FB2024_02 , released April 23, 2024
Gene: Dmel\Top1
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General Information
Symbol
Dmel\Top1
Species
D. melanogaster
Name
Topoisomerase 1
Annotation Symbol
CG6146
Feature Type
FlyBase ID
FBgn0004924
Gene Model Status
Stock Availability
Enzyme Name (EC)
DNA topoisomerase (5.6.2.1)
Gene Summary
Topoisomerase 1 (Top1) encodes a topoisomerase with essential functions in cell proliferation during stages of oogenesis, embryogenesis, larva, and pupa. [Date last reviewed: 2019-03-14] (FlyBase Gene Snapshot)
Also Known As

topoisomerase I, Topo I, l(1)G0229, TopoI, l(1)G0278

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
1-50
RefSeq locus
NC_004354 REGION:15319479..15328029
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (18 terms)
Molecular Function (3 terms)
Biological Process (7 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from mutant phenotype
involved_in oogenesis
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
Cellular Component (8 terms)
Terms Based on Experimental Evidence (7 terms)
CV Term
Evidence
References
located_in cytoplasm
inferred from direct assay
located_in cytosol
inferred from high throughput direct assay
part_of euchromatin
inferred from direct assay
located_in nucleolus
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
is_active_in nucleolus
inferred from biological aspect of ancestor with PANTHER:PTN000033230
Gene Group (FlyBase)
Protein Family (UniProt)
Belongs to the type IB topoisomerase family. (P30189)
Catalytic Activity (EC/Rhea)
DNA topoisomerase type I (single strand cut, ATP-independent) activity
ATP-independent breakage of single-stranded DNA, followed by passage and rejoining (5.6.2.1)
Summaries
Gene Snapshot
Topoisomerase 1 (Top1) encodes a topoisomerase with essential functions in cell proliferation during stages of oogenesis, embryogenesis, larva, and pupa. [Date last reviewed: 2019-03-14]
Gene Group (FlyBase)
DNA TOPOISOMERASES TYPE I -
DNA topoisomerases perform topological transformations of DNA by generating a transient DNA break through which strand passage can occur. These enzymes are grouped into types I and II based on structure and mechanism: type I enzymes carry out strand passage through a reversible single-strand break. DNA topoisomerases have critical roles in DNA replication, transcription, recombination, repair, and chromatin remodeling. (Adapted from PMID:23495937.)
Protein Function (UniProtKB)
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 (By similarity). Introduces a single-strand break via transesterification at a target site in duplex DNA (By similarity). 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 (By similarity). The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils (By similarity). 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).
(UniProt, P30189)
Gene Model and Products
Number of Transcripts
5
Number of Unique Polypeptides
4

Please see the JBrowse view of Dmel\Top1 for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry P30189)

If you don't see a structure in the viewer, refresh your browser.
Model Confidence:
  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Gene model reviewed during 5.50

Low-frequency RNA-Seq exon junction(s) not annotated.

Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.

Gene model reviewed during 5.39

Gene model reviewed during 5.55

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0074005
4265
974
FBtr0074006
2378
581
FBtr0100294
5325
974
FBtr0308699
4600
970
FBtr0340434
3942
593
Additional Transcript Data and Comments
Reported size (kB)

5.2, 4.0 (northern blot)

5.2, 4.0 (unknown)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0073822
111.9
974
9.55
FBpp0073823
68.6
581
9.56
FBpp0099689
111.9
974
9.55
FBpp0300905
111.6
970
9.59
FBpp0309379
70.0
593
9.91
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

974 aa isoforms: Top1-PA, Top1-PC
Additional Polypeptide Data and Comments
Reported size (kDa)

972 (aa); 135 (kD)

Comments

Homology to other Top1 proteins is concentrated in two regions. The Drosophila enzyme is larger than the enzymes from yeast and human and is uniquely characterized by a Ser/His rich hydrophilic domain of 200aa at its amino terminus. The bacterially expressed protein was shown to have classic eukaryotic DNA topoisomerase I activity, distinguished by the fact that it can relax both positively and negatively supercoiled DNA in the absence of a divalent cation.

Camptothecin-induced Top1 protein cleavage sites were mapped in the Act5C, Act57B, and hsp70 genes. Top1 protein cleavage sites were localized to the transcribed portions of the Hsp70B and Act5C genes, and only when they are transcriptionally active. None were found in a transcriptionally inactive Act57B gene.

External Data
Subunit Structure (UniProtKB)

Interacts with Topors.

(UniProt, P30189)
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Top1 using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-0.51

Transcript Expression
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

A substantial amount of maternally derived Top1 protein is present in early embryos. Protein levels peak at 6-12 hours and decline to near zero in pupae. Some expression is observed in the ovary.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in cytoplasm
inferred from direct assay
located_in cytosol
inferred from high throughput direct assay
part_of euchromatin
inferred from direct assay
located_in nucleolus
inferred from direct assay
inferred from direct assay
Expression Deduced from Reporters
Stage
Tissue/Position (including subcellular localization)
Reference
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Top1 in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 29 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 17 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Top1
Transgenic constructs containing regulatory region of Top1
Aberrations (Deficiencies and Duplications) ( 3 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
nurse cell & nucleus, with Top177
nurse cell & nucleus, with Top1hs.2
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (2)
13 of 14
Yes
Yes
11 of 14
No
Yes
3  
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (3)
12 of 14
Yes
Yes
11 of 14
No
Yes
1 of 14
No
Yes
Mus musculus (laboratory mouse) (2)
12 of 14
Yes
Yes
12 of 14
Yes
Yes
Xenopus tropicalis (Western clawed frog) (4)
7 of 13
Yes
Yes
6 of 13
No
Yes
6 of 13
No
Yes
5 of 13
No
No
Danio rerio (Zebrafish) (4)
13 of 14
Yes
Yes
11 of 14
No
Yes
10 of 14
No
Yes
9 of 14
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (1)
13 of 14
Yes
Yes
Anopheles gambiae (African malaria mosquito) (1)
7 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (3)
12 of 13
Yes
Yes
12 of 13
Yes
Yes
3 of 13
No
Yes
Saccharomyces cerevisiae (Brewer's yeast) (1)
13 of 13
Yes
Yes
Schizosaccharomyces pombe (Fission yeast) (1)
12 of 12
Yes
Yes
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:Top1. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 0 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 2 )
    Allele
    Disease
    Interaction
    References
    ameliorates  epilepsy
    ameliorates  epilepsy
    Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Homo sapiens (Human)
    Gene name
    Score
    OMIM
    OMIM Phenotype
    DO term
    Complementation?
    Transgene?
    Functional Complementation Data
    Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
    Interactions
    Summary of Physical Interactions
    esyN Network Diagram
    Show neighbor-neighbor interactions:
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    Select Layout:
    Legend:
    Protein
    RNA
    Selected Interactor(s)
    Interactions Browser

    Please see the Physical Interaction reports below for full details
    MIST Molecular Interaction Search Tool

    Please see the Physical Interaction reports below for full details
    protein-protein
    Physical Interaction
    Assay
    References
    Summary of Genetic Interactions
    esyN Network Diagram
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    esyN Network Key:
    Suppression
    Enhancement

    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Subunit Structure (UniProtKB)
    Interacts with Topors.
    (UniProt, P30189 )
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    External Data
    Linkouts
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    X
    Recombination map
    1-50
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    13B6-13B6
    Limits computationally determined from genome sequence between P{EP}hiwEP1308 and P{EP}Ahcy13EP1007
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    13B6-13B8
    (determined by in situ hybridisation) 13B5--9 (determined by in situ hybridisation) 13B8--9 (determined by in situ hybridisation) 13C (determined by in situ hybridisation)
    13B8-13B9
    (determined by in situ hybridisation) 13B6--9 (determined by in situ hybridisation)
    13B5-13B9
    (determined by in situ hybridisation) 13C1--2 (determined by in situ hybridisation) 13C (determined by in situ hybridisation)
    13C1-13C1
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (24)
    Genomic Clones (11)
     

    Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

    cDNA Clones (99)
     

    Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequenced
    BDGP DGC clones
    Other clones
    Drosophila Genomics Resource Center cDNA clones

    For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

    cDNA Clones, End Sequenced (ESTs)
    RNAi and Array Information
    Linkouts
    DRSC - Results frm RNAi screens
    Antibody Information
    Laboratory Generated Antibodies
     

    polyclonal

    Commercially Available Antibodies
     
    Cell Line Information
    Publicly Available Cell Lines
     
      Other Stable Cell Lines
       
        Other Comments

        DNA-protein interactions: genome-wide binding profile assayed for Top1 protein in Kc167 cells; see Chromatin_types_NKI collection report. Individual protein-binding experiments listed under "Samples" at GEO_GSE22069 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22069).

        Top1 plays an essential role in many developmental stages active in cell proliferation.

        The genomic organisation of the Top1 locus has been determined and its expression pattern has been analysed.

        The N-terminal 430 amino acid residues of Top1 are inconsequential for its catalytic activity. The N-terminal region directs Top1-Ecol\lacZ fusion constructs to transcriptionally active loci in the polytene chromosomes.

        Using P element mutagenesis a mutant deficient in topoisomerase 1 was generated: topoisomerase 1 is essential for growth and development.

        Top1 has been isolated and partially characterised.

        DNA topoisomerase 1 was cloned by homology to consensus eukaryotic DNA topoisomerase 1 sequence, and expressed in an E.coli expression system.

        The interaction of Top1 and Top2 gene products with transcriptionally active and inactive Act5C, Act57B and Hsp70B has been compared. Topoisomerase I binding sites are found in the transcribed portions of the Hsp70B and Act5C genes, and only when they are transcriptionally active. It does not associate with a transcriptionally inactive Act57B gene.

        Top1 enzyme has been purified and characterised.

        Relationship to Other Genes
        Source for database merge of

        Source for merge of: Top1 l(1)G0229 l(1)G0278 l(1)G0134 l(1)G0201

        Additional comments
        Nomenclature History
        Source for database identify of

        Source for identity of: Top1 CG6146

        Nomenclature comments
        Etymology
        Synonyms and Secondary IDs (24)
        Reported As
        Symbol Synonym
        topoisomerase I
        Secondary FlyBase IDs
        • FBgn0027237
        • FBgn0027261
        • FBgn0027275
        • FBgn0040195
        Datasets (1)
        Study focus (1)
        Experimental Role
        Project
        Project Type
        Title
        • transgene_used
        Protein profiling reveals five principal chromatin types in Drosophila cells.
        Study result (0)
        Result
        Result Type
        Title
        External Crossreferences and Linkouts ( 69 )
        Sequence Crossreferences
        NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
        GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
        GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
        RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
        UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.
        UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
        UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
        Other crossreferences
        AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.
        DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
        EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
        FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
        FlyMine - An integrated database for Drosophila genomics
        KEGG Genes - Molecular building blocks of life in the genomic space.
        MARRVEL_MODEL - MARRVEL (model organism gene)
        Linkouts
        BioGRID - A database of protein and genetic interactions.
        Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
        DroID - A comprehensive database of gene and protein interactions.
        DRSC - Results frm RNAi screens
        Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
        FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
        FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
        Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
        Flygut - An atlas of the Drosophila adult midgut
        MIST (protein-protein) - An integrated Molecular Interaction Database
        References (133)