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Q04750

- TOP1_MOUSE

UniProt

Q04750 - TOP1_MOUSE

Protein

DNA topoisomerase 1

Gene

Top1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 2 (24 Jul 2007)
      Previous versions | rss
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    Functioni

    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.By similarity

    Catalytic activityi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei318 – 3181Interaction with DNABy similarity
    Sitei366 – 3661Interaction with DNABy similarity
    Sitei414 – 4141Interaction with DNABy similarity
    Sitei445 – 4451Interaction with DNABy similarity
    Sitei503 – 5031Interaction with DNABy similarity
    Sitei534 – 5341Interaction with DNABy similarity
    Sitei576 – 5761Interaction with DNABy similarity
    Sitei634 – 6341Interaction with DNABy similarity
    Sitei652 – 6521Interaction with DNABy similarity
    Active sitei725 – 7251O-(3'-phospho-DNA)-tyrosine intermediatePROSITE-ProRule annotation

    GO - Molecular functioni

    1. chromatin binding Source: Ensembl
    2. DNA binding Source: UniProtKB-KW
    3. DNA topoisomerase type I activity Source: MGI
    4. DNA topoisomerase type II (ATP-hydrolyzing) activity Source: InterPro

    GO - Biological processi

    1. chromatin remodeling Source: RefGenome
    2. chromosome segregation Source: RefGenome
    3. DNA replication Source: MGI
    4. DNA topological change Source: MGI
    5. embryonic cleavage Source: MGI
    6. response to drug Source: Ensembl

    Keywords - Molecular functioni

    Isomerase, Topoisomerase

    Keywords - Ligandi

    DNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA topoisomerase 1 (EC:5.99.1.2)
    Alternative name(s):
    DNA topoisomerase I
    Gene namesi
    Name:Top1
    Synonyms:Top-1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 2

    Organism-specific databases

    MGIiMGI:98788. Top1.

    Subcellular locationi

    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.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: MGI
    2. cytoplasmic mRNA processing body Source: Ensembl
    3. nucleolus Source: RefGenome
    4. nucleoplasm Source: UniProtKB-SubCell
    5. nucleus Source: MGI
    6. perikaryon Source: MGI
    7. replication fork protection complex Source: RefGenome

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 767766DNA topoisomerase 1PRO_0000145202Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserineBy similarity
    Modified residuei10 – 101PhosphoserineBy similarity
    Modified residuei59 – 591PhosphoserineBy similarity
    Cross-linki105 – 105Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
    Modified residuei114 – 1141PhosphoserineBy similarity
    Cross-linki119 – 119Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
    Cross-linki155 – 155Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
    Modified residuei174 – 1741N6-acetyllysine1 Publication
    Modified residuei282 – 2821N6-acetyllysineBy similarity
    Modified residuei508 – 5081Phosphoserine; by CK2By similarity

    Post-translational modificationi

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

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ04750.
    PaxDbiQ04750.
    PRIDEiQ04750.

    PTM databases

    PhosphoSiteiQ04750.

    Miscellaneous databases

    PMAP-CutDBQ04750.

    Expressioni

    Gene expression databases

    ArrayExpressiQ04750.
    BgeeiQ04750.
    CleanExiMM_TOP1.
    GenevestigatoriQ04750.

    Interactioni

    Subunit structurei

    Monomer.

    Protein-protein interaction databases

    BioGridi204275. 3 interactions.
    IntActiQ04750. 2 interactions.
    MINTiMINT-1868161.

    Structurei

    3D structure databases

    ProteinModelPortaliQ04750.
    SMRiQ04750. Positions 203-767.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni427 – 4282Interaction with DNABy similarity
    Regioni490 – 4956Interaction with DNABy similarity
    Regioni587 – 5893Interaction with DNABy similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi23 – 206184Lys-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the type IB topoisomerase family.Curated

    Phylogenomic databases

    eggNOGiCOG3569.
    GeneTreeiENSGT00390000016347.
    HOGENOMiHOG000105469.
    HOVERGENiHBG007988.
    InParanoidiQ04750.
    KOiK03163.
    OMAiEFDFPGK.
    OrthoDBiEOG7CVPX5.
    PhylomeDBiQ04750.
    TreeFamiTF105281.

    Family and domain databases

    Gene3Di1.10.10.41. 1 hit.
    1.10.132.10. 1 hit.
    2.170.11.10. 2 hits.
    3.90.15.10. 1 hit.
    InterProiIPR011010. 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]
    PfamiPF14370. Topo_C_assoc. 1 hit.
    PF01028. Topoisom_I. 1 hit.
    PF02919. Topoisom_I_N. 1 hit.
    [Graphical view]
    PRINTSiPR00416. EUTPISMRASEI.
    SMARTiSM00435. TOPEUc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56349. SSF56349. 2 hits.
    SSF56741. SSF56741. 1 hit.
    PROSITEiPS00176. TOPOISOMERASE_I_EUK. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q04750-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK DKDKDREKSK    50
    HSNSEHKDSE KKHKEKEKTK HKDGSSEKHK DKHKDRDKER RKEEKIRAAG 100
    DAKIKKEKEN GFSSPPRIKD EPEDDGYFAP PKEDIKPLKR LRDEDDADYK 150
    PKKIKTEDIK KEKKRKSEEE EDGKLKKPKN KDKDKKVAEP DNKKKKPKKE 200
    EEQKWKWWEE ERYPEGIKWK FLEHKGPVFA PPYEPLPESV KFYYDGKVMK 250
    LSPKAEEVAT FFAKMLDHEY TTKEIFRKNF FKDWRKEMTN DEKNTITNLS 300
    KCDFTQMSQY FKAQSEARKQ MSKEEKLKIK EENEKLLKEY GFCVMDNHRE 350
    RIANFKIEPP GLFRGRGNHP KMGMLKRRIM PEDIIINCSK DAKVPSPPPG 400
    HKWKEVRHDN KVTWLVSWTE NIQGSIKYIM LNPSSRIKGE KDWQKYETAR 450
    RLKKCVDKIR NQYREDWKSK EMKVRQRAVA LYFIDKLALR AGNEKEEGET 500
    ADTVGCCSLR VEHINLHPEL DGQEYVVEFD FPGKDSIRYY NKVPVEKRVF 550
    KNLQLFMENK QPEDDLFDRL NTGILNKHLQ DLMEGLTAKV FRTYNASITL 600
    QQQLKELTAP DENVPAKILS YNRANRAVAI LCNHQRAPPK TFEKSMMNLQ 650
    SKIDAKKDQL ADARRDLKSA KADAKVMKDA KTKKVVESKK KAVQRLEEQL 700
    MKLEVQATDR EENKQIALGT SKLNYLDPRI TVAWCKKWGV PIEKIYNKTQ 750
    REKFAWAIDM TDEDYEF 767
    Length:767
    Mass (Da):90,876
    Last modified:July 24, 2007 - v2
    Checksum:i4EA654244F07D5C1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti91 – 911R → P in AAA40466. 1 PublicationCurated
    Sequence conflicti121 – 1211E → D in BAA00950. (PubMed:8096488)Curated
    Sequence conflicti129 – 1291A → V in AAA40466. 1 PublicationCurated
    Sequence conflicti161 – 1611Missing in AAA40466. 1 PublicationCurated
    Sequence conflicti167 – 1671S → L in AAA40466. 1 PublicationCurated
    Sequence conflicti277 – 2771R → W in AAA40466. 1 PublicationCurated
    Sequence conflicti292 – 2921E → G in BAA00950. (PubMed:8096488)Curated
    Sequence conflicti522 – 5221G → V in AAA40466. 1 PublicationCurated
    Sequence conflicti533 – 5331G → W in AAA40466. 1 PublicationCurated
    Sequence conflicti762 – 7621D → Y in AAA40466. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D10061 mRNA. Translation: BAA00950.1.
    L20632 mRNA. Translation: AAA40466.1.
    AL590414, AL591673 Genomic DNA. Translation: CAM20297.1.
    AL591673, AL590414 Genomic DNA. Translation: CAM25349.1.
    CCDSiCCDS16995.1.
    PIRiJU0144.
    RefSeqiNP_033434.2. NM_009408.2.
    UniGeneiMm.217233.

    Genome annotation databases

    EnsembliENSMUST00000109468; ENSMUSP00000105094; ENSMUSG00000070544.
    GeneIDi21969.
    KEGGimmu:21969.
    UCSCiuc008nqy.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D10061 mRNA. Translation: BAA00950.1 .
    L20632 mRNA. Translation: AAA40466.1 .
    AL590414 , AL591673 Genomic DNA. Translation: CAM20297.1 .
    AL591673 , AL590414 Genomic DNA. Translation: CAM25349.1 .
    CCDSi CCDS16995.1.
    PIRi JU0144.
    RefSeqi NP_033434.2. NM_009408.2.
    UniGenei Mm.217233.

    3D structure databases

    ProteinModelPortali Q04750.
    SMRi Q04750. Positions 203-767.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204275. 3 interactions.
    IntActi Q04750. 2 interactions.
    MINTi MINT-1868161.

    Chemistry

    BindingDBi Q04750.
    ChEMBLi CHEMBL2814.

    PTM databases

    PhosphoSitei Q04750.

    Proteomic databases

    MaxQBi Q04750.
    PaxDbi Q04750.
    PRIDEi Q04750.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000109468 ; ENSMUSP00000105094 ; ENSMUSG00000070544 .
    GeneIDi 21969.
    KEGGi mmu:21969.
    UCSCi uc008nqy.1. mouse.

    Organism-specific databases

    CTDi 7150.
    MGIi MGI:98788. Top1.

    Phylogenomic databases

    eggNOGi COG3569.
    GeneTreei ENSGT00390000016347.
    HOGENOMi HOG000105469.
    HOVERGENi HBG007988.
    InParanoidi Q04750.
    KOi K03163.
    OMAi EFDFPGK.
    OrthoDBi EOG7CVPX5.
    PhylomeDBi Q04750.
    TreeFami TF105281.

    Miscellaneous databases

    ChiTaRSi TOP1. mouse.
    NextBioi 301666.
    PMAP-CutDB Q04750.
    PROi Q04750.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q04750.
    Bgeei Q04750.
    CleanExi MM_TOP1.
    Genevestigatori Q04750.

    Family and domain databases

    Gene3Di 1.10.10.41. 1 hit.
    1.10.132.10. 1 hit.
    2.170.11.10. 2 hits.
    3.90.15.10. 1 hit.
    InterProi 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.
    [Graphical view ]
    Pfami PF14370. Topo_C_assoc. 1 hit.
    PF01028. Topoisom_I. 1 hit.
    PF02919. Topoisom_I_N. 1 hit.
    [Graphical view ]
    PRINTSi PR00416. EUTPISMRASEI.
    SMARTi SM00435. TOPEUc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56349. SSF56349. 2 hits.
    SSF56741. SSF56741. 1 hit.
    PROSITEi PS00176. TOPOISOMERASE_I_EUK. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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.

    Entry informationi

    Entry nameiTOP1_MOUSE
    AccessioniPrimary (citable) accession number: Q04750
    Secondary accession number(s): A2A4B7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1993
    Last sequence update: July 24, 2007
    Last modified: October 1, 2014
    This is version 119 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

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

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3