:0000269|PubMed:1328202,
CC ECO:0000269|PubMed:14600258, ECO:0000269|PubMed:18752348,
CC ECO:0000269|PubMed:21304601, ECO:0000269|PubMed:23989663,
CC ECO:0000269|PubMed:25340780, ECO:0000269|PubMed:2547764,
CC ECO:0000269|PubMed:6308011, ECO:0000269|PubMed:8383533,
CC ECO:0000269|PubMed:8978614, ECO:0000269|PubMed:9545289}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP-dependent breakage, passage and rejoining of double-
CC stranded DNA.; EC=5.6.2.2; Evidence={ECO:0000269|PubMed:10751154,
CC ECO:0000269|PubMed:10786800, ECO:0000269|PubMed:1328202,
CC ECO:0000269|PubMed:2547764, ECO:0000269|PubMed:6308011,
CC ECO:0000269|PubMed:8978614, ECO:0000269|PubMed:9545289};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:1328202, ECO:0000269|PubMed:2547764,
CC ECO:0000269|PubMed:6308011, ECO:0000269|PubMed:8383533};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00995};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:1328202, ECO:0000269|PubMed:8383533};
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};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=200 uM for negatively supercoiled double-stranded plasmid DNA (at
CC 30 degrees Celsius) {ECO:0000269|PubMed:6308011};
CC KM=140 uM for negatively supercoiled double-stranded viral DNA (at 30
CC degrees Celsius) {ECO:0000269|PubMed:6308011};
CC KM=270 uM for positively supercoiled double-stranded linear DNA
CC {ECO:0000269|PubMed:10786800};
CC KM=280 uM for ATP (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:6308011};
CC KM=630 uM for dATP (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:6308011};
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with mod(mdg4)
CC (PubMed:21304601). Interacts with barr (PubMed:8978614,
CC PubMed:11172718). Interacts with ph-p (PubMed:11172718). Interacts with
CC mle; the interaction mediates association with the MSL dosage
CC compensation complex (PubMed:23989663). {ECO:0000250|UniProtKB:P06786,
CC ECO:0000269|PubMed:11172718, ECO:0000269|PubMed:21304601,
CC ECO:0000269|PubMed:23989663, ECO:0000269|PubMed:8978614}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10751154,
CC ECO:0000269|PubMed:10885744, ECO:0000269|PubMed:11172718,
CC ECO:0000269|PubMed:14600258}. Chromosome {ECO:0000269|PubMed:14600258,
CC ECO:0000269|PubMed:18752348, ECO:0000269|PubMed:21304601,
CC ECO:0000269|PubMed:8978614}. Cytoplasm {ECO:0000269|PubMed:10885744}.
CC Note=Nuclear at interphase, becoming diffusely dispersed in the
CC cytoplasm at later cell cycle stages (PubMed:10885744,
CC PubMed:10751154). However in early developing embryos, some may remain
CC associated with condensed chromosomes at metaphase (PubMed:10885744).
CC {ECO:0000269|PubMed:10751154, ECO:0000269|PubMed:10885744}.
CC -!- DEVELOPMENTAL STAGE: Detected in germline and follicle cells (at
CC protein level). Predominantly expressed in follicle cells where
CC expression persists throughout oogenesis (at protein level). In
CC germline cells, expression levels decrease as cells develop and move to
CC the posterior region of the germarium. {ECO:0000269|PubMed:10885744}.
CC -!- PTM: Phosphorylated (PubMed:1328202, PubMed:8383533, PubMed:10751154).
CC Phosphorylation by casein kinase II enhances ATPase activity
CC (PubMed:1328202). {ECO:0000269|PubMed:10751154,
CC ECO:0000269|PubMed:1328202, ECO:0000269|PubMed:8383533}.
CC -!- DISRUPTION PHENOTYPE: Homozygous lethal (PubMed:21304601).
CC Embryogenesis appears normal, probably due to maternal contribution of
CC the protein (PubMed:21304601). However after hatching flies show a 2-3
CC day delay in development and most die before the third instar stage
CC (PubMed:21304601). Conditional RNAi-mediated knockdown in the female
CC germline does not affect fertilization but embryos fail to initiate
CC proper mitotic divisions and do not hatch (PubMed:25340780). Embryos
CC contain only two nuclei; a small nucleus with a centriolar spindle and
CC a large round nucleus (PubMed:25340780). Knockdown in stage 3 oocytes
CC often results in the heterochromatic regions of all four chromosomes
CC failing to separate during prometaphase I and metaphase I of meiosis I
CC (PubMed:25340780). In some instances, the anchored heterochromatic
CC regions become stretched as the centromeres attempt to move towards the
CC spindles poles creating long, abnormal heterochromatin structures that
CC project from the main chromosome mass with centromeres at their tips
CC (PubMed:25340780). Spindle assembly is not affected (PubMed:25340780).
CC Spindles are bipolar although one or both sides of the spindle are
CC elongated due to the abnormal heterochromatin projections
CC (PubMed:25340780). {ECO:0000269|PubMed:21304601,
CC ECO:0000269|PubMed:25340780}.
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 -!- SEQUENCE CAUTION:
CC Sequence=AAQ23558.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AE014134; AGB93115.1; -; Genomic_DNA.
DR EMBL; X61209; CAA43523.1; -; Genomic_DNA.
DR EMBL; AE014134; AAF53802.2; -; Genomic_DNA.
DR EMBL; BT010240; AAQ23558.1; ALT_FRAME; mRNA.
DR EMBL; BT150455; AJP62077.1; -; mRNA.
DR PIR; S02160; S02160.
DR RefSeq; NP_001260580.1; NM_001273651.1.
DR RefSeq; NP_476760.1; NM_057412.5.
DR AlphaFoldDB; P15348; -.
DR SMR; P15348; -.
DR BioGRID; 61203; 25.
DR IntAct; P15348; 13.
DR MINT; P15348; -.
DR STRING; 7227.FBpp0304598; -.
DR BindingDB; P15348; -.
DR ChEMBL; CHEMBL2671; -.
DR iPTMnet; P15348; -.
DR PaxDb; P15348; -.
DR PRIDE; P15348; -.
DR EnsemblMetazoa; FBtr0081287; FBpp0080825; FBgn0284220.
DR EnsemblMetazoa; FBtr0332320; FBpp0304598; FBgn0284220.
DR GeneID; 35225; -.
DR KEGG; dme:Dmel_CG10223; -.
DR CTD; 35225; -.
DR FlyBase; FBgn0284220; Top2.
DR VEuPathDB; VectorBase:FBgn0284220; -.
DR eggNOG; KOG0355; Eukaryota.
DR GeneTree; ENSGT00940000168342; -.
DR HOGENOM; CLU_001935_1_0_1; -.
DR InParanoid; P15348; -.
DR OMA; TWTQDFK; -.
DR OrthoDB; 117851at2759; -.
DR PhylomeDB; P15348; -.
DR Reactome; R-DME-4615885; SUMOylation of DNA replication proteins.
DR SABIO-RK; P15348; -.
DR SignaLink; P15348; -.
DR ChiTaRS; Top2; fly.
DR GenomeRNAi; 35225; -.
DR PRO; PR:P15348; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0284220; Expressed in eye disc (Drosophila) and 22 other tissues.
DR Genevisible; P15348; DM.
DR GO; GO:0005694; C:chromosome; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:FlyBase.
DR GO; GO:0003682; F:chromatin binding; IDA:FlyBase.
DR GO; GO:0003677; F:DNA binding; IDA:FlyBase.
DR GO; GO:0003918; F:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity; IDA:FlyBase.
DR GO; GO:0000400; F:four-way junction DNA binding; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003729; F:mRNA binding; IDA:FlyBase.
DR GO; GO:0000182; F:rDNA binding; IDA:FlyBase.
DR GO; GO:0003696; F:satellite DNA binding; IDA:FlyBase.
DR GO; GO:0030261; P:chromosome condensation; IMP:FlyBase.
DR GO; GO:0006265; P:DNA topological change; IDA:FlyBase.
DR GO; GO:0031507; P:heterochromatin assembly; IDA:FlyBase.
DR GO; GO:0007060; P:male meiosis chromosome segregation; IMP:FlyBase.
DR GO; GO:0051321; P:meiotic cell cycle; TAS:FlyBase.
DR GO; GO:0051310; P:metaphase plate congression; IDA:FlyBase.
DR GO; GO:0000278; P:mitotic cell cycle; HMP:FlyBase.
DR GO; GO:0007076; P:mitotic chromosome condensation; IMP:FlyBase.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; IMP:FlyBase.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central.
DR GO; GO:0000819; P:sister chromatid segregation; IDA:FlyBase.
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 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; 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 Pfam; PF00204; DNA_gyraseB; 1.
DR Pfam; PF00521; DNA_topoisoIV; 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 ATP-binding; Chromosome; Cytoplasm; DNA-binding; Isomerase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Topoisomerase.
FT CHAIN 1..1447
FT /note="DNA topoisomerase 2"
FT /id="PRO_0000145374"
FT DOMAIN 435..552
FT /note="Toprim"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT REGION 323..325
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P11388"
FT REGION 972..981
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P11388"
FT REGION 1079..1110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1183..1231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1246..1447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1095..1110
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1254..1284
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1306..1364
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1391..1415
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1430..1447
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 785
FT /note="O-(5'-phospho-DNA)-tyrosine intermediate"
FT /evidence="ECO:0000250|UniProtKB:P06786"
FT BINDING 72
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11388"
FT BINDING 101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11388"
FT BINDING 129..131
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11388"
FT BINDING 142..149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11388"
FT BINDING 357..359
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11388"
FT BINDING 441
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 521
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 521
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT BINDING 523
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 469
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 472
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 641
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 642
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 703
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 737
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 743
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 784
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT SITE 836
FT /note="Important for DNA bending; intercalates between base
FT pairs of target DNA"
FT /evidence="ECO:0000250"
FT SITE 911
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P11388"
FT MOD_RES 1284
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1344
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1352
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1374
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1385
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1392
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 1396
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MUTAGEN 359
FT /note="K->Q,E: No effect on double-stranded DNA cleavage.
FT Strong decrease in ATPase activity and strand passage
FT activity."
FT /evidence="ECO:0000269|PubMed:9545289"
FT MUTAGEN 359
FT /note="K->R: No effect on enzyme activity."
FT /evidence="ECO:0000269|PubMed:9545289"
SQ SEQUENCE 1447 AA; 164396 MW; 63B5D2814AD06419 CRC64;
MENGNKALSI EQMYQKKSQL EHILLRPDSY IGSVEFTKEL MWVYDNSQNR MVQKEISFVP
GLYKIFDEIL VNAADNKQRD KSMNTIKIDI DPERNMVSVW NNGQGIPVTM HKEQKMYVPT
MIFGHLLTSS NYNDDEKKVT GGRNGYGAKL CNIFSTSFTV ETATREYKKS FKQTWGNNMG
KASDVQIKDF NGTDYTRITF SPDLAKFKMD RLDEDIVALM SRRAYDVAAS SKGVSVFLNG
NKLGVRNFKD YIDLHIKNTD DDSGPPIKIV HEVANERWEV ACCPSDRGFQ QVSFVNSIAT
YKGGRHVDHV VDNLIKQLLE VLKKKNKGGI NIKPFQVRNH LWVFVNCLIE NPTFDSQTKE
NMTLQQKGFG SKCTLSEKFI NNMSKSGIVE SVLAWAKFKA QNDIAKTGGR KSSKIKGIPK
LEDANEAGGK NSIKCTLILT EGDSAKSLAV SGLGVIGRDL YGVFPLRGKL LNVREANFKQ
LSENAEINNL CKIIGLQYKK KYLTEDDLKT LRYGKVMIMT DQDQDGSHIK GLLINFIHTN
WPELLRLPFL EEFITPIVKA TKKNEELSFY SLPEFEEWKN DTANHHTYNI KYYKGLGTST
SKEAKEYFQD MDRHRILFKY DGSVDDESIV MAFSKKHIES RKVWLTNHMD EVKRRKELGL
PERYLYTKGT KSITYADFIN LELVLFSNAD NERSIPSLVD GLKPGQRKVM FTCFKRNDKR
EVKVAQLSGS VAEMSAYHHG EVSLQMTIVN LAQNFVGANN INLLEPRGQF GTRLSGGKDC
ASARYIFTIM SPLTRLIYHP LDDPLLDYQV DDGQKIEPLW YLPIIPMVLV NGAEGIGTGW
STKISNYNPR EIMKNLRKMI NGQEPSVMHP WYKNFLGRME YVSDGRYIQT GNIQILSGNR
LEISELPVGV WTQNYKENVL EPLSNGTEKV KGIISEYREY HTDTTVRFVI SFAPGEFERI
HAEEGGFYRV FKLTTTLSTN QMHAFDQNNC LRRFPTAIDI LKEYYKLRRE YYARRRDFLV
GQLTAQADRL SDQARFILEK CEKKLVVENK QRKAMCDELL KRGYRPDPVK EWQRRIKMED
AEQADEEDEE EEEAAPSVSS KAKKEKEVDP EKAFKKLTDV KKFDYLLGMS MWMLTEEKKN
ELLKQRDTKL SELESLRKKT PEMLWLDDLD ALESKLNEVE EKERAEEQGI NLKTAKALKG
QKSASAKGRK VKSMGGGAGA GDVFPDPDGE PVEFKITEEI IKKMAAAAKV AQAAKEPKKP
KEPKEPKVKK EPKGKQIKAE PDASGDEVDE FDAMVEGGSK TSPKAKKAVV KKEPGEKKPR
QKKENGGGLK QSKIDFSKAK AKKSDDDVEE VTPRAERPGR RQASKKIDYS SLFSDEEEDG
GNVGSDDDGN ASDDDSPKRP AKRGREDESS GGAKKKAPPK KRRAVIESDD DDIEIDEDDD
DDSDFNC
