Q01068 (ESM3_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Enhancer of split m3 protein
Short name=E(spl)m3

Alternative name(s):
HLH-m3

Gene names

Name:	HLHm3
ORF Names:	CG8346

Organism

Drosophila melanogaster (Fruit fly)

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	224 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	Transcription repression requires formation of a complex with a corepressor protein (Groucho).
Subcellular location	Nucleus Probable.
Developmental stage	The RNA is supplied maternally, and later on, expression is ubiquitous during all stages of embryonic development.
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). Ref.7 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. Ref.7
Sequence similarities	Contains 1 basic helix-loop-helix (bHLH) domain. Contains 1 Orange domain.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis Notch signaling pathway Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Notch signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW compound eye development Traceable author statement. Source: FlyBase nervous system development Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct sequence-specific DNA binding Inferred from direct assay. Source: FlyBase sequence-specific DNA binding transcription factor activity Traceable author statement. Source: FlyBase
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
gro	P16371	4	EBI-121622,EBI-153866

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 224	224	Enhancer of split m3 protein		PRO_0000127171
Regions
	Domain	25 – 69	45	Helix-loop-helix motif
	Domain	98 – 130	33	Orange
	DNA binding	12 – 24	13	Basic motif
	Motif	221 – 224	4	WRPW motif
	Compositional bias	143 – 155	13	Poly-Gln
	Compositional bias	174 – 179	6	Poly-Ala
Natural variations
	Natural variant	83	1	V → F in strain: NVIII-m11. Ref.3
	Natural variant	143	1	Missing in strain: NVIII-1, NVIII-18, NVIII-2, NVIII-22, NVIII-24, NVIII-41, NVIII-42, NVIII-46, NVIII-5, NVIII-9, NVIII-m12, NVIII-m15, NVIII-m19 and Oregon-R.
	Natural variant	151	1	H → Q in strain: NVIII-m11. Ref.3
Experimental info
	Sequence conflict	174 – 177	4	AAAA → SRR in CAA47431. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q01068 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: E16D13530FD283C9	FASTA	224	24,983
	10 20 30 40 50 60 MVMEMSKTYQ YRKVMKPLLE RKRRARINKC LDDLKDLMVE CLQQEGEHVT RLEKADILEL 70 80 90 100 110 120 TVDHMRKLKQ RGGLSLQGVV AGVGSPPTST STAHVESFRS GYVHAADQIT QVLLQTQQTD 130 140 150 160 170 180 EIGRKIMKFL STRLIELQTQ LLQQQQQQQQ HQQQQIPQSS GRLAFPLLGG YGPAAAAAAI 190 200 210 220 SYSSFLTSKD ELIDVTSVDG NALSETASVS SQESGASEPV WRPW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Enhancer of split [E(spl)] locus of Drosophila encodes seven independent helix-loop-helix proteins." Delidakis C., Artavanis-Tsakonas S. Proc. Natl. Acad. Sci. U.S.A. 89:8731-8735(1992) [PubMed: 1528887] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Canton-S. Tissue: Embryo.
[2]	"Seven genes of the Enhancer of split complex of Drosophila melanogaster encode helix-loop-helix proteins." Knust E., Schrons H., Grawe F., Campos-Ortega J.A. Genetics 132:505-518(1992) [PubMed: 1427040] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLN-143 DEL. Strain: Oregon-R. Tissue: Embryo.
[3]	"Identifying signatures of selection at the enhancer of split neurogenic gene complex in Drosophila." Macdonald S.J., Long A.D. Mol. Biol. Evol. 22:607-619(2005) [PubMed: 15537803] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PHE-83; GLN-143 DEL AND GLN-151. Strain: NVIII-1, NVIII-18, NVIII-2, NVIII-22, NVIII-24, NVIII-28, NVIII-41, NVIII-42, NVIII-46, NVIII-5, NVIII-9, NVIII-m11, NVIII-m12, NVIII-m13, NVIII-m15 and NVIII-m19.
[4]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[5]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[6]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Embryo.
[7]	"Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins." Paroush Z., Finley R.L. Jr., Kidd T., Wainwright S.M., Ingham P.W., Brent R., Ish-Horowicz D. Cell 79:805-815(1994) [PubMed: 8001118] [Abstract] Cited for: DOMAIN WRPW MOTIF.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M96165 mRNA. Translation: AAA28908.1. X67046 mRNA. Translation: CAA47431.1. AY779906 Genomic DNA. Translation: AAV59048.1. AY779907 Genomic DNA. Translation: AAV59060.1. AY779908 Genomic DNA. Translation: AAV59072.1. AY779909 Genomic DNA. Translation: AAV59084.1. AY779910 Genomic DNA. Translation: AAV59096.1. AY779911 Genomic DNA. Translation: AAV59108.1. AY779912 Genomic DNA. Translation: AAV59120.1. AY779913 Genomic DNA. Translation: AAV59132.1. AY779914 Genomic DNA. Translation: AAV59144.1. AY779915 Genomic DNA. Translation: AAV59156.1. AY779916 Genomic DNA. Translation: AAV59168.1. AY779917 Genomic DNA. Translation: AAV59180.1. AY779918 Genomic DNA. Translation: AAV59192.1. AY779919 Genomic DNA. Translation: AAV59204.1. AY779920 Genomic DNA. Translation: AAV59216.1. AY779921 Genomic DNA. Translation: AAV59228.1. AE014297 Genomic DNA. Translation: AAF56550.1. AY094858 mRNA. Translation: AAM11211.1.
PIR	D46177.
RefSeq	NP_524509.2. NM_079785.3.
3D structure databases
ProteinModelPortal	Q01068.
SMR	Q01068. Positions 12-72.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-356N.
IntAct	Q01068. 13 interactions.
MINT	MINT-314506.
STRING	Q01068.
Proteomic databases
PRIDE	Q01068.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0084958; FBpp0084332; FBgn0002609.
GeneID	43156.
KEGG	dme:Dmel_CG8346.
Organism-specific databases
CTD	43156.
FlyBase	FBgn0002609. HLHm3.
Phylogenomic databases
eggNOG	inNOG10658.
InParanoid	Q01068.
OMA	GASEPVW.
OrthoDB	EOG47M0F3.
PhylomeDB	Q01068.
Gene expression databases
Bgee	Q01068.
GermOnline	CG8346. Drosophila melanogaster.
Family and domain databases
InterPro	IPR011598. HLH_DNA-bd. IPR003650. Orange. IPR018352. Orange_subgr. [Graphical view]
Gene3D	G3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
KO	K09090.
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. SM00511. ORANGE. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. HLH. 1 hit. PS51054. ORANGE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	832457.

Entry information

Entry name

ESM3_DROME

Accession

Primary (citable) accession number: Q01068
Secondary accession number(s): Q5S455, Q5S479, Q5S4J9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project