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P11387

- TOP1_HUMAN

UniProt

P11387 - TOP1_HUMAN

Protein

DNA topoisomerase 1

Gene

TOP1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 169 (01 Oct 2014)
      Sequence version 2 (01 Dec 2000)
      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 By similarity. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.By similarity4 Publications

    Catalytic activityi

    ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.3 PublicationsPROSITE-ProRule annotation

    Enzyme regulationi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei316 – 3161Interaction with DNA
    Sitei364 – 3641Interaction with DNA
    Sitei412 – 4121Interaction with DNA
    Sitei443 – 4431Interaction with DNA
    Sitei501 – 5011Interaction with DNA
    Sitei532 – 5321Interaction with DNA
    Sitei574 – 5741Interaction with DNA
    Sitei632 – 6321Interaction with DNA
    Sitei650 – 6501Interaction with DNA
    Active sitei723 – 7231O-(3'-phospho-DNA)-tyrosine intermediate7 PublicationsPROSITE-ProRule annotation

    GO - Molecular functioni

    1. chromatin binding Source: UniProtKB
    2. DNA binding Source: UniProtKB
    3. DNA topoisomerase type I activity Source: UniProtKB
    4. DNA topoisomerase type II (ATP-hydrolyzing) activity Source: InterPro
    5. poly(A) RNA binding Source: UniProtKB
    6. protein binding Source: UniProtKB

    GO - Biological processi

    1. chromatin remodeling Source: RefGenome
    2. chromosome segregation Source: RefGenome
    3. DNA replication Source: RefGenome
    4. DNA topological change Source: UniProtKB
    5. embryonic cleavage Source: Ensembl
    6. phosphorylation Source: UniProtKB
    7. programmed cell death Source: UniProtKB
    8. response to drug Source: UniProtKB
    9. viral process Source: UniProtKB-KW

    Keywords - Molecular functioni

    Isomerase, Topoisomerase

    Keywords - Biological processi

    Host-virus interaction

    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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:11986. TOP1.

    Subcellular locationi

    Nucleusnucleolus 1 Publication. Nucleusnucleoplasm 1 Publication
    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.

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi103 – 1031K → R: Localizes in both nucleoplasm and nucleoli; when associated with R-117 or R-153. Almost complete loss of sumoylation, concentrates in nucleoli and no clearing from nucleoli on CPT treatment; when associated with R-117 and R-153. 1 Publication
    Mutagenesisi117 – 1171K → R: 5-fold decrease in sumoylation. Localizes in both nucleoplasm and nucleoli; when associated with or without R-103 or R-153. Almost complete loss of sumoylation, concentrates in nucleoli and no clearing from nucleoli on CPT treatment; when associated with R-103 and R-153. 1 Publication
    Mutagenesisi153 – 1531K → R: Localizes in both nucleoplasm and nucleoli; when associated with R-103 or R-117. Almost complete loss of sumoylation, concentrates in nucleoli and no clearing from nucleoli on CPT treatment; when associated with R-103 and R-117. 1 Publication
    Mutagenesisi532 – 5321K → A: Almost abolishes enzyme activity. 1 Publication
    Mutagenesisi532 – 5321K → R: Strongly reduced enzyme activity. 1 Publication
    Mutagenesisi723 – 7231Y → F: No change in CPT-induced clearing from nuclei. 1 Publication

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    PharmGKBiPA353.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed3 Publications
    Chaini2 – 765764DNA topoisomerase 1PRO_0000145201Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserine3 Publications
    Modified residuei10 – 101Phosphoserine2 Publications
    Modified residuei57 – 571Phosphoserine1 Publication
    Cross-linki103 – 103Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
    Modified residuei112 – 1121Phosphoserine1 Publication
    Cross-linki117 – 117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
    Cross-linki153 – 153Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)Curated
    Modified residuei172 – 1721N6-acetyllysineBy similarity
    Modified residuei280 – 2801N6-acetyllysine1 Publication
    Modified residuei506 – 5061Phosphoserine; by CK21 Publication

    Post-translational modificationi

    Sumoylated. Lys-117 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.1 Publication
    Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin.3 Publications

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP11387.
    PaxDbiP11387.
    PeptideAtlasiP11387.
    PRIDEiP11387.

    2D gel databases

    SWISS-2DPAGEP11387.

    PTM databases

    PhosphoSiteiP11387.

    Miscellaneous databases

    PMAP-CutDBP11387.

    Expressioni

    Tissue specificityi

    Endothelial cells.1 Publication

    Gene expression databases

    ArrayExpressiP11387.
    BgeeiP11387.
    CleanExiHS_TOP1.
    GenevestigatoriP11387.

    Organism-specific databases

    HPAiCAB009058.
    HPA019039.

    Interactioni

    Subunit structurei

    Monomer. Interacts with SV40 Large T antigen; this interactions allows viral DNA replication.8 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ABL1P005197EBI-876302,EBI-375543
    MYCP011062EBI-876302,EBI-447544
    NKX3-1Q998016EBI-876302,EBI-1385894

    Protein-protein interaction databases

    BioGridi113003. 130 interactions.
    IntActiP11387. 57 interactions.
    MINTiMINT-94018.
    STRINGi9606.ENSP00000354522.

    Structurei

    Secondary structure

    1
    765
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi205 – 2073
    Beta strandi220 – 2223
    Beta strandi236 – 2383
    Beta strandi240 – 2423
    Beta strandi245 – 2473
    Helixi251 – 26111
    Turni262 – 2654
    Helixi267 – 2704
    Helixi272 – 28514
    Helixi288 – 2936
    Helixi297 – 2993
    Helixi303 – 31715
    Helixi321 – 33818
    Beta strandi339 – 3435
    Beta strandi346 – 3516
    Beta strandi358 – 3603
    Beta strandi364 – 3663
    Turni368 – 3714
    Helixi379 – 3813
    Beta strandi383 – 3853
    Beta strandi396 – 3983
    Beta strandi402 – 4054
    Beta strandi413 – 4175
    Turni419 – 4213
    Beta strandi424 – 4274
    Beta strandi431 – 4333
    Helixi434 – 46431
    Helixi470 – 48516
    Turni495 – 4973
    Helixi504 – 5063
    Helixi509 – 5113
    Beta strandi514 – 5185
    Beta strandi521 – 53010
    Helixi532 – 5343
    Beta strandi536 – 5427
    Helixi545 – 5539
    Turni554 – 5574
    Turni564 – 5674
    Helixi570 – 58011
    Beta strandi581 – 5833
    Helixi586 – 60520
    Beta strandi608 – 6103
    Helixi612 – 62514
    Turni626 – 6316
    Helixi640 – 6434
    Helixi644 – 67330
    Helixi678 – 71033
    Beta strandi712 – 7143
    Turni721 – 7233
    Helixi726 – 73510
    Helixi740 – 7423
    Helixi746 – 7516
    Helixi753 – 7586

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1A31X-ray2.10A175-765[»]
    1A35X-ray2.50A175-765[»]
    1A36X-ray2.80A175-765[»]
    1EJ9X-ray2.60A203-765[»]
    1K4SX-ray3.20A174-765[»]
    1K4TX-ray2.10A174-765[»]
    1LPQX-ray3.14A202-765[»]
    1NH3X-ray3.10A203-765[»]
    1R49X-ray3.13A174-765[»]
    1RR8X-ray2.60C203-765[»]
    1RRJX-ray2.30A201-765[»]
    1SC7X-ray3.00A174-765[»]
    1SEUX-ray3.00A174-765[»]
    1T8IX-ray3.00A174-765[»]
    1TL8X-ray3.10A174-765[»]
    DisProtiDP00075.
    ProteinModelPortaliP11387.
    SMRiP11387. Positions 201-765.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11387.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni425 – 4262Interaction with DNA
    Regioni488 – 4936Interaction with DNA
    Regioni585 – 5873Interaction with DNA

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi23 – 204182Lys-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the type IB topoisomerase family.Curated

    Phylogenomic databases

    eggNOGiCOG3569.
    HOVERGENiHBG007988.
    InParanoidiP11387.
    KOiK03163.
    OMAiEFDFPGK.
    OrthoDBiEOG7CVPX5.
    PhylomeDBiP11387.
    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.

    P11387-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK EKDREKSKHS    50
    NSEHKDSEKK HKEKEKTKHK DGSSEKHKDK HKDRDKEKRK EEKVRASGDA 100
    KIKKEKENGF SSPPQIKDEP EDDGYFVPPK EDIKPLKRPR DEDDADYKPK 150
    KIKTEDTKKE KKRKLEEEED GKLKKPKNKD KDKKVPEPDN KKKKPKKEEE 200
    QKWKWWEEER YPEGIKWKFL EHKGPVFAPP YEPLPENVKF YYDGKVMKLS 250
    PKAEEVATFF AKMLDHEYTT KEIFRKNFFK DWRKEMTNEE KNIITNLSKC 300
    DFTQMSQYFK AQTEARKQMS KEEKLKIKEE NEKLLKEYGF CIMDNHKERI 350
    ANFKIEPPGL FRGRGNHPKM GMLKRRIMPE DIIINCSKDA KVPSPPPGHK 400
    WKEVRHDNKV TWLVSWTENI QGSIKYIMLN PSSRIKGEKD WQKYETARRL 450
    KKCVDKIRNQ YREDWKSKEM KVRQRAVALY FIDKLALRAG NEKEEGETAD 500
    TVGCCSLRVE HINLHPELDG QEYVVEFDFL GKDSIRYYNK VPVEKRVFKN 550
    LQLFMENKQP EDDLFDRLNT GILNKHLQDL MEGLTAKVFR TYNASITLQQ 600
    QLKELTAPDE NIPAKILSYN RANRAVAILC NHQRAPPKTF EKSMMNLQTK 650
    IDAKKEQLAD ARRDLKSAKA DAKVMKDAKT KKVVESKKKA VQRLEEQLMK 700
    LEVQATDREE NKQIALGTSK LNYLDPRITV AWCKKWGVPI EKIYNKTQRE 750
    KFAWAIDMAD EDYEF 765
    Length:765
    Mass (Da):90,726
    Last modified:December 1, 2000 - v2
    Checksum:i6FBED540BCF7BE28
    GO

    Sequence cautioni

    The sequence CAA36834.1 differs from that shown. Reason: Erroneous gene model prediction.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti145 – 1451A → V in AAA61207. (PubMed:2833744)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti214 – 2141G → S.
    Corresponds to variant rs6029542 [ dbSNP | Ensembl ].
    VAR_052592
    Natural varianti326 – 3261K → R in breast cancer; somatic mutation. 1 Publication
    VAR_036555
    Natural varianti370 – 3701M → T in CPT-resistant leukemia. 1 Publication
    VAR_010666
    Natural varianti533 – 5331D → G in CPT-resistant leukemia. 1 Publication
    VAR_007530
    Natural varianti722 – 7221N → S in CPT-resistant leukemia. 1 Publication
    VAR_010667
    Natural varianti729 – 7291T → A in CPT-resistant lung cancer. 1 Publication
    VAR_007531

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J03250 mRNA. Translation: AAA61207.1.
    M60706
    , M60688, M60689, M60690, M60691, M60692, M60693, M60694, M60695, M60696, M60697, M60698, M60699, M60700, M60701, M60702, M60703, M60704, M60705 Genomic DNA. Translation: AAA61206.1.
    AK292943 mRNA. Translation: BAF85632.1.
    AL035652, AL022394 Genomic DNA. Translation: CAI19767.1.
    AL022394, AL035652 Genomic DNA. Translation: CAI42886.1.
    CH471077 Genomic DNA. Translation: EAW75994.1.
    CH471077 Genomic DNA. Translation: EAW75995.1.
    X52601 Genomic DNA. Translation: CAA36834.1. Sequence problems.
    U07804 mRNA. Translation: AAB60379.1.
    U07806 mRNA. Translation: AAB60380.1.
    X16479 mRNA. Translation: CAA34500.2.
    M27913 mRNA. Translation: AAA61208.1.
    CCDSiCCDS13312.1.
    PIRiA30887. ISHUT1.
    RefSeqiNP_003277.1. NM_003286.2.
    UniGeneiHs.472737.

    Genome annotation databases

    EnsembliENST00000361337; ENSP00000354522; ENSG00000198900.
    GeneIDi7150.
    KEGGihsa:7150.
    UCSCiuc002xjl.3. human.

    Polymorphism databases

    DMDMi12644118.

    Keywords - Coding sequence diversityi

    Chromosomal rearrangement, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J03250 mRNA. Translation: AAA61207.1 .
    M60706
    , M60688 , M60689 , M60690 , M60691 , M60692 , M60693 , M60694 , M60695 , M60696 , M60697 , M60698 , M60699 , M60700 , M60701 , M60702 , M60703 , M60704 , M60705 Genomic DNA. Translation: AAA61206.1 .
    AK292943 mRNA. Translation: BAF85632.1 .
    AL035652 , AL022394 Genomic DNA. Translation: CAI19767.1 .
    AL022394 , AL035652 Genomic DNA. Translation: CAI42886.1 .
    CH471077 Genomic DNA. Translation: EAW75994.1 .
    CH471077 Genomic DNA. Translation: EAW75995.1 .
    X52601 Genomic DNA. Translation: CAA36834.1 . Sequence problems.
    U07804 mRNA. Translation: AAB60379.1 .
    U07806 mRNA. Translation: AAB60380.1 .
    X16479 mRNA. Translation: CAA34500.2 .
    M27913 mRNA. Translation: AAA61208.1 .
    CCDSi CCDS13312.1.
    PIRi A30887. ISHUT1.
    RefSeqi NP_003277.1. NM_003286.2.
    UniGenei Hs.472737.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1A31 X-ray 2.10 A 175-765 [» ]
    1A35 X-ray 2.50 A 175-765 [» ]
    1A36 X-ray 2.80 A 175-765 [» ]
    1EJ9 X-ray 2.60 A 203-765 [» ]
    1K4S X-ray 3.20 A 174-765 [» ]
    1K4T X-ray 2.10 A 174-765 [» ]
    1LPQ X-ray 3.14 A 202-765 [» ]
    1NH3 X-ray 3.10 A 203-765 [» ]
    1R49 X-ray 3.13 A 174-765 [» ]
    1RR8 X-ray 2.60 C 203-765 [» ]
    1RRJ X-ray 2.30 A 201-765 [» ]
    1SC7 X-ray 3.00 A 174-765 [» ]
    1SEU X-ray 3.00 A 174-765 [» ]
    1T8I X-ray 3.00 A 174-765 [» ]
    1TL8 X-ray 3.10 A 174-765 [» ]
    DisProti DP00075.
    ProteinModelPortali P11387.
    SMRi P11387. Positions 201-765.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113003. 130 interactions.
    IntActi P11387. 57 interactions.
    MINTi MINT-94018.
    STRINGi 9606.ENSP00000354522.

    Chemistry

    BindingDBi P11387.
    ChEMBLi CHEMBL1781.
    DrugBanki DB00762. Irinotecan.
    DB04967. Lucanthone.
    DB01030. Topotecan.

    PTM databases

    PhosphoSitei P11387.

    Polymorphism databases

    DMDMi 12644118.

    2D gel databases

    SWISS-2DPAGE P11387.

    Proteomic databases

    MaxQBi P11387.
    PaxDbi P11387.
    PeptideAtlasi P11387.
    PRIDEi P11387.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000361337 ; ENSP00000354522 ; ENSG00000198900 .
    GeneIDi 7150.
    KEGGi hsa:7150.
    UCSCi uc002xjl.3. human.

    Organism-specific databases

    CTDi 7150.
    GeneCardsi GC20P039657.
    H-InvDB HIX0015818.
    HIX0040702.
    HGNCi HGNC:11986. TOP1.
    HPAi CAB009058.
    HPA019039.
    MIMi 126420. gene.
    neXtProti NX_P11387.
    PharmGKBi PA353.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG3569.
    HOVERGENi HBG007988.
    InParanoidi P11387.
    KOi K03163.
    OMAi EFDFPGK.
    OrthoDBi EOG7CVPX5.
    PhylomeDBi P11387.
    TreeFami TF105281.

    Miscellaneous databases

    ChiTaRSi TOP1. human.
    EvolutionaryTracei P11387.
    GeneWikii TOP1.
    GenomeRNAii 7150.
    NextBioi 27982.
    PMAP-CutDB P11387.
    PROi P11387.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P11387.
    Bgeei P11387.
    CleanExi HS_TOP1.
    Genevestigatori P11387.

    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. "cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment."
      D'Arpa P., Machlin P.S., Ratrie H. III, Rothfield N.F., Cleveland D.W., Earnshaw W.C.
      Proc. Natl. Acad. Sci. U.S.A. 85:2543-2547(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY.
    2. "Structure of the human type I DNA topoisomerase gene."
      Kunze N., Yang G., Dolberg M., Sundarp R., Knippers R., Richter A.
      J. Biol. Chem. 266:9610-9616(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Trachea.
    4. "The DNA sequence and comparative analysis of human chromosome 20."
      Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
      , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
      Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "Structural characterisation of the human DNA topoisomerase I gene promoter."
      Kunze N., Klein M., Richter A., Knippers R.
      Eur. J. Biochem. 194:323-330(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
    7. Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.
      Submitted (DEC-2008) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 2-17; 107-117; 224-239; 253-262; 292-299; 355-362; 426-434; 476-484; 509-532; 550-587; 591-615; 625-634; 656-663; 694-712; 721-734 AND 736-742, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Ovarian carcinoma.
    8. "Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin."
      Fujimori A., Harker W.G., Kohlhagen G., Hoki Y., Pommier Y.
      Cancer Res. 55:1339-1346(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-765, VARIANTS CPT-RESISTANT LEUKEMIA THR-370 AND SER-722.
      Tissue: Peripheral blood.
    9. "Monoclonal antibodies neutralizing mammalian DNA topoisomerase I activity."
      Oddou P., Schmidt U., Knippers R., Richter A.
      Eur. J. Biochem. 177:523-529(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE OF 344-765.
    10. "Characterization of the 3' region of the human DNA topoisomerase I gene."
      Zhou B.S., Bastow K.F., Cheng Y.C.
      Cancer Res. 49:3922-3927(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 541-765.
    11. "Determination of an epitope of the diffuse systemic sclerosis marker antigen DNA topoisomerase I: sequence similarity with retroviral p30gag protein suggests a possible cause for autoimmunity in systemic sclerosis."
      Maul G.G., Jimenez S.A., Riggs E., Ziemnicka-Kotula D.
      Proc. Natl. Acad. Sci. U.S.A. 86:8492-8496(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 657-765.
    12. "The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion."
      Ahuja H.G., Felix C.A., Aplan P.D.
      Blood 94:3258-3261(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHROMOSOMAL TRANSLOCATION WITH NUP98.
    13. "Sumoylation of topoisomerase I is involved in its partitioning between nucleoli and nucleoplasm and its clearing from nucleoli in response to camptothecin."
      Rallabhandi P., Hashimoto K., Mo Y.-Y., Beck W.T., Moitra P.K., D'Arpa P.
      J. Biol. Chem. 277:40020-40026(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUMOYLATION AT LYS-117, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-103; LYS-117; LYS-153 AND TYR-723.
    14. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    15. "Simian virus 40 DNA replication is dependent on an interaction between topoisomerase I and the C-terminal end of T antigen."
      Khopde S., Simmons D.T.
      J. Virol. 82:1136-1145(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SV40 LARGE T ANTIGEN.
    16. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    17. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    18. "Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells."
      Eisenreich A., Bogdanov V.Y., Zakrzewicz A., Pries A., Antoniak S., Poller W., Schultheiss H.P., Rauch U.
      Circ. Res. 104:589-599(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    19. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
      Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
      Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    20. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; SER-57 AND SER-112, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    21. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    22. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    23. "CK2-mediated hyperphosphorylation of topoisomerase I targets serine 506, enhances topoisomerase I-DNA Binding, and increases cellular camptothecin sensitivity."
      Bandyopadhyay K., Li P., Gjerset R.A.
      PLoS ONE 7:E50427-E50427(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-506.
    24. "Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA."
      Redinbo M.R., Stewart L., Kuhn P., Champoux J.J., Hol W.G.J.
      Science 279:1504-1513(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 175-765 IN COMPLEX WITH DNA, ACTIVE SITE.
    25. "A model for the mechanism of human topoisomerase I."
      Stewart L., Redinbo M.R., Qiu X., Hol W.G.J., Champoux J.J.
      Science 279:1534-1541(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 215-765 OF MUTANT PHE-723 IN COMPLEX WITH DNA.
    26. "Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA."
      Redinbo M.R., Champoux J.J., Hol W.G.J.
      Biochemistry 39:6832-6840(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 203-765 IN COMPLEX WITH DNA, ACTIVE SITE.
    27. "8-Oxoguanine rearranges the active site of human topoisomerase I."
      Lesher D.T., Pommier Y., Stewart L., Redinbo M.R.
      Proc. Natl. Acad. Sci. U.S.A. 99:12102-12107(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.14 ANGSTROMS) OF 202-765 IN COMPLEX WITH DNA.
    28. Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 174-765 IN COMPLEXES WITH DNA AND TOPOTECAN, ACTIVE SITE.
    29. "Structural impact of the leukemia drug 1-beta-D-arabinofuranosylcytosine (Ara-C) on the covalent human topoisomerase I-DNA complex."
      Chrencik J.E., Burgin A.B., Pommier Y., Stewart L., Redinbo M.R.
      J. Biol. Chem. 278:12461-12466(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 203-764 IN COMPLEX WITH DNA, ACTIVE SITE.
    30. "The role of lysine 532 in the catalytic mechanism of human topoisomerase I."
      Interthal H., Quigley P.M., Hol W.G., Champoux J.J.
      J. Biol. Chem. 279:2984-2992(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.13 ANGSTROMS) OF 174-765, MUTAGENESIS OF LYS-532, CATALYTIC ACTIVITY, FUNCTION.
    31. "Mechanisms of camptothecin resistance by human topoisomerase I mutations."
      Chrencik J.E., Staker B.L., Burgin A.B., Pourquier P., Pommier Y., Stewart L., Redinbo M.R.
      J. Mol. Biol. 339:773-784(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 201-765 IN COMPLEX WITH DNA AND TOPOTECAN, ACTIVE SITE.
    32. "Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex."
      Staker B.L., Feese M.D., Cushman M., Pommier Y., Zembower D., Stewart L., Burgin A.B.
      J. Med. Chem. 48:2336-2345(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 174-765 IN COMPLEXES WITH DNA AND SYNTHETIC INHIBITORS, ACTIVE SITE.
    33. "Synthesis and mechanism of action studies of a series of norindenoisoquinoline topoisomerase I poisons reveal an inhibitor with a flipped orientation in the ternary DNA-enzyme-inhibitor complex as determined by X-ray crystallographic analysis."
      Ioanoviciu A., Antony S., Pommier Y., Staker B.L., Stewart L., Cushman M.
      J. Med. Chem. 48:4803-4814(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 174-765 IN COMPLEX WITH DNA AND SYNTHETIC INHIBITORS, CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE.
    34. "Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites."
      Tamura H., Kohchi C., Yamada R., Ikeda T., Koiwai O., Patterson E., Keene J.D., Okada K., Kjeldsen E., Nishikawa K.
      Nucleic Acids Res. 19:69-75(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CPT-RESISTANT LEUKEMIA GLY-533.
    35. "Detection of topoisomerase I gene point mutation in CPT-11 resistant lung cancer cell line."
      Kubota N., Kanzawa F., Nishio K., Takeda Y., Ohmori T., Fujiwara Y., Terashima Y., Saijo N.
      Biochem. Biophys. Res. Commun. 188:571-577(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CPT-RESISTANT LUNG CANCER ALA-729.
    36. Cited for: VARIANT [LARGE SCALE ANALYSIS] BREAST CANCER ARG-326.

    Entry informationi

    Entry nameiTOP1_HUMAN
    AccessioniPrimary (citable) accession number: P11387
    Secondary accession number(s): A8KA78
    , E1P5W3, O43256, Q12855, Q12856, Q15610, Q5TFY3, Q9UJN0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: December 1, 2000
    Last modified: October 1, 2014
    This is version 169 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3