TLE6_MOUSE
ID TLE6_MOUSE Reviewed; 581 AA.
AC Q9WVB3;
DT 28-MAR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Transducin-like enhancer protein 6;
DE AltName: Full=Groucho-related protein 6;
GN Name=Tle6; Synonyms=Grg6 {ECO:0000303|PubMed:23990468};
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], TISSUE SPECIFICITY, AND INDUCTION BY E2A-HLF.
RC TISSUE=Premonocytic lymphoma;
RX PubMed=11486032; DOI=10.1128/mcb.21.17.5935-5945.2001;
RA Dang J., Inukai T., Kurosawa H., Goi K., Inaba T., Lenny N.T.,
RA Downing J.R., Stifani S., Look A.T.;
RT "The E2A-HLF oncoprotein activates Groucho-related genes and suppresses
RT Runx1.";
RL Mol. Cell. Biol. 21:5935-5945(2001).
RN [2]
RP FUNCTION, SUBUNIT, INTERACTION WITH FOXG1, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
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 [3]
RP FUNCTION, IDENTIFICATION IN THE SCMC COMPLEX, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=18804437; DOI=10.1016/j.devcel.2008.07.010;
RA Li L., Baibakov B., Dean J.;
RT "A subcortical maternal complex essential for preimplantation mouse
RT embryogenesis.";
RL Dev. Cell 15:416-425(2008).
RN [4]
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 [5]
RP FUNCTION, INTERACTION WITH NFATC1, TISSUE SPECIFICITY, AND INDUCTION BY
RP TNFSF11-INDUCED OSTEOCLAST DIFFERENTIATION.
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).
RN [6]
RP FUNCTION, INTERACTION WITH CFL1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=25208553; DOI=10.1038/ncomms5887;
RA Yu X.J., Yi Z., Gao Z., Qin D., Zhai Y., Chen X., Ou-Yang Y., Wang Z.B.,
RA Zheng P., Zhu M.S., Wang H., Sun Q.Y., Dean J., Li L.;
RT "The subcortical maternal complex controls symmetric division of mouse
RT zygotes by regulating F-actin dynamics.";
RL Nat. Commun. 5:4887-4887(2014).
RN [7]
RP IDENTIFICATION IN THE SCMC COMPLEX, AND DISRUPTION PHENOTYPE.
RX PubMed=28992324; DOI=10.1093/jmcb/mjx035;
RA Gao Z., Zhang X., Yu X., Qin D., Xiao Y., Yu Y., Xiang Y., Nie X., Lu X.,
RA Liu W., Yi Z., Li L.;
RT "Zbed3 participates in the subcortical maternal complex and regulates the
RT distribution of organelles.";
RL J. Mol. Cell Biol. 10:74-88(2018).
RN [8]
RP FUNCTION, IDENTIFICATION IN THE SCMC COMPLEX, INTERACTION WITH NLRP4F;
RP NLRP5; OOEP AND ZBED3, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=31575650; DOI=10.1242/dev.183616;
RA Qin D., Gao Z., Xiao Y., Zhang X., Ma H., Yu X., Nie X., Fan N., Wang X.,
RA Ouyang Y., Sun Q.Y., Yi Z., Li L.;
RT "The subcortical maternal complex protein Nlrp4f is involved in cytoplasmic
RT lattice formation and organelle distribution.";
RL Development 146:0-0(2019).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=32823735; DOI=10.3390/ijms21165827;
RA Feng M., Bai Y., Chen Y., Wang K.;
RT "Knockout of the Transducin-Like Enhancer of Split 6 Gene Affects the
RT Proliferation and Cell Cycle Process of Mouse Spermatogonia.";
RL Int. J. Mol. Sci. 21:0-0(2020).
CC -!- FUNCTION: As a member of the subcortical maternal complex (SCMC), plays
CC an essential role for zygotes to progress beyond the first embryonic
CC cell divisions via regulation of actin dynamics (PubMed:18804437,
CC PubMed:25208553). Required for the formation of F-actin cytoplasmic
CC lattices in oocytes which in turn are responsible for symmetric
CC division of zygotes via the regulation of mitotic spindle formation and
CC positioning (PubMed:31575650). Regulates spermatogonia proliferation
CC and cell cycle progression, potentially via regulation of cell cycle
CC regulatory genes such as; CEBPB, CEBPA, CSF3, PCNA, and CDK4
CC (PubMed:32823735). Suppresses FOXG1/BF-1-mediated transcriptional
CC repression by inhibiting interaction of the transcriptional corepressor
CC TLE1 with FOXG1 which promotes cortical neuron differentiation
CC (PubMed:16314515). Acts as a transcriptional corepressor of NFATC1-
CC mediated gene expression by contributing to PAX6-mediated repression
CC (PubMed:23990468). {ECO:0000269|PubMed:16314515,
CC ECO:0000269|PubMed:18804437, ECO:0000269|PubMed:23990468,
CC ECO:0000269|PubMed:25208553, ECO:0000269|PubMed:31575650,
CC ECO:0000269|PubMed:32823735}.
CC -!- SUBUNIT: Homodimers (PubMed:16314515). Component of the subcortical
CC maternal complex (SCMC), at least composed of NLRP5, KHDC3, OOEP, and
CC TLE6 (PubMed:18804437, PubMed:28992324). Within the complex, interacts
CC with NLRP5, KHDC3 and OOEP (PubMed:28992324, PubMed:31575650). The SCMC
CC may facilitate translocation of its components between the nuclear and
CC cytoplasmic compartments (By similarity). As part of the SCMC interacts
CC with the SCMC-associated protein ZBED3 (PubMed:31575650). As part of
CC the SCMC interacts with the SCMC-associated protein NLRP4F
CC (PubMed:31575650). As part of the SCMC interacts with the SCMC-
CC associated protein CFL1/Cofilin-1 (PubMed:25208553). Interacts with
CC FOXG1/BF-1; the interaction inhibits TLE1 interaction with FOXG1/BF-1
CC (PubMed:16314515). Interacts with NFATC1 (PubMed:23990468). Interacts
CC with PAX6 (PubMed:23990468). {ECO:0000250|UniProtKB:Q9H808,
CC ECO:0000269|PubMed:16314515, ECO:0000269|PubMed:18804437,
CC ECO:0000269|PubMed:23990468, ECO:0000269|PubMed:25208553,
CC ECO:0000269|PubMed:28992324, ECO:0000269|PubMed:31575650}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16314515,
CC ECO:0000269|PubMed:18804437}. Nucleus {ECO:0000269|PubMed:16314515}.
CC Note=In the subcortical cytoplasm of early embryos from the 1-cell to
CC the blastocyst stages (PubMed:18804437, PubMed:25208553). At the 2-cell
CC and morular stage, still detected in the subcortex, but excluded from
CC cell-cell contact regions (PubMed:18804437, PubMed:25208553).
CC Expression largely disappears in blastocysts (PubMed:25208553).
CC {ECO:0000269|PubMed:18804437, ECO:0000269|PubMed:25208553}.
CC -!- TISSUE SPECIFICITY: Expressed in spermatogonia (at protein level)
CC (PubMed:32823735). Expressed predominantly in ovaries, where it is
CC restricted to growing oocytes, with greatest levels in fully grown
CC oocytes (PubMed:18804437, PubMed:25208553). Expressed predominantly in
CC testis, heart, lung, liver and muscle, and at very low levels in the
CC brain, spleen and kidney (PubMed:11486032). Expressed in bone marrow-
CC derived macrophages and osteoclasts (PubMed:23990468).
CC {ECO:0000269|PubMed:11486032, ECO:0000269|PubMed:18804437,
CC ECO:0000269|PubMed:23990468, ECO:0000269|PubMed:25208553,
CC ECO:0000269|PubMed:32823735}.
CC -!- DEVELOPMENTAL STAGE: Transcripts first detected at 15.5 dpc and peak 1
CC week after birth. Transcripts accumulate during oogenesis
CC (PubMed:18804437). During meiotic maturation, the vast majority of the
CC transcripts are degraded and virtually none is detected by 2-cell stage
CC embryogenesis (PubMed:18804437). The protein however persists during
CC preimplantation up to the blastocyst stage (PubMed:18804437). At 2-cell
CC stage, excluded from cell-cell contact regions. Continuous exclusion
CC from these regions during preimplantation development leads to the
CC absence of the protein from the inner cells of the morula and the inner
CC cell mass of the blastocyst (PubMed:18804437). Expressed in the
CC forebrain, midbrain, ventricular zone and superficial cortical plate at
CC 14.5 dpc (PubMed:16314515). Expressed in cortical progenitors in the
CC forebrain dorsal telencephalon and the midbrain at 15.5 dpc
CC (PubMed:16314515). Expressed in ovaries at postnatal day 2 (P2),
CC expression peaks at P10, expression is then decreased at P17 and
CC further decreased at P21 (PubMed:31575650).
CC {ECO:0000269|PubMed:16314515, ECO:0000269|PubMed:18804437,
CC ECO:0000269|PubMed:31575650}.
CC -!- INDUCTION: Induced by E2A-HLF, a chimeric transcription factor
CC containing the transactivation domain of E2A linked to the DNA-binding
CC and dimerization domain of HLF (PubMed:11486032). Induced during
CC TNFSF11/RANKL-induced osteoclast differentiation (PubMed:23990468).
CC {ECO:0000269|PubMed:11486032, ECO:0000269|PubMed:23990468}.
CC -!- DOMAIN: Contrary to other WD repeat Groucho/TLE family members, does
CC not contain any identifiable Q, GP, CcN or SP domains. Only the C-
CC terminal WD-repeat domain is conserved. {ECO:0000305|PubMed:18254933}.
CC -!- DISRUPTION PHENOTYPE: Females show normal ovarian histology, ovulation
CC and egg morphology, however fail to produce offspring following
CC successful mating (PubMed:25208553). Progression from one- to two-cell
CC embryos is delayed by 4-6 hours and embryos failed to develop into
CC morulae and blastocysts (PubMed:25208553). Embryos form unequal sized
CC blastomeres due to smaller, dysmorphic, and displaced mitotic spindles
CC resulting to asymmetric division (PubMed:25208553). Loss of FMN2-
CC expressing endoplasmic reticulum localization to the mitotic spindle
CC periphery, and incorrect localization of mitochondria to the
CC subcortical region prior to nuclear envelope breakdown in zygotes and
CC oocytes (PubMed:28992324). Extension of the alpha-tubulin pool into the
CC subcortical region following microtubule-organizing center congression
CC in oocytes (PubMed:28992324). Decrease in expression of the SCMC
CC components ZBED3, NLRP5/MATER, KHDC3/FILIA and OOEP/FLOPED in oocytes
CC (PubMed:25208553, PubMed:28992324). Loss of F-actin cytoplasmic
CC lattices in oocytes, zygotes and embryos (PubMed:25208553,
CC PubMed:31575650). Decrease in thickness of subcortical F-actin in
CC zygotes and thickening of F-actin bundles in the cytoplasm is evident
CC (PubMed:25208553). Decrease in CFL1/Cofilin-1 expression in the
CC subcortex, diffused distribution in the cytoplasm of zygotes and
CC decrease in phosphorylated CFL1/Cofilin-1 expression in oocytes and
CC zygotes (PubMed:25208553). {ECO:0000269|PubMed:25208553,
CC ECO:0000269|PubMed:28992324, ECO:0000269|PubMed:31575650}.
CC -!- SIMILARITY: Belongs to the WD repeat Groucho/TLE family. {ECO:0000305}.
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DR EMBL; AF145957; AAD37693.1; -; mRNA.
DR CCDS; CCDS24064.1; -.
DR RefSeq; NP_444484.1; NM_053254.2.
DR AlphaFoldDB; Q9WVB3; -.
DR SMR; Q9WVB3; -.
DR BioGRID; 227763; 20.
DR CORUM; Q9WVB3; -.
DR IntAct; Q9WVB3; 22.
DR STRING; 10090.ENSMUSP00000071905; -.
DR iPTMnet; Q9WVB3; -.
DR PhosphoSitePlus; Q9WVB3; -.
DR MaxQB; Q9WVB3; -.
DR PaxDb; Q9WVB3; -.
DR PRIDE; Q9WVB3; -.
DR ProteomicsDB; 260666; -.
DR Antibodypedia; 23085; 74 antibodies from 18 providers.
DR DNASU; 114606; -.
DR Ensembl; ENSMUST00000072020; ENSMUSP00000071905; ENSMUSG00000034758.
DR GeneID; 114606; -.
DR KEGG; mmu:114606; -.
DR UCSC; uc007giu.1; mouse.
DR CTD; 79816; -.
DR MGI; MGI:2149593; Tle6.
DR VEuPathDB; HostDB:ENSMUSG00000034758; -.
DR eggNOG; KOG0639; Eukaryota.
DR GeneTree; ENSGT01030000234519; -.
DR InParanoid; Q9WVB3; -.
DR OMA; NGQWWVS; -.
DR OrthoDB; 1025572at2759; -.
DR PhylomeDB; Q9WVB3; -.
DR TreeFam; TF314167; -.
DR BioGRID-ORCS; 114606; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q9WVB3; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9WVB3; protein.
DR Bgee; ENSMUSG00000034758; Expressed in primary oocyte and 166 other tissues.
DR ExpressionAtlas; Q9WVB3; baseline and differential.
DR Genevisible; Q9WVB3; MM.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0106333; C:subcortical maternal complex; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0007015; P:actin filament organization; IMP:UniProtKB.
DR GO; GO:0060136; P:embryonic process involved in female pregnancy; ISO:MGI.
DR GO; GO:0051643; P:endoplasmic reticulum localization; IMP:UniProtKB.
DR GO; GO:0051293; P:establishment of spindle localization; IMP:UniProtKB.
DR GO; GO:0051646; P:mitochondrion localization; IMP:UniProtKB.
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:UniProtKB.
DR GO; GO:0040019; P:positive regulation of embryonic development; IMP:UniProtKB.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IGI:MGI.
DR GO; GO:0051302; P:regulation of cell division; IMP:UniProtKB.
DR GO; GO:0007284; P:spermatogonial cell division; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR009146; Groucho_enhance.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR10814; PTHR10814; 1.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Transcription; Transcription regulation; WD repeat.
FT CHAIN 1..581
FT /note="Transducin-like enhancer protein 6"
FT /id="PRO_0000051287"
FT REPEAT 246..283
FT /note="WD 1"
FT REPEAT 291..329
FT /note="WD 2"
FT REPEAT 341..381
FT /note="WD 3"
FT REPEAT 384..424
FT /note="WD 4"
FT REPEAT 427..464
FT /note="WD 5"
FT REPEAT 466..505
FT /note="WD 6"
FT REPEAT 508..547
FT /note="WD 7"
FT REPEAT 549..580
FT /note="WD 8"
FT REGION 90..134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 175..216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 132..138
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 175..208
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT MOD_RES 519
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H808"
SQ SEQUENCE 581 AA; 65116 MW; 946369E084B800F6 CRC64;
MTSHRQSSDT FGGILPSTLS SRYLSIVNQL PEEFSSVVSE MMVHLENIFS LAENFFQAIE
RFSRTPDLLE RNKMSIGVGA EGDSWPCHVS HEAPMGSAQT TENSAKEEDK QVPESAALQH
PKFKSTPGPQ LPTRRRFLSE SDELQDPQPV WDAEPQFCQG FLIQGLWELF MDSRQKNQQE
HGGEDSSQES KDSGLCDFKP EPQPRHRNSL SDSADPFLIK SPSALLDYYQ EDVSRPQPET
QESSGRADKF LKPLSWGSEV LESSCNQPST ALWQLERFTV PQALQKVRVL KHQELLLVVA
VSSFTRHVFT CSQSGIKVWN LVNQVAEDRD PESHLKCSVQ DNKVYLRTCL LSSNSRTLFA
GGYNLPGVIV WDLAAPSLYE KCQLPCEGLS CQALANTKEN MALAGFTDGT VRIWDLRTQE
IVRNLKGPTN SARNLVVKDD NIWTGGLDAC LRCWDLRMAK VSLEHLFQSQ IMSLAHSPTE
DWLLLGLANG QHCLFNSRKR DQVLTVDTKD NTILGLKFSP NGKWWASVGM GNFITVHSMP
TGAKLFQVPE VGPVRCFDMT ENGRLIITGS RDCASVYHIK Y
