FB2024_04 , released June 25, 2024
Gene: Dmel\tsg
Open Close
General Information
Symbol
Dmel\tsg
Species
D. melanogaster
Name
twisted gastrulation
Annotation Symbol
CG1502
Feature Type
FlyBase ID
FBgn0003865
Gene Model Status
Stock Availability
Gene Summary
twisted gastrulation (tsg) encodes a BMP binding protein that makes a tripartite complex with the product of sog and a heterodimer formed with the products of dpp and scw. This complex is a favoured substrate for the product of tld, which processes the product of sog and liberates the heterodimer formed with the products of dpp and scw. [Date last reviewed: 2019-03-14] (FlyBase Gene Snapshot)
Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
1-38
RefSeq locus
NC_004354 REGION:11988062..11988948
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (8 terms)
Molecular Function (3 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
enables BMP binding
inferred from physical interaction with FLYBASE:dpp; FB:FBgn0000490,FLYBASE:gbb; FB:FBgn0024234
inferred from direct assay
Terms Based on Predictions or Assertions (0 terms)
Biological Process (3 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000267834
Cellular Component (2 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
is_active_in extracellular space
inferred from biological aspect of ancestor with PANTHER:PTN000267834
Gene Group (FlyBase)
Protein Family (UniProt)
Belongs to the twisted gastrulation protein family. (P54356)
Summaries
Gene Snapshot
twisted gastrulation (tsg) encodes a BMP binding protein that makes a tripartite complex with the product of sog and a heterodimer formed with the products of dpp and scw. This complex is a favoured substrate for the product of tld, which processes the product of sog and liberates the heterodimer formed with the products of dpp and scw. [Date last reviewed: 2019-03-14]
Pathway (FlyBase)
Negative Regulators of BMP Signaling Pathway -
Negative regulators of Bone Morphogenetic Protein (BMP) signaling down-regulate the pathway, ultimately resulting in the decreased nuclear activity of the Mad/Med transcription factor complex.
Protein Function (UniProtKB)
Involved in dorsal-ventral patterning. Required for specification of a narrow strip of dorsal midline cells that will give rise to the amnioserosa, but not for specification of dorsal ectoderm cells. Inhibits BMP signaling; enhances the binding of sog to dpp, thus enhancing the antagonistic activity of sog.
(UniProt, P54356)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
tsg: twisted gastrulation
Gene expressed 1.5-3.5 hours after oviposition. Mutants are embryonic lethals and show abnormal gastrulation, with deep dorsal folds resulting in temporary blockage of germband extension. Later, dorsal folds released, but posterior midgut abnormal in position, dorsal cells very thick, and cephalic folds very deep (Zusman and Wieschaus, 1985). At the end of embryonic development, tsg cuticle shows head defects and condensed, retracted posterior spiracles. Ventral nervous system split posteriorly. No particular cell must be wild type for survival in tsg//+ mosaics, but wild-type cells on dorsal side are most effective in rescue (Zusman and Wieschaus, 1985).
Summary (Interactive Fly)

secreted growth factor - Tsg dislodges latent BMPs bound to Short gastrulation thus activating BMP signaling - makes a tripartite complex with Sog and a Dpp/Scw heterodimer - a favoured substrate for Tolloid, which processes Sog and liberates the Dpp/Scw heterodimer

Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\tsg 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 P54356)

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 5.39

Gene model reviewed during 5.41

Gene model reviewed during 5.45

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0073582
887
249
Additional Transcript Data and Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0073426
27.2
249
4.00
Polypeptides with Identical Sequences

There is only one protein coding transcript and one polypeptide associated with this gene

Additional Polypeptide Data and Comments
Reported size (kDa)

249 (aa); 27 (kD predicted)

Comments
External Data
Subunit Structure (UniProtKB)

Component of a complex composed of dpp, sog and tsg.

(UniProt, P54356)
Crossreferences
InterPro - A database of protein families, domains and functional sites
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\tsg 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).

NA

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference

Comment: reference states 1.5-3 hr AEL

Additional Descriptive Data

tsg transcripts are expressed only in early embryos.

tsg transcripts are detected at 1.5-3hr of embryonic development and not at any other time during development. They first appear at 1hr and 45min of development in two domains, a broad dorsal saddle and an anterior cap. During cellularization, expression disappears from the dorsal midline and refines into a series of 4 diffuse stripes along the A/P axis. As the germband extends during stages 7 and 8, anterior expression fades and the mid dorsal stripes are located between the anterior transverse furrow (ATF) and the posterior transverse furrow (PTF). As the PTF deepens, the tsg-expressing cells become incorporated into the PTF. Double staining with ftz shows that the domain of tsg expression lies between parasegments 4 and 10.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\tsg 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
Flygut - An atlas of the Drosophila adult midgut
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 16 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 11 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of tsg
Transgenic constructs containing regulatory region of tsg
Aberrations (Deficiencies and Duplications) ( 20 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (1)
14 of 14
Yes
Yes
1  
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (1)
14 of 14
Yes
Yes
Mus musculus (laboratory mouse) (1)
13 of 14
Yes
Yes
Xenopus tropicalis (Western clawed frog) (2)
10 of 13
Yes
No
7 of 13
No
Yes
Danio rerio (Zebrafish) (2)
13 of 14
Yes
Yes
12 of 14
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (0)
Anopheles gambiae (African malaria mosquito) (1)
Arabidopsis thaliana (thale-cress) (0)
Saccharomyces cerevisiae (Brewer's yeast) (0)
Schizosaccharomyces pombe (Fission yeast) (0)
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:tsg. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (3)
12 of 13
6 of 13
1 of 13
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 ( 1 )
    Allele
    Disease
    Interaction
    References
    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)
    Other Interaction Browsers

    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
    Other Interaction Browsers

    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    suppressible
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Subunit Structure (UniProtKB)
    Component of a complex composed of dpp, sog and tsg.
    (UniProt, P54356 )
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    MIST (genetic) - An integrated Molecular Interaction Database
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Signaling Pathways (FlyBase)
    Negative Regulators of BMP Signaling Pathway -
    Negative regulators of Bone Morphogenetic Protein (BMP) signaling down-regulate the pathway, ultimately resulting in the decreased nuclear activity of the Mad/Med transcription factor complex.
    Metabolic Pathways
    External Data
    Linkouts
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    X
    Recombination map
    1-38
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    11A1-11A1
    Limits computationally determined from genome sequence between P{EP}ATP7EP308 and P{EP}EP1451&P{EP}EP1629
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    Experimentally Determined Recombination Data
    Left of (cM)
    Right of (cM)
    Notes

    97 of 129 recombinants between m and fw ocurred distal to cac. 5 of 8 recombinants between cac and fw were distal to gd. 2 of 10 gd/fw recombinants were distal to tsg.

    Stocks and Reagents
    Stocks (8)
    Genomic Clones (13)
     

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

    cDNA Clones (11)
     

    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)
      BDGP DGC clones
        RNAi and Array Information
        Linkouts
        DRSC - Results frm RNAi screens
        Antibody Information
        Laboratory Generated Antibodies
         
        Commercially Available Antibodies
         
        Cell Line Information
        Publicly Available Cell Lines
         
          Other Stable Cell Lines
           
            Other Comments

            The tsg product negatively regulates dac expression in the embryonic head.

            The tsg protein functions with sog to antagonize BMP signalling.

            The expression pattern of tsg from 5 Drosophila species is studied. Evidence for recent changes in the expression pattern between sibling species diverged only 2-5 million years ago is found and examples of changes that have been fixed to certain lineages 60 million years ago.

            tsg protein is secreted and can act over a long range.

            Mis-expression studies suggest that tsg does not modulate an activity gradient of dpp, but instead functions in a permissive rather than an instructive role to elaborate cell fates along the dorsal midline.

            tsg gene is a secreted molecule that is required only for dorsal midline structures. Embryos that lack tsg fail to form the amnioserosa membrane and other dorsal midline derived structures in the head and tail region.

            Mutations in tsg disrupt amnioserosa formation. Injection of dpp RNA into the ventral side results in an asymmetric response, lateral expansion of the preexisting dorsal amnioserosa rather than formation of a second amnioserosa at the site of injection.

            Genetic and phenotypic data reveals that tsg is involved in post-transcriptional regulation of dpp activity by elevating dpp activity dorsally.

            The restricted effect of tsg mutants, in contrast to those of dpp, tld and scw, and the structural features of a secreted protein suggest an alternative to the single morphogen (dpp) gradient model. Namely that tsg represents a second class of peptide growth factor that may be part of a combinatorial signalling mechanism that specifies dorsal patterning.

            tsg is required for the normal ontogeny of the zen pattern and fating of the amnioserosa.

            Zygotically active locus involved in the terminal developmental program in the embryo.

            Involved in the regulatory hierarchy responsible for the asymmetric distribution and function of zygotic regulatory gene products along the DV axis of early embryos. tsg is required for the refinement of the zen expression pattern during cellularization and gastrulation: zen products do not become restricted to the presumptive amnioserosa.

            Mutants are embryonic lethals and show abnormal gastrulation, with deep dorsal folds resulting in temporary blockage of germband extension. Later, dorsal folds released, but posterior midgut abnormal in position, dorsal cells very thick and cephalic folds very deep. At the end of embryonic development, tsg cuticle shows head defects and condensed, retracted posterior spiracles. Ventral nervous system split posteriorly. No particular cell must be wild type for survival in tsg/+ mosaics, but wild-type cells on dorsal side are most effective in rescue.

            tsg mutants display abnormal gastrulation, head and posterior spiracles are defective in larval cuticle, ventral nervous system is split anteriorly.

            Relationship to Other Genes
            Source for database merge of

            Source for merge of: tsg l(1)11Ac

            Additional comments
            Nomenclature History
            Source for database identify of

            Source for identity of: tsg CG1502

            Nomenclature comments
            Etymology
            Synonyms and Secondary IDs (12)
            Datasets (0)
            Study focus (0)
            Experimental Role
            Project
            Project Type
            Title
            Study result (0)
            Result
            Result Type
            Title
            External Crossreferences and Linkouts ( 28 )
            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
            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
            InterPro - A database of protein families, domains and functional sites
            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
            Flygut - An atlas of the Drosophila adult midgut
            iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
            Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
            MIST (genetic) - An integrated Molecular Interaction Database
            MIST (protein-protein) - An integrated Molecular Interaction Database
            References (147)