TOP1_DROME
ID TOP1_DROME Reviewed; 972 AA.
AC P30189; Q9VXW6;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=DNA topoisomerase 1;
DE EC=5.6.2.1 {ECO:0000255|PROSITE-ProRule:PRU10130};
DE AltName: Full=DNA topoisomerase I;
GN Name=Top1 {ECO:0000312|FlyBase:FBgn0004924};
GN ORFNames=CG6146 {ECO:0000312|FlyBase:FBgn0004924};
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 [MRNA].
RX PubMed=1335568; DOI=10.1093/nar/20.23.6177;
RA Hsieh T.-S., Brown S.D., Huang P., Fostel J.;
RT "Isolation and characterization of a gene encoding DNA topoisomerase I in
RT Drosophila melanogaster.";
RL Nucleic Acids Res. 20:6177-6182(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Oregon-R;
RX PubMed=8769417; DOI=10.1083/jcb.134.4.923;
RA Zhang C.X., Lee M.P., Chen A.D., Brown S.D., Hsieh T.-S.;
RT "Isolation and characterization of a Drosophila gene essential for early
RT embryonic development and formation of cortical cleavage furrows.";
RL J. Cell Biol. 134:923-934(1996).
RN [3]
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 [4]
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 [5]
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 [6]
RP INTERACTION WITH TOPORS.
RX PubMed=14871887; DOI=10.1074/jbc.m310097200;
RA Secombe J., Parkhurst S.M.;
RT "Drosophila Topors is a RING finger-containing protein that functions as a
RT ubiquitin-protein isopeptide ligase for the hairy basic helix-loop-helix
RT repressor protein.";
RL J. Biol. Chem. 279:17126-17133(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303 AND TYR-304, AND
RP IDENTIFICATION BY MASS 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).
CC -!- FUNCTION: Releases the supercoiling and torsional tension of DNA
CC introduced during the DNA replication and transcription by transiently
CC cleaving and rejoining one strand of the DNA duplex (By similarity).
CC Introduces a single-strand break via transesterification at a target
CC site in duplex DNA (By similarity). The scissile phosphodiester is
CC attacked by the catalytic tyrosine of the enzyme, resulting in the
CC formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the
CC expulsion of a 5'-OH DNA strand (By similarity). The free DNA strand
CC then undergoes passage around the unbroken strand thus removing DNA
CC supercoils (By similarity). Finally, in the religation step, the DNA
CC 5'-OH attacks the covalent intermediate to expel the active-site
CC tyrosine and restore the DNA phosphodiester backbone (By similarity).
CC {ECO:0000250|UniProtKB:Q13472}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP-independent breakage of single-stranded DNA, followed by
CC passage and rejoining.; EC=5.6.2.1; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10130};
CC -!- SUBUNIT: Interacts with Topors. {ECO:0000269|PubMed:14871887}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10885744}. Cytoplasm
CC {ECO:0000269|PubMed:10885744}. Note=During early cell divisions of
CC developing embryos, it is detected in the nucleus at interphase then
CC diffusely dispersed in the cytoplasm at metaphase.
CC {ECO:0000269|PubMed:10885744}.
CC -!- DEVELOPMENTAL STAGE: Detected in germline and follicle cells. Expressed
CC in follicle cells throughout oogenesis. In germline cells, expression
CC levels increase as cells develop and move to the posterior region of
CC the germarium, then at stage 5 of egg chamber development levels
CC decrease until it is no longer detected (at protein level).
CC {ECO:0000269|PubMed:10885744}.
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 IB topoisomerase family. {ECO:0000305}.
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DR EMBL; M74557; AAA28951.1; -; mRNA.
DR EMBL; U80064; AAC24158.1; -; Genomic_DNA.
DR EMBL; AE014298; AAF48440.1; -; Genomic_DNA.
DR PIR; S35521; S35521.
DR RefSeq; NP_001014742.1; NM_001014742.2.
DR RefSeq; NP_511161.2; NM_078606.4.
DR AlphaFoldDB; P30189; -.
DR SMR; P30189; -.
DR BioGRID; 58813; 10.
DR IntAct; P30189; 1.
DR STRING; 7227.FBpp0073822; -.
DR iPTMnet; P30189; -.
DR PaxDb; P30189; -.
DR PRIDE; P30189; -.
DR DNASU; 32458; -.
DR GeneID; 32458; -.
DR KEGG; dme:Dmel_CG6146; -.
DR CTD; 7150; -.
DR FlyBase; FBgn0004924; Top1.
DR VEuPathDB; VectorBase:FBgn0004924; -.
DR eggNOG; KOG0981; Eukaryota.
DR HOGENOM; CLU_009193_0_0_1; -.
DR InParanoid; P30189; -.
DR PhylomeDB; P30189; -.
DR BioGRID-ORCS; 32458; 0 hits in 3 CRISPR screens.
DR ChiTaRS; Top1; fly.
DR GenomeRNAi; 32458; -.
DR PRO; PR:P30189; -.
DR Proteomes; UP000000803; Chromosome X.
DR ExpressionAtlas; P30189; baseline and differential.
DR Genevisible; P30189; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; HDA:FlyBase.
DR GO; GO:0000791; C:euchromatin; IDA:FlyBase.
DR GO; GO:0005730; C:nucleolus; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0005700; C:polytene chromosome; IDA:FlyBase.
DR GO; GO:0005703; C:polytene chromosome puff; IDA:FlyBase.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003916; F:DNA topoisomerase activity; IDA:FlyBase.
DR GO; GO:0003917; F:DNA topoisomerase type I (single strand cut, ATP-independent) activity; IDA:FlyBase.
DR GO; GO:0030261; P:chromosome condensation; IMP:FlyBase.
DR GO; GO:0007059; P:chromosome segregation; IMP:FlyBase.
DR GO; GO:0006260; P:DNA replication; IBA:GO_Central.
DR GO; GO:0006265; P:DNA topological change; IDA:FlyBase.
DR GO; GO:0002168; P:instar larval development; IMP:FlyBase.
DR GO; GO:0007275; P:multicellular organism development; IMP:FlyBase.
DR GO; GO:0048477; P:oogenesis; IMP:FlyBase.
DR GO; GO:0045995; P:regulation of embryonic development; IMP:FlyBase.
DR CDD; cd00659; Topo_IB_C; 1.
DR Gene3D; 1.10.10.41; -; 1.
DR Gene3D; 1.10.132.10; -; 1.
DR Gene3D; 2.170.11.10; -; 1.
DR Gene3D; 3.90.15.10; -; 1.
DR InterPro; IPR011010; DNA_brk_join_enz.
DR InterPro; IPR013034; DNA_topo_DNA_db_N_dom1.
DR InterPro; IPR013030; DNA_topo_DNA_db_N_dom2.
DR InterPro; IPR001631; TopoI.
DR InterPro; IPR018521; TopoI_AS.
DR InterPro; IPR025834; TopoI_C_dom.
DR InterPro; IPR014711; TopoI_cat_a-hlx-sub_euk.
DR InterPro; IPR014727; TopoI_cat_a/b-sub_euk.
DR InterPro; IPR013500; TopoI_cat_euk.
DR InterPro; IPR008336; TopoI_DNA-bd_euk.
DR InterPro; IPR036202; TopoI_DNA-bd_euk_N_sf.
DR InterPro; IPR013499; TopoI_euk.
DR Pfam; PF14370; Topo_C_assoc; 1.
DR Pfam; PF01028; Topoisom_I; 1.
DR Pfam; PF02919; Topoisom_I_N; 1.
DR PRINTS; PR00416; EUTPISMRASEI.
DR SMART; SM00435; TOPEUc; 1.
DR SUPFAM; SSF56349; SSF56349; 1.
DR SUPFAM; SSF56741; SSF56741; 1.
DR PROSITE; PS00176; TOPOISOMERASE_I_EUK; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; DNA-binding; Isomerase; Nucleus; Phosphoprotein;
KW Reference proteome; Topoisomerase.
FT CHAIN 1..972
FT /note="DNA topoisomerase 1"
FT /id="PRO_0000145205"
FT REGION 1..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 300..416
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 648..649
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 711..716
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 807..809
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT COMPBIAS 7..30
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..47
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..127
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 135..173
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..202
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 312..328
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 329..346
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 371..416
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 930
FT /note="O-(3'-phospho-DNA)-tyrosine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10130"
FT SITE 539
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 587
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 635
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 666
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 723
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 754
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 796
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 854
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 872
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 304
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 40
FT /note="S -> H (in Ref. 3; AAF48440)"
FT /evidence="ECO:0000305"
FT CONFLICT 46
FT /note="S -> SSS (in Ref. 3; AAF48440)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="H -> Q (in Ref. 3; AAF48440)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 972 AA; 111688 MW; 3764B8BDEEFA30CD CRC64;
MSGDVAAENS IHIQNGGSCE VVQSNGVTTN GHGHHHHHHS SSSSSSKHKS SSKDKHRDRE
REHKSSNSSS SSKEHKSSSR DKDRHKSSSS SSKHRDKDKE RDGSSNSHRS GSSSSHKDKD
GSSSSKHKSS SGHHKRSSKD KERRDKDKDR GSSSSSRHKS SSSSRDKERS SSSHKSSSSS
SSSKSKHSSS RHSSSSSSKD HPSYDGVFVK PEPVSQQLMH SGSVDAFQMQ QLGSYEAAAA
GTNFNGNGNV AGANYKNGYE ESIVDIKKEE ESFNNLSQAS SCDYSMSQFR ADEPPFVVKH
EQSYAEEDST MNYNDHDDDA DEMNDDEEDV PLAMRKRKQE ATDRPDGGMD NDDDDDIPLL
ARKKVKKEKI KKESKEKSKK RVKEEPSDDY GNVKPKKKKM KKEPEPAVSP GKRQKAKAKV
EEEEVWRWWE EEKRADGVKW STLEHKGPVF APRYERVPRN VRFYYDGKPL ELSEETEEAA
TFYAKMLNHD YCTKEVFNNN FFKDFRKSMT PREREIIKDF RKCNFQEMFN YFQAESEKRK
AASKEEKLIK KNENEALMKE FGFCMIDGHK EKIGNFRLEP PGLFRGRGEH PKMGMIKRRI
QASDVSINCG KDSKVPSPPP GSRWKEVRHD NTVTWLASWI ENVQGQVKYI MLNPSSKLKG
EKDHIKYETA RRLDKVIDKI RATYRDEWKS KEMRVRQRAV ALYFIDKLAL RAGNEKDEDQ
ADTVGCCSLR VEHVQLHKEL NGKENVVVFD FPGKDSIRYY NEVEVEKRVF KNLELFMEHK
KEGDDLFDRL NTQVLNEHLK ELMEGLTAKV FRTYNASKTL QSQLDLLTDP SATVPEKLLA
YNRANRAVAI LCNHQRSVPK SHEKSMENLK EKIKAKREAI EKCESEYHSR DEKKGKQLER
LRDQLKKLEL QETDRDENKT IALGTSKLNY LDPRISVAWC KKHDVPIEKI FNKTQRTKFL
WAVHMADENY RF
