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Gene Dmel\HLHmγ

General Information
Symbol	Dmel\HLHmγ	Species	D. melanogaster
Name	E(spl) region transcript mγ	Annotation symbol	CG8333
Feature type	protein_coding_gene	FlyBase ID	FBgn0002735
Created / Updated	2003-12-01/2003-12-01
Genomic Location
Chromosome (arm)	3R	Recombination map	3-89.1
Cytogenetic map	96F9-96F9	Sequence location	3R:21,825,580..21,826,421 [+]
Map ( GBrowse )	Decorated FastA GenBankGFF Gene region Extended Gene region CDSIntronsExonsTranslationsTranscripts3' UTR5' UTR
Summary Information
Automatically generated summary See sections below for more information	The gene E(spl) region transcript mγ is referred to in FlyBase by the symbol HLHmγ (CG8333, FBgn0002735). It has the cytological map location 96F9. Its sequence location is 3R:21825580..21826421. Its molecular function is described as: transcription factor activity; DNA binding; transcription repressor activity; specific transcriptional repressor activity. It is involved in the biological processes: negative regulation of transcription from RNA polymerase II promoter; Notch signaling pathway; negative regulation of transcription; nervous system development; compound eye development. 9 alleles are reported. The phenotypes of these alleles are annotated with: scutellar bristle; wing vein; wing margin bristle; macrochaeta; microchaeta; adult thorax. It has one annotated transcript and one annotated polypeptide.
Detailed Mapping Data
FlyBase Computed Cytological Location
Cytogenetic map Evidence for location 96F9-96F9   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   (Lai, 1997.7.30)
Experimentally Determined Recombination Data
Location	3-89.1   3-89 (Lai, 1997.7.30)
Left of (cM)
Right of (cM)
Notes
Molecular Map Data
Gene Order (in direction of increasing cytology) References In direction of increasing cytology: HLHmδ+ HLHmγ- HLHmβ- mα+ m1? m2? HLHm3+ m4- HLHm5- m6+ HLHm7+ E(spl)+ gro+ (Ligoxygakis et al., 1998) Gene Order (overall orientation not stated) References Overall orientation not stated: HLHmδ+ HLHmγ+ HLHmβ- mα+ m1+ m2- HLHm3+ m4- HLHm5- m6+ HLHm7+ E(spl)+ gro+ (Lai et al., 2000)
Gene Model & Products
Please see the GBrowse view of Dmel\HLHmγ for information on other features
Comments on Gene Model
Transcript Data
Annotated Transcripts
Name FlyBase ID RefSeq ID Length (nt) Associated CDS (aa) HLHmgamma-RA FBtr0084955  NM_079780   842   205
Additional Transcript Data & Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name FlyBase ID Predicted MW (kD) Length (aa) Theoretical pI RefSeq ID GenBank protein HLHmgamma-PA   FBpp0084329   23.1   205   7.24     NP_524504   AAF56545
Additional Polypeptide Data & Comments
Reported size (kD)
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
Linkouts	PANTHER - Protein classification by function, families, and pathways • FBgn0002735
Crossreferences	InterPro domains - A database of protein families, domains, and functional sites • Basic helix-loop-helix dimerisation region bHLH (IPR001092) Orange (IPR003650) Helix-loop-helix DNA-binding (IPR011598)
Sequences Consistent with the Gene Model
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name AE003754 AAF56545   AF016543   AI124279   AJ276315 CAB77021   AY779906 AAV59046   AY779907 AAV59058   AY779908 AAV59070   AY779909 AAV59082   AY779910 AAV59094   AY779911 AAV59106   AY779912 AAV59118   AY779913 AAV59130   AY779915 AAV59154   AY779916 AAV59166   AY779917 AAV59178   AY779918 AAV59190   AY779919 AAV59202   AY779920 AAV59214   AY779921 AAV59226   BT022125   CO186485   CO315683   CO316832   CO324576   CO327760   EL879052   EL879053   EL879122   EL879123   EL879180   EL879181   M96167 AAA28910   X67049 CAA47434
UniProtKB/Swiss-Prot	Q01070
UniProtKB/TrEMBL
Maps to
Does NOT map to
Identified with	IP08862 (Hoskins et al., 2005)
Mapped Features & Mutations
Please see GBrowse or insertion reports for information on insertions of transgenic constructs and features not listed here Type Symbol & Location Additional Notes References protein binding site HLHmgamma-protein_bind-1 3R:21,824,650..21,824,662 bound_moiety=Su(H)-XP comment=Su(H)-protein-binding site mgammaS5 (complement) evidence=experimental (Eastman et al., 1997) protein binding site HLHmgamma-protein_bind-2 3R:21,824,902..21,824,910 bound_moiety=Su(H)-XP comment=Su(H)-protein-binding site mgammaS4 (complement) evidence=experimental (Bailey and Posakony, 1995, Lecourtois and Schweisguth, 1995) protein binding site HLHmgamma-protein_bind-3 3R:21,825,085..21,825,093 bound_moiety=Su(H)-XP comment=Su(H)-protein-binding site mgammaS3 evidence=experimental (Bailey and Posakony, 1995, Lecourtois and Schweisguth, 1995) protein binding site HLHmgamma-protein_bind-4 3R:21,825,279..21,825,287 bound_moiety=Su(H)-XP comment=Su(H)-protein-binding site mgammaS2 evidence=experimental (Bailey and Posakony, 1995) protein binding site HLHmgamma-protein_bind-5 3R:21,825,303..21,825,311 bound_moiety=Su(H)-XP comment=Su(H)-protein-binding site mgammaS1 (complement) evidence=experimental (Bailey and Posakony, 1995, Lecourtois and Schweisguth, 1995)
External Data
Linkouts	DEDB - Drosophila exon database: splicing graphs • 10871
Crossreferences
Expression Data
FlyBase-Curated Data
Transcript and Protein data	Please see the FlyBase Gene Expression Report for details of gene expression from the literature.
Summary of Transcript Expression
Stage Tissue/Position Reference
Marker for
Subcellular Localization
CV Term
Summary of Polypeptide Expression
Stage Tissue/Position Reference
Marker for
Subcellular Localization
CV Term
External Data & Images
Linkouts	FLIGHT - Cell culture data for RNAi and other high-throughput technologies • FBgn0002735 FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array • FBgn0002735 GEO (NCBI) - Gene expression data: microarray and other high-throughput technologies • FBgn0002735 FlyExpress - Embryonic expression images (BDGP data) • Show all FlyExpress processed images for HLHmγ Stage(s) 1-3 Stage(s) 4-6 Stage(s) 7-8 Stage(s) 9-10 Stage(s) 11-12 Stage(s) 13-16
Alleles & Phenotypes
Summary of Allele Phenotypes
Other Phenotypes Allele visible, with Scer\GAL432B HLHmγScer\UAS.cLa visible, with Scer\GAL4455.2 HLHmγScer\UAS.cLa visible, with Scer\GAL4sca-537.4 HLHmγScer\UAS.cLa visible, with Scer\GAL4h-1J3 HLHmγScer\UAS.cLa visible, with Scer\GAL4pnr-MD237 HLHmγKNEQ.Scer\UAS visible, with Scer\GAL4ap-md544 HLHmγScer\UAS.cLa Phenotype manifest in Allele macrochaeta, with Scer\GAL4pnr-MD237 HLHmγKNEQ.Scer\UAS microchaeta, with Scer\GAL4pnr-MD237 HLHmγKNEQ.Scer\UAS adult thorax, with Scer\GAL4pnr-MD237 HLHmγKNEQ.Scer\UAS dorsal row & sensory mother cell, with Scer\GAL4ap-md544 HLHmγScer\UAS.cLa scutum & microchaeta, with Scer\GAL4ap-md544 HLHmγScer\UAS.cLa scutum & macrochaeta, with Scer\GAL4ap-md544 HLHmγScer\UAS.cLa scutellar bristle, with Scer\GAL4455.2 HLHmγScer\UAS.cLa wing vein, with Scer\GAL432B HLHmγScer\UAS.cLa wing margin bristle, with Scer\GAL432B HLHmγScer\UAS.cLa scutum & microchaeta, with Scer\GAL432B HLHmγScer\UAS.cLa scutum & macrochaeta, with Scer\GAL4h-1J3 HLHmγScer\UAS.cLa macrochaeta, with Scer\GAL4sca-537.4 HLHmγScer\UAS.cLa chordotonal organ precursor cell & ventral thoracic disc, with Scer\GAL4sca-109-68 HLHmγScer\UAS.cLa
Classical Alleles ( 2 )
For All Classical Alleles Show
Allele of HLHmγ Class Mutagen Stocks Known lesion HLHmγA5891C natural population 0 -- HLHmγG6121T natural population 0 Yes
Alleles Carried on Transgenic Constructs ( 7 )
For All Alleles Carried on Transgenic Constructs Show
Allele of HLHmγ Class Mutagen Stocks Known lesion HLHmγ+t13 in vitro construct | genomic fragment 0 Yes HLHmγAct5C.PG in vitro construct | regulatory fusion 0 Yes HLHmγGD4459 in vitro construct | RNAi in vitro construct | regulatory fusion 1 Yes HLHmγKNEQ.Scer\UAS.T:Hsim\VP16 in vitro construct | regulatory fusion in vitro construct | amino acid replacement in vitro construct | coding region fusion 0 Yes HLHmγKNEQ.Scer\UAS in vitro construct | regulatory fusion in vitro construct | amino acid replacement 0 Yes HLHmγScer\UAS.T:Hsim\VP16 in vitro construct | regulatory fusion in vitro construct | coding region fusion 0 Yes HLHmγScer\UAS.cLa in vitro construct | regulatory fusion 0 Yes
Aneuploid Aberrations
Useful deficiency	Df(3R)Espl9   Df(3R)boss16
Useful duplication	Dp(3;3)Su8
Disrupted in	Df(3R)Espl4 (Heitzler et al., 1996) Df(3R)Nf1P1 (Cooper and Bray, 1999) Df(3R)P11 (Nagel et al., 2000) Df(3R)boss16 (Heitzler et al., 1996) Df(3R)grob32.2 (Ligoxygakis et al., 1998, Heitzler et al., 1996, de Celis et al., 1996, de Celis et al., 1997)
Transgenic Constructs & Insertions
Transgenic Constructs
	Type of construct Name Expression data reporter construct P{12xSu(H)bs-lacZ} No P{HLHmγ-lacZ.1.2} No P{HLHmγ-lacZ.155} No P{HLHmγ-lacZ.KXE1,2m} No P{HLHmγ-lacZ.KXS1,2m} No P{HLHmγ-lacZ.KXTCCTm} No P{HLHmγ-lacZ.KX} No P{lacZ-mγ1.1-CD2} No P{mγ0.5-lacZ} No P{mγ0.6-lacZ} No P{mγ1.1-lacZ} No UAS construct P{UAS-HLHmγ.KNEQ-VP16} NA P{UAS-HLHmγ.KNEQ} NA P{UAS-HLHmγ.L} NA P{UAS-HLHmγ.VP16} NA characterization construct P{HLHmβ,mγ,mδ+} NA
Insertions
	Type of insertions Name Expression data
Related Comments
	Please look at the allele reports for the complete phenotype data 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) 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) 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) Gel retardation experiments demonstrate the 5' regulatory region contains putative in vitro binding sites for Su(H). (Lecourtois and Schweisguth, 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) 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) 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)
Gene Ontology: Function, Process & Cellular Component ( 10 )
Molecular Function
CV term Evidence References
DNA binding inferred from sequence or structural similarity with MGD:Hes1; MGI:MGI:104853 (FlyBase, 1992-) non-traceable author statement (Swiss-Prot Project Members, 2000.10.1)
specific transcriptional repressor activity non-traceable author statement (Swiss-Prot Project Members, 2000.10.1)
transcription factor activity traceable author statement (Kumar and Moses, 2000)
transcription repressor activity inferred from sequence or structural similarity with MGD:Hes1; MGI:MGI:104853 (FlyBase, 1992-)
Biological Process
CV term Evidence References
Notch signaling pathway non-traceable author statement (Swiss-Prot Project Members, 2000.10.1)
compound eye development traceable author statement (Kumar and Moses, 2000)
negative regulation of transcription non-traceable author statement (Swiss-Prot Project Members, 2000.10.1)
negative regulation of transcription from RNA polymerase II promoter traceable author statement (Kumar and Moses, 2000) inferred from sequence or structural similarity with MGD:Hes1; MGI:MGI:104853 (FlyBase, 1992-)
nervous system development non-traceable author statement (Swiss-Prot Project Members, 2000.10.1)
Cellular Component
CV term Evidence References
nucleus inferred by curator from GO:0003677 (FlyBase, 1992-) non-traceable author statement (Swiss-Prot Project Members, 2000.10.1) inferred from electronic annotation with InterPro:IPR001092, InterPro:IPR011598 (FlyBase Curators et al., 2004-)
Sequence Ontology: Class of Gene
	protein_coding_gene   nuclear_gene
Interactions & Pathways
Summary of Genetic Interactions
Interacts with	Please look at the allele data for full details of the genetic interactions HLHmγ allele Gene References HLHmγKNEQ.Scer\UAS sc (Giagtzoglou et al., 2003) HLHmγScer\UAS.cLa sc (Giagtzoglou et al., 2003) N (Ligoxygakis et al., 1999)
External Data
Linkouts	BioGRID - Interaction data, including yeast 2-hybrid and genetic interactions • 68051 Drosophila PIMRider - The Drosophila Protein Interaction map • 522437
Orthologs
Genome-wide drosophilid orthologs	Dana\GF16796 Dere\GG11450 Dgri\GH19452 Dmoj\GI24686 Dper\GL21815 Dpse\GA20996 Dsec\GM10294 Dsim\HLHmγ Dvir\GJ23903 Dwil\GK14455 Dyak\HLHmγ
Curated drosophilid orthologs	Dhyd\HLHmγ   Dpse\GA20996   Dsim\HLHmγ   Dyak\HLHmγ
Linkouts	InParanoid orthologs - Eukaryotic orthologs • ENSGALP00000008850 Gallus gallus (Ensembl)
Functional Complementation between Species
Inter-Species Misexpression Data
Produces phenotype in
Produces NO phenotype in
Stocks & Reagents
Stocks Listed in FlyBase ( 1 )
VDRC	v10950 w1118; P{GD4459}v10950/TM3
Genomic Clones ( 2 )
	BACR22N13 BACR13F13
cDNA Clones ( 10 )
	Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
cDNA Clones, Fully Sequenced
BDGP DGC clones	IP08862
Other clones
cDNA Clones, End Sequenced (ESTs)
BDGP DGC clones
Other clones	IP09062 EK194256 IP09162 EK262155 EK020215 IP08962 AI124279 EP08001 EK266015
RNAi & Array Information
Affy Oligo
Linkouts	DRSC - RNAi screening (Harvard): high-throughput cell culture data and design • FBgn0002735 GenomeRNAi - RNAi phenotypes (Heidelberg): high-throughput cell culture data • FBgn0002735
Antibody Information
Other Information
Discoverer
Etymology
Identification
Position Effect Variegation Data
Relationship to Other Genes
Source for database identity of
Source for database merge of
Additional comments
Comments About Role
	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) N-inducible expression of HLHmδ and HLHmγ both in cultured cells and in vivo is dependent on functional Su(H) protein. (Eastman et al., 1997)
Comments About Molecular Function
	The distinct expression patterns of genes of the E(spl) complex in imaginal tissues depend to a significant degree on the capacity of their transcriptional cis-regulatory apparatus to respond selectively to direct proneural and Su(H)-mediated activation, often in a subset of the territories and cells in which proneural and Su(H) regulation is occurring. The m4 and HLHmγ enhancers are distinctly similar though the genes are expressed in dissimilar patterns in the wing disc. The HLHmγ enhancer shows a selective response to the N signalling pathway. (Nellesen et al., 1999)
Other Comments
	Direction of transcription of HLHmγ reported is at odds with that reported in Delidakis et al., PNAS 89:8731--8735. (Knust et al., 1992) 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)
External Crossreferences & Linkouts
Sequence Crossreferences
	RefSeq (Transcripts) • NM_079780 RefSeq (Proteins) • NP_524504 DDBJ / EMBL / GenBank • AE003754 AAF56545 AF016543 AI124279 AJ276315 CAB77021 AY779906 AAV59046 AY779907 AAV59058 AY779908 AAV59070 AY779909 AAV59082 AY779910 AAV59094 AY779911 AAV59106 AY779912 AAV59118 AY779913 AAV59130 AY779914 AV59142 AY779915 AAV59154 AY779916 AAV59166 AY779917 AAV59178 AY779918 AAV59190 AY779919 AAV59202 AY779920 AAV59214 AY779921 AAV59226 M96167 AAA28910 X67049 CAA47434 UniProtKB/Swiss-Prot • Q01070
Other Crossreferences
	InterPro domains - A database of protein families, domains, and functional sites • Basic helix-loop-helix dimerisation region bHLH (IPR001092) Orange (IPR003650) Helix-loop-helix DNA-binding (IPR011598)