Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q04750 (TOP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

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

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.

Ontologies

Keywords
   Cellular componentNucleus
   LigandATP-binding
DNA-binding
Nucleotide-binding
   Molecular functionIsomerase
Topoisomerase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from mutant phenotype PubMed 11756244. Source: MGI

DNA topological change

Inferred from direct assay PubMed 16261531PubMed 7842491. Source: MGI

chromatin remodeling

Inferred from Biological aspect of Ancestor. Source: RefGenome

chromosome segregation

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic cleavage

Inferred from mutant phenotype PubMed 8943335. Source: MGI

response to drug

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 16261531. Source: MGI

cytoplasmic mRNA processing body

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from Biological aspect of Ancestor. Source: RefGenome

nucleoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 16261531PubMed 8943335PubMed 9094096. Source: MGI

perikaryon

Inferred from direct assay PubMed 16261531. Source: MGI

replication fork protection complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA topoisomerase type I activity

Inferred from direct assay PubMed 16261531PubMed 7842491PubMed 9094096. Source: MGI

DNA topoisomerase type II (ATP-hydrolyzing) activity

Inferred from electronic annotation. Source: InterPro

chromatin binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 767766DNA topoisomerase 1
PRO_0000145202

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 Ref.4
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

Experimental info

Sequence conflict911R → P in AAA40466. Ref.2
Sequence conflict1211E → D in BAA00950. Ref.1
Sequence conflict1291A → V in AAA40466. Ref.2
Sequence conflict1611Missing in AAA40466. Ref.2
Sequence conflict1671S → L in AAA40466. Ref.2
Sequence conflict2771R → W in AAA40466. Ref.2
Sequence conflict2921E → G in BAA00950. Ref.1
Sequence conflict5221G → V in AAA40466. Ref.2
Sequence conflict5331G → W in AAA40466. Ref.2
Sequence conflict7621D → Y in AAA40466. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q04750 [UniParc].

Last modified July 24, 2007. Version 2.
Checksum: 4EA654244F07D5C1

FASTA76790,876
        10         20         30         40         50         60 
MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK DKDKDREKSK HSNSEHKDSE 

        70         80         90        100        110        120 
KKHKEKEKTK HKDGSSEKHK DKHKDRDKER RKEEKIRAAG DAKIKKEKEN GFSSPPRIKD 

       130        140        150        160        170        180 
EPEDDGYFAP PKEDIKPLKR LRDEDDADYK PKKIKTEDIK KEKKRKSEEE EDGKLKKPKN 

       190        200        210        220        230        240 
KDKDKKVAEP DNKKKKPKKE EEQKWKWWEE ERYPEGIKWK FLEHKGPVFA PPYEPLPESV 

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

       310        320        330        340        350        360 
KCDFTQMSQY FKAQSEARKQ 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 ADTVGCCSLR 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

« Hide 'large scale' references
[1]"Cloning of the mouse cDNA encoding DNA topoisomerase I and chromosomal location of the gene."
Koiwai O., Yasui Y., Sakai Y., Watanabe T., Ishii K., Yanagihara S., Andoh T.
Gene 125:211-216(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]"Cloning and characterization of mouse topoisomerase I cDNA."
Hui C.-F., Lo C.K., Hwang J.
Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-174, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D10061 mRNA. Translation: BAA00950.1.
L20632 mRNA. Translation: AAA40466.1.
AL590414, AL591673 Genomic DNA. Translation: CAM20297.1.
AL591673, AL590414 Genomic DNA. Translation: CAM25349.1.
PIRJU0144.
RefSeqNP_033434.2. NM_009408.2.
UniGeneMm.217233.

3D structure databases

ProteinModelPortalQ04750.
SMRQ04750. Positions 203-767.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204275. 2 interactions.
IntActQ04750. 2 interactions.
MINTMINT-1868161.

Chemistry

BindingDBQ04750.
ChEMBLCHEMBL2814.

PTM databases

PhosphoSiteQ04750.

Proteomic databases

PaxDbQ04750.
PRIDEQ04750.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000109468; ENSMUSP00000105094; ENSMUSG00000070544.
GeneID21969.
KEGGmmu:21969.
UCSCuc008nqy.1. mouse.

Organism-specific databases

CTD7150.
MGIMGI:98788. Top1.

Phylogenomic databases

eggNOGCOG3569.
GeneTreeENSGT00390000016347.
HOGENOMHOG000105469.
HOVERGENHBG007988.
InParanoidQ04750.
KOK03163.
OMAEFDFPGK.
OrthoDBEOG7CVPX5.
PhylomeDBQ04750.
TreeFamTF105281.

Gene expression databases

ArrayExpressQ04750.
BgeeQ04750.
CleanExMM_TOP1.
GenevestigatorQ04750.

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...

Other

ChiTaRSTOP1. mouse.
NextBio301666.
PMAP-CutDBQ04750.
PROQ04750.
SOURCESearch...

Entry information

Entry nameTOP1_MOUSE
AccessionPrimary (citable) accession number: Q04750
Secondary accession number(s): A2A4B7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: July 24, 2007
Last modified: April 16, 2014
This is version 115 of the entry and version 2 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot