FlyBase Gene Report: Dmel\E(spl)m6-BFM

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).

Gene Model and Products

Number of Transcripts

Number of Unique Polypeptides

Please see the JBrowse view of Dmel\E(spl)m6-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 O97179)

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

Transcript Data

Annotated Transcripts

Name

FlyBase ID

RefSeq ID

Length (nt)

Assoc. CDS (aa)

E(spl)m6-BFM-RA

FBtr0084959

NM_079788

1137

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)m6-BFM-PA

FBpp0084333

8.1

6.51

O97179

NP_524512

AAF56553

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)

70 (aa)

(Wurmbach et al., 1999)

Comments

External Data

Crossreferences

InterPro - A database of protein families, domains and functional sites

Enhancer of split m6 protein

Linkouts

Sequences Consistent with the Gene Model

Nucleotide / Polypeptide Records

UniProt

O97179

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)m6-BFM using the Feature Mapper tool.

External Data

Crossreferences

Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.

E(spl)m6-BFM_1

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).

-0.40

Transcript Expression

in situ

Stage

Tissue/Position (including subcellular localization)

Reference

embryonic stage

embryonic brain

(Wurmbach et al., 1999)

presumptive embryonic/larval peripheral nervous system

(Wurmbach et al., 1999)

presumptive embryonic/larval central nervous system

(Wurmbach et al., 1999)

larval ventral nerve cord

(Wurmbach et al., 1999)

third instar larval stage

wing disc | restricted

(Wurmbach et al., 1999)

adepithelial cell of wing disc | subset

(Lai et al., 2000)

adepithelial cell of haltere disc | subset

(Lai et al., 2000)

prepupal stage P4(i)

anterior wing margin | precursor

(Lai et al., 2000)

pupal stage P6

cell | subset of posterior wing margin

Comment: pairs of expressing cells

(Lai et al., 2000)

northern blot

Stage

Tissue/Position (including subcellular localization)

Reference

embryonic stage 13 -- 15

embryonic/larval midgut | restricted

(Knust et al., 1987)

organism | segmentally repeated

(Knust et al., 1987)

embryonic stage 13 -- 16

Comment: reference states 10-14 hr AEL

(Knust et al., 1987)

Additional Descriptive Data

m6 transcripts are first detected in stage 9 embryos in the developing CNS. After germ band retraction, they are observed in the brain, the ventral nerve cord, and in the presumptive PNS. Weak expression is observed in imaginal discs. Specific staining is seen in the notal anlagen of the wing disc.

(Wurmbach et al., 1999)

High levels of m6 expression is seen in 10-14 hr embryos. In stage 13-15 embryos, m6 is detected in cell clusters in a segmental pattern; these cells may be sensory organs. Additional expression is detected on midgut walls, and may correspond to midgut neurons.

(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

Reporter: P{E(spl)m6-BFM-gapGFP}

Stage

Tissue/Position (including subcellular localization)

Reference

embryonic stage 13 -- 14

fusion competent cell

(Tixier et al., 2013)

High-Throughput Expression Data

Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\E(spl)m6-BFM in JBrowse

RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region

View exonic expression by developmental stage for Dmel\E(spl)m6-BFM

View exonic expression by tissue for Dmel\E(spl)m6-BFM

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

DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species

43159/tissue=All

EMBL-EBI Single Cell Expression Atlas - Single cell expression across species

FBgn0002632

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0002632

FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FBgn0002632

Flygut - An atlas of the Drosophila adult midgut

FBgn0002632

Images

FlyBase Wiki

Image Based Resources

Alleles, Insertions, Transgenic Constructs, and Aberrations

Classical and Insertion Alleles ( 3 )

For All Classical and Insertion Alleles Show

Other relevant insertions

Transgenic Constructs ( 5 )

For All Alleles Carried on Transgenic Constructs Show

Transgenic constructs containing/affecting coding region of E(spl)m6-BFM

Transgenic constructs containing regulatory region of E(spl)m6-BFM

Aberrations (Deficiencies and Duplications) ( 9 )

Inferred from experimentation ( 9 )

Gene disrupted in

Df(3R)boss15

(Nagel et al., 2000)

Df(3R)E(spl)δ-6

(Bardin et al., 2010, Chanet et al., 2009)

Df(3R)E(spl)mδ-m8

(Arias et al., 2025)

Df(3R)E(spl)-rv27

(Tietze et al., 1993)

Df(3R)Exel6204

(Ryder, 2004.4.26)

Df(3R)P11

(Nagel et al., 2000)

Df(3R)R20

(Wurmbach and Preiss, 2014)

Gene duplicated in

Dp(3;2)E(spl)δ-8

(Chanet et al., 2009)

Gene not disrupted in

Df(3R)E(spl)-Δm7-m8

(Couturier et al., 2019)

Inferred from location ( 7 )

Variants

Variant Molecular Consequences

Alleles Representing Disease-Implicated Variants

Phenotypes

For more details about a specific phenotype click on the relevant allele symbol.

Lethality

Allele

viable, with Dcr-2^UAS.cDa, Scer\GAL4^elav.PLu

E(spl)m6-BFM^GD13722

viable, with Scer\GAL4^Mef2.PR

E(spl)m6-BFM^GD13722

viable, with Scer\GAL4^pnr-MD237

E(spl)m6-BFM^GD13722

Other Phenotypes

Allele

visible, with Scer\GAL4^sca-537.4

E(spl)m6-BFM^UAS.cLa

Phenotype manifest in

Allele

campaniform sensillum of dorsal radius, with Scer\GAL4^sca-537.4

E(spl)m6-BFM^UAS.cLa

chemosensory ventral triple row bristle, with Scer\GAL4^sca-537.4

E(spl)m6-BFM^UAS.cLa

dorsal row of triple row of wing sensilla, with Scer\GAL4^sca-537.4

E(spl)m6-BFM^UAS.cLa

macrochaeta, with Scer\GAL4^sca-537.4

E(spl)m6-BFM^UAS.cLa

medial row of triple row of wing sensilla, with Scer\GAL4^sca-537.4

E(spl)m6-BFM^UAS.cLa

microchaeta, with Scer\GAL4^sca-537.4

E(spl)m6-BFM^UAS.cLa

sensory mother cell, with Scer\GAL4^sca-537.4

E(spl)m6-BFM^UAS.cLa

wing margin, with Scer\GAL4^Bx-MS1096

E(spl)m6-BFM^UAS.cLa

wing margin bristle, with Scer\GAL4^Bx-MS1096

E(spl)m6-BFM^UAS.cLa

Orthologs

Downloads

Download All DIOPT Orthologs

Human Orthologs (via DIOPT v9.1)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Homo sapiens (Human) (0)

Model Organism Orthologs (via DIOPT v9.1)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

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) (0)

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)m6-BFM. Refer to their site for version information.

Paralogs

Downloads

Download All DIOPT Paralogs

Paralogs (via DIOPT v9.1)

Gene Symbol

Score

Source

Alignment

Drosophila melanogaster (Fruit fly) (0)

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

Interaction Browsers

View in FlyBase Interactions Browser View in MIST tool (external link)

Please see the Physical Interaction reports below for full details

protein-protein

Physical Interaction

Assay

References

E(spl)m6-BFM - neur

two hybrid

(Bardin and Schweisguth, 2006)

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

Linkouts

DroID - A comprehensive database of gene and protein interactions.

FBgn0002632

Pathways

Signaling Pathways (FlyBase)

NEGATIVE REGULATORS OF NOTCH SIGNALING PATHWAY

Metabolic Pathways

FlyBase

External Links

External Data

Linkouts

Class of Gene

nuclear_gene

protein_coding_gene

Genomic Location and Detailed Mapping Data

Chromosome (arm)

Recombination map

3-89

Cytogenetic map

96F10-96F10

Sequence location

3R:26,032,911..26,034,047 [+]

FlyBase Computed Cytological Location

Cytogenetic map

Evidence for location

96F10-96F10

Limits computationally determined from genome sequence between P{PZ}l(3)rQ197^rQ197 and P{lacW}scrib^j7B3

Experimentally Determined Cytological Location

Cytogenetic map

Notes

References

96F11-96F14

(Wurmbach, 1998.10.18)

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 (5)

Aberrations including deletions of this gene Aberrations including duplications of this gene

Bloomington

26430

w¹¹¹⁸; Mi{ET1}E(spl)m6-BFM^MB09027

37187

y¹ w^*; Mi{MIC}E(spl)m6-BFM^MI03383

66950

y¹ sc^* v¹ sev²¹; P{TRiP.HMS05416}attP40

VDRC

v101965

P{KK110344}VIE-260B

v28848

w¹¹¹⁸; P{GD13722}v28848/TM3

Genomic Clones (16)

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

cDNA Clones (5)

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.

FBgn0002632

cDNA Clones, End Sequenced (ESTs)

BDGP DGC clones

Other clones

RNAi and Array Information

Linkouts

DRSC - Results frm RNAi screens

FBgn0002632

Antibody Information

Laboratory Generated Antibodies

Commercially Available Antibodies

Cell Line Information

Publicly Available Cell Lines

Other Stable Cell Lines

Other Comments

m2 and m6 are direct targets of regulation by the N-activated Su(H) transcription factor. Overall orientation not stated: HLHmδ+ HLHmγ+ HLHmβ- mα+ m1+ m2- HLHm3+ m4- HLHm5- m6+ HLHm7+ E(spl)+ gro+

(Lai et al., 2000)

Overexpression of m2 or m6 interferes with N dependent cell fate decisions in adult PNS development. Overexpression of m6 impairs lateral inhibition.

(Lai et al., 2000)

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)

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

(Jennings 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)

The neurogenic phenotype of various embryonic combinations have been studied and include intermediate neurogenic embryos and weak neurogenic embryos.

(Delidakis et al., 1991)

Relationship to Other Genes

Source for database merge of

Additional comments

Nomenclature History

Source for database identify of

Source for identity of: E(spl)m6-BFM m6

(Artavanis-Tsakonas et al., 2012.8.8)

Nomenclature comments

Etymology

Synonyms and Secondary IDs (14)

Reported As

Symbol Synonym

CG8354

(Keleman et al., 2009.8.5, Krejcí et al., 2009, Perkins et al., 2009, Bhutkar et al., 2008, Mohit et al., 2006, Schlatter and Maier, 2005, Moehring and Mackay, 2004)

DmelCG8354

(Duncan and Dearden, 2010)

E(spl)-m6

(Boukhatmi, 2021)

E(spl)M6

(Zmojdzian and Jagla, 2021, Aradhya and Jagla, 2020, Figeac et al., 2010)

E(spl)m6

(Aradhya et al., 2015, Tseng et al., 2014, Di Stefano et al., 2011, Duan et al., 2011, Endo et al., 2011, Bernard et al., 2010, Figeac et al., 2010, Bernard et al., 2009, Krejcí et al., 2009, Bernard et al., 2006, Lai et al., 2005, Butler et al., 2003, Lai, 2002, Lai et al., 2000, Wurmbach, 1998.10.18)

E(spl)m6-BFM

(Tu et al., 2025, Josserand et al., 2023, Corrales et al., 2022, Michki et al., 2021, Fast et al., 2020, Wurmbach and Preiss, 2014)

HLHm6

(Moshkin et al., 2013, Bhutkar et al., 2008, Mohit et al., 2006)

(Tixier et al., 2013, Figeac et al., 2010, Inlow and Restifo, 2004)

Name Synonyms

E(spl) region transcript m6

(Krejcí et al., 2009)

Enhancer of Split Region Transcript m6

(Bernard et al., 2006)

Enhancer of split m6

(Aradhya et al., 2015)

Enhancer of split m6, Bearded family member

(Dequéant et al., 2015)

Enhancer of split region transcript m6

(Bernard et al., 2009)

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 ( 56 )

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.

43159

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.

O97179

UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information

O97179

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.

O97179

DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species

43159/tissue=All

EMBL-EBI Single Cell Expression Atlas - Single cell expression across species

FBgn0002632

FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FBgn0002632

FlyMine - An integrated database for Drosophila genomics

FBgn0002632

InterPro - A database of protein families, domains and functional sites

Enhancer of split m6 protein

KEGG Genes - Molecular building blocks of life in the genomic space.

dme:Dmel_CG8354

MARRVEL_MODEL - MARRVEL (model organism gene)

43159

Linkouts

Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones

FBgn0002632

DroID - A comprehensive database of gene and protein interactions.

FBgn0002632

DRSC - Results frm RNAi screens

FBgn0002632

Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.

E(spl)m6-BFM_1

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0002632

FlyCyc Genes - Genes from a BioCyc PGDB for Dmel

DMEL:FBGN0002632

Flygut - An atlas of the Drosophila adult midgut

FBgn0002632

References (97)

The following external sites may use different assemblies or annotations than FlyBase.

-0.40

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