ID   TOP1_CHLAE              Reviewed;         767 AA.
AC   Q7YR26;
DT   21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 1.
DT   24-JAN-2024, entry version 104.
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;
OS   Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Chlorocebus.
OX   NCBI_TaxID=9534;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=12829794; DOI=10.1073/pnas.1430827100;
RA   Shoya Y., Tokunaga K., Sawa H., Maeda M., Ueno T., Yoshikawa T.,
RA   Hasegawa H., Sata T., Kurata T., Hall W.W., Cullen B.R., Takahashi H.;
RT   "Human topoisomerase I promotes HIV-1 proviral DNA synthesis: Implications
RT   for the species specificity and cellular tropism of HIV-1 infection.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:8442-8447(2003).
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. Introduces a
CC       single-strand break via transesterification at a target site in duplex
CC       DNA. The scissile phosphodiester is attacked by the catalytic tyrosine
CC       of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-
CC       enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free
CC       DNA strand then rotates around the intact phosphodiester bond on the
CC       opposing strand, thus removing DNA supercoils. Finally, in the
CC       religation step, the DNA 5'-OH attacks the covalent intermediate to
CC       expel the active-site tyrosine and restore the DNA phosphodiester
CC       backbone. Regulates the alternative splicing of tissue factor (F3) pre-
CC       mRNA in endothelial cells. Involved in the circadian transcription of
CC       the core circadian clock component BMAL1 by altering the chromatin
CC       structure around the ROR response elements (ROREs) on the BMAL1
CC       promoter. {ECO:0000250|UniProtKB:P11387}.
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   -!- ACTIVITY REGULATION: Specifically inhibited by camptothecin (CPT), a
CC       plant alkaloid with antitumor activity.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P11387}.
CC   -!- SUBCELLULAR LOCATION: Nucleus, nucleolus
CC       {ECO:0000250|UniProtKB:P11387}. Nucleus, nucleoplasm
CC       {ECO:0000250|UniProtKB:P11387}. Note=Diffuse nuclear localization with
CC       some enrichment in nucleoli. On CPT treatment, cleared from nucleoli
CC       into nucleoplasm. Sumoylated forms found in both nucleoplasm and
CC       nucleoli. {ECO:0000250|UniProtKB:P11387}.
CC   -!- PTM: Sumoylated. Lys-119 is the main site of sumoylation. Sumoylation
CC       plays a role in partitioning TOP1 between nucleoli and nucleoplasm.
CC       Levels are dramatically increased on camptothecin (CPT) treatment.
CC       {ECO:0000250|UniProtKB:P11387}.
CC   -!- PTM: Phosphorylation at Ser-508 by CK2 increases binding to supercoiled
CC       DNA and sensitivity to camptothecin. {ECO:0000250|UniProtKB:P11387}.
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; AB089321; BAC78678.1; -; mRNA.
DR   AlphaFoldDB; Q7YR26; -.
DR   SMR; Q7YR26; -.
DR   BindingDB; Q7YR26; -.
DR   ChEMBL; CHEMBL5265; -.
DR   GO; GO:0005694; C:chromosome; IEA:InterPro.
DR   GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR   GO; GO:0003917; F:DNA topoisomerase type I (single strand cut, ATP-independent) activity; ISS:UniProtKB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR   GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB.
DR   GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR   GO; GO:0006265; P:DNA topological change; ISS:UniProtKB.
DR   CDD; cd00659; Topo_IB_C; 1.
DR   CDD; cd03488; Topoisomer_IB_N_htopoI_like; 1.
DR   Gene3D; 1.10.132.10; -; 1.
DR   Gene3D; 2.170.11.10; DNA Topoisomerase I, domain 2; 1.
DR   Gene3D; 1.10.10.41; Yeast DNA topoisomerase - domain 1; 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   InterPro; IPR048045; Topoisomer_I_DNA-bd.
DR   PANTHER; PTHR10290:SF5; DNA TOPOISOMERASE 1; 1.
DR   PANTHER; PTHR10290; DNA TOPOISOMERASE I; 1.
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; DNA breaking-rejoining enzymes; 1.
DR   SUPFAM; SSF46596; Eukaryotic DNA topoisomerase I, dispensable insert domain; 1.
DR   SUPFAM; SSF56741; Eukaryotic DNA topoisomerase I, N-terminal DNA-binding fragment; 1.
DR   PROSITE; PS00176; TOPO_IB_1; 1.
DR   PROSITE; PS52038; TOPO_IB_2; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Biological rhythms; DNA-binding; Isomerase; Isopeptide bond;
KW   Nucleus; Phosphoprotein; Topoisomerase; Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CHAIN           2..767
FT                   /note="DNA topoisomerase 1"
FT                   /id="PRO_0000145199"
FT   DOMAIN          434..767
FT                   /note="Topo IB-type catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01382"
FT   REGION          1..201
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          427..428
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   REGION          490..495
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   REGION          587..589
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        1..26
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        36..201
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        725
FT                   /note="O-(3'-phospho-DNA)-tyrosine intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01382,
FT                   ECO:0000255|PROSITE-ProRule:PRU10130"
FT   SITE            318
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            366
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            414
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            445
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            503
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            534
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            576
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            634
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   SITE            652
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   MOD_RES         10
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   MOD_RES         59
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   MOD_RES         114
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   MOD_RES         174
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q04750"
FT   MOD_RES         282
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   MOD_RES         508
FT                   /note="Phosphoserine; by CK2"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        103
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        105
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT                   /evidence="ECO:0000305"
FT   CROSSLNK        105
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        119
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT                   /evidence="ECO:0000250"
FT   CROSSLNK        119
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO1); alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        119
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        136
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        150
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        155
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT                   /evidence="ECO:0000305"
FT   CROSSLNK        155
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        160
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        166
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        174
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        206
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        338
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        551
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        644
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        702
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
FT   CROSSLNK        714
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P11387"
SQ   SEQUENCE   767 AA;  90954 MW;  3E6B4B6738923A5D CRC64;
     MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK DKEKDREKSK HSNSEHKDSE
     KKHKEKEKTK HKDGSSEKHK DKHKDRDKEK RKEEKVRASG DAKIKKEKEN GFSSPPQIKD
     EPEDDGYFVP PKEDIKPLKR PRDEDDADYK PKKIKTEDIK KEKKRKLEEE EDGKLRKPKN
     KDKDKKVPEP DNKKKKPKKE EEQKWKWWEE ERYPEGIKWK FLEHKGPVFA PPYEPLPDSV
     KFYYDGKVMK LSPKAEEVAT FFAKMLDHEY TTKEIFRKNF FKDWRKEMTN EEKNIITNLS
     KCDFTQMSQY FKAQTEARKQ MSKEEKLKIK EENEKLLKEY GFCIMDNHKE RIANFKIEPP
     GLFRGRGNHP KMGMLKRRIM PEDIIINCSK DAKVPSPPPG HKWKEVRHDN KVTWLVSWTE
     NIQGSIKYIM LNPSSRIKGE KDWQKYETAR RLKKCVDKIR NQYREDWKSK EMKVRQRAVA
     LYFIDKLALR AGNEKEEGET ADTVGCCSLR VEHINLHPEL DGQEYVVEFD FLGKDSIRYY
     NKVPVEKRVF KNLQLFMENK QPEDDLFDRL NTGILNKHLQ DLMEGLTAKV FRTYNASITL
     QQQLKELTAP DENIPAKILS YNRANRAVAI LCNHQRAPPK TFEKSMMNLQ SKIDAKKEQL
     ADARRDLKSA KADAKVMKDA KTKKVVESKK KAVQRLEEQL MKLEVQATDR EENKQIALGT
     SKLNYLDPRI TVAWCKKWGV PIEKIYNKTQ REKFAWAIDM ADEDYEF
//