TOP1_CAEEL
ID TOP1_CAEEL Reviewed; 806 AA.
AC O17966; O17965; Q27529;
DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=DNA topoisomerase 1;
DE EC=5.6.2.1 {ECO:0000255|PROSITE-ProRule:PRU10130};
DE AltName: Full=DNA topoisomerase I;
DE Short=topoI;
GN Name=top-1; ORFNames=M01E5.5;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC STRAIN=Bristol N2;
RX PubMed=8647074; DOI=10.1111/j.1432-1033.1996.00367.x;
RA Kim J., Kim Y.-C., Lee J.H., Jang Y.J., Chung I.K., Koo H.-S.;
RT "cDNA cloning, expression, and chromosomal localization of Caenorhabditis
RT elegans DNA topoisomerase I.";
RL Eur. J. Biochem. 237:367-372(1996).
RN [2]
RP SEQUENCE REVISION, ALTERNATIVE SPLICING, AND DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2;
RX PubMed=9540836; DOI=10.1016/s0167-4781(97)00209-1;
RA Lee M.H., Jang Y.J., Koo H.-S.;
RT "Alternative splicing in the Caenorhabditis elegans DNA topoisomerase I
RT gene.";
RL Biochim. Biophys. Acta 1396:207-214(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=16943775; DOI=10.1038/nature05050;
RA Chu D.S., Liu H., Nix P., Wu T.F., Ralston E.J., Yates J.R. III,
RA Meyer B.J.;
RT "Sperm chromatin proteomics identifies evolutionarily conserved fertility
RT factors.";
RL Nature 443:101-105(2006).
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 (By similarity). Required for normal spermatogenesis and
CC oogenesis (PubMed:16943775). {ECO:0000250|UniProtKB:Q13472,
CC ECO:0000269|PubMed:16943775}.
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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P11387}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:16943775}. Chromosome
CC {ECO:0000269|PubMed:16943775}. Note=Localizes around sperm chromatids.
CC {ECO:0000269|PubMed:16943775}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=O17966-1; Sequence=Displayed;
CC Name=b;
CC IsoId=O17966-2; Sequence=VSP_033045;
CC -!- TISSUE SPECIFICITY: Expressed in male germ cells and in mature sperm.
CC {ECO:0000269|PubMed:16943775}.
CC -!- DEVELOPMENTAL STAGE: Isoform a: only expressed in embryos
CC (PubMed:9540836). Isoform b: present at all developmental stages
CC (PubMed:9540836). Not expressed during spermatocyte meiosis
CC (PubMed:16943775). {ECO:0000269|PubMed:16943775,
CC ECO:0000269|PubMed:9540836}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes abnormal gonad
CC morphology, enlarged sperm nuclei and aberrant progression through
CC meiosis. Oocytes appear to have undergone endomitotic reduplication.
CC {ECO:0000269|PubMed:16943775}.
CC -!- MISCELLANEOUS: Eukaryotic topoisomerase I and II can relax both
CC negative and positive supercoils, whereas prokaryotic enzymes relax
CC only negative supercoils. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform b]: Predominant isoform. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the type IB topoisomerase family. {ECO:0000305}.
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DR EMBL; X96762; CAA65537.1; -; mRNA.
DR EMBL; Z93385; CAB07639.1; -; Genomic_DNA.
DR EMBL; Z93385; CAB07640.1; -; Genomic_DNA.
DR PIR; S65469; S65469.
DR PIR; T23647; T23647.
DR PIR; T23648; T23648.
DR RefSeq; NP_001021578.1; NM_001026407.5.
DR RefSeq; NP_493337.1; NM_060936.5. [O17966-1]
DR AlphaFoldDB; O17966; -.
DR SMR; O17966; -.
DR BioGRID; 57335; 13.
DR STRING; 6239.M01E5.5a; -.
DR EPD; O17966; -.
DR PaxDb; O17966; -.
DR PeptideAtlas; O17966; -.
DR EnsemblMetazoa; M01E5.5a.1; M01E5.5a.1; WBGene00006595. [O17966-1]
DR EnsemblMetazoa; M01E5.5b.1; M01E5.5b.1; WBGene00006595. [O17966-2]
DR GeneID; 266847; -.
DR KEGG; cel:CELE_M01E5.5; -.
DR UCSC; M01E5.5b; c. elegans. [O17966-1]
DR CTD; 266847; -.
DR WormBase; M01E5.5a; CE12282; WBGene00006595; top-1. [O17966-1]
DR WormBase; M01E5.5b; CE12284; WBGene00006595; top-1. [O17966-2]
DR eggNOG; KOG0981; Eukaryota.
DR GeneTree; ENSGT00940000167650; -.
DR HOGENOM; CLU_009193_0_1_1; -.
DR InParanoid; O17966; -.
DR OMA; GLRYQKW; -.
DR OrthoDB; 303947at2759; -.
DR PhylomeDB; O17966; -.
DR Reactome; R-CEL-4615885; SUMOylation of DNA replication proteins.
DR PRO; PR:O17966; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00006595; Expressed in germ line (C elegans) and 5 other tissues.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0031616; C:spindle pole centrosome; IDA:WormBase.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003917; F:DNA topoisomerase type I (single strand cut, ATP-independent) activity; IDA:WormBase.
DR GO; GO:0007059; P:chromosome segregation; IBA:GO_Central.
DR GO; GO:0006260; P:DNA replication; IBA:GO_Central.
DR GO; GO:0006265; P:DNA topological change; IBA:GO_Central.
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 Alternative splicing; Chromosome; DNA-binding; Isomerase; Nucleus;
KW Reference proteome; Topoisomerase.
FT CHAIN 1..806
FT /note="DNA topoisomerase 1"
FT /id="PRO_0000330482"
FT REGION 1..236
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 467..468
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 530..535
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 634..636
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 22..100
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 151..188
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 213..236
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 761
FT /note="O-(3'-phospho-DNA)-tyrosine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10130"
FT SITE 358
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 406
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 454
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 485
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 543
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 581
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 623
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 681
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 699
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT VAR_SEQ 134..205
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_033045"
FT CONFLICT 172
FT /note="E -> K (in Ref. 1; CAA65537)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 806 AA; 94030 MW; 5979AD386DEBD004 CRC64;
MSVVSNHHSN GNGNSTVYDT NGNDEIKKEV KDEPMASDSE VPFGELMKRD KKEKKQKKRK
AESGSDEDDY KPEKRKSSAK NGKKKDVGSD SEDDYKPEKK KSKKNNKKKA QESSEDDDEE
SEGDVSEEDV KPQIHSDDEL EEEDEAPTTD DEEEQKRKEK ERRKKEKREK KERKEKKRLE
KENRKIKEED DEDSDDEDDE KAKKKKRKSK GAEKSKPSTS KKDAGGKKEP PKKKVKKEED
IEDIWEWWKE EKKPAGVKWN SLQHCGPLFA PPYIPLPSHV HFKYGGEKMK LTLETEEIAQ
FYAGVLDHEY STKEAFNKNF MKDWRKVMTV EERERIHDLK KCDFRAIDAY QKEQREIRKA
MTKEEKLKIK EEKEAEVKIY GIAIIDGHRQ KVANFRIEPP GVFRGRGGHP KMGLIKKRIM
PEDVIINCGK DTEIPKPPPG HKWKEVRHDN TVTWLCSWTE SVLGQNKYIM LNPSSKIKGE
KDFEKYETAR RLKKKIGGIR ERYTDDFKSK EMRVRQRATA LYFIDKLALR AGNEKDVDEA
ADTVGCCSLR VEHIKLFDSA KLNEDDKKEK EFVVEFDFLG KDSIRYFNRV SVEKRVYKNL
KIFMEGKAPS DDLFDRLDTA TLNDHLRSLM DGLTVKVFRT YNASITLQEQ LIKLTNPKDN
VAAKILSYNR ANRQVAILCN HQRAVSKGFD ESMQKLEQKI KDKKKEVKEA EAALKSARGA
EKEKAQKKYD RLKEQLKKLK ISRTDKDENK QIALGTSKLN YIDPRITVAW CKKFEVPLEK
VFTKTHREKF RWAIDMTNSS DEEYVF
