FlyBase Gene Report: Dmel\E(spl)mβ-HLH

General Information

Symbol

Dmel\E(spl)mβ-HLH

Species

D. melanogaster

Name

Enhancer of split mβ, helix-loop-helix

Annotation Symbol

CG14548

Feature Type

protein_coding_gene

FlyBase ID

FBgn0002733

Gene Model Status

Current

Stock Availability

11 publicly available

Gene Summary

Transcriptional repressor of genes that require a bHLH protein for their transcription (By similarity). May serve as a transcriptional regulator of the Achaete-scute complex (AS-C) genes (PubMed:1528887). Contributes to the neural-epidermal lineage decision during early neurogenesis (PubMed:1427040). Part of the Notch signaling pathway (PubMed:1427040). (UniProt, Q01069)

Contribute a Gene Snapshot for this gene.

All Summaries

Also Known As

E(spl)mβ, mβ, HLHmβ, HLHmbeta, E(spl)mbeta

Key Links

Genomic Location

Cytogenetic map

96F9-96F9

Sequence location

3R:26,005,046..26,006,023 [-]

Recombination map

3-89

RefSeq locus

NT_033777 REGION:26005046..26006023

Sequence

Get Decorated FASTA

Genomic Maps

JBrowse

Other Genome Views

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

Function

Gene Ontology (GO) Annotations (16 terms)

Molecular Function (8 terms)

Terms Based on Experimental Evidence (4 terms)

CV Term

Evidence

References

enables DNA-binding transcription factor activity

inferred from mutant phenotype

(Li et al., 2017)

enables DNA-binding transcription repressor activity, RNA polymerase II-specific

inferred from mutant phenotype

(Xu et al., 2019)

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 (7 terms)

Terms Based on Experimental Evidence (4 terms)

CV Term

Evidence

References

acts_upstream_of_negative_effect chaeta development

inferred from mutant phenotype

(Xu et al., 2019)

involved_in negative regulation of transcription by RNA polymerase II

inferred from mutant phenotype

(Li et al., 2017)

inferred from expression pattern

(Jennings et al., 1999)

inferred from mutant phenotype

(Xu et al., 2019)

involved_in positive regulation of neuroblast proliferation

inferred from mutant phenotype

(Zacharioudaki et al., 2012)

involved_in regulation of neuroblast proliferation

inferred from mutant phenotype

(Li et al., 2017)

inferred from genetic interaction with UniProtKB:Q9VQ56

(Li et al., 2017)

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 (1 term)

CV Term

Evidence

References

located_in nucleus

inferred from mutant phenotype

(Li et al., 2017)

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)

ENHANCER OF SPLIT GENE COMPLEX

BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS

Protein Family (UniProt)

Protein Signatures (InterPro)

Summaries

Gene Group (FlyBase)

ENHANCER OF SPLIT GENE COMPLEX -: The Enhancer of split complex (E(spl)-C) of D.mel is a well characterized genetic locus on chromosome 3R containing 12 genes - with the exception of Kaz-m1, all are Notch responsive. Seven genes are basic helix-loop-helix (bHLH) transcription factors, four are bearded family genes. Kaz-m1 is unrelated, sharing some sequence similarity to Kazal class protease inhibitors. (Adapted from FBrf0211195).
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)

(UniProt, Q01069)

Gene Model and Products

Number of Transcripts

Number of Unique Polypeptides

Please see the JBrowse view of Dmel\E(spl)mβ-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 Q01069)

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 5.53

Transcript Data

Annotated Transcripts

Name

FlyBase ID

RefSeq ID

Length (nt)

Assoc. CDS (aa)

E(spl)mβ-HLH-RA

FBtr0084982

NM_079781

978

195

Additional Transcript Data and Comments

Reported size (kB)

Comments

External Data

Crossreferences

Polypeptide Data

Annotated Polypeptides

Name

FlyBase ID

Predicted MW (kDa)

Length (aa)

Theoretical pI

UniProt

RefSeq ID

GenBank

E(spl)mβ-HLH-PA

FBpp0084355

21.5

195

7.50

Q01069

NP_524505

AAF56546

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

The predicted protein products of the seven HLH

genes in the E(spl) complex exhibit a great degree of sequence

similarity extending over the first 120 amino acids of the proteins. The

carboxy terminus is unique for each except for the terminal 4 amino acids,

which are identical in all of the proteins.

(Delidakis and Artavanis-Tsakonas, 1992)

External Data

Subunit Structure (UniProtKB)

Transcription repression requires formation of a complex with a corepressor protein (Groucho).

(UniProt, Q01069)

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, Q01069)

Crossreferences

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

Linkouts

Sequences Consistent with the Gene Model

Nucleotide / Polypeptide Records

UniProt

Q01069

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)mβ-HLH 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)mbeta-HLH_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).

-0.63

Transcript Expression

in situ

Stage

Tissue/Position (including subcellular localization)

Reference

embryonic stage 5 -- 6

mesectoderm

(Kearney et al., 2004)

embryonic stage 7 -- 8

antennal anlage

Comment: reported as procephalic ectoderm anlage

(Fisher et al., 2012)

central brain anlage

Comment: reported as procephalic ectoderm anlage

(Fisher et al., 2012)

dorsal head epidermis anlage

Comment: reported as procephalic ectoderm anlage

(Fisher et al., 2012)

visual anlage

Comment: reported as procephalic ectoderm anlage

(Fisher et al., 2012)

ventral ectoderm

(Fisher et al., 2012)

ventral nerve cord primordium

Comment: reported as ventral nerve cord anlage

(Fisher et al., 2012)

mesectoderm anlage

(Kearney et al., 2004)

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)

ventral nerve cord primordium

(Fisher et al., 2012)

embryonic stage 9 -- 12

midline primordium

(Kearney et al., 2004)

embryonic stage 12 -- 15

embryonic head segment

(Wech et al., 1999)

embryonic thoracic segment

(Wech et al., 1999)

embryonic stage 13 -- 16

embryonic precursor of adult hindgut

(Fisher et al., 2012)

larval foregut atrium

(Fisher et al., 2012)

dorsal head epidermis

(Fisher et al., 2012)

embryonic dorsal epidermis

(Fisher et al., 2012)

embryonic epipharynx

(Fisher et al., 2012)

embryonic foregut

(Fisher et al., 2012)

embryonic head sensory system

(Fisher et al., 2012)

embryonic hindgut

(Fisher et al., 2012)

embryonic hypopharynx

(Fisher et al., 2012)

embryonic leading edge cell

(Fisher et al., 2012)

embryonic ventral epidermis

(Fisher et al., 2012)

embryonic/larval dorsal vessel

(Fisher et al., 2012)

embryonic/larval fat body

(Fisher et al., 2012)

embryonic/larval midgut

(Fisher et al., 2012)

larval nervous system

(Fisher et al., 2012)

lateral cord neuron

(Fisher et al., 2012)

sensory nervous system primordium

(Fisher et al., 2012)

ventral sensory complex primordium

(Fisher et al., 2012)

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)mβ-HLH expression dropped 5 fold by the late third instar stage compared to early third instar. It increased by 4.1 fold at puparium formation and by an additional 2 fold at 2-3 hours post-puparium formation. It is one of 4 genes to increase in expression at puparium formation and one of 5 genes that shows an increase at 2-3 hours post-puparium formation.

(Maeder et al., 2009)

Marker for

Subcellular Localization

CV Term

Polypeptide Expression

Additional Descriptive Data

Marker for

leg joint

(Guarner et al., 2014)

Subcellular Localization

CV Term

Evidence

References

located_in nucleus

inferred from mutant phenotype

(Li et al., 2017)

Expression Deduced from Reporters

Reporter: P{E(spl)mβ-HLH-CD2.dC}

Stage

Tissue/Position (including subcellular localization)

Reference

pupal stage

wing vein | lateral | restricted

(Sotillos and De Celis, 2005)

Reporter: P{E(spl)mβ-HLH-lacZ.0.9}

Stage

Tissue/Position (including subcellular localization)

Reference

embryonic stage 9 -- 10

ventral neurectoderm

(Nellesen et al., 1999)

third instar larval stage

proneural cluster of wing disc

Comment: pattern is broad, overlapping but not limited to proneural clusters

(Nellesen et al., 1999)

antennal disc | restricted

(Luque and Milan, 2007)

eye disc | anterior

(Luque and Milan, 2007)

prepupal stage P4

wing | restricted

Comment: reference states 6-8 hours APF; expression in regions complementary to developing wing veins

(Nellesen et al., 1999)

Reporter: P{mβ1.5-lacZ}

Stage

Tissue/Position (including subcellular localization)

Reference

third instar larval stage

leg joint | presumptive

(de Celis Ibeas and Bray, 2003, Hao et al., 2003)

wing disc | restricted

(Furriols and Bray, 2000)

leg disc | restricted

(de Celis Ibeas and Bray, 2003, Hao et al., 2003)

wandering third instar larval stage

wing disc | restricted

(Okajima and Irvine, 2002)

prepupal stage

tarsal segment | striped

(Capilla et al., 2012)

leg | restricted

(Capilla et al., 2012)

adult stage

enteroblast of posterior adult midgut epithelium

(Bardin et al., 2010)

oogenesis stage S3

primordial germ cell

(Grammont and Irvine, 2001)

High-Throughput Expression Data

Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\E(spl)mβ-HLH 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)mβ-HLH

View exonic expression by tissue for Dmel\E(spl)mβ-HLH

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

FBgn0002733

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

43152/tissue=All

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

FBgn0002733

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0002733

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

FBgn0002733

Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns

CG14548

Flygut - An atlas of the Drosophila adult midgut

FBgn0002733

Images

FlyExpress - Embryonic expression images (BDGP data)

Show all FlyExpress processed images for Dmel\E(spl)mβ-HLH

Stages(s) 7-8
Stages(s) 9-10
Stages(s) 11-12
Stages(s) 13-16

FlyBase Wiki

Image Based Resources

Alleles, Insertions, Transgenic Constructs, and Aberrations

Classical and Insertion Alleles ( 9 )

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)mβ-HLH

Transgenic constructs containing regulatory region of E(spl)mβ-HLH

Aberrations (Deficiencies and Duplications) ( 12 )

Inferred from experimentation ( 12 )

Gene disrupted in

Df(3R)boss16

(Heitzler et al., 1996)

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)Espl4

(Heitzler et al., 1996)

Df(3R)gro^b32.2

(Ligoxygakis et al., 1998, de Celis et al., 1997, de Celis et al., 1996, Heitzler et al., 1996)

Df(3R)P11

(Nagel et al., 2000)

Gene partially disrupted in

Df(3R)E(spl)Δmγ-mβ-DK33-10.1

(Babaoğlan et al., 2013)

Gene duplicated in

Dp(3;2)E(spl)δ-8Δα46

(Chanet et al., 2009)

Dp(3;2)E(spl)δ-8

(Chanet et al., 2009)

Dp(3;2)E(spl)-m3^null,mδ^null

(Bivik et al., 2016)

Dp(3;2)E(spl)-m3^null

(Bivik et al., 2016)

Gene not duplicated in

Dp(3;2)E(spl)-m3^null,mβ^null

(Bivik et al., 2016)

Inferred from location ( 6 )

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

lethal - all die before end of pupal stage, with Scer\GAL4^h-H10

E(spl)mβ-HLH^UAS.cdCa

viable

Sterility

Allele

fertile

E(spl)mβ-HLH^d06732

Other Phenotypes

Allele

some die during pupal stage, with Scer\GAL4^h-H10

E(spl)mβ-HLH^UAS.cdCa

visible, with Scer\GAL4^32B

E(spl)mβ-HLH^UAS.cdCa

visible, with Scer\GAL4^455.2

E(spl)mβ-HLH^UAS.cdCa

visible, with Scer\GAL4^A9

E(spl)mβ-HLH^UAS.cdCa

visible, with Scer\GAL4^ap-md544

E(spl)mβ-HLH^UAS.cdCa

visible, with Scer\GAL4^Bx-MS1096

visible, with Scer\GAL4^h-1J3

E(spl)mβ-HLH^UAS.cdCa

visible, with Scer\GAL4^ptc-559.1

visible | adult stage, with Scer\GAL4^nub.PU

E(spl)mβ-HLH^{UAS.ORF.GW.Tag:HA}

visible | adult stage | dominant

E(spl)mβ-HLH^12-11

Phenotype manifest in

Allele

anterior crossvein, with Scer\GAL4^ptc-559.1

E(spl)mβ-HLH^UAS.cdCa

macrochaeta, with Scer\GAL4^Bx-MS1096

E(spl)mβ-HLH^UAS.cdCa

macrochaeta | ectopic, with Scer\GAL4^ptc-559.1

E(spl)mβ-HLH^VP16.ACT.UAS

microchaeta, with Scer\GAL4^Bx-MS1096

E(spl)mβ-HLH^UAS.cdCa

scutellar bristle, with Scer\GAL4^455.2

E(spl)mβ-HLH^UAS.cdCa

scutellar bristle, with Scer\GAL4^ptc-559.1

E(spl)mβ-HLH^UAS.cdCa

scutellar bristle | increased number

E(spl)mβ-HLH^12-11

scutum & macrochaeta, with Scer\GAL4^ap-md544

E(spl)mβ-HLH^UAS.cdCa

scutum & macrochaeta, with Scer\GAL4^h-1J3

E(spl)mβ-HLH^UAS.cdCa

scutum & macrochaeta, with Scer\GAL4^ptc-559.1

E(spl)mβ-HLH^VP16.ACT.UAS

scutum & microchaeta, with Scer\GAL4^32B

E(spl)mβ-HLH^UAS.cdCa

scutum & microchaeta, with Scer\GAL4^ap-md544

E(spl)mβ-HLH^UAS.cdCa

wing, with Scer\GAL4^Bx-MS1096

E(spl)mβ-HLH^{UAS.ORF.GW.Tag:HA}

wing & macrochaeta, with Scer\GAL4^ptc-559.1

E(spl)mβ-HLH^VP16.ACT.UAS

wing margin bristle, with Scer\GAL4^32B

E(spl)mβ-HLH^UAS.cdCa

wing vein, with Scer\GAL4^32B

E(spl)mβ-HLH^UAS.cdCa

wing vein, with Scer\GAL4^A9

E(spl)mβ-HLH^UAS.cdCa

wing vein, with Scer\GAL4^Bx-MS1096

E(spl)mβ-HLH^UAS.cdCa

wing vein | absent, with Scer\GAL4^nub.PU

E(spl)mβ-HLH^{UAS.ORF.GW.Tag:HA}

wing vein L5, with Scer\GAL4^32B

E(spl)mβ-HLH^UAS.cdCa

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) (18)

Hsap\HES2

6 of 14

Yes

Hsap\HES1

5 of 14

Hsap\HES4

5 of 14

Hsap\BHLHE40

4 of 14

Yes

Hsap\BHLHE41

4 of 14

Yes

Hsap\HES3

4 of 14

Yes

4 of 14

3 of 14

3 of 14

3 of 14

3 of 14

3 of 14

3 of 14

1 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Model Organism Orthologs (via DIOPT v9.1)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Rattus norvegicus (Norway rat) (15)

Rnor\Hes2

6 of 14

Yes

Rnor\Hes1

5 of 14

Rnor\Hes6

5 of 14

Rnor\Bhlhe40

4 of 14

Yes

Rnor\Hes3

4 of 14

Yes

Rnor\Bhlhe41

3 of 14

Yes

3 of 14

3 of 14

3 of 14

3 of 14

2 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Mus musculus (laboratory mouse) (16)

Mmus\Hes2

7 of 14

Yes

Mmus\Hes1

5 of 14

Mmus\Bhlhe40

4 of 14

Yes

Mmus\Bhlhe41

4 of 14

Yes

Mmus\Hes3

4 of 14

Yes

Mmus\Helt

3 of 14

Mmus\Hes5

3 of 14

Yes

3 of 14

3 of 14

3 of 14

3 of 14

3 of 14

1 of 14

1 of 14

1 of 14

1 of 14

Xenopus tropicalis (Western clawed frog) (30)

Xtro\hes2

4 of 13

Yes

Xtro\hes1

3 of 13

Xtro\hes3

3 of 13

Yes

Xtro\hes4

3 of 13

Xtro\hes6.1

3 of 13

Xtro\bhlhe40

2 of 13

Yes

2 of 13

2 of 13

2 of 13

2 of 13

2 of 13

Yes

Xtro\LOC116412194

2 of 13

Yes

Xtro\ada.2

1 of 13

Yes

Xtro\bhlhe41

1 of 13

Yes

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

Yes

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

1 of 13

Yes

Danio rerio (Zebrafish) (31)

Drer\her8a

7 of 14

Yes

6 of 14

5 of 14

5 of 14

5 of 14

5 of 14

Yes

Drer\hes6

5 of 14

Drer\bhlhe40

4 of 14

Yes

Drer\bhlhe41

4 of 14

Yes

Drer\her3

4 of 14

Yes

Drer\hes2.1

4 of 14

Yes

Drer\helt

3 of 14

Drer\her1

3 of 14

Drer\her5

3 of 14

Yes

3 of 14

3 of 14

3 of 14

3 of 14

3 of 14

3 of 14

3 of 14

2 of 14

2 of 14

2 of 14

2 of 14

2 of 14

2 of 14

Yes

1 of 14

1 of 14

1 of 14

1 of 14

Caenorhabditis elegans (Nematode, roundworm) (2)

Cele\lin-22

4 of 14

Yes

Cele\ref-1

1 of 14

Yes

Anopheles gambiae (African malaria mosquito) (7)

Agam\AgaP_AGAP012342

10 of 12

Yes

3 of 12

3 of 12

2 of 12

2 of 12

1 of 12

1 of 12

Arabidopsis thaliana (thale-cress) (10)

Atha\ALC

1 of 13

Yes

Atha\AT1G68810

1 of 13

Yes

Atha\AT2G40200

1 of 13

Yes

Atha\AT3G56770

1 of 13

Yes

Atha\AT4G28800

1 of 13

Yes

Atha\AT4G38070

1 of 13

Yes

Atha\AT5G62610

1 of 13

Yes

Atha\BHLH32

1 of 13

Yes

Atha\PIF3

1 of 13

Yes

Atha\PIL1

1 of 13

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)mβ-HLH. 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) (13)

11 of 13

9 of 13

9 of 13

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

Hey

4 of 13

Sidpn

4 of 13

cyc

1 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?

HES2; hes family bHLH transcription factor 2

6 of 14

609970

HES1; hes family bHLH transcription factor 1

5 of 14

139605

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

SHORT SLEEP, FAMILIAL NATURAL, 1; FNSS1

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

SPONDYLOCOSTAL DYSOSTOSIS 4, AUTOSOMAL RECESSIVE; SCDO4

spondylocostal dysostosis 4

3 of 14

602953

3 of 14

604674

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

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)mβ-HLH

two hybrid

(Alifragis et al., 1997)

E(spl)mβ-HLH - E(spl)m3-HLH

two hybrid

(Alifragis et al., 1997)

E(spl)mβ-HLH - E(spl)m5-HLH

two hybrid

(Alifragis et al., 1997)

E(spl)mβ-HLH - E(spl)m7-HLH

two hybrid

(Alifragis et al., 1997)

E(spl)mβ-HLH - E(spl)m8-HLH

two hybrid

(Alifragis et al., 1997)

E(spl)mβ-HLH - E(spl)mγ-HLH

two hybrid

(Alifragis et al., 1997)

E(spl)mβ-HLH - E(spl)mδ-HLH

two hybrid

(Alifragis et al., 1997)

E(spl)mβ-HLH - Hr78

two hybrid array

(Shokri et al., 2019)

E(spl)mβ-HLH - ac

two hybrid

(Alifragis et al., 1997)

E(spl)mβ-HLH - ase

two hybrid

(Alifragis et al., 1997)

E(spl)mβ-HLH - ato

two hybrid

(Alifragis et al., 1997)

E(spl)mβ-HLH - da

one hybrid, two hybrid

(Zarifi et al., 2012, Alifragis et al., 1997)

E(spl)mβ-HLH - dgrn

pull down, autoradiography

(Barry et al., 2011)

E(spl)mβ-HLH - gro

two hybrid, pull down, autoradiography, inferred by curator

(Jennings et al., 2006, Poortinga et al., 1998, Alifragis et al., 1997)

E(spl)mβ-HLH - sc

two hybrid

(Poortinga et al., 1998, Alifragis et al., 1997)

RNA-protein

Physical Interaction

Assay

References

E(spl)mβ-HLH - lncRNA:SMRG

anti bait coimmunoprecipitation, quantitative reverse transcription pcr

(Xu et al., 2019)

Summary of Genetic Interactions

Interaction Browsers

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

Please look at the allele data for full details of the genetic interactions

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

E(spl)mβ-HLH

enhanceable

emc

(Baonza et al., 2000)

E(spl)mβ-HLH

suppressible

(Xu et al., 2019)

E(spl)mβ-HLH

enhanceable

(Xu et al., 2019)

E(spl)mβ-HLH

enhanceable

Su(dx)

(Fostier et al., 1998)

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

dsh

suppressible

E(spl)mβ-HLH

(Cooper and Bray, 1999)

gro

enhanceable

E(spl)mβ-HLH

(Hasson et al., 2005)

suppressible

E(spl)mβ-HLH

(Ligoxygakis et al., 1999)

enhanceable

E(spl)mβ-HLH

(Ligoxygakis et al., 1999)

nmo

suppressible

E(spl)mβ-HLH

(Verheyen et al., 2001)

suppressible

(de Celis, 1997)

suppressible

(Xie et al., 2012)

External Data

Subunit Structure (UniProtKB)

Transcription repression requires formation of a complex with a corepressor protein (Groucho).

(UniProt, Q01069 )

Linkouts

BioGRID - A database of protein and genetic interactions.

68052

DroID - A comprehensive database of gene and protein interactions.

FBgn0002733

MIST (genetic) - An integrated Molecular Interaction Database

43152

MIST (protein-protein) - An integrated Molecular Interaction Database

43152

Pathways

Signaling Pathways (FlyBase)

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

96F9-96F9

Sequence location

3R:26,005,046..26,006,023 [-]

FlyBase Computed Cytological Location

Cytogenetic map

Evidence for location

96F9-96F9

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

(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)

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

Bloomington

26675

y¹ w^*; P{UAS-E(spl)mβ}48.1

65294

y¹ w^*; P{E(spl)mβ-HLH-GFP.FPTB}attP40

43620

y¹ w^*; Mi{MIC}E(spl)mβ-HLH^MI07238

26202

y¹ v¹; P{TRiP.JF02100}attP2/TM3, Sb¹

50674

y¹ sc^* v¹ sev²¹; P{TRiP.HMC03075}attP2

61162

w^*; E(spl)mβ-HLH^E47K/TM3, P{GAL4-twi.G}2.3, P{UAS-2xEGFP}AH2.3, Sb¹ Ser¹

61163

w^*; E(spl)mβ-HLH^H105Q/TM3, P{GAL4-twi.G}2.3, P{UAS-2xEGFP}AH2.3, Sb¹ Ser¹

FlyORF

F001794

M{UAS-E(spl)mβ-HLH.ORF.3xHA.GW}ZH-86Fb

NIG-Fly

14548R-2

P{NIG.14548R}2

HMC03075

y¹ sc^* v¹ sev²¹; P{TRiP.HMC03075}attP2

VDRC

v341193

P{hsFLP}1, y¹ w¹¹¹⁸; P{HD_CFD00220}attP40/CyO-GFP

Genomic Clones (14)

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

cDNA Clones (12)

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

GH01842

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.

FBgn0002733

cDNA Clones, End Sequenced (ESTs)

BDGP DGC clones

Other clones

RNAi and Array Information

Linkouts

DRSC - Results frm RNAi screens

FBgn0002733

Antibody Information

Laboratory Generated Antibodies

polyclonal

(Xu et al., 2019)

Commercially Available Antibodies

Cell Line Information

Publicly Available Cell Lines

Other Stable Cell Lines

New stable cell line derived from Kc167 : A stable Kc167 cell line was created to be a "Notch reporter". It contains 24 MS2 stem loops and the coding sequence of LacZ in the endogenous N-regulated E(spl)mbeta-HLH gene in the context of a stable cell line expressing MCP-GFP (MCP-GFP is a MS2-binding protein).
(Boukhatmi et al., 2020)

Other Comments

Gene expression is increased in response to the presence of two copies of Scer\GAL4^hs.PB.

(Liu and Lehmann, 2008)

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)

Study of expression and function of different components of the N pathway in both the wing disc and pupal wings proposes that the establishment of vein thickness utilises a combination of mechanisms. A mechanisms includes repression of rho transcription by HLHmβ and maintenance of Dl expression by rho/Egfr activity.

(de Celis et al., 1997)

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. 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.

(Heitzler et al., 1996)

The expression pattern of proneural genes of the AS-C and neurogenic genes of the E(spl)-C are examined in the procephlon and a map of the cells is constructed.

(Younossi-Hartenstein 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, HLHmA and HLHmB and the last includes HLHmC.

(Delidakis and Artavanis-Tsakonas, 1992)

Molecular analysis established identity of HLHmβ, HLHmγ and HLHmδ with HLHmA, HLHmB and HLHmC of Delidakis et al., respectively. 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)

One of the Enhancer-of-split complex.

Relationship to Other Genes

Source for database merge of

Additional comments

Nomenclature History

Source for database identify of

Source for identity of: E(spl)mβ-HLH HLHmβ

(Artavanis-Tsakonas et al., 2012.8.8)

Nomenclature comments

Etymology

Synonyms and Secondary IDs (38)

Reported As

Symbol Synonym

CG14548

(Widmer et al., 2018, Ellis and Carney, 2011, Ni et al., 2010.12.1, Krejcí et al., 2009, Perkins et al., 2009.3.31, Bhutkar et al., 2008, Stevens et al., 2008, Stevens et al., 2008, Schlatter and Maier, 2005)

Dm-mA

(Trott et al., 2001)

E(Spl) HLH-Mbeta

(Knust, 1992.6.22)

E(Spl)mβ

(Wang et al., 2024, Shyu et al., 2009, Sun et al., 2008)

E(spl)

(de Celis, 1997)

E(spl) mbeta

(Johannes et al., 1999)

E(spl)-Mβ

(Jennings et al., 1999)

E(spl)-mβ

(Bahrampour and Thor, 2020, Gomez-Lamarca et al., 2018, Yang and Deng, 2018, Shirai et al., 2007, Dominguez et al., 2004)

E(spl)-mβ-HLH

(DeHaro-Arbona et al., 2024)

E(spl)Mβ

(Smith-Bolton et al., 2009, Jennings et al., 1999)

E(spl)mA

(Ledent and Vervoort, 2001)

E(spl)mb

(Glavic et al., 2011)

E(spl)mbeta

(Tian et al., 2023, Lu and Li, 2015, Li and White, 2003, Campuzano, 2001, Nellesen, 1998.12.18)

E(spl)mbeta-HLH

(Collins et al., 2024, Iyer et al., 2013)

E(spl)mβ

(Voutyraki et al., 2022, Salazar et al., 2020, Gahr et al., 2019, Lo et al., 2019, Xu et al., 2019, Widmer et al., 2018, Wissel et al., 2018, Li et al., 2017, Prince and Rand, 2017, Shukla et al., 2017, Bonfini et al., 2015, Guarner et al., 2014, Babaoğlan et al., 2013, Díaz-García and Baonza, 2013, Yu et al., 2013, Capilla et al., 2012, Engel et al., 2012, Heck et al., 2012, Xie et al., 2012, Zacharioudaki et al., 2012, Barry et al., 2011, Duan et al., 2011, Pi et al., 2011, San-Juán and Baonza, 2011, Tong et al., 2011, Beam and Moberg, 2010, Rendina et al., 2010, Robinson et al., 2010, Roignant et al., 2010, Vaccari et al., 2010, Vachias et al., 2010, Krejcí et al., 2009, Bray et al., 2008, del Alamo and Mlodzik, 2008, Maeda et al., 2008, Parks et al., 2008, Song et al., 2007, Pereira et al., 2006, Lai et al., 2005, Sotillos and De Celis, 2005, Vaccari and Bilder, 2005, de Celis, 2003, de Celis Ibeas and Bray, 2003, Okajima and Irvine, 2003, Furriols and Bray, 2001, Verheyen et al., 2001, Baonza et al., 2000, de Celis and Barrio, 2000, de Celis and Bray, 2000, Cooper and Bray, 1999, Ligoxygakis et al., 1999, de Celis, 1998, de Celis et al., 1998, Lai et al., 1998, de Celis et al., 1997, Tyler et al., 1997)

E(spl)mβ-HLH

(Zhao et al., 2025, Li et al., 2024, Meyer et al., 2024, Josserand et al., 2023, Jia et al., 2022, Ferguson et al., 2021, Slaidina et al., 2021, Cho et al., 2020, Hung et al., 2020, Shokri et al., 2019, Schertel et al., 2015, Wurmbach and Preiss, 2014)

E(spl)β

(Bray et al., 1998)

HLH-mβ

(Campos-Ortega, 1993)

HLHMβ

(Schaaf et al., 2013)

HLHm β

(Kearney et al., 2004)

HLHmA

HLHmbeta

(Reim et al., 2014, Schaaf et al., 2013, Southall et al., 2013, Terriente-Felix et al., 2013, Japanese National Institute of Genetics, 2012.5.21, Johnson et al., 2011, Toku et al., 2011, Blanco et al., 2010, Krejcí et al., 2009, Kadener et al., 2007, Giot et al., 2003)

HLHmβ

(Zhao et al., 2023, Miller and Posakony, 2020, Housden et al., 2014, Reim et al., 2014, Moshkin et al., 2013, Ellis and Carney, 2011, Guest et al., 2011, Duncan and Dearden, 2010, Schaaf et al., 2009, Bhutkar et al., 2008, Liu and Lehmann, 2008, Maeder et al., 2007, Zeitlinger et al., 2007)

Mβ

(Delwig and Rand, 2008, Nagel et al., 1999)

bHLHb34

(Stevens et al., 2008)

m beta

(Singh et al., 2025)

m-beta

(Karaiskos et al., 2017)

m-β

(Flaherty et al., 2009)

(Delidakis and Artavanis-Tsakonas, 1992)

(Kux et al., 2013)

mbeta

(Eastman et al., 2007, Eastman and Eby, 2003)

mβ

(Couturier et al., 2019, Guo et al., 2019, Houtz et al., 2019, Singh et al., 2019, Bivik et al., 2016, Horvath et al., 2016, Kux et al., 2013, Moshkin et al., 2013, San Juan et al., 2012, Zarifi et al., 2012, Bardin et al., 2010, Duncan and Dearden, 2010, Vaccari et al., 2010, Chanet et al., 2009, Classen et al., 2009, Maeder et al., 2009, Wang and Huang, 2009, Rand et al., 2008, Goodfellow et al., 2007, Krejci and Bray, 2007, Giagtzoglou et al., 2005, Kan and Kessler, 2005, Macdonald and Long, 2005, Macdonald et al., 2005, Schlatter and Maier, 2005, Nagel et al., 2004, Kumar and Moses, 2001, Kumar and Moses, 2001, Kumar and Moses, 2000, Lai et al., 2000, Nellesen et al., 1999, Wech et al., 1999, Wurmbach et al., 1999, Ligoxygakis et al., 1998, de Celis et al., 1997, 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, Knust et al., 1991)

Name Synonyms

E(spl) region transcript mβ

(Krejcí et al., 2009, Zhou et al., 2008)

Enhancer of split m-β

(Flaherty et al., 2009, Luque and Milan, 2007)

Enhancer of split mβ

(Roignant et al., 2010, Bray et al., 2008, Sotillos and De Celis, 2005)

Enhancer of split mβ, helix-loop-helix

Enhancer of split region transcript HLHmA

split locus enhancer protein mA

(Delidakis, 1992.9.29)

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 ( 73 )

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.

43152

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.

Q01069

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

Q01069

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.

Q01069

BDGP expression data - Patterns of gene expression in Drosophila embryogenesis

FBgn0002733

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

43152/tissue=All

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

FBgn0002733

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

FBgn0002733

FlyMine - An integrated database for Drosophila genomics

FBgn0002733

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

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

dme:Dmel_CG14548

MARRVEL_MODEL - MARRVEL (model organism gene)

43152

Linkouts

BioGRID - A database of protein and genetic interactions.

68052

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

FBgn0002733

DroID - A comprehensive database of gene and protein interactions.

FBgn0002733

DRSC - Results frm RNAi screens

FBgn0002733

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

E(spl)mbeta-HLH_1

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0002733

FlyCyc Genes - Genes from a BioCyc PGDB for Dmel

FBGN0002733

Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns

CG14548

Flygut - An atlas of the Drosophila adult midgut

FBgn0002733

iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)

MIST (genetic) - An integrated Molecular Interaction Database

43152

MIST (protein-protein) - An integrated Molecular Interaction Database

43152

References (248)

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

-0.63

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