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General Information
Symbol
Dmel\E(spl)m5-HLH
Species
D. melanogaster
Name
Enhancer of split m5, helix-loop-helix
Annotation Symbol
CG6096
Feature Type
FlyBase ID
FBgn0002631
Gene Model Status
Stock Availability
Gene Snapshot
In progress.Contributions welcome.
Also Known As
m5, E(spl)m5, HLHm5, HLH-m5, E(spl) region transcript m5
Key Links
Genomic Location
Cytogenetic map
Sequence location
3R:26,028,854..26,029,735 [-]
Recombination map
3-89
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Protein Family (UniProt)
-
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).
BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS -
Basic helix-loop-helix (bHLH) transcription factors are sequence-specific DNA-binding proteins that regulate transcription. They are characterized by a 60 amino acid region comprising a basic DNA binding domain followed by a HLH motif formed from two amphipathic α-helices connected by a loop. bHLH transcription factors form homo- and hetero-dimeric complexes, which bind to a E box consensus sequence. (Adapted from PMID:15186484).
Protein Function (UniProtKB)
Participates in the control of cell fate choice by uncommitted neuroectodermal cells in the embryo. Transcriptional repressor. Binds DNA on N-box motifs: 5'-CACNAG-3'.
(UniProt, P13096)
Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the GBrowse view of Dmel\E(spl)m5-HLH or the JBrowse view of Dmel\E(spl)m5-HLH 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
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)
FBtr0084979
882
178
Additional Transcript Data and Comments
Reported size (kB)
1.0 (northern blot)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0084352
19.9
178
9.54
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)
178 (aa); 19 (kD predicted)
Comments
External Data
Subunit Structure (UniProtKB)
Transcription repression requires formation of a complex with a corepressor protein (Groucho). Forms homodimers.
(UniProt, P13096)
Domain
The orange domain and the basic helix-loop-helix motif mediate repression of specific transcriptional activators, such as basic helix-loop-helix protein dimers. The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho, a transcriptional corepressor recruited to specific target DNA by Hairy-related proteins.
(UniProt, P13096)
Crossreferences
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)m5-HLH using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (10 terms)
Molecular Function (5 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000105427
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000105427
(assigned by GO_Central )
Biological Process (4 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000105428
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000105428
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000105427
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000105428
(assigned by GO_Central )
Cellular Component (1 term)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
inferred from direct assay
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000105427
(assigned by GO_Central )
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
mesectoderm anlage

Comment: anlage in statu nascendi

antennal anlage in statu nascendi

Comment: reported as procephalic ectoderm anlage in statu nascendi

dorsal head epidermis anlage in statu nascendi

Comment: reported as procephalic ectoderm anlage in statu nascendi

visual anlage in statu nascendi

Comment: reported as procephalic ectoderm anlage in statu nascendi

antennal anlage

Comment: reported as procephalic ectoderm anlage

central brain anlage

Comment: reported as procephalic ectoderm anlage

dorsal head epidermis anlage

Comment: reported as procephalic ectoderm anlage

visual anlage

Comment: reported as procephalic ectoderm anlage

endoderm

Comment: transiently expressed

antennal primordium

Comment: reported as procephalic ectoderm primordium

central brain primordium

Comment: reported as procephalic ectoderm primordium

visual primordium

Comment: reported as procephalic ectoderm primordium

dorsal head epidermis primordium

Comment: reported as procephalic ectoderm primordium

lateral head epidermis primordium

Comment: reported as procephalic ectoderm primordium

ventral head epidermis primordium

Comment: reported as procephalic ectoderm primordium

northern blot
Stage
Tissue/Position (including subcellular localization)
Reference

Comment: reference states 2-6 hr AEL

RT-PCR
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
E(spl)m5-HLH is strongly expressed in neuroepithelial cells in the optic lobe and downregulated in neuroblasts.
E(spl) genes were found to be differentially expressed during metamorphosis. E(spl)m5-HLH is one of 4 genes to increase in expression at puparium formation.
The peak of HLHm5 expression during embryogenesis occurs at 2-6 hours. In the late blastoderm, expression is detected in a 2-3 cell-wide stripe on each side of the embryo, weakly in the vitellophage, and strongly 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 HLHm5. 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
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\E(spl)m5-HLH in GBrowse 2
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
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
  • Stages(s) 4-6
  • Stages(s) 7-8
  • Stages(s) 9-10
  • Stages(s) 11-12
  • Stages(s) 13-16
Alleles, Insertions, and Transgenic Constructs
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (9)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
3 of 15
Yes
No
2 of 15
No
Yes
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
 
1 of 15
No
Yes
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (8)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
4 of 15
No
Yes
2 of 15
Yes
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
Yes
No
1 of 15
No
No
Rattus norvegicus (Norway rat) (8)
3 of 13
Yes
No
2 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
No
Xenopus tropicalis (Western clawed frog) (2)
2 of 12
Yes
No
1 of 12
No
No
Danio rerio (Zebrafish) (23)
4 of 15
Yes
No
2 of 15
No
No
2 of 15
No
No
2 of 15
No
Yes
2 of 15
No
No
2 of 15
No
Yes
2 of 15
No
Yes
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
Yes
No
1 of 15
Yes
No
1 of 15
Yes
No
1 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (3)
3 of 15
Yes
No
1 of 15
No
Yes
1 of 15
No
Yes
Arabidopsis thaliana (thale-cress) (0)
No records found.
Saccharomyces cerevisiae (Brewer's yeast) (1)
1 of 15
Yes
Yes
Schizosaccharomyces pombe (Fission yeast) (0)
No records found.
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG09190GNM )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Drosophila suzukii
Spotted wing Drosophila
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG09150CDN )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Musca domestica
House fly
Lucilia cuprina
Australian sheep blowfly
Lucilia cuprina
Australian sheep blowfly
Lucilia cuprina
Australian sheep blowfly
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( None identified )
No non-Dipteran orthologies identified
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( None identified )
No non-Insect Arthropod orthologies identified
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( None identified )
No non-Arthropod Metazoa orthologies identified
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (11)
2 of 10
2 of 10
2 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Model Summary Ribbon
    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
    Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
     
    Disease Associations of Human Orthologs (via DIOPT v7.1 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
    Summary of Genetic Interactions
    esyN Network Diagram
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Subunit Structure (UniProtKB)
    Transcription repression requires formation of a complex with a corepressor protein (Groucho). Forms homodimers.
    (UniProt, P13096 )
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Gene Group - Pathway Membership (FlyBase)
    External Data
    Linkouts
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3R
    Recombination map
    3-89
    Cytogenetic map
    Sequence location
    3R:26,028,854..26,029,735 [-]
    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
    Experimentally Determined Recombination Data
    Location
    3-89.1
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (16)
    Genomic Clones (15)
     

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

    cDNA Clones (88)
     

    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 GBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequences
    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
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    Antibody Information
    Laboratory Generated Antibodies
     
    Commercially Available Antibodies
     
    Other Information
    Relationship to Other Genes
    Source for database identify of
    Source for identity of: E(spl)m5-HLH HLHm5
    Source for database merge of
    Additional comments
    Other Comments
    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.
    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.
    The bHLH domains of the gene products encoded by the E(spl)-C and AS-C differ in their ability to form homo- and/or heterodimers. The interactions established through the bHLH link the products of the two complexes in a single interaction network which may function to ensure that a given cell retains the capacity to choose between epidermoblast and neuroblast fates until the cell becomes definitively determined.
    Clones mutant for E(spl)-C bHLH-encoding genes or for gro display bristle hyperplasia. The E(spl)-C genes participate in the N signalling pathway. E(spl)-C mutants are epistatic over a gain of function mutant of N and ac-sc mutants are epistatic over E(spl)-C mutants. Expression in Schneider cells demonstrates HLHm5 and E(spl) mediate transcriptional repression of an ac Ecol\CAT reporter gene, gro potentiates this effect.
    Persistent expression of E(spl) and HLHm5 suppresses neural development.
    Almost all E(spl)-complex bHLH proteins can homo-hetero-dimerise, but not with the same efficiency. All E(spl)-complex bHLH proteins interact with gro protein via their C-terminal domain. E(spl)-complex bHLH proteins interact with proneural proteins, with members of the E(spl) family exhibiting distinct preferences for different proneural proteins.
    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 from position -897 to +20 contains in vitro binding sites for Su(H).
    E(spl) complex basic helix loop helix genes inhibit neural fate during the selection of neural precursors, and play a role in restricting the neuronal fate to one of the four progeny cells of the bristle precursor.
    The gene products of ac, sc and l(1)sc together with vnd act synergistically to specify the neuroectodermal E(spl) and HLHm5 expression. Negative cross- and autoregulatory interactions of the E(spl) complex contribute, directly or indirectly tot he regulation.
    DNaseI footprinting analysis of bacterially expressed E(spl) and HLHm5 demonstrates the gene products can bind as homo- and heterodimers to a sequence in the promoters of the E(spl) and ac genes, called the N-box, which differs slightly from the consensus binding site for other 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.
    E(spl) complex gene expression pattern in N and neur mutants suggests the protein is required in dictating cell fates during embryogenesis.
    On basis of cross-hybridization and sequence data the E(spl) HLH genes can be placed into 3 groups. The first includes E(spl) and HLHm5, the second includes HLHm7, HLHm3, HLHmA and HLHmB and the last includes HLHmC.
    Genes of the E(spl) complex act as a functional unit composed of redundant genes which can partially substitute for each other. Eight E(spl)-region genes are required for the development of neurectodermal cells: HLHmδ, HLHmβ, HLHmγ, HLHm3, HLHm5, HLHm7, E(spl) and gro. The E(spl)-region gene m4 may also play a role in this process.
    The neurogenic phenotype of various embryonic combinations have been studied and include intermediate neurogenic embryos and weak neurogenic embryos.
    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.
    One of the Enhancer-of-split complex.
    Origin and Etymology
    Discoverer
    Etymology
    Identification
    External Crossreferences and Linkouts ( 732 )
    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/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
    BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
    Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
    Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
    Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
    Flygut - An atlas of the Drosophila adult midgut
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    KEGG Genes - Molecular building blocks of life in the genomic space.
    modMine - A data warehouse for the modENCODE project
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DPiM - Drosophila Protein interaction map
    DroID - A comprehensive database of gene and protein interactions.
    DRSC - Results frm RNAi screens
    FLIGHT - Cell culture data for RNAi and other high-throughput technologies
    FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
    FlyMine - An integrated database for Drosophila genomics
    InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Synonyms and Secondary IDs (15)
    Reported As
    Symbol Synonym
    E(spl) transcription unit m5
    Name Synonyms
    E(spl) region transcript m5
    Enhancer of split m5, helix-loop-helix
    Secondary FlyBase IDs
      Datasets (0)
      Study focus (0)
      Experimental Role
      Project
      Project Type
      Title
      References (179)