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Q07050 (TOP1_CRIGR) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 89. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA topoisomerase 1

EC=5.99.1.2
Alternative name(s):
DNA topoisomerase I
Gene names
Name:TOP1
Synonyms:TOP-1
OrganismCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Taxonomic identifier10029 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeCricetulus

Protein attributes

Sequence length767 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells By similarity.

Catalytic activity

ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.

Enzyme regulation

Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.

Subunit structure

Monomer.

Subcellular location

Nucleusnucleolus. Nucleusnucleoplasm. Note: Diffuse nuclear localization with some enrichment in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumolyated forms found in both nucleoplasm and nucleoli By similarity.

Post-translational modification

Sumoylated. Lys-119 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment By similarity.

Phosphorylation at Ser-508 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin By similarity.

Miscellaneous

Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.

Sequence similarities

Belongs to the type IB topoisomerase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 767766DNA topoisomerase 1
PRO_0000145200

Regions

Region427 – 4282Interaction with DNA By similarity
Region490 – 4956Interaction with DNA By similarity
Region587 – 5893Interaction with DNA By similarity
Compositional bias23 – 206184Lys-rich

Sites

Active site7251O-(3'-phospho-DNA)-tyrosine intermediate By similarity
Site3181Interaction with DNA By similarity
Site3661Interaction with DNA By similarity
Site4141Interaction with DNA By similarity
Site4451Interaction with DNA By similarity
Site5031Interaction with DNA By similarity
Site5341Interaction with DNA By similarity
Site5761Interaction with DNA By similarity
Site6341Interaction with DNA By similarity
Site6521Interaction with DNA By similarity

Amino acid modifications

Modified residue21N-acetylserine By similarity
Modified residue101Phosphoserine By similarity
Modified residue591Phosphoserine By similarity
Modified residue1141Phosphoserine By similarity
Modified residue1741N6-acetyllysine By similarity
Modified residue2821N6-acetyllysine By similarity
Modified residue5081Phosphoserine; by CK2 By similarity
Cross-link105Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
Cross-link119Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link155Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable

Natural variations

Natural variant5051S → G in CPT-resistant cell.

Sequences

Sequence LengthMass (Da)Tools
Q07050 [UniParc].

Last modified October 1, 1994. Version 1.
Checksum: 347336D424EF35A9

FASTA76790,868
        10         20         30         40         50         60 
MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK DKEKDREKSK HSNSEHKDSE 

        70         80         90        100        110        120 
KKHKEKEKTK HKDGSSEKHK DKHKDRDKEK RKEEKIRASG DAKIKKEKEN GFSSPPRIKD 

       130        140        150        160        170        180 
EPDDDGYFAP PKEDIKPLKR PRDEDDADYK PKKIKTEDIK KEKKRKLEEE EDGKLKKTKN 

       190        200        210        220        230        240 
KDKDKKGAES DNKKKKPKKE EEQKWKWWEE ERYPEGIKWK FLEHKGPVFA PPYEPLPEGV 

       250        260        270        280        290        300 
KFYYDGKVMK LSPKAEEVAT FFAKMLDHEY TTKEIFRKNF FKDWRKEMTN DEKNVITNLS 

       310        320        330        340        350        360 
KCDFTQMSQY FKDQSEARKQ MSKEEKLKIK EENEKLLKEY GFCVMDNHRE RIANFKIEPP 

       370        380        390        400        410        420 
GLFRGRGNHP KMGMLKRRIM PEDIIINCSK DAKVPSPPPG HKWKEVRHDN KVTWLVSWTE 

       430        440        450        460        470        480 
NIQGSIKYIM LNPSSRIKGE KDWQKYETAR RLKKCVDKIR NQYREDWKSK EMKVRQRAVA 

       490        500        510        520        530        540 
LYFIDKLALR AGNEKEEGET ADTVSCCSLR VEHINLHPEL DGQEYVVEFD FPGKDSIRYY 

       550        560        570        580        590        600 
NKVPVEKRVF KNLQLFMENK QPEDDLFDRL NTGILNKHLQ DLMEGLTAKV FRTYNASITL 

       610        620        630        640        650        660 
QQQLKELTAP DENVPAKILS YNRANRAVAI LCNHQRAPPK TFEKSMMNLQ SKIDAKKDQL 

       670        680        690        700        710        720 
ADARRDLKSA KADAKVMKDA KTKKVVESKK KAVQRLEEQL MKLEVQATDR EENKQIALGT 

       730        740        750        760 
SKLNYLDPRI TVAWCKKWGV PIEKIYNKTQ REKFAWAIDM TDEDYEF 

« Hide

References

[1]"Cloning of Chinese hamster DNA topoisomerase I cDNA and identification of a single point mutation responsible for camptothecin resistance."
Tanizawa A., Bertrand R., Kohlhagen G., Tabuchi A., Jenkins J., Pommier Y.
J. Biol. Chem. 268:25463-25468(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z21624 mRNA. Translation: CAA79747.1.
Z21625 mRNA. Translation: CAA79748.1.
PIRA49546.
RefSeqNP_001230963.1. NM_001244034.1.

3D structure databases

ProteinModelPortalQ07050.
SMRQ07050. Positions 201-767.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEQ07050.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100689046.
KEGGcge:100689046.

Organism-specific databases

CTD7150.

Phylogenomic databases

HOVERGENHBG007988.
KOK03163.

Family and domain databases

Gene3D1.10.10.41. 1 hit.
1.10.132.10. 1 hit.
2.170.11.10. 2 hits.
3.90.15.10. 1 hit.
InterProIPR011010. DNA_brk_join_enz.
IPR013034. DNA_topo_domain1.
IPR001631. TopoI.
IPR018521. TopoI_AS.
IPR025834. TopoI_C_dom.
IPR014711. TopoI_cat_a-hlx-sub_euk.
IPR014727. TopoI_cat_a/b-sub_euk.
IPR013500. TopoI_cat_euk.
IPR008336. TopoI_DNA-bd_euk.
IPR013030. TopoI_DNA-bd_mixed-a/b_euk.
IPR013499. TopoI_euk.
[Graphical view]
PfamPF14370. Topo_C_assoc. 1 hit.
PF01028. Topoisom_I. 1 hit.
PF02919. Topoisom_I_N. 1 hit.
[Graphical view]
PRINTSPR00416. EUTPISMRASEI.
SMARTSM00435. TOPEUc. 1 hit.
[Graphical view]
SUPFAMSSF56349. SSF56349. 2 hits.
SSF56741. SSF56741. 1 hit.
PROSITEPS00176. TOPOISOMERASE_I_EUK. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameTOP1_CRIGR
AccessionPrimary (citable) accession number: Q07050
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: July 9, 2014
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families