FB2024_03 , released April 23, 2024
Gene: Dmel\E(spl)m4-BFM
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General Information
Symbol
Dmel\E(spl)m4-BFM
Species
D. melanogaster
Name
Enhancer of split m4, Bearded family member
Annotation Symbol
CG6099
Feature Type
FlyBase ID
FBgn0002629
Gene Model Status
Stock Availability
Gene Summary
Part of the Notch signaling pathway. (UniProt, P13095)
Contribute a Gene Snapshot for this gene.
Also Known As

m4, E(spl)m4, E(spl) region transcript m4

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-89
RefSeq locus
NT_033777 REGION:26023821..26024579
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (5 terms)
Molecular Function (1 term)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (0 terms)
Biological Process (4 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR029686
inferred from electronic annotation with InterPro:IPR029686
Cellular Component (0 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (0 terms)
Protein Family (UniProt)
Belongs to the M4-like protein family. (P13095)
Protein Signatures (InterPro)
Summaries
Gene Group (FlyBase)
ENHANCER OF SPLIT GENE COMPLEX -
The Enhancer of split complex (E(spl)-C) of D.mel is a well characterized genetic locus on chromosome 3R containing 12 genes - with the exception of Kaz-m1, all are Notch responsive. Seven genes are basic helix-loop-helix (bHLH) transcription factors, four are bearded family genes. Kaz-m1 is unrelated, sharing some sequence similarity to Kazal class protease inhibitors. (Adapted from FBrf0211195).
BEARDED GENE FAMILY -
The Bearded gene family, named from homology with Brd, encode small proteins containing predicted basic amphipathic α-helical domains in their N-terminal regions. They are located in two genomic complexes - the Bearded Complex and the Enhancer of Split Complex. Some members have been implicated in Notch signaling. (Adapted from FBrf0123097).
Pathway (FlyBase)
Negative Regulators of Notch Signaling Pathway -
The Notch receptor signaling pathway is activated by the binding of the transmembrane receptor Notch (N) to transmembrane ligands, Dl or Ser, presented on adjacent cells. This results in the proteolytic cleavage of N, releasing the intracellular domain (NICD). NICD translocates into the nucleus, interacting with Su(H) and mam to form a transcription complex, which up-regulates transcription of Notch-responsive genes. Negative regulators of the pathway down-regulate the signal from the sending cell or the response in the receiving cell. (Adapted from FBrf0225731 and FBrf0192604).
Protein Function (UniProtKB)
Part of the Notch signaling pathway.
(UniProt, P13095)
Summary (Interactive Fly)

Bearded family - required to positively transduce the Notch signal during neurogenesis, and presumably during bristle development as well

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

Please see the JBrowse view of Dmel\E(spl)m4-BFM 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 P13095)

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 5.42

Gene model reviewed during 5.48

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0084980
759
152
Additional Transcript Data and Comments
Reported size (kB)

1.1 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
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)

152 (aa); 17.23 (kD predicted)

Comments
External Data
Crossreferences
InterPro - A database of protein families, domains and functional sites
Linkouts
Sequences Consistent with the Gene Model
Nucleotide / Polypeptide Records
 
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\E(spl)m4-BFM 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).

-0.37

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

Comment: reference states 2-10 hr AEL

RT-PCR
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

E(spl) genes were found to be differentially expressed during metamorphosis.

m4 transcripts are detected in third instar larval eye discs in the morphogenetic furrow in a strong band just anterior to the stripe of dpp staining in the furrow. They are detected in the pupal wing at 8h APF in large clusters of proximal campaniform sensilla and in the wing margin.

m4 transcripts are expressed in the mesectoderm shortly before gastrulation. After gastrulation they are expressed in the neurectoderm and in the mesoderm in a highly dynamic pattern. In imaginal discs, m4 transcripts are expressed in presumptive proneural clusters of eye-antennal, wing, and leg discs.

The peak of m4 expression during embryogenesis occurs at 2-10 hours. In the late blastoderm, expression is detected in a 2-3 cell-wide stripe on each side of the embryo, in groups of cells over the dorsal half of the poles, in the vitellophage, and weakly in a dorsomedian band spanning the anterioposterior axis. During germ band extension, ectodermal expression is detected, and at the extended germ band stage, epidermal expression is abundant. In late stage 11, epidermal expression becomes patchy. At stage 10, the primordia of the supraoesophageal ganglion and the posterior midgut express m4. From stage 11 through late stage 12, expression is detected in the entire mesodermal layer. From late stage 11 through stage 14, expression is also detected in the primordia of the stomatogastric nervous system and in the optic lobes.

Marker for
Subcellular Localization
CV Term
Polypeptide Expression
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
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\E(spl)m4-BFM in JBrowse
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 ( 2 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 15 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of E(spl)m4-BFM
Transgenic constructs containing regulatory region of E(spl)m4-BFM
Aberrations (Deficiencies and Duplications) ( 9 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Other Phenotypes
Allele
Phenotype manifest in
Allele
dorsal row & sensory mother cell, with Scer\GAL4ap-md544
wing sensillum & wing vein, with Scer\GAL469B
wing sensillum & wing vein, with Scer\GAL4Bx-MS1096
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (0)
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (0)
Mus musculus (laboratory mouse) (0)
Xenopus tropicalis (Western clawed frog) (0)
Danio rerio (Zebrafish) (0)
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:E(spl)m4-BFM. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (3)
3 of 13
3 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 ( 0 )
    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
    RNA-RNA
    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
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    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 Notch Signaling Pathway -
    The Notch receptor signaling pathway is activated by the binding of the transmembrane receptor Notch (N) to transmembrane ligands, Dl or Ser, presented on adjacent cells. This results in the proteolytic cleavage of N, releasing the intracellular domain (NICD). NICD translocates into the nucleus, interacting with Su(H) and mam to form a transcription complex, which up-regulates transcription of Notch-responsive genes. Negative regulators of the pathway down-regulate the signal from the sending cell or the response in the receiving cell. (Adapted from FBrf0225731 and FBrf0192604).
    Metabolic Pathways
    External Data
    Linkouts
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3R
    Recombination map
    3-89
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    96F10-96F10
    Limits computationally determined from genome sequence between P{PZ}l(3)rQ197rQ197 and P{lacW}scribj7B3
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    96F11-96F14
    Experimentally Determined Recombination Data
    Location

    3-89.1

    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (15)
    Genomic Clones (10)
     

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

    cDNA Clones (21)
     

    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

            Overexpression of m4 antagonises the N pathway in multiple cell fate decisions during adult sensory organ development.

            m4 and are involved in N mediated lateral inhibition in sensory organ precursor singularization.

            The distinct expression patterns of genes of the E(spl) complex in imaginal tissues depend to a significant degree on the capacity of their transcriptional cis-regulatory apparatus to respond selectively to direct proneural and Su(H)-mediated activation, often in a subset of the territories and cells in which proneural and Su(H) regulation is occurring. The m4 and HLHmγ enhancers are distinctly similar though the genes are expressed in dissimilar patterns in the wing disc.

            In a sample of 79 genes with multiple introns, 33 showed significant heterogeneity in G+C content among introns of the same gene and significant positive correspondence between the intron and the third codon position G+C content within genes. These results are consistent with selection adding against preferred codons at the start of genes.

            Proximal upstream region contains multiple specific binding sites for Su(H). Integrity of these sites and Su(H) activity are required not only for normal levels of E(spl) complex gene expression in imaginal disc proneural clusters but also for their transcriptional response to hyperactivity of the N receptor. Su(H) is a direct regulatory link between N receptor activity and the expression of E(spl) complex genes, extending the known lineage of the N cell-cell signaling pathway.

            The bristle loss phenotype of H mutants can be suppressed by deleting components of the E(spl)-complex. The degree of suppression depends on both the number and identity of E(spl)-complex transcription units removed.

            E(spl) bHLH proteins are turned on in cells which are inhibited from becoming neural by signals from the delaminating neuroblast.

            Gel retardation experiments demonstrate the 5' regulatory region contains putative in vitro binding sites for Su(H).

            Electrophoretic mobility shift assays demonstrate that m4 is directly activated in proneural clusters of the late third-instar wing imaginal disc by protein complexes that include the ac and sc bHLH proteins.

            Arrangement and sequence of E(spl)-complex genes in D.melanogaster and D.hydei revealed that the E(spl)-gene, and the structure of complex are highly conserved, suggesting that each individual gene, as well as the organization of the complex, is of functional importance.

            Eight E(spl)-region genes are required for the development of neurectodermal cells, HLHmδ, HLHmβ, HLHmγ, HLHm3, HLHm5, HLHm7, E(spl) and gro, and m4 may also play a role in this process.

            Genetic analysis demonstrates that Dl, neu, E(spl), HLHm5, HLHm7 and m4 are functionally related. Spatial distribution of mRNA in neurogenic mutant embryos suggests that some of the functional interactions take place at the transcriptional level.

            Relationship to Other Genes
            Source for database merge of
            Additional comments
            Nomenclature History
            Source for database identify of

            Source for identity of: E(spl)m4-BFM m4

            Nomenclature comments
            Etymology
            Synonyms and Secondary IDs (12)
            Reported As
            Symbol Synonym
            Name Synonyms
            E(spl) region transcript 4
            E(spl) region transcript m4
            Enhancer of split m4
            Enhancer of split m4, Bearded family member
            enhancer of split m4
            Secondary FlyBase IDs
              Datasets (0)
              Study focus (0)
              Experimental Role
              Project
              Project Type
              Title
              Study result (0)
              Result
              Result Type
              Title
              External Crossreferences and Linkouts ( 247 )
              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.
              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 (131)