TOP1_CRIGR
ID TOP1_CRIGR Reviewed; 767 AA.
AC Q07050;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 25-MAY-2022, entry version 124.
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; Synonyms=TOP-1;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8244980; DOI=10.1016/s0021-9258(19)74414-7;
RA Tanizawa A., Bertrand R., Kohlhagen G., Tabuchi A., Jenkins J., Pommier Y.;
RT "Cloning of Chinese hamster DNA topoisomerase I cDNA and identification of
RT a single point mutation responsible for camptothecin resistance.";
RL J. Biol. Chem. 268:25463-25468(1993).
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 ARNTL/BMAL1 by altering the
CC chromatin structure around the ROR response elements (ROREs) on the
CC ARNTL/BMAL1 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 (By similarity). Interacts with ERCC6 (By similarity).
CC {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; Z21624; CAA79747.1; -; mRNA.
DR EMBL; Z21625; CAA79748.1; -; mRNA.
DR PIR; A49546; A49546.
DR RefSeq; NP_001230963.1; NM_001244034.1.
DR AlphaFoldDB; Q07050; -.
DR SMR; Q07050; -.
DR STRING; 10029.NP_001230963.1; -.
DR PRIDE; Q07050; -.
DR GeneID; 100689046; -.
DR KEGG; cge:100689046; -.
DR CTD; 7150; -.
DR eggNOG; KOG0981; Eukaryota.
DR OrthoDB; 303947at2759; -.
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 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 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_0000145200"
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: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"
FT VARIANT 505
FT /note="S -> G (in CPT-resistant cell)"
SQ SEQUENCE 767 AA; 90868 MW; 347336D424EF35A9 CRC64;
MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK DKEKDREKSK HSNSEHKDSE
KKHKEKEKTK HKDGSSEKHK DKHKDRDKEK RKEEKIRASG DAKIKKEKEN GFSSPPRIKD
EPDDDGYFAP PKEDIKPLKR PRDEDDADYK PKKIKTEDIK KEKKRKLEEE EDGKLKKTKN
KDKDKKGAES DNKKKKPKKE EEQKWKWWEE ERYPEGIKWK FLEHKGPVFA PPYEPLPEGV
KFYYDGKVMK LSPKAEEVAT FFAKMLDHEY TTKEIFRKNF FKDWRKEMTN DEKNVITNLS
KCDFTQMSQY FKDQSEARKQ MSKEEKLKIK EENEKLLKEY GFCVMDNHRE RIANFKIEPP
GLFRGRGNHP KMGMLKRRIM PEDIIINCSK DAKVPSPPPG HKWKEVRHDN KVTWLVSWTE
NIQGSIKYIM LNPSSRIKGE KDWQKYETAR RLKKCVDKIR NQYREDWKSK EMKVRQRAVA
LYFIDKLALR AGNEKEEGET ADTVSCCSLR VEHINLHPEL DGQEYVVEFD FPGKDSIRYY
NKVPVEKRVF KNLQLFMENK QPEDDLFDRL NTGILNKHLQ DLMEGLTAKV FRTYNASITL
QQQLKELTAP DENVPAKILS YNRANRAVAI LCNHQRAPPK TFEKSMMNLQ SKIDAKKDQL
ADARRDLKSA KADAKVMKDA KTKKVVESKK KAVQRLEEQL MKLEVQATDR EENKQIALGT
SKLNYLDPRI TVAWCKKWGV PIEKIYNKTQ REKFAWAIDM TDEDYEF
