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TOP1 Gene

protein-coding   GIFtS: 70
GCID: GC20P039657

Topoisomerase (DNA) I

  See TOP1-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Topoisomerase (DNA) I1 2
EC 5.99.1.23 8
TOPI2
DNA Topoisomerase 12
Type I DNA Topoisomerase2
DNA Topoisomerase I3

External Ids:    HGNC: 119861   Entrez Gene: 71502   Ensembl: ENSG000001989007   OMIM: 1264205   UniProtKB: P113873   

Export aliases for TOP1 gene to outside databases

Previous GC identifers: GC20P039385 GC20P040295 GC20P040342 GC20P039090 GC20P036395


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TOP1 Gene:
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during
transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows
the strands to pass through one another, thus altering the topology of DNA. This gene is localized to chromosome
20 and has pseudogenes which reside on chromosomes 1 and 22. (provided by RefSeq, Jul 2008)

GeneCards Summary for TOP1 Gene:
TOP1 (topoisomerase (DNA) I) is a protein-coding gene. Diseases associated with TOP1 include dna topoisomerase i, camptothecin-resistant, and scleroderma. GO annotations related to this gene include chromatin binding and DNA topoisomerase type II (ATP-hydrolyzing) activity. An important paralog of this gene is TOP1MT.

UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387
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 (By similarity). Regulates the
alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells

summary for TOP1 Gene:
Topoisomerases are ubiquitously expressed enzymes that overcome topological problems in genomic DNA, which
can result from DNA replication, transcription and repair. Common problems such as overwinding (positive
supercoiling), knots and tangles are resolved by topoisomerases by catalysing the breaking of one or two
strands of DNA. Topoisomerase type I enzymes cut just one strand of the DNA double helix, and hence relax
supercoiling of the DNA. Four genes encode Type I topoisomerases, which include nuclear topoisomerase I
(TOP1) and mitochondrial topoisomerase I (TOP1MT). Type I enzymes can also be sub-divided into Types A and B
based on their different catalytic mechanism for generating single DNA strand breaks. TOP1 and TOP1MT are
both type 1B since they form 3'-phosphotyrosyl bonds. Camptothecin is a natural product inhibitor of TOP1
that has led to the discovery of derivatives that are clinically used anti-cancer drugs. Such inhibitors
trap the enzyme in a cleavage complex with DNA. Type II topoisomerases (IIA and IIB) are particular
important for the disentanglement of DNA, which is overcome by generating double stranded DNA breaks.
Dysregulation of type II enzymes can therefore have a potentially significant genotoxic effect. There is a
broad range of topoisomerase II inhibitors that are used clinically as anticancer agents.

Gene Wiki entry for TOP1 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000020.10  NC_018931.2  NT_011362.11  
Regulatory elements:
   Regulatory transcription factor binding sites in the TOP1 gene promoter:
         CREB   c-Fos   Sp1   AP-1   ATF-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): TOP1 promoter sequence
   Search Chromatin IP Primers for TOP1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TOP1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q12-q13.1   Ensembl cytogenetic band:  20q12   HGNC cytogenetic band: 20q12-q13.1

TOP1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TOP1 gene location

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20P039657:  view genomic region     (about GC identifiers)

Start:
39,657,458 bp from pter      End:
39,753,127 bp from pter
Size:
95,670 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387 (See protein sequence)
Recommended Name: DNA topoisomerase 1  
Size: 765 amino acids; 90726 Da
Subunit: Monomer. Interacts with SV40 Large T antigen; this interactions allows viral DNA replication
Miscellaneous: Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas
prokaryotic enzymes relax only negative supercoils
Sequence caution: Sequence=CAA36834.1; Type=Erroneous gene model prediction;
Selected PDB 3D structures from and Proteopedia for TOP1 (see all 15):
1A31 (3D)        1A35 (3D)        1A36 (3D)        1EJ9 (3D)        1K4S (3D)        1K4T (3D)    
Secondary accessions: A8KA78 E1P5W3 O43256 Q12855 Q12856 Q15610 Q5TFY3 Q9UJN0

Explore the universe of human proteins at neXtProt for TOP1: NX_P11387

Explore proteomics data for TOP1 at MOPED

Post-translational modifications: 

  • 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) treatment1
  • Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin1
  • Ubiquitination2 at Lys223, Lys245, Lys252, Lys262, Lys354, Lys484, Lys549, Lys587, Lys642, Lys742
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for TOP1 (P11387) (see all 27)
     DFLGKDS  VKFYYDG  KHKDKHK  LRAGNEK 


    See TOP1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_003277.1  
    ENSEMBL proteins: 
     ENSP00000354522  

    TOP1 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for TOP1
    OriGene Custom MassSpec
    OriGene Custom Protein Services for TOP1
    GenScript Custom Purified and Recombinant Proteins Services for TOP1
    Novus Biologicals TOP1 Protein
    Novus Biologicals TOP1 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for TOP1
    Cloud-Clone Corp. Proteins for TOP1

     
    Search eBioscience for Proteins for TOP1 

    TOP1 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of TOP1
    Browse R&D Systems for Antibodies
    OriGene Antibodies for TOP1
    OriGene Custom Antibody Services for TOP1
    Novus Biologicals TOP1 Antibodies
    Abcam antibodies for TOP1
    Cloud-Clone Corp. Antibodies for TOP1
    ThermoFisher Antibodies for TOP1
    LSBio Antibodies in human, mouse, rat for TOP1

    TOP1 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for TOP1
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for TOP1
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for TOP1
    Cloud-Clone Corp. CLIAs for TOP1
    Search eBioscience for ELISAs for TOP1 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 11):
     IPR013030 TopoI_DNA-bd_mixed-a/b_euk
     IPR008336 TopoI_DNA-bd_euk
     IPR001631 TopoI
     IPR018521 TopoI_AS
     IPR014727 TopoI_cat_a/b-sub_euk

    Graphical View of Domain Structure for InterPro Entry P11387

    ProtoNet protein and cluster: P11387

    2 Blocks protein domains:
    IPB001631 Eukaryotic-like DNA topoisomerase I
    IPB008336 Eukaryotic DNA topoisomerase I


    UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387
    Similarity: Belongs to the type IB topoisomerase family


    Find genes that share domains with TOP1           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TOP1_HUMAN, P11387
    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 (By similarity). Regulates the
    alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells
    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

         Genatlas biochemistry entry for TOP1:
    DNA topoisomerase I,ubiquitous,catalyzing the ATP independent breakage and rejoining of single strand of
    DNA,relaxing negatively supercoiled DNA,involved in DNA repair

         Enzyme Number (IUBMB): EC 5.99.1.21 2

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003677DNA binding IDA17355975
    GO:0003682chromatin binding IDA9049244
    GO:0003917DNA topoisomerase type I activity IMP17355975
    GO:0003918DNA topoisomerase type II (ATP-hydrolyzing) activity IEA--
    GO:0005515protein binding IPI10352183
         
    Find genes that share ontologies with TOP1           About GenesLikeMe


    Phenotypes:
         1 MGI mutant phenotype (inferred from 2 alleles(MGI details for Top1):
     mortality/aging 

    Find genes that share phenotypes with TOP1           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Top1tm1Unc for TOP1

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TOP1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for TOP1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TOP1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for TOP1

    miRNA
    Products:
        
    miRTarBase miRNAs that target TOP1:
    hsa-mir-24-3p (MIRT030382), hsa-mir-215-5p (MIRT024385), hsa-mir-186-5p (MIRT044929), hsa-mir-484 (MIRT042230), hsa-mir-26b-5p (MIRT028857), hsa-mir-192-5p (MIRT026200)

    Block miRNA regulation of human, mouse, rat TOP1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TOP1 (see all 52):
    hsa-miR-549 hsa-miR-4307 hsa-miR-3607-3p hsa-miR-1197 hsa-miR-139-5p hsa-miR-25 hsa-miR-485-3p hsa-miR-374a
    SwitchGear 3'UTR luciferase reporter plasmidTOP1 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for TOP1
    Predesigned siRNA for gene silencing in human, mouse, rat TOP1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for TOP1

    Clone
    Products:
         
    OriGene clones in human, mouse for TOP1 (see all 7)
    OriGene ORF clones in mouse, rat for TOP1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: TOP1 (NM_003286)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TOP1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TOP1

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for TOP1
    Browse ESI BIO Cell Lines and PureStem Progenitors for TOP1 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TOP1

    Flow Cytometry
    Products:
       

     
    eBioscience FlowRNA Probe Sets ( VA4-13772) for TOP1 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TOP1_HUMAN, P11387: 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
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus5
    cytosol2
    mitochondrion2
    chloroplast1
    cytoskeleton1
    extracellular1
    plasma membrane1

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000228colocalizes with nuclear chromosome IDA9049244
    GO:0000932cytoplasmic mRNA processing body IDA12878161
    GO:0005634nucleus IDA11016921
    GO:0005654nucleoplasm IDA9049244
    GO:0005694chromosome ----

    Find genes that share ontologies with TOP1           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for TOP1 About    
    See pathways by source

    SuperPathContained pathways About
    1Irinotecan Pathway, Pharmacokinetics
    Irinotecan Pathway, Pharmacodynamics0.50
    2Telomere C-strand (Lagging Strand) Synthesis
    Cell cycle Transition and termination of DNA replication0.43
    3Apoptosis and survival Caspase cascade
    Caspase cascade in apoptosis0.42
    4Integrated Pancreatic Cancer Pathway
    Integrated Pancreatic Cancer Pathway
    5Cell cycle Chromosome condensation in prometaphase
    Cell cycle Chromosome condensation in prometaphase

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    2 GeneGo (Thomson Reuters) Pathways for TOP1
        Cell cycle Chromosome condensation in prometaphase
    Cell cycle Transition and termination of DNA replication

    2 BioSystems Pathways for TOP1
        Integrated Pancreatic Cancer Pathway
    Caspase cascade in apoptosis

    1 PharmGKB Pathway for TOP1
        Irinotecan Pathway, Pharmacodynamics

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TOP1: 
              Multiple Sclerosis in human mouse rat
              Cancer Drug Resistance in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for TOP1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for TOP1 (P113871, 2, 3 ENSP000003545224) via UniProtKB, MINT, STRING, and/or I2D (see all 713)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ABL1P005191, 2, 3, ENSP000003614234EBI-876302,EBI-375543 MINT-7300976 MINT-7301061 MINT-7301032 MINT-7301050 MINT-7300988 MINT-7301011 MINT-7300967 I2D: score=1 STRING: ENSP00000361423
    HIST1H4HP628053, ENSP000002893524I2D: score=1 STRING: ENSP00000289352
    HIST1H4FP628053, ENSP000003669744I2D: score=1 STRING: ENSP00000366974
    HIST1H4AP628053I2D: score=1 
    HIST1H4BP628053I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006260DNA replication IBA--
    GO:0006265DNA topological change IDA14594810
    GO:0006338chromatin remodeling IBA--
    GO:0007059chromosome segregation IBA--
    GO:0012501programmed cell death NAS17172417

    Find genes that share ontologies with TOP1           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Enzo Life Sciences drugs & compounds for TOP1
    Selected ApexBio Compounds for TOP1 (see all 20)     About this table
    CompoundAction CAS #
    4'-Demethylepipodophyllotoxinkey intermediate compound for the preparation of podophyllotoxin-type anti-cancer drugs[6559-91-7]
    AmonafideDNA intercalator and Topo II (topoisomerase II) inhibitor[69408-81-7]
    AmrubicinTopoisomerase II inhibitor, anthracycline agent[110267-81-7]
    Camptothecinprototypic DNA topoisomerase I inhibitor[7689-3-4]
    Deferasirox Fe3+ chelaterationally-designed oral iron chelator[554435-83-5]
    Dexrazoxane HCl (ICRF-187, ADR-529)cardioprotective agent[149003-01-0]
    DoxorubicinDNA topoisomerase I inhibitor[23214-92-8]
    Doxorubicin (Adriamycin) HClAntitumor antibiotic agent, inhibits DNA topoisomerase II[25316-40-9]
    Ellagic acidATP-competitive inhibitor of casein kinase 2 (CK2)[476-66-4]
    Epirubicin HClAntibiotic antitumor agent[56390-09-1]

    Compounds for TOP1 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    CPT 11DNA topoisomerase I inhibitor; antitumor[100286-90-6]
    Doxorubicin hydrochlorideAntitumor antibiotic agent. Inhibits DNA topoisomerase II[25316-40-9]
    EtoposideTopoisomerase II inhibitor[33419-42-0]
    SN 38DNA topoisomerase I inhibitor; antitumor[86639-52-3]
    CamptothecinDNA topoisomerase inhibitor[7689-03-4]

    7 DrugBank Compounds for TOP1    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    TopotecanTopotecan Hcl (see all 5)119413-54-6targetinhibitor9885371 11752352 12437383 12855624 8853931 11443926 12520736 9122737 11166732
    IrinotecanCamptothecin-11 (see all 2)100286-90-6targetinhibitor15975002 19852077 15170677 9342501 11752352 15255290 16309825 16454746
    Camptothecin(+)-camptothecin (see all 8)7689-03-4target--18056711 11752352 10592235 18061144
    Sodium stibogluconateAntimony sodium gluconate (see all 6)16037-91-5targetinhibitor15562618 2835038 10592235
    Lucanthone1-((2-(Diethylamino)ethyl)amino)-4-methylthioxanthen-9-one (see all 7)479-50-5targetinhibitor9169823 10487533
    2,3-DIMETHOXY-12H-[1,3]DIOXOLO[5,6]INDENO[1,2-C]ISOQUINOLIN-6-IUM-- --target--10592235
    4-(5,11-DIOXO-5H-INDENO[1,2-C]ISOQUINOLIN-6(11H)-YL)BUTANOATE-- --target--10592235

    Selected Novoseek inferred chemical compound relationships for TOP1 gene (see all 124)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    camptothecin 98 1214 11479235 (8), 9305865 (7), 7538195 (7), 14729676 (6) (see all 99)
    topotecan 96 364 9717830 (4), 8621255 (3), 15471886 (3), 14587067 (3) (see all 99)
    irinotecan 92.1 270 18823053 (3), 2168285 (3), 15160997 (3), 8162152 (2) (see all 99)
    9-aminocamptothecin 90.7 43 8892462 (2), 9815685 (2), 8634995 (1), 10912951 (1) (see all 24)
    sn 38 88.5 30 15574786 (2), 9771954 (1), 9825730 (1), 11000580 (1) (see all 28)
    lurtotecan 86.4 13 8611374 (1), 9328158 (1), 11870164 (1), 7834631 (1) (see all 11)
    tdp-1 86.2 52 15494395 (6), 15920477 (3), 16793421 (2), 13679147 (2) (see all 23)
    rebeccamycin 85.8 25 11032967 (3), 12901916 (2), 10322124 (2), 11733535 (1) (see all 19)
    saintopin 82.8 29 9203632 (5), 1646001 (3), 7961822 (2), 7890748 (2) (see all 7)
    9-nitrocamptothecin 82.5 27 11585748 (1), 18434109 (1), 11193897 (1), 9328159 (1) (see all 13)

    1 PharmGKB related drug/compound annotation for TOP1 gene    About this table
    Drug/compound PharmGKB Annotation
    irinotecanCA  



    Find genes that share compounds with TOP1           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for TOP1 gene: 
    NM_003286.2  

    Unigene Cluster for TOP1:

    Topoisomerase (DNA) I
    Hs.472737  [show with all ESTs]
    Unigene Representative Sequence: NM_003286
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000361337(uc010ggd.1 uc010gge.1 uc002xjl.3)
    miRNA
    Products:
         
    Block miRNA regulation of human, mouse, rat TOP1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate TOP1 (see all 52):
    hsa-miR-549 hsa-miR-4307 hsa-miR-3607-3p hsa-miR-1197 hsa-miR-139-5p hsa-miR-25 hsa-miR-485-3p hsa-miR-374a
    SwitchGear 3'UTR luciferase reporter plasmidTOP1 3' UTR sequence
    Inhib. RNA
    Products:
         
    OriGene RNAi products in human, mouse, rat for TOP1
    Predesigned siRNA for gene silencing in human, mouse, rat TOP1
    Clone
    Products:
         
    OriGene clones in human, mouse for TOP1 (see all 7)
    OriGene ORF clones in mouse, rat for TOP1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: TOP1 (NM_003286)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for TOP1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TOP1
    Primer
    Products:
        
    OriGene qSTAR qPCR primer pairs in human, mouse for TOP1
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat TOP1
      QuantiTect SYBR Green Assays in human, mouse, rat TOP1
      QuantiFast Probe-based Assays in human, mouse, rat TOP1
    Flow Cytometry
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    eBioscience FlowRNA Probe Sets ( VA4-13772) for TOP1 

    Additional mRNA sequence: 

    AK225095.1 AK292943.1 AK310508.1 AK310516.1 BC000943.2 BC004475.2 BC039009.1 BC056681.1 
    BC067349.1 BC136297.1 J03250.1 M27913.1 U07804.1 U07806.1 X16479.2 

    14 DOTS entries:

    DT.97780620  DT.425139  DT.99987653  DT.75183810  DT.99955016  DT.120819606  DT.40209313  DT.95191468 
    DT.120819634  DT.40261268  DT.86840413  DT.95194887  DT.95191472  DT.95210182 

    Selected AceView cDNA sequences (see all 299):

    CA487823 BM985011 AL559809 AA371544 BQ918804 BF726053 AA233029 BF224041 
    BM974259 CA438301 BF111463 AA830283 BC000943 AI493041 AI479910 NM_003286 
    BU632004 BM541278 AW206091 F07589 AI828741 R00391 BG778556 CR604483 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    TOP1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AATTCCCTTT
    TOP1 Expression
    About this image


    TOP1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     
     Neural Tube (Nervous System)
             Telencephalon
    TOP1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    TOP1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.472737

    UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387
    Tissue specificity: Endothelial cells

        Pathway & Disease-focused RT2 Profiler PCR Arrays including TOP1: 
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for TOP1 gene from Selected species (see all 28)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Top11 , 5 topoisomerase (DNA) I1, 5 90.85(n)1
    97.25(a)1
      2 (80.96 cM)5
    219691  NM_009408.21  NP_033434.21 
     1606458885 
    chicken
    (Gallus gallus)
    Aves TOP11 topoisomerase (DNA) I 83.25(n)
    92.26(a)
      396004  NM_205110.1  NP_990441.1 
    lizard
    (Anolis carolinensis)
    Reptilia TOP16
    topoisomerase (DNA) I
    90(a)
    1 ↔ 1
    GL343291.1(732962-828849)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.622 Xenopus laevis DNA topoisomerase I (TOP1) mRNA, complete more 78.4(n)    L07777.1 
    zebrafish
    (Danio rerio)
    Actinopterygii 570641002   -- 75.23(n)    57064100 
    fruit fly
    (Drosophila melanogaster)
    Insecta Top11 , 3 embryonic morphogenesis DNA
    topoisomerase I3
    Topoisomerase 11
    67(a)3
    65.2(n)1
    69.23(a)1
      1 13B63
    324581  NM_001014742.11  NP_001014742.11 
    worm
    (Caenorhabditis elegans)
    Secernentea top-11 top-1 63.29(n)
    66.67(a)
      266847  NM_001026407.5  NP_001021578.1 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes TOP11 TOP1 56.88(n)
    53.83(a)
      854156   NP_014637.1 
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons TOP1BETA1 TOP1BETA 55.58(n)
    49.44(a)
      835624  NM_124913.3  NP_200342.1 
    rice
    (Oryza sativa)
    Liliopsida Os08g01546001 Os08g0154600 55.25(n)
    51.11(a)
      4344685  NM_001067550.1  NP_001061015.1 


    ENSEMBL Gene Tree for TOP1 (if available)
    TreeFam Gene Tree for TOP1 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for TOP1 gene
    TOP1MT2  
    1 SIMAP similar gene for TOP1 using alignment to 4 protein entries:     TOP1_HUMAN (see all proteins):
    TOP1MT

    Find genes that share paralogs with TOP1           About GenesLikeMe


    1 Pseudogenes.org Pseudogene for TOP1
    PGOHUM00000245083


    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
    About This Section

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    Selected SNPs for TOP1 (see all 1678)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 20 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0075314
    CPT-resistant lung cancer4--see VAR_0075312 T A mis40--------
    VAR_0106674
    CPT-resistant leukemia4--see VAR_0106672 N S mis40--------
    VAR_0106664
    CPT-resistant leukemia4--see VAR_0106662 M T mis40--------
    VAR_0075304
    CPT-resistant leukemia4--see VAR_0075302 D G mis40--------
    VAR_0365554
    Breast cancer4--see VAR_0365552 K R mis40--------
    rs1820487021,2
    C--39623374(+) GGCCAA/GGCTGT 1 -- us2k10--------
    rs1472233141,2
    C--39623454(+) CCACCA/GCGCCT 1 -- us2k10--------
    rs1857151511,2
    --39623460(+) CGCCTG/TGCCTA 1 -- us2k10--------
    rs1901281211,2
    --39623461(+) GCCTGA/GCCTAT 1 -- us2k10--------
    rs1825271121,2
    C--39623508(+) TAGTGC/TGCCGG 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for TOP1 (39657458 - 39753127 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 2 variations for TOP1:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv833982CNV Loss17160897
    nsv833983CNV Loss17160897

    Human Gene Mutation Database (HGMD): TOP1
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing TOP1
    DNA2.0 Custom Variant and Variant Library Synthesis for TOP1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 126420    OMIM disorders: --

    UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387
  • Note=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic
    syndrome. Translocation t(11;20)(p15;q11) with NUP98

  • 10 diseases for TOP1:    
    About MalaCards
    dna topoisomerase i, camptothecin-resistant    scleroderma    molluscum contagiosum    pericardial effusion
    hereditary ataxia    esophageal cancer    colon cancer    ovarian cancer
    colorectal cancer    lung cancer

    11 diseases from the University of Copenhagen DISEASES database for TOP1:
    Neutropenia     Systemic scleroderma     Colorectal cancer     Lung cancer
    Diarrhea     Ovarian cancer     Thrombocytopenia     Leukemia
    Vaccinia     Axonal neuropathy     Carcinoma

    Find genes that share disorders with TOP1           About GenesLikeMe

    Selected Novoseek inferred disease relationships for TOP1 gene (see all 93)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    scan1 81.7 13 15920477 (2), 17600775 (1), 17707402 (1), 16935573 (1)
    solid tumor 67.7 36 16807458 (2), 8835290 (1), 9058732 (1), 10021292 (1) (see all 32)
    neutropenia 67.3 5 8611374 (1), 11081458 (1), 19604089 (1), 15470958 (1) (see all 5)
    sclerosis systemic 66.6 45 7615831 (2), 11465716 (2), 19211583 (2), 1319697 (2) (see all 37)
    colon carcinoma 66.3 16 11594758 (2), 1310066 (1), 9321666 (1), 18538108 (1) (see all 15)
    cancer 64.2 186 19584232 (3), 15735043 (2), 11020283 (2), 12852757 (2) (see all 99)
    ovarian cancer 61.8 29 16462890 (4), 18405948 (2), 9497914 (2), 10502731 (2) (see all 21)
    small cell lung cancer 61.7 16 17645849 (2), 8853931 (1), 15735665 (1), 19996589 (1) (see all 15)
    leukemia p388 61.6 7 9927631 (1), 11205907 (1), 9892183 (1), 11118036 (1) (see all 5)
    leukemia 60.8 40 17418582 (2), 1997159 (1), 1848545 (1), 8914817 (1) (see all 36)

    Genetic Association Database (GAD): TOP1
    Human Genome Epidemiology (HuGE) Navigator: TOP1 (3 documents)

    Export disorders for TOP1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for TOP1 gene, integrated from 10 sources (see all 1458):
    (articles sorted by number of sources associating them with TOP1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Sumoylation of topoisomerase I is involved in its partitioning between nucleoli and nucleoplasm and its clearing from nucleoli in response to camptothecin. (PubMed id 12149243)1, 2, 9 Rallabhandi P....D'Arpa P. (J. Biol. Chem. 2002)
    2. 8-Oxoguanine rearranges the active site of human topoisomerase I. (PubMed id 12209008)1, 2, 9 Lesher D.T.... Redinbo M.R. (Proc. Natl. Acad. Sci. U.S.A. 2002)
    3. Pharmacodynamic genes do not influence risk of neutropenia in cancer patients treated with moderately high-dose irinotecan. (PubMed id 19604089)1, 4, 9 Hoskins J.M....Innocenti F. (Pharmacogenomics 2009)
    4. Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin. (PubMed id 7882333)1, 2, 9 Fujimori A.... Pommier Y. (Cancer Res. 1995)
    5. The mechanism of topoisomerase I poisoning by a camptothecin analog. (PubMed id 12426403)1, 2, 9 Staker B.L....Stewart L. (Proc. Natl. Acad. Sci. U.S.A. 2002)
    6. Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites. (PubMed id 1849260)1, 2, 9 Tamura H.... Nishikawa K. (Nucleic Acids Res. 1991)
    7. Biological, clinical and population relevance of 95 loci for blood lipids. (PubMed id 20686565)1, 4 Teslovich T.M....Kathiresan S. (Nature 2010)
    8. Simian virus 40 DNA replication is dependent on an interaction between topoisomerase I and the C-terminal end of T antigen. (PubMed id 18003733)1, 2 Khopde S. and Simmons D.T. (J. Virol. 2008)
    9. The role of lysine 532 in the catalytic mechanism of human topoisomerase I. (PubMed id 14594810)1, 2 Interthal H.... Champoux J.J. (J. Biol. Chem. 2004)
    10. The DNA sequence and comparative analysis of human chromosome 20. (PubMed id 11780052)1, 2 Deloukas P....Rogers J. (Nature 2001)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 7150 HGNC: 11986 AceView: TOP1 Ensembl:ENSG00000198900 euGenes: HUgn7150
    ECgene: TOP1 H-InvDB: TOP1

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for TOP1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for TOP1 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for TOP1 gene:
    Search GeneIP for patents involving TOP1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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