FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Gene: Dmel\E(spl)m3-HLH
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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
protein_coding_gene
FlyBase ID
FBgn0002609
Gene Model Status
Current
Stock Availability
11 publicly available
Gene Summary
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] (FlyBase Gene Snapshot)
All Summaries
Also Known As

m3, E(spl)m3, HLHm3, E(spl)-m3, E(spl)C m3

Key Links
Genomic Location
Cytogenetic map
96F10-96F10
Sequence location
Recombination map
3-89
RefSeq locus
NT_033777 REGION:26021823..26023127
Sequence
Get Decorated FASTA
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
NCBI
UCSC
Ensembl
PopFly
Function
Gene Ontology (GO) Annotations (12 terms)
Molecular Function (6 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
enables sequence-specific DNA binding
inferred from direct assay
(Jennings et al., 1999)
enables sequence-specific double-stranded DNA binding
inferred from direct assay
(Li et al., 2017)
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
enables DNA binding
inferred from electronic annotation with InterPro:IPR003650
(InterPro Project Members, 2004-)
enables DNA-binding transcription factor activity, RNA polymerase II-specific
inferred from biological aspect of ancestor with PANTHER:PTN004213585
(GO Reference Genome Project, 2011-)
enables protein dimerization activity
inferred from electronic annotation with InterPro:IPR011598, InterPro:IPR036638
(InterPro Project Members, 2004-)
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding
inferred from biological aspect of ancestor with PANTHER:PTN004213585
(GO Reference Genome Project, 2011-)
Biological Process (5 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
involved_in positive regulation of neuroblast proliferation
inferred from mutant phenotype
(Zacharioudaki et al., 2012)
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
involved_in anterior/posterior pattern specification
inferred from biological aspect of ancestor with PANTHER:PTN000105428
(GO Reference Genome Project, 2011-)
involved_in negative regulation of transcription by RNA polymerase II
inferred from biological aspect of ancestor with PANTHER:PTN004213585
(GO Reference Genome Project, 2011-)
involved_in regulation of DNA-templated transcription
inferred from electronic annotation with InterPro:IPR003650
(InterPro Project Members, 2004-)
involved_in regulation of neurogenesis
inferred from biological aspect of ancestor with PANTHER:PTN000105428
(GO Reference Genome Project, 2011-)
Cellular Component (1 term)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
is_active_in nucleus
inferred from biological aspect of ancestor with PANTHER:PTN004213585
(GO Reference Genome Project, 2011-)
Gene Group (FlyBase)
Protein Family (UniProt)
-
Protein Signatures (InterPro)
Summaries
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]
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 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
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry Q01068)

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 5.48

Gene model reviewed during 5.42

Gene model reviewed during 5.53

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
E(spl)m3-HLH-RA
FBtr0084958
NM_079785
1305
224
Additional Transcript Data and Comments
Reported size (kB)

1.4 (northern blot)

(Knust et al., 1987)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
E(spl)m3-HLH-PA
FBpp0084332
25.0
224
8.23
Q01068
NP_524509
AAF56550
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
InterPro - A database of protein families, domains and functional sites
Linkouts
Sequences Consistent with the Gene Model
Nucleotide / Polypeptide Records
 
UniProt
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
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).

-0.44

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
embryonic stage 8 -- 11
ventral neurectoderm
(Wech et al., 1999)
proneural cluster
(Wech et al., 1999)
embryonic stage 9
endoderm

Comment: transiently expressed

(Wech et al., 1999)
embryonic stage 9 -- 10
antennal primordium

Comment: reported as procephalic ectoderm primordium

(Fisher et al., 2012)
central brain primordium

Comment: reported as procephalic ectoderm primordium

(Fisher et al., 2012)
visual primordium

Comment: reported as procephalic ectoderm primordium

(Fisher et al., 2012)
dorsal head epidermis primordium

Comment: reported as procephalic ectoderm primordium

(Fisher et al., 2012)
lateral head epidermis primordium

Comment: reported as procephalic ectoderm primordium

(Fisher et al., 2012)
ventral head epidermis primordium

Comment: reported as procephalic ectoderm primordium

(Fisher et al., 2012)
ventral ectoderm
(Fisher et al., 2012)
embryonic stage 11 -- 12
antennal primordium

Comment: reported as procephalon primordium

(Fisher et al., 2012)
central brain primordium

Comment: reported as procephalon primordium

(Fisher et al., 2012)
dorsal head epidermis primordium

Comment: reported as procephalon primordium

(Fisher et al., 2012)
lateral head epidermis primordium

Comment: reported as procephalon primordium

(Fisher et al., 2012)
ventral head epidermis primordium

Comment: reported as procephalon primordium

(Fisher et al., 2012)
visual primordium

Comment: reported as procephalon primordium

(Fisher et al., 2012)
anterior midgut primordium
(Fisher et al., 2012)
larval foregut atrium | precursor

Comment: reported as atrium primordium

(Fisher et al., 2012)
dorsal epidermis primordium
(Fisher et al., 2012)
dorsal ridge primordium
(Fisher et al., 2012)
head mesoderm
(Fisher et al., 2012)
posterior midgut primordium
(Fisher et al., 2012)
trunk mesoderm
(Fisher et al., 2012)
ventral epidermis primordium
(Fisher et al., 2012)
embryonic stage 12 -- 15
embryonic head segment
(Wech et al., 1999)
embryonic thoracic segment
(Wech et al., 1999)
embryonic stage 13 -- 16
embryonic dorsal epidermis
(Fisher et al., 2012)
embryonic head epidermis
(Fisher et al., 2012)
embryonic hindgut
(Fisher et al., 2012)
embryonic ventral epidermis
(Fisher et al., 2012)
embryonic/larval midgut
(Fisher et al., 2012)
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
embryonic stage 11 -- 16

Comment: reference states 6-14 hr AEL

(Knust et al., 1987)
embryonic stage 13
Malpighian tubule
(Knust et al., 1987)
embryonic/larval midgut | restricted
(Knust et al., 1987)
adult stage | female
(Knust et al., 1987)
RT-PCR
Stage
Tissue/Position (including subcellular localization)
Reference
wandering third instar larval stage
organism
(Maeder et al., 2009)
prepupal stage
organism
(Maeder et al., 2009)
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.

(Maeder et al., 2009)

The peak of E(spl)m3-HLH 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.

(Knust et al., 1987)
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

JBrowse - Visual display of RNA-Seq signals

View Dmel\E(spl)m3-HLH in JBrowse
Bulk Downloads
RNA-Seq RPKM values for all genes
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
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
FlyBase Wiki
Image Based Resources
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 5 )
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 E(spl)m3-HLH
Transgenic constructs containing regulatory region of E(spl)m3-HLH
Aberrations (Deficiencies and Duplications) ( 15 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
Orthologs
Downloads
Download All DIOPT Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Source
Compara
Domainoid
eggNOG
Hieranoid
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (14)
Hsap\HES1
5 of 14
Yes
No
Hsap\HES2
5 of 14
Yes
No
Hsap\HES4
5 of 14
Yes
No
1  
Hsap\BHLHE40
4 of 14
No
Yes
Hsap\BHLHE41
4 of 14
No
Yes
4  
Hsap\HES3
4 of 14
No
Yes
Hsap\HES6
4 of 14
No
No
Hsap\HELT
3 of 14
No
No
Hsap\HES5
3 of 14
No
No
Hsap\HES7
3 of 14
No
No
Hsap\HEY1
3 of 14
No
No
1  
Hsap\HEY2
3 of 14
No
No
1  
Hsap\HEYL
3 of 14
No
No
Hsap\BMAL1
1 of 14
No
No
1  
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Source
Compara
Domainoid
eggNOG
Hieranoid
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (12)
Rnor\Hes1
5 of 14
Yes
No
Rnor\Hes2
5 of 14
Yes
No
Rnor\Hes6
5 of 14
Yes
No
Rnor\Bhlhe40
4 of 14
No
Yes
Rnor\Hes3
4 of 14
No
Yes
Rnor\Bhlhe41
3 of 14
No
Yes
Rnor\Hes5
3 of 14
No
No
Rnor\Hes7
3 of 14
No
No
Rnor\Hey2
3 of 14
No
No
Rnor\Heyl
3 of 14
No
No
Rnor\Helt
2 of 14
No
No
Rnor\Hey1
1 of 14
No
No
Mus musculus (laboratory mouse) (12)
Mmus\Hes2
6 of 14
Yes
No
Mmus\Hes1
5 of 14
No
No
Mmus\Bhlhe40
4 of 14
No
Yes
Mmus\Bhlhe41
4 of 14
No
Yes
Mmus\Hes3
4 of 14
No
Yes
Mmus\Helt
3 of 14
No
No
Mmus\Hes5
3 of 14
No
Yes
Mmus\Hes6
3 of 14
No
No
Mmus\Hes7
3 of 14
No
No
Mmus\Hey1
3 of 14
No
No
Mmus\Hey2
3 of 14
No
No
Mmus\Heyl
3 of 14
No
No
Xenopus tropicalis (Western clawed frog) (30)
Xtro\hes1
3 of 13
Yes
No
Xtro\hes2
3 of 13
Yes
No
Xtro\hes3
3 of 13
Yes
Yes
Xtro\hes4
3 of 13
Yes
No
Xtro\hes6.1
3 of 13
Yes
No
Xtro\bhlhe40
2 of 13
No
Yes
Xtro\hes5.1
2 of 13
No
No
Xtro\hes5.4
2 of 13
No
No
Xtro\hes5.7
2 of 13
No
No
Xtro\hes5.9
2 of 13
No
No
Xtro\hes6.2
2 of 13
No
Yes
Xtro\LOC116412194
2 of 13
No
Yes
Xtro\ada.2
1 of 13
No
Yes
Xtro\bhlhe41
1 of 13
No
Yes
Xtro\cers5
1 of 13
No
No
Xtro\ctdp1
1 of 13
No
No
Xtro\dlst
1 of 13
No
No
Xtro\gnrhr2/nmi
1 of 13
No
No
Xtro\helt
1 of 13
No
No
Xtro\hes5.2
1 of 13
No
No
Xtro\hes5.3
1 of 13
No
No
Xtro\hes5.10
1 of 13
No
No
Xtro\hes7.1
1 of 13
No
Yes
Xtro\hes7.2
1 of 13
No
No
Xtro\hey1
1 of 13
No
No
Xtro\lrrk2
1 of 13
No
No
Xtro\sptlc3
1 of 13
No
No
Xtro\sult6b1.4
1 of 13
No
No
Xtro\usp10
1 of 13
No
No
Xtro\vim.2
1 of 13
No
Yes
Danio rerio (Zebrafish) (30)
Drer\her8.2
6 of 14
Yes
No
Drer\her8a
6 of 14
Yes
No
Drer\her6
5 of 14
No
No
Drer\her9
5 of 14
No
No
Drer\her13
5 of 14
No
No
Drer\hes2.2
5 of 14
No
Yes
Drer\hes6
5 of 14
No
No
Drer\bhlhe40
4 of 14
No
Yes
Drer\bhlhe41
4 of 14
No
Yes
Drer\her3
4 of 14
No
Yes
Drer\hes2.1
4 of 14
No
Yes
Drer\helt
3 of 14
No
No
Drer\her1
3 of 14
No
No
Drer\her5
3 of 14
No
Yes
Drer\her7
3 of 14
No
No
Drer\her12
3 of 14
No
No
Drer\her15.1
3 of 14
No
No
Drer\her15.2
3 of 14
No
No
Drer\hey1
3 of 14
No
No
Drer\hey2
3 of 14
No
No
Drer\heyl
3 of 14
No
No
Drer\her2
2 of 14
No
No
Drer\her4.1
2 of 14
No
No
Drer\her4.2
2 of 14
No
No
Drer\her4.3
2 of 14
No
No
Drer\her4.4
2 of 14
No
No
Drer\her11
2 of 14
No
Yes
Drer\arntl1a
1 of 14
No
No
Drer\arntl1b
1 of 14
No
No
Drer\her4.5
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (2)
Cele\lin-22
5 of 14
Yes
Yes
Cele\ref-1
1 of 14
No
Yes
Anopheles gambiae (African malaria mosquito) (6)
Agam\AgaP_AGAP012342
6 of 12
Yes
No
Agam\AgaP_AGAP006699
3 of 12
No
No
Agam\AgaP_AGAP012346
3 of 12
No
No
Agam\AgaP_AGAP003844
2 of 12
No
No
Agam\AgaP_AGAP007450
2 of 12
No
No
Agam\AgaP_AGAP005655
1 of 12
No
No
Arabidopsis thaliana (thale-cress) (6)
Atha\AT1G68810
1 of 13
Yes
Yes
Atha\AT2G40200
1 of 13
Yes
No
Atha\AT3G56770
1 of 13
Yes
Yes
Atha\AT4G38070
1 of 13
Yes
Yes
Atha\BHLH32
1 of 13
Yes
Yes
Atha\LNO1
1 of 13
Yes
Yes
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)m3-HLH. Refer to their site for version information.
Paralogs
Downloads
Download All DIOPT Paralogs
Paralogs (via DIOPT v9.1)
Gene Symbol
Score
Source
Compara
Domainoid
eggNOG
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Drosophila melanogaster (Fruit fly) (12)
E(spl)m7-HLH
9 of 13
E(spl)mβ-HLH
9 of 13
E(spl)mγ-HLH
9 of 13
E(spl)mδ-HLH
7 of 13
dpn
6 of 13
E(spl)m5-HLH
6 of 13
E(spl)m8-HLH
6 of 13
hry
6 of 13
cwo
5 of 13
Hesr
5 of 13
Sidpn
5 of 13
Hey
4 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?
    HES1; hes family bHLH transcription factor 1
    5 of 14
    139605
        HES2; hes family bHLH transcription factor 2
        5 of 14
        609970
            HES4; hes family bHLH transcription factor 4
            5 of 14
            HES FAMILY bHLH TRANSCRIPTION FACTOR 4; HES4
                 
                BHLHE40; basic helix-loop-helix family member e40
                4 of 14
                604256
                    BHLHE41; basic helix-loop-helix family member e41
                    4 of 14
                    606200
                       
                      HES3; hes family bHLH transcription factor 3
                      4 of 14
                      609971
                          HES6; hes family bHLH transcription factor 6
                          4 of 14
                          610331
                              HELT; helt bHLH transcription factor
                              3 of 14
                              617546
                                  HES5; hes family bHLH transcription factor 5
                                  3 of 14
                                  607348
                                      HES7; hes family bHLH transcription factor 7
                                      3 of 14
                                      608059
                                      HEY1; hes related family bHLH transcription factor with YRPW motif 1
                                      3 of 14
                                      602953
                                           
                                          HEY2; hes related family bHLH transcription factor with YRPW motif 2
                                          3 of 14
                                          604674
                                               
                                              HEYL; hes related family bHLH transcription factor with YRPW motif like
                                              3 of 14
                                              609034
                                                  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
                                                  Interaction Browsers
                                                  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.
                                                  MIST (protein-protein) - An integrated Molecular Interaction Database
                                                  Pathways
                                                  Signaling Pathways (FlyBase)
                                                  Metabolic Pathways
                                                  FlyBase
                                                  External Links
                                                  External Data
                                                  Linkouts
                                                  Class of Gene
                                                  Genomic Location and Detailed Mapping Data
                                                  Chromosome (arm)
                                                  3R
                                                  Recombination map
                                                  3-89
                                                  Cytogenetic map
                                                  96F10-96F10
                                                  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
                                                  (Nellesen, 1998.12.18)
                                                  Experimentally Determined Recombination Data
                                                  Location

                                                  3-89

                                                  (FlyBase, 2016)

                                                  3-87.4

                                                  (Comeron et al., 2012)

                                                  3-89.1

                                                  Left of (cM)
                                                  Right of (cM)
                                                  Notes
                                                  Stocks and Reagents
                                                  Stocks (11)
                                                  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 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
                                                  Other 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 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.

                                                      (Nellesen et al., 1999)

                                                      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.

                                                      (Gigliani et al., 1996)

                                                      Clones mutant for E(spl)-C bHLH-encoding genes or for gro display bristle hyperplasia.

                                                      (Heitzler et al., 1996)

                                                      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.

                                                      (Heitzler et al., 1996)

                                                      The E(spl)-C genes participate in the N signalling pathway.

                                                      (Heitzler et al., 1996)

                                                      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.

                                                      (Alifragis et al., 1995)

                                                      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.

                                                      (Bang et al., 1995)

                                                      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.

                                                      (Maier et al., 1993)

                                                      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.

                                                      (Delidakis and Artavanis-Tsakonas, 1992)

                                                      HLHm3, HLHmβ, HLHmγ and HLHmδ encode helix-loop-helix proteins, bringing the total of such proteins in the E(spl) complex to seven.

                                                      (Knust et al., 1992)

                                                      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.

                                                      (Schrons et al., 1992)
                                                      Relationship to Other Genes
                                                      Source for database merge of
                                                      Additional comments
                                                      Nomenclature History
                                                      Source for database identify of

                                                      Source for identity of: E(spl)m3-HLH HLHm3

                                                      (Artavanis-Tsakonas et al., 2012.8.8)
                                                      Nomenclature comments
                                                      Etymology
                                                      Synonyms and Secondary IDs (19)
                                                      Reported As
                                                      Symbol Synonym
                                                      CG8346
                                                      (Ni et al., 2010.12.1, Krejcí et al., 2009, Perkins et al., 2009.1.15, Bhutkar et al., 2008, Stevens et al., 2008, Stevens et al., 2008, Schlatter and Maier, 2005)
                                                      E(Spl)-HLH-m3
                                                      (Knust, 1992.6.22)
                                                      E(spl)-C
                                                      (Reddy Onteddu et al., 2024, Boumard and Bardin, 2021, Hu and Yang, 2014)
                                                      E(spl)-m3
                                                      (Bahrampour and Thor, 2020, Guo et al., 2019, Gomez-Lamarca et al., 2018, Le Borgne et al., 2005)
                                                      E(spl)C
                                                      (Bose et al., 2008, Ahimou et al., 2004)
                                                      E(spl)C m3
                                                      (Tremmel et al., 2013, Bardot et al., 2005, Mok et al., 2005, Ahimou et al., 2004)
                                                      E(spl)M3
                                                      (Jennings et al., 1999)
                                                      E(spl)m3
                                                      (Frankenreiter et al., 2021, Prince and Rand, 2017, Kux et al., 2013, Engel et al., 2012, Barry et al., 2011, Duan et al., 2011, Endo et al., 2011, Leonardi et al., 2011, Bernard et al., 2010, Krejcí et al., 2009, Goodfellow et al., 2007, Lai et al., 2005, Brody et al., 2002, Lai, 2002, Rebeiz et al., 2002, Rosenberg and Parkhurst, 2002, Ledent and Vervoort, 2001, Ligoxygakis et al., 1999, Fisher and Caudy, 1998, Lai et al., 1998, Nellesen, 1998.12.18, Leviten et al., 1997, Gallant et al., 1996)
                                                      E(spl)m3-HLH
                                                      (Joly et al., 2025, Xu et al., 2025, Collins et al., 2024, Li et al., 2024, Ridgway et al., 2024, Josserand et al., 2023, Zhao et al., 2023, Jia et al., 2022, Ferguson et al., 2021, Girard et al., 2021, Slaidina et al., 2021, Cho et al., 2020, Hung et al., 2020, Shokri et al., 2019, Bischof et al., 2018, Franz et al., 2017, Schertel et al., 2015, Wurmbach and Preiss, 2014)
                                                      HLH-m3
                                                      (Campos-Ortega, 1993, Tietze et al., 1993)
                                                      HLHM3
                                                      (Morgenstern and Atchley, 1999)
                                                      HLHm3
                                                      (McClelland et al., 2017, Ugrankar et al., 2015, Schaaf et al., 2013, Terriente-Felix et al., 2013, Garcia et al., 2012, Japanese National Institute of Genetics, 2012.5.21, Fay et al., 2011, Johnson et al., 2011, Toku et al., 2011, Blanco et al., 2010, Cunha et al., 2010, Duncan and Dearden, 2010, Schaaf et al., 2009, Lu et al., 2008, Kadener et al., 2007, Maeder et al., 2007, Zeitlinger et al., 2007, Dorner et al., 2006, Sandmann et al., 2006)
                                                      bHLHc14
                                                      (Stevens et al., 2008)
                                                      m3
                                                      (Singh et al., 2025, Couturier et al., 2019, Guo et al., 2019, Singh et al., 2019, Bivik et al., 2016, Horvath et al., 2016, Kux et al., 2013, San Juan et al., 2012, Zarifi et al., 2012, Cave et al., 2011, Bardin et al., 2010, Bernard et al., 2010, Duncan and Dearden, 2010, Chanet et al., 2009, Maeder et al., 2009, Bhutkar et al., 2008, Rand et al., 2008, Eastman et al., 2007, Krejci and Bray, 2007, Chan et al., 2005, Giagtzoglou et al., 2005, Kan and Kessler, 2005, Lai et al., 2005, Macdonald and Long, 2005, Macdonald et al., 2005, Schlatter and Maier, 2005, Ahimou et al., 2004, Nagel et al., 2004, Secombe and Parkhurst, 2004, Trott et al., 2001, Kumar and Moses, 2000, Lai et al., 2000, Nellesen et al., 1999, Wech et al., 1999, Wurmbach et al., 1999, Lai and Posakony, 1998, Ligoxygakis et al., 1998, Preiss et al., 1997, de Celis et al., 1996, Gigliani et al., 1996, Hartenstein et al., 1996, Heitzler et al., 1996, Alifragis et al., 1995, Alifragis et al., 1995, Bang et al., 1995, Tepass and Hartenstein, 1995, Tietze et al., 1993, Delidakis and Artavanis-Tsakonas, 1992, Schrons et al., 1991, Campos-Ortega and Knust, 1990, Campos-Ortega and Knust, 1990, Knust et al., 1987)
                                                      Name Synonyms
                                                      E(spl) region transcript m3
                                                      (Krejcí et al., 2009, Rehmsmeier et al., 2004)
                                                      Enhancer of split m3
                                                      (Ahimou et al., 2004, Wesley and Mok, 2003)
                                                      Enhancer of split m3, helix-loop-helix
                                                      (Young and Marcotte, 2017)
                                                      enhancer of split m3, helix-loop-helix
                                                      (Hagen et al., 2021)
                                                      split locus enhancer protein m3
                                                      (Delidakis, 1992.9.29)
                                                      Secondary FlyBase IDs
                                                      • FBgn0010046
                                                      Datasets (0)
                                                      Study focus (0)
                                                      Experimental Role
                                                      Project
                                                      Project Type
                                                      Title
                                                      Study result (0)
                                                      Result
                                                      Result Type
                                                      Title
                                                      External Crossreferences and Linkouts ( 257 )
                                                      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.
                                                      BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
                                                      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
                                                      Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
                                                      Flygut - An atlas of the Drosophila adult midgut
                                                      iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
                                                      MIST (protein-protein) - An integrated Molecular Interaction Database
                                                      References (203)