TLE4_MOUSE
ID TLE4_MOUSE Reviewed; 773 AA.
AC Q62441; Q9JKQ9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 4.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Transducin-like enhancer protein 4;
DE AltName: Full=Grg-4;
DE AltName: Full=Groucho-related protein 4;
GN Name=Tle4; Synonyms=Grg4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, AND INTERACTION WITH PAX5.
RC TISSUE=Embryo;
RX PubMed=10811620; DOI=10.1093/emboj/19.10.2292;
RA Eberhard D., Jimenez G., Heavey B., Busslinger M.;
RT "Transcriptional repression by Pax5 (BSAP) through interaction with
RT corepressors of the Groucho family.";
RL EMBO J. 19:2292-2303(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 197-773.
RX PubMed=8892234; DOI=10.1016/0925-4773(96)00582-5;
RA Koop K.E., Macdonald L.M., Lobe C.G.;
RT "Transcripts of Grg4, a murine groucho-related gene, are detected in
RT adjacent tissues to other murine neurogenic gene homologues during
RT embryonic development.";
RL Mech. Dev. 59:73-87(1996).
RN [3]
RP SEQUENCE REVISION.
RA Lobe C.G., Koop K.E., Macdonald L.M.;
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INTERACTION WITH LEF1; TCF7; TCF7L1 AND TCF7L2.
RX PubMed=11266540; DOI=10.1093/nar/29.7.1410;
RA Brantjes H., Roose J., van De Wetering M., Clevers H.;
RT "All Tcf HMG box transcription factors interact with Groucho-related co-
RT repressors.";
RL Nucleic Acids Res. 29:1410-1419(2001).
RN [5]
RP FUNCTION, AND INTERACTION WITH SIX3 AND SIX6.
RX PubMed=12050133; DOI=10.1242/dev.129.12.2835;
RA Zhu C.C., Dyer M.A., Uchikawa M., Kondoh H., Lagutin O.V., Oliver G.;
RT "Six3-mediated auto repression and eye development requires its interaction
RT with members of the Groucho-related family of co-repressors.";
RL Development 129:2835-2849(2002).
RN [6]
RP INTERACTION WITH TLE1.
RX PubMed=16314515; DOI=10.1128/mcb.25.24.10916-10929.2005;
RA Marcal N., Patel H., Dong Z., Belanger-Jasmin S., Hoffman B.,
RA Helgason C.D., Dang J., Stifani S.;
RT "Antagonistic effects of Grg6 and Groucho/TLE on the transcription
RT repression activity of brain factor 1/FoxG1 and cortical neuron
RT differentiation.";
RL Mol. Cell. Biol. 25:10916-10929(2005).
RN [7]
RP REVIEW.
RX PubMed=18254933; DOI=10.1186/gb-2008-9-1-205;
RA Jennings B.H., Ish-Horowicz D.;
RT "The Groucho/TLE/Grg family of transcriptional co-repressors.";
RL Genome Biol. 9:R205.1-R205.7(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292; THR-318; SER-321 AND
RP THR-325, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, AND INTERACTION WITH ZNF703.
RX PubMed=21317240; DOI=10.1101/gad.1998111;
RA Slorach E.M., Chou J., Werb Z.;
RT "Zeppo1 is a novel metastasis promoter that represses E-cadherin expression
RT and regulates p120-catenin isoform expression and localization.";
RL Genes Dev. 25:471-484(2011).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=23990468; DOI=10.1074/jbc.m113.461848;
RA Kogawa M., Hisatake K., Atkins G.J., Findlay D.M., Enoki Y., Sato T.,
RA Gray P.C., Kanesaki-Yatsuka Y., Anderson P.H., Wada S., Kato N., Fukuda A.,
RA Katayama S., Tsujimoto M., Yoda T., Suda T., Okazaki Y., Matsumoto M.;
RT "The paired-box homeodomain transcription factor Pax6 binds to the upstream
RT region of the TRAP gene promoter and suppresses receptor activator of NF-
RT kappaB ligand (RANKL)-induced osteoclast differentiation.";
RL J. Biol. Chem. 288:31299-31312(2013).
CC -!- FUNCTION: Transcriptional corepressor that binds to a number of
CC transcription factors. Inhibits the transcriptional activation mediated
CC by PAX5, and by CTNNB1 and TCF family members in Wnt signaling. The
CC effects of full-length TLE family members may be modulated by
CC association with dominant-negative AES. Essential for the
CC transcriptional repressor activity of SIX3 during retina and lens
CC development and for SIX3 transcriptional auto-repression.
CC {ECO:0000269|PubMed:12050133, ECO:0000269|PubMed:21317240}.
CC -!- SUBUNIT: Homooligomer and heterooligomer with other family members.
CC Interacts with PAX5 (PubMed:10811620). Interacts with LEF1, TCF7,
CC TCF7L1 and TCF7L2 (PubMed:11266540). Interacts with ZNF703; TLE4 may
CC mediate ZNF703 transcriptional repression (PubMed:21317240). Interacts
CC with SIX3 and SIX6 (PubMed:12050133). Interacts with PAX2 (By
CC similarity). Interacts with TLE1 (PubMed:16314515).
CC {ECO:0000250|UniProtKB:Q04727, ECO:0000269|PubMed:10811620,
CC ECO:0000269|PubMed:11266540, ECO:0000269|PubMed:12050133,
CC ECO:0000269|PubMed:16314515, ECO:0000269|PubMed:21317240}.
CC -!- INTERACTION:
CC Q62441; Q62233: Six3; NbExp=2; IntAct=EBI-2297871, EBI-2297327;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in bone marrow-derived macrophages.
CC {ECO:0000269|PubMed:23990468}.
CC -!- DOMAIN: WD repeat Groucho/TLE family members are characterized by 5
CC regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a
CC central CcN domain, containing a nuclear localization signal, and a
CC serine/proline-rich SP domain. The most highly conserved are the N-
CC terminal Q domain and the C-terminal WD-repeat domain.
CC {ECO:0000305|PubMed:18254933}.
CC -!- PTM: Phosphorylated. PAX5 binding increases phosphorylation.
CC {ECO:0000269|PubMed:10811620}.
CC -!- PTM: Ubiquitinated by XIAP/BIRC4. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the WD repeat Groucho/TLE family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-8 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF43203.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF229633; AAF43203.1; ALT_INIT; mRNA.
DR EMBL; U61363; AAC97070.1; -; mRNA.
DR CCDS; CCDS50399.1; -.
DR RefSeq; NP_035730.2; NM_011600.3.
DR AlphaFoldDB; Q62441; -.
DR SMR; Q62441; -.
DR BioGRID; 204219; 9.
DR CORUM; Q62441; -.
DR IntAct; Q62441; 3.
DR STRING; 10090.ENSMUSP00000057527; -.
DR iPTMnet; Q62441; -.
DR PhosphoSitePlus; Q62441; -.
DR EPD; Q62441; -.
DR jPOST; Q62441; -.
DR MaxQB; Q62441; -.
DR PaxDb; Q62441; -.
DR PRIDE; Q62441; -.
DR ProteomicsDB; 260665; -.
DR Antibodypedia; 27418; 281 antibodies from 29 providers.
DR DNASU; 21888; -.
DR Ensembl; ENSMUST00000052011; ENSMUSP00000057527; ENSMUSG00000024642.
DR GeneID; 21888; -.
DR KEGG; mmu:21888; -.
DR UCSC; uc008gwk.2; mouse.
DR CTD; 7091; -.
DR MGI; MGI:104633; Tle4.
DR VEuPathDB; HostDB:ENSMUSG00000024642; -.
DR eggNOG; KOG0639; Eukaryota.
DR GeneTree; ENSGT01030000234519; -.
DR HOGENOM; CLU_007612_3_0_1; -.
DR InParanoid; Q62441; -.
DR PhylomeDB; Q62441; -.
DR TreeFam; TF314167; -.
DR Reactome; R-MMU-201722; Formation of the beta-catenin:TCF transactivating complex.
DR Reactome; R-MMU-3769402; Deactivation of the beta-catenin transactivating complex.
DR Reactome; R-MMU-4641265; Repression of WNT target genes.
DR BioGRID-ORCS; 21888; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Tle4; mouse.
DR PRO; PR:Q62441; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q62441; protein.
DR Bgee; ENSMUSG00000024642; Expressed in renal corpuscle and 302 other tissues.
DR ExpressionAtlas; Q62441; baseline and differential.
DR Genevisible; Q62441; MM.
DR GO; GO:1990907; C:beta-catenin-TCF complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IDA:MGI.
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; 1.
DR Pfam; PF03920; TLE_N; 1.
DR Pfam; PF00400; WD40; 2.
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 Acetylation; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation; Ubl conjugation;
KW WD repeat; Wnt signaling pathway.
FT CHAIN 1..773
FT /note="Transducin-like enhancer protein 4"
FT /id="PRO_0000051284"
FT REPEAT 485..523
FT /note="WD 1"
FT REPEAT 531..570
FT /note="WD 2"
FT REPEAT 575..614
FT /note="WD 3"
FT REPEAT 617..656
FT /note="WD 4"
FT REPEAT 658..697
FT /note="WD 5"
FT REPEAT 699..738
FT /note="WD 6"
FT REPEAT 740..773
FT /note="WD 7"
FT REGION 1..136
FT /note="Q domain"
FT /evidence="ECO:0000250|UniProtKB:Q04727"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 137..204
FT /note="GP domain"
FT /evidence="ECO:0000250|UniProtKB:Q04727"
FT REGION 140..162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 205..274
FT /note="CcN domain"
FT /evidence="ECO:0000250|UniProtKB:Q04727"
FT REGION 275..452
FT /note="SP domain"
FT /evidence="ECO:0000250|UniProtKB:Q04727"
FT COMPBIAS 182..202
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 217..256
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 293..341
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 208
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04727"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04726"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04726"
FT MOD_RES 222
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04726"
FT MOD_RES 237
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q04727"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04724"
FT MOD_RES 250
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q04727, ECO:0000255"
FT MOD_RES 265
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000255"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04727"
FT MOD_RES 273
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04726"
FT MOD_RES 281
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q04727"
FT MOD_RES 292
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 318
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04726"
FT MOD_RES 325
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 327
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q04726"
FT MOD_RES 334
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q04726"
FT MOD_RES 340
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q04726"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q04726"
FT CONFLICT 197..199
FT /note="RDR -> QTN (in Ref. 2; AAC97070)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="A -> R (in Ref. 2; AAC97070)"
FT /evidence="ECO:0000305"
FT CONFLICT 454..455
FT /note="SA -> RS (in Ref. 2; AAC97070)"
FT /evidence="ECO:0000305"
FT CONFLICT 608..609
FT /note="NQ -> KE (in Ref. 2; AAC97070)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 773 AA; 83787 MW; 5A0090789774CACC CRC64;
MIRDLSKMYP QTRHPAPHQP AQPFKFTISE SCDRIKEEFQ FLQAQYHSLK LECEKLASEK
TEMQRHYVMY YEMSYGLNIE MHKQAEIVKR LNAICAQVIP FLSQEHQQQV VQAVERAKQV
TMAELNAIIG QQLQAQHLSH GHGLPVPLTP HPSGLQPPAI PPIGSSAGLL ALSSALGGQS
HLPIKDEKKH HDNDHQRDRD SIKSSSVSPS ASFRGSEKHR NSTDYSSESK KQKTEEKEIA
ARYDSDGEKS DDNLVVDVSN EDPSSPRGSP AHSPRENGLD KTRLLKKDAP ISPASVASSS
STPSSKSKEL SLNEKSTTPV SKSNTPTPRT DAPTPGSNST PGLRPVPGKP PGVDPLASSL
RTPMAVPCPY PTPFGIVPHA GMNGELTSPG AAYAGLHNIS PQMSAAAAAA AAAAAYGRSP
VVGFDPHHHM RVPAIPPNLT GIPGGKPAYS FHVSADGQMQ PVPFPPDALI GPGIPRHARQ
INTLNHGEVV CAVTISNPTR HVYTGGKGCV KVWDISHPGN KSPVSQLDCL NRDNYIRSCR
LLPDGRTLIV GGEASTLSIW DLAAPTPRIK AELTSSAPAC YALAISPDSK VCFSCCSDGN
IAVWDLHNQT LVRQFQGHTD GASCIDISND GTKLWTGGLD NTVRSWDLRE GRQLQQHDFT
SQIFSLGYCP TGEWLAVGME NSNVEVLHVT KPDKYQLHLH ESCVLSLKFA HCGKWFVSTG
KDNLLNAWRT PYGASIFQSK ESSSVLSCDI SVDDKYIVTG SGDKKATVYE VIY
