DNA topoisomerase 1 - Mus musculus (Mouse)

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Q04750 (TOP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 106. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
DNA topoisomerase 1
EC=5.99.1.2

Alternative name(s):
DNA topoisomerase I

Gene names

Name:	Top1
Synonyms:	Top-1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	767 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Nucleus › nucleolus. Nucleus › nucleoplasm. 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 component	Nucleus
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Isomerase Topoisomerase
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication Inferred from mutant phenotype PubMed 11756244. Source: MGI DNA topological change Inferred from direct assay PubMed 16261531 PubMed 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: Compara
Cellular_component	cytoplasm Inferred from direct assay PubMed 16261531. Source: MGI cytoplasmic mRNA processing body Inferred from electronic annotation. Source: Compara nucleolus Inferred from Biological aspect of Ancestor. Source: RefGenome nucleoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell perikaryon Inferred from direct assay PubMed 16261531. Source: MGI replication fork protection complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW DNA topoisomerase type I activity Inferred from direct assay PubMed 16261531 PubMed 7842491 PubMed 9094096. Source: MGI DNA topoisomerase type II (ATP-hydrolyzing) activity Inferred from electronic annotation. Source: InterPro chromatin binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed By similarity

Chain

2 – 767

766

DNA topoisomerase 1

PRO_0000145202

Regions

Region

427 – 428

Interaction with DNA By similarity

Region

490 – 495

Interaction with DNA By similarity

Region

587 – 589

Interaction with DNA By similarity

Compositional bias

23 – 206

184

Lys-rich

Sites

Active site

725

O-(3'-phospho-DNA)-tyrosine intermediate By similarity

Site

318

Interaction with DNA By similarity

Site

366

Interaction with DNA By similarity

Site

414

Interaction with DNA By similarity

Site

445

Interaction with DNA By similarity

Site

503

Interaction with DNA By similarity

Site

534

Interaction with DNA By similarity

Site

576

Interaction with DNA By similarity

Site

634

Interaction with DNA By similarity

Site

652

Interaction with DNA By similarity

Amino acid modifications

Modified residue

N-acetylserine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

114

Phosphoserine By similarity

Modified residue

282

N6-acetyllysine By similarity

Modified residue

508

Phosphoserine; by CK2 By similarity

Cross-link

105

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable

Cross-link

119

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Cross-link

155

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable

Experimental info

Sequence conflict

R → P in AAA40466. Ref.2

Sequence conflict

121

E → D in BAA00950. Ref.1

Sequence conflict

129

A → V in AAA40466. Ref.2

Sequence conflict

161

Missing in AAA40466. Ref.2

Sequence conflict

167

S → L in AAA40466. Ref.2

Sequence conflict

277

R → W in AAA40466. Ref.2

Sequence conflict

292

E → G in BAA00950. Ref.1

Sequence conflict

522

G → V in AAA40466. Ref.2

Sequence conflict

533

G → W in AAA40466. Ref.2

Sequence conflict

762

D → Y in AAA40466. Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

Q04750 [UniParc].

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

767

90,876

        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' referencesShow '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. Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
+	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.
IPI	IPI00109764.
PIR	JU0144.
RefSeq	NP_033434.2. NM_009408.2.
UniGene	Mm.217233.
3D structure databases
ProteinModelPortal	Q04750.
SMR	Q04750. Positions 203-767.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1868161.
PTM databases
PhosphoSite	Q04750.
Proteomic databases
PaxDb	Q04750.
PRIDE	Q04750.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000109468; ENSMUSP00000105094; ENSMUSG00000070544.
GeneID	21969.
KEGG	mmu:21969.
UCSC	uc008nqy.1. mouse.
Organism-specific databases
CTD	7150.
MGI	MGI:98788. Top1.
Phylogenomic databases
eggNOG	COG3569.
GeneTree	ENSGT00390000016347.
HOGENOM	HOG000105469.
HOVERGEN	HBG007988.
InParanoid	Q04750.
KO	K03163.
OMA	ESVKFYY.
OrthoDB	EOG4V170F.
Gene expression databases
ArrayExpress	Q04750.
Bgee	Q04750.
CleanEx	MM_TOP1.
Genevestigator	Q04750.
GermOnline	ENSMUSG00000070544. Mus musculus.
Family and domain databases
Gene3D	1.10.10.41. 1 hit. 1.10.132.10. 1 hit. 2.170.11.10. 2 hits. 3.90.15.10. 1 hit.
InterPro	IPR011010. 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. IPR009054. TopoI_insert_euk. [Graphical view]
Pfam	PF14370. Topo_C_assoc. 1 hit. PF01028. Topoisom_I. 1 hit. PF02919. Topoisom_I_N. 1 hit. [Graphical view]
PRINTS	PR00416. EUTPISMRASEI.
SMART	SM00435. TOPEUc. 1 hit. [Graphical view]
SUPFAM	SSF56349. DNA_brk_join_enz. 1 hit. SSF46596. Topismrse_insert. 1 hit. SSF56741. TopoI_DNA_bd_euk. 1 hit.
PROSITE	PS00176. TOPOISOMERASE_I_EUK. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q04750.
ChEMBL	CHEMBL2814.
ChiTaRS	TOP1. mouse.
NextBio	301666.
PMAP-CutDB	Q04750.
SOURCE	Search...

Entry information

Entry name

TOP1_MOUSE

Accession

Primary (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 3, 2013
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents