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General Information
Symbol
Dmel\E(spl)m3-HLH
Species
D. melanogaster
Name
Enhancer of split m3, helix-loop-helix
Annotation Symbol
CG8346
Feature Type
FlyBase ID
FBgn0002609
Gene Model Status
Stock Availability
Gene Snapshot
Enhancer of split m3, helix-loop-helix (E(spl)m3-HLH) is a member the enhancer of split gene (E(spl)) complex. E(spl)m3-HLH encodes a transcriptional repressor executing Notch-mediated cellular differentiation. [Date last reviewed: 2019-09-26]
Also Known As
m3, E(spl)m3, HLHm3, E(spl)C m3, E(spl) region transcript m3
Key Links
Genomic Location
Cytogenetic map
Sequence location
3R:26,021,823..26,023,127 [+]
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)
Transcriptional repressor of genes that require a bHLH protein for their transcription. May serve as a transcriptional regulator of the Achaete-scute complex (AS-C) genes. Belongs to notch signaling pathway and depends on Su(H) for transcriptional activation.
(UniProt, Q01068)
Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the GBrowse view of Dmel\E(spl)m3-HLH or the JBrowse view of Dmel\E(spl)m3-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 5.48
Gene model reviewed during 5.42
Gene model reviewed during 5.53
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0084958
1305
224
Additional Transcript Data and Comments
Reported size (kB)
1.4 (northern blot)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0084332
25.0
224
8.23
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)
Comments
External Data
Subunit Structure (UniProtKB)
Transcription repression requires formation of a complex with a corepressor protein (Groucho).
(UniProt, Q01068)
Domain
Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG). 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, Q01068)
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)m3-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 (11 terms)
Molecular Function (5 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from direct assay
(assigned by UniProt )
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000105427
(assigned by GO_Central )
inferred from electronic annotation with InterPro:IPR011598
(assigned by InterPro )
inferred from biological aspect of ancestor with PANTHER:PTN000105427
(assigned by GO_Central )
Biological Process (5 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
inferred from mutant phenotype
(assigned by UniProt )
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 (0 terms)
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
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 6-14 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. E(spl)m3-HLH is one of 4 genes to increase in expression at puparium formation and one of 5 genes that increases at 2-3 hours post-puparium formation.
The peak of HLHm3 expression during embryogenesis occurs at 6-14 hours. Low levels of expression are also detected in adult females. By in situ hybridization, ubiquitous expression is detected throughout embryogenesis, with high levels in stage 11-15 embryos. At stage 13, expression is detected in unidentified structures in midgut walls, and in Malpighian tubules.
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\E(spl)m3-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
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 3 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 9 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of E(spl)m3-HLH
Transgenic constructs containing regulatory region of E(spl)m3-HLH
Deletions and Duplications ( 14 )
Phenotypes
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (13)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
5 of 15
Yes
No
5 of 15
Yes
Yes
4 of 15
No
No
4 of 15
No
No
 
2 of 15
No
Yes
2 of 15
No
Yes
 
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (12)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
6 of 15
Yes
No
5 of 15
No
Yes
3 of 15
No
No
2 of 15
No
Yes
2 of 15
No
Yes
2 of 15
No
Yes
1 of 15
No
No
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
Rattus norvegicus (Norway rat) (11)
5 of 13
Yes
No
5 of 13
Yes
No
3 of 13
No
No
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
Xenopus tropicalis (Western clawed frog) (11)
4 of 12
Yes
Yes
3 of 12
No
Yes
2 of 12
No
No
2 of 12
No
No
2 of 12
No
No
1 of 12
No
Yes
1 of 12
No
Yes
1 of 12
No
No
1 of 12
No
Yes
1 of 12
No
No
1 of 12
No
No
Danio rerio (Zebrafish) (27)
5 of 15
Yes
No
5 of 15
Yes
Yes
4 of 15
No
No
4 of 15
No
No
4 of 15
No
No
3 of 15
No
Yes
3 of 15
No
No
3 of 15
No
No
3 of 15
No
No
2 of 15
No
Yes
2 of 15
No
Yes
2 of 15
No
Yes
2 of 15
No
Yes
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
Yes
1 of 15
No
Yes
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
No
1 of 15
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (3)
7 of 15
Yes
No
1 of 15
No
Yes
1 of 15
No
Yes
Arabidopsis thaliana (thale-cress) (1)
1 of 9
Yes
Yes
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) ( EOG09190GKH )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
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) ( EOG09150BBR )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Musca domestica
House fly
Lucilia cuprina
Australian sheep blowfly
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W0FLV )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
Apis florea
Little honeybee
Apis florea
Little honeybee
Apis mellifera
Western honey bee
Apis mellifera
Western honey bee
Apis mellifera
Western honey bee
Bombus impatiens
Common eastern bumble bee
Bombus impatiens
Common eastern bumble bee
Bombus impatiens
Common eastern bumble bee
Bombus terrestris
Buff-tailed bumblebee
Bombus terrestris
Buff-tailed bumblebee
Bombus terrestris
Buff-tailed bumblebee
Linepithema humile
Argentine ant
Linepithema humile
Argentine ant
Linepithema humile
Argentine ant
Megachile rotundata
Alfalfa leafcutting bee
Megachile rotundata
Alfalfa leafcutting bee
Megachile rotundata
Alfalfa leafcutting bee
Dendroctonus ponderosae
Mountain pine beetle
Dendroctonus ponderosae
Mountain pine beetle
Dendroctonus ponderosae
Mountain pine beetle
Tribolium castaneum
Red flour beetle
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X0FLT )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Strigamia maritima
European centipede
Strigamia maritima
European centipede
Strigamia maritima
European centipede
Strigamia maritima
European centipede
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Daphnia pulex
Water flea
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G0P1S )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (12)
5 of 10
5 of 10
5 of 10
5 of 10
4 of 10
3 of 10
2 of 10
2 of 10
2 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.
    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).
    (UniProt, Q01068 )
    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:26,021,823..26,023,127 [+]
    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 (7)
    Genomic Clones (10)
     

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

    cDNA Clones (51)
     

    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)m3-HLH HLHm3
    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.
    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.
    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.
    The E(spl)-C genes participate in the N signalling pathway.
    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.
    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) region gene encoding HLH protein identified by low stringency hybridization to previously defined HLHm5 and HLHm7 probes. 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, HLHmβ and HLHmγ and the last includes HLHmδ.
    HLHm3, HLHmβ, HLHmγ and HLHmδ encode helix-loop-helix proteins, bringing the total of such proteins in the E(spl) complex to seven.
    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.
    Origin and Etymology
    Discoverer
    Etymology
    Identification
    External Crossreferences and Linkouts ( 253 )
    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/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
    iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
    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 (17)
    Reported As
    Symbol Synonym
    E(Spl)-HLH-m3
    Name Synonyms
    E(spl) region transcript m3
    Enhancer of split m3, helix-loop-helix
    split locus enhancer protein m3
    Secondary FlyBase IDs
    • FBgn0010046
    Datasets (0)
    Study focus (0)
    Experimental Role
    Project
    Project Type
    Title
    References (169)