GROU_DROME
ID GROU_DROME Reviewed; 730 AA.
AC P16371; A4V3F6; Q0KI08; Q7KRZ4; Q9V3F7;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Protein groucho;
DE AltName: Full=Enhancer of split m9/10 protein;
DE Short=E(spl)m9/10;
GN Name=gro; Synonyms=E(spl)m9/m10; ORFNames=CG8384;
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 [MRNA] (ISOFORM A).
RX PubMed=3142687; DOI=10.1016/0092-8674(88)90134-1;
RA Hartley D., Preiss A., Artavanis-Tsakonas S.;
RT "A deduced gene product from the Drosophila neurogenic locus, enhancer of
RT split, shows homology to mammalian G-protein beta subunit.";
RL Cell 55:785-795(1988).
RN [2]
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 [3]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA Harvey D.A.;
RT "A Drosophila complementary DNA resource.";
RL Science 287:2222-2224(2000).
RN [5]
RP FUNCTION, BINDING TO HAIRY-RELATED PROTEINS, AND DEVELOPMENTAL STAGE.
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205; SER-207; SER-218;
RP SER-242; SER-258; SER-267; THR-326 AND THR-328, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [7]
RP UBIQUITINATION BY XIAP/BIRC4.
RX PubMed=22304967; DOI=10.1016/j.molcel.2011.12.032;
RA Hanson A.J., Wallace H.A., Freeman T.J., Beauchamp R.D., Lee L.A., Lee E.;
RT "XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling.";
RL Mol. Cell 45:619-628(2012).
CC -!- FUNCTION: Transcriptional corepressor that regulates transcription when
CC recruited to specific target DNA by hairy-related bHLH proteins.
CC Maternally required for neurogenesis; in the segregation of the
CC neuroectoderm. Directly or indirectly interacts with Notch and Delta.
CC {ECO:0000269|PubMed:8001118}.
CC -!- SUBUNIT: Forms a complex with the hairy/Enhancer of split/deadpan
CC family of basic helix-loop-helix proteins in order to repress
CC transcription. Its activity in regulating transcription depends on
CC other proteins as it lacks a DNA-binding motif.
CC -!- INTERACTION:
CC P16371; Q01068: E(spl)m3-HLH; NbExp=4; IntAct=EBI-153866, EBI-121622;
CC P16371; P13096: E(spl)m5-HLH; NbExp=3; IntAct=EBI-153866, EBI-104760;
CC P16371; P13098: E(spl)m8-HLH; NbExp=4; IntAct=EBI-153866, EBI-185388;
CC P16371; Q01071: E(spl)mdelta-HLH; NbExp=4; IntAct=EBI-153866, EBI-118907;
CC P16371; P14003: h; NbExp=6; IntAct=EBI-153866, EBI-123011;
CC P16371; P10734: kni; NbExp=5; IntAct=EBI-153866, EBI-170297;
CC P16371; Q9W4S7: Myc; NbExp=3; IntAct=EBI-153866, EBI-120162;
CC P16371; P91943: pan; NbExp=2; IntAct=EBI-153866, EBI-147301;
CC P16371; Q9GRA9: sbb; NbExp=2; IntAct=EBI-153866, EBI-7461944;
CC P16371; O97102: smt3; NbExp=2; IntAct=EBI-153866, EBI-114439;
CC P16371; Q01196-1: RUNX1; Xeno; NbExp=4; IntAct=EBI-153866, EBI-925940;
CC P16371; Q62233: Six3; Xeno; NbExp=2; IntAct=EBI-153866, EBI-2297327;
CC P16371-2; P14003: h; NbExp=2; IntAct=EBI-15661898, EBI-123011;
CC P16371-2; Q9W4S7: Myc; NbExp=3; IntAct=EBI-15661898, EBI-120162;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=E;
CC IsoId=P16371-1; Sequence=Displayed;
CC Name=A; Synonyms=B;
CC IsoId=P16371-2; Sequence=VSP_022308;
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:8001118}.
CC -!- PTM: Ubiquitinated by XIAP/BIRC4. {ECO:0000269|PubMed:22304967}.
CC -!- SIMILARITY: Belongs to the WD repeat Groucho/TLE family. {ECO:0000305}.
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DR EMBL; M20571; AAA28512.1; -; mRNA.
DR EMBL; AE014297; AAF56557.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN14068.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN14069.1; -; Genomic_DNA.
DR EMBL; AE014297; AAS65218.1; -; Genomic_DNA.
DR EMBL; AF145695; AAD38670.1; -; mRNA.
DR PIR; A30047; A30047.
DR RefSeq; NP_001189293.1; NM_001202364.1. [P16371-2]
DR RefSeq; NP_524514.2; NM_079790.5. [P16371-2]
DR RefSeq; NP_733133.1; NM_170254.3. [P16371-2]
DR RefSeq; NP_733134.1; NM_170255.4. [P16371-2]
DR RefSeq; NP_733135.1; NM_170256.2. [P16371-2]
DR RefSeq; NP_996298.1; NM_206575.3. [P16371-1]
DR AlphaFoldDB; P16371; -.
DR SMR; P16371; -.
DR BioGRID; 68062; 88.
DR DIP; DIP-40N; -.
DR ELM; P16371; -.
DR IntAct; P16371; 39.
DR MINT; P16371; -.
DR STRING; 7227.FBpp0089115; -.
DR iPTMnet; P16371; -.
DR PaxDb; P16371; -.
DR EnsemblMetazoa; FBtr0084962; FBpp0084336; FBgn0001139. [P16371-2]
DR EnsemblMetazoa; FBtr0084963; FBpp0084337; FBgn0001139. [P16371-2]
DR EnsemblMetazoa; FBtr0084964; FBpp0084338; FBgn0001139. [P16371-2]
DR EnsemblMetazoa; FBtr0084965; FBpp0084339; FBgn0001139. [P16371-2]
DR EnsemblMetazoa; FBtr0084966; FBpp0089115; FBgn0001139. [P16371-1]
DR EnsemblMetazoa; FBtr0302951; FBpp0292077; FBgn0001139. [P16371-2]
DR GeneID; 43162; -.
DR KEGG; dme:Dmel_CG8384; -.
DR UCSC; CG8384-RA; d. melanogaster.
DR CTD; 43162; -.
DR FlyBase; FBgn0001139; gro.
DR VEuPathDB; VectorBase:FBgn0001139; -.
DR eggNOG; KOG0639; Eukaryota.
DR GeneTree; ENSGT01030000234519; -.
DR InParanoid; P16371; -.
DR PhylomeDB; P16371; -.
DR Reactome; R-DME-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-DME-209421; Transcription activation by ARM.
DR Reactome; R-DME-209441; WG ligand not bound to FZ receptors.
DR Reactome; R-DME-3769402; Deactivation of the beta-catenin transactivating complex.
DR Reactome; R-DME-4641265; Repression of WNT target genes.
DR SignaLink; P16371; -.
DR BioGRID-ORCS; 43162; 1 hit in 3 CRISPR screens.
DR ChiTaRS; gro; fly.
DR GenomeRNAi; 43162; -.
DR PRO; PR:P16371; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0001139; Expressed in brain and 32 other tissues.
DR ExpressionAtlas; P16371; baseline and differential.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IPI:FlyBase.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0071906; F:CRD domain binding; IPI:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IGI:FlyBase.
DR GO; GO:0071837; F:HMG box domain binding; IPI:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0008134; F:transcription factor binding; IMP:FlyBase.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IMP:FlyBase.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IEP:FlyBase.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0045751; P:negative regulation of Toll signaling pathway; IGI:FlyBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:FlyBase.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IMP:FlyBase.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:FlyBase.
DR GO; GO:0007541; P:sex determination, primary response to X:A ratio; TAS:FlyBase.
DR GO; GO:0008293; P:torso signaling pathway; IMP:FlyBase.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR005617; Groucho/TLE_N.
DR InterPro; IPR009146; Groucho_enhance.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR10814; PTHR10814; 2.
DR Pfam; PF03920; TLE_N; 1.
DR Pfam; PF00400; WD40; 3.
DR PRINTS; PR01850; GROUCHOFAMLY.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 3.
DR PROSITE; PS50294; WD_REPEATS_REGION; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Differentiation; Neurogenesis;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation; WD repeat;
KW Wnt signaling pathway.
FT CHAIN 1..730
FT /note="Protein groucho"
FT /id="PRO_0000051010"
FT REPEAT 442..480
FT /note="WD 1"
FT REPEAT 488..527
FT /note="WD 2"
FT REPEAT 532..571
FT /note="WD 3"
FT REPEAT 574..613
FT /note="WD 4"
FT REPEAT 615..654
FT /note="WD 5"
FT REPEAT 656..695
FT /note="WD 6"
FT REPEAT 697..730
FT /note="WD 7"
FT REGION 144..411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 206..267
FT /note="CCN domain"
FT REGION 262..425
FT /note="Binding to basic helix-loop-helix domain"
FT MOTIF 227..230
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 204..250
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 258..280
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 281..308
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 341..384
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 207
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 218
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 242
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000255"
FT MOD_RES 258
FT /note="Phosphoserine; by CDC2"
FT /evidence="ECO:0000255"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 326
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 328
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 127..137
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:10731138,
FT ECO:0000303|PubMed:3142687"
FT /id="VSP_022308"
FT CONFLICT 41
FT /note="Q -> H (in Ref. 1; AAA28512)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 730 AA; 80231 MW; 9DA08E1ED343B2F5 CRC64;
MYPSPVRHPA AGGPPPQGPI KFTIADTLER IKEEFNFLQA QYHSIKLECE KLSNEKTEMQ
RHYVMYYEMS YGLNVEMHKQ TEIAKRLNTL INQLLPFLQA DHQQQVLQAV ERAKQVTMQE
LNLIIGHQQQ HGIQQLLQQI HAQQVPGGPP QPMGALNPFG ALGATMGLPH GPQGLLNKPP
EHHRPDIKPT GLEGPAAAEE RLRNSVSPAD REKYRTRSPL DIENDSKRRK DEKLQEDEGE
KSDQDLVVDV ANEMESHSPR PNGEHVSMEV RDRESLNGER LEKPSSSGIK QERPPSRSGS
SSSRSTPSLK TKDMEKPGTP GAKARTPTPN AAAPAPGVNP KQMMPQGPPP AGYPGAPYQR
PADPYQRPPS DPAYGRPPPM PYDPHAHVRT NGIPHPSALT GGKPAYSFHM NGEGSLQPVP
FPPDALVGVG IPRHARQINT LSHGEVVCAV TISNPTKYVY TGGKGCVKVW DISQPGNKNP
VSQLDCLQRD NYIRSVKLLP DGRTLIVGGE ASNLSIWDLA SPTPRIKAEL TSAAPACYAL
AISPDSKVCF SCCSDGNIAV WDLHNEILVR QFQGHTDGAS CIDISPDGSR LWTGGLDNTV
RSWDLREGRQ LQQHDFSSQI FSLGYCPTGD WLAVGMENSH VEVLHASKPD KYQLHLHESC
VLSLRFAACG KWFVSTGKDN LLNAWRTPYG ASIFQSKETS SVLSCDISTD DKYIVTGSGD
KKATVYEVIY
