ESM8_DROME
ID ESM8_DROME Reviewed; 179 AA.
AC P13098; Q0IGQ3; Q2XYK0; Q5S426; Q5S462; Q5S474; Q5S4H0; Q5S4I2; Q9VBI5;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Enhancer of split m8 protein;
DE Short=E(spl)m8;
GN Name=E(spl)m8-HLH {ECO:0000312|FlyBase:FBgn0000591};
GN Synonyms=E(spl) {ECO:0000303|PubMed:2540957},
GN m8 {ECO:0000312|FlyBase:FBgn0000591};
GN ORFNames=CG8365 {ECO:0000312|FlyBase:FBgn0000591};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=2540957; DOI=10.1002/j.1460-2075.1989.tb03365.x;
RA Klaembt C., Knust E., Tietze K., Campos-Ortega J.A.;
RT "Closely related transcripts encoded by the neurogenic gene complex
RT enhancer of split of Drosophila melanogaster.";
RL EMBO J. 8:203-210(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-114; THR-133; ASN-134;
RP VAL-141 AND THR-174.
RC STRAIN=NVIII-1, NVIII-18, NVIII-2, NVIII-22, NVIII-24, NVIII-28, NVIII-41,
RC NVIII-42, NVIII-46, NVIII-5, NVIII-9, NVIII-m11, NVIII-m12, NVIII-m13,
RC NVIII-m15, and NVIII-m19;
RX PubMed=15537803; DOI=10.1093/molbev/msi046;
RA Macdonald S.J., Long A.D.;
RT "Identifying signatures of selection at the enhancer of split neurogenic
RT gene complex in Drosophila.";
RL Mol. Biol. Evol. 22:607-619(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Testis;
RA Stapleton M., Carlson J.W., Booth B., Chavez C., Frise E., George R.A.,
RA Pacleb J.M., Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 8-173.
RC STRAIN=Ral1;
RX PubMed=16120803; DOI=10.1093/molbev/msi246;
RA Comeron J.M., Guthrie T.B.;
RT "Intragenic Hill-Robertson interference influences selection intensity on
RT synonymous mutations in Drosophila.";
RL Mol. Biol. Evol. 22:2519-2530(2005).
RN [7]
RP FUNCTION, INTERACTION WITH GRO, AND DOMAIN WRPW MOTIF.
RX PubMed=8001118; DOI=10.1016/0092-8674(94)90070-1;
RA Paroush Z., Finley R.L. Jr., Kidd T., Wainwright S.M., Ingham P.W.,
RA Brent R., Ish-Horowicz D.;
RT "Groucho is required for Drosophila neurogenesis, segmentation, and sex
RT determination and interacts directly with hairy-related bHLH proteins.";
RL Cell 79:805-815(1994).
RN [8]
RP FUNCTION, SUBUNIT, INTERACTION WITH DPN, AND DEVELOPMENTAL STAGE.
RX PubMed=22357926; DOI=10.1242/dev.071779;
RA Zacharioudaki E., Magadi S.S., Delidakis C.;
RT "bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and
RT mediate Notch-induced overproliferation.";
RL Development 139:1258-1269(2012).
CC -!- FUNCTION: Participates in the control of cell fate choice by
CC uncommitted neuroectodermal cells in the embryo (PubMed:2540957).
CC Transcriptional repressor (PubMed:8001118). Binds DNA on N-box motifs:
CC 5'-CACNAG-3' (PubMed:8001118). Part of the Notch signaling pathway
CC (PubMed:22357926). {ECO:0000269|PubMed:22357926,
CC ECO:0000269|PubMed:2540957, ECO:0000269|PubMed:8001118}.
CC -!- SUBUNIT: Homodimer (PubMed:22357926). Heterodimers with dpn
CC (PubMed:22357926).Transcription repression requires formation of a
CC complex with a corepressor protein (Groucho) (PubMed:8001118).
CC {ECO:0000269|PubMed:22357926, ECO:0000269|PubMed:8001118}.
CC -!- INTERACTION:
CC P13098; P08181: CkIIalpha; NbExp=3; IntAct=EBI-185388, EBI-93115;
CC P13098; P16371: gro; NbExp=4; IntAct=EBI-185388, EBI-153866;
CC P13098; Q24142: Hr78; NbExp=3; IntAct=EBI-185388, EBI-163133;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: In larvae, detected in neuroblasts (at protein
CC level) (PubMed:22357926). Mesectodermal expression appears shortly
CC before the onset of gastrulation (PubMed:2540957). In imaginal disks,
CC expression is seen primarily within presumptive proneural clusters of
CC eye-antennal, wing and leg disks (PubMed:2540957).
CC {ECO:0000269|PubMed:22357926, ECO:0000269|PubMed:2540957}.
CC -!- DOMAIN: The orange domain and the basic helix-loop-helix motif mediate
CC repression of specific transcriptional activators, such as basic helix-
CC loop-helix protein dimers. {ECO:0000269|PubMed:8001118}.
CC -!- DOMAIN: The C-terminal WRPW motif is a transcriptional repression
CC domain necessary for the interaction with Groucho, a transcriptional
CC corepressor recruited to specific target DNA by Hairy-related proteins.
CC {ECO:0000269|PubMed:8001118}.
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DR EMBL; X16553; CAA34554.1; -; Genomic_DNA.
DR EMBL; AY779906; AAV59051.1; -; Genomic_DNA.
DR EMBL; AY779907; AAV59063.1; -; Genomic_DNA.
DR EMBL; AY779908; AAV59075.1; -; Genomic_DNA.
DR EMBL; AY779909; AAV59087.1; -; Genomic_DNA.
DR EMBL; AY779910; AAV59099.1; -; Genomic_DNA.
DR EMBL; AY779911; AAV59111.1; -; Genomic_DNA.
DR EMBL; AY779912; AAV59123.1; -; Genomic_DNA.
DR EMBL; AY779913; AAV59135.1; -; Genomic_DNA.
DR EMBL; AY779914; AAV59147.1; -; Genomic_DNA.
DR EMBL; AY779915; AAV59159.1; -; Genomic_DNA.
DR EMBL; AY779916; AAV59171.1; -; Genomic_DNA.
DR EMBL; AY779917; AAV59183.1; -; Genomic_DNA.
DR EMBL; AY779918; AAV59195.1; -; Genomic_DNA.
DR EMBL; AY779919; AAV59207.1; -; Genomic_DNA.
DR EMBL; AY779920; AAV59219.1; -; Genomic_DNA.
DR EMBL; AY779921; AAV59231.1; -; Genomic_DNA.
DR EMBL; AE014297; AAF56555.1; -; Genomic_DNA.
DR EMBL; BT028829; ABI34210.1; -; mRNA.
DR EMBL; BT028834; ABI34215.2; -; mRNA.
DR EMBL; BT028861; ABI34242.1; -; mRNA.
DR EMBL; BT028867; ABI34248.2; -; mRNA.
DR EMBL; DQ138662; ABA86268.1; -; Genomic_DNA.
DR PIR; S03627; S03627.
DR RefSeq; NP_524513.1; NM_079789.3.
DR AlphaFoldDB; P13098; -.
DR SMR; P13098; -.
DR BioGRID; 68061; 41.
DR DIP; DIP-22511N; -.
DR ELM; P13098; -.
DR IntAct; P13098; 17.
DR MINT; P13098; -.
DR STRING; 7227.FBpp0084335; -.
DR iPTMnet; P13098; -.
DR PaxDb; P13098; -.
DR EnsemblMetazoa; FBtr0084961; FBpp0084335; FBgn0000591.
DR GeneID; 43161; -.
DR KEGG; dme:Dmel_CG8365; -.
DR CTD; 43161; -.
DR FlyBase; FBgn0000591; E(spl)m8-HLH.
DR VEuPathDB; VectorBase:FBgn0000591; -.
DR eggNOG; KOG4304; Eukaryota.
DR GeneTree; ENSGT00940000167178; -.
DR HOGENOM; CLU_068550_2_2_1; -.
DR InParanoid; P13098; -.
DR OMA; YHSDCES; -.
DR OrthoDB; 1378299at2759; -.
DR PhylomeDB; P13098; -.
DR SignaLink; P13098; -.
DR BioGRID-ORCS; 43161; 0 hits in 3 CRISPR screens.
DR ChiTaRS; E(spl)mbeta-HLH; fly.
DR GenomeRNAi; 43161; -.
DR PRO; PR:P13098; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0000591; Expressed in stomodeal invagination (Drosophila) and 41 other tissues.
DR Genevisible; P13098; DM.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:FlyBase.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:FlyBase.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:FlyBase.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:FlyBase.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0048749; P:compound eye development; IMP:FlyBase.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:FlyBase.
DR GO; GO:0007498; P:mesoderm development; IMP:FlyBase.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:FlyBase.
DR GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0016360; P:sensory organ precursor cell fate determination; IMP:FlyBase.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR003650; Orange_dom.
DR Pfam; PF07527; Hairy_orange; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00511; ORANGE; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS51054; ORANGE; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; DNA-binding; Neurogenesis; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..179
FT /note="Enhancer of split m8 protein"
FT /id="PRO_0000127175"
FT DOMAIN 10..65
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 83..116
FT /note="Orange"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT REGION 146..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 176..179
FT /note="WRPW motif"
FT COMPBIAS 146..166
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 114
FT /note="T -> I (in strain: NVIII-2, NVIII-5 and NVIII-m15)"
FT /evidence="ECO:0000269|PubMed:15537803"
FT VARIANT 133
FT /note="A -> T (in strain: NVIII-m11 and NVIII-m19)"
FT /evidence="ECO:0000269|PubMed:15537803"
FT VARIANT 134
FT /note="D -> N (in strain: NVIII-m19)"
FT /evidence="ECO:0000269|PubMed:15537803"
FT VARIANT 141
FT /note="D -> V (in strain: NVIII-m19)"
FT /evidence="ECO:0000269|PubMed:15537803"
FT VARIANT 174
FT /note="P -> T (in strain: NVIII-m12)"
FT /evidence="ECO:0000269|PubMed:15537803"
FT CONFLICT 165..167
FT /note="APS -> PPT (in Ref. 1; CAA34554)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 179 AA; 20303 MW; 017B139DE0C328B4 CRC64;
MEYTTKTQIY QKVKKPMLER QRRARMNKCL DNLKTLVAEL RGDDGILRMD KAEMLESAVI
FMRQQKTPKK VAQEEQSLPL DSFKNGYMNA VNEVSRVMAS TPGMSVDLGK SVMTHLGRVY
KNLQQFHEAQ SAADFIQNSM DCSSMDKAPL SPASSGYHSD CDSPAPSPQP MQQPLWRPW
