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Protein

Transducin-like enhancer protein 4

Gene

Tle4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional corepressor that binds to a number of transcription factors. Inhibits the transcriptional activation mediated by PAX5, and by CTNNB1 and TCF family members in Wnt signaling. The effects of full-length TLE family members may be modulated by association with dominant-negative AES. Essential for the transcriptional repressor activity of SIX3 during retina and lens development and for SIX3 transcriptional auto-repression.2 Publications

GO - Molecular functioni

  • chromatin binding Source: MGI
  • repressing transcription factor binding Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: MGI

GO - Biological processi

  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
  • Wnt signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-201722. Formation of the beta-catenin:TCF transactivating complex.
R-MMU-3769402. Deactivation of the beta-catenin transactivating complex.
R-MMU-4641265. Repression of WNT target genes.

Names & Taxonomyi

Protein namesi
Recommended name:
Transducin-like enhancer protein 4
Alternative name(s):
Grg-4
Groucho-related protein 4
Gene namesi
Name:Tle4
Synonyms:Grg4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:104633. Tle4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 773773Transducin-like enhancer protein 4PRO_0000051284Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei208 – 2081PhosphoserineBy similarity
Modified residuei212 – 2121PhosphoserineBy similarity
Modified residuei216 – 2161PhosphoserineBy similarity
Modified residuei222 – 2221PhosphoserineBy similarity
Modified residuei237 – 2371N6-acetyllysineBy similarity
Modified residuei245 – 2451PhosphoserineBy similarity
Modified residuei250 – 2501Phosphoserine; by CK2Sequence analysisBy similarity
Modified residuei265 – 2651Phosphoserine; by CDK1Sequence analysis
Modified residuei269 – 2691PhosphoserineBy similarity
Modified residuei273 – 2731PhosphoserineBy similarity
Modified residuei281 – 2811N6-acetyllysineBy similarity
Modified residuei292 – 2921PhosphoserineCombined sources
Modified residuei318 – 3181PhosphothreonineCombined sources
Modified residuei321 – 3211PhosphoserineCombined sources
Modified residuei323 – 3231PhosphoserineBy similarity
Modified residuei325 – 3251PhosphothreonineCombined sources
Modified residuei327 – 3271PhosphothreonineBy similarity
Modified residuei334 – 3341PhosphothreonineBy similarity
Modified residuei340 – 3401PhosphothreonineBy similarity
Modified residuei419 – 4191PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated. PAX5 binding increases phosphorylation.1 Publication
Ubiquitinated by XIAP/BIRC4.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ62441.
MaxQBiQ62441.
PaxDbiQ62441.
PRIDEiQ62441.

PTM databases

iPTMnetiQ62441.
PhosphoSiteiQ62441.

Expressioni

Gene expression databases

BgeeiQ62441.
ExpressionAtlasiQ62441. baseline and differential.
GenevisibleiQ62441. MM.

Interactioni

Subunit structurei

Homooligomer and heterooligomer with other family members (By similarity). Binds PAX5, LEF1, TCF7, TCF7L1 and TCF7L2. Interacts with ZNF703; TLE4 may mediate ZNF703 transcriptional repression. Interacts with SIX3 and SIX6. Interacts with PAX2 (By similarity).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Six3Q622332EBI-2297871,EBI-2297327

GO - Molecular functioni

  • repressing transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi204219. 9 interactions.
IntActiQ62441. 3 interactions.
STRINGi10090.ENSMUSP00000057527.

Structurei

3D structure databases

ProteinModelPortaliQ62441.
SMRiQ62441. Positions 27-132, 441-773.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati485 – 52339WD 1Add
BLAST
Repeati531 – 57040WD 2Add
BLAST
Repeati575 – 61440WD 3Add
BLAST
Repeati617 – 65640WD 4Add
BLAST
Repeati658 – 69740WD 5Add
BLAST
Repeati699 – 73840WD 6Add
BLAST
Repeati740 – 77334WD 7Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 136136Q domainBy similarityAdd
BLAST
Regioni137 – 20468GP domainBy similarityAdd
BLAST
Regioni205 – 27470CcN domainBy similarityAdd
BLAST
Regioni275 – 452178SP domainBy similarityAdd
BLAST

Domaini

WD repeat Groucho/TLE family members are characterized by 5 regions, a glutamine-rich Q domain, a glycine/proline-rich GP domain, a central CcN domain, containing a nuclear localization signal, and a serine/proline-rich SP domain. The most highly conserved are the N-terminal Q domain and the C-terminal WD-repeat domain.1 Publication

Sequence similaritiesi

Belongs to the WD repeat Groucho/TLE family.Curated
Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0639. Eukaryota.
ENOG410XPX3. LUCA.
GeneTreeiENSGT00550000074465.
HOVERGENiHBG004689.
InParanoidiQ62441.
OMAiCPYPAPF.
OrthoDBiEOG7HQNC3.
PhylomeDBiQ62441.
TreeFamiTF314167.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR005617. Groucho/TLE_N.
IPR009146. Groucho_enhance.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF03920. TLE_N. 1 hit.
PF00400. WD40. 2 hits.
[Graphical view]
PRINTSiPR01850. GROUCHOFAMLY.
SMARTiSM00320. WD40. 7 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 3 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q62441-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIRDLSKMYP QTRHPAPHQP AQPFKFTISE SCDRIKEEFQ FLQAQYHSLK
60 70 80 90 100
LECEKLASEK TEMQRHYVMY YEMSYGLNIE MHKQAEIVKR LNAICAQVIP
110 120 130 140 150
FLSQEHQQQV VQAVERAKQV TMAELNAIIG QQLQAQHLSH GHGLPVPLTP
160 170 180 190 200
HPSGLQPPAI PPIGSSAGLL ALSSALGGQS HLPIKDEKKH HDNDHQRDRD
210 220 230 240 250
SIKSSSVSPS ASFRGSEKHR NSTDYSSESK KQKTEEKEIA ARYDSDGEKS
260 270 280 290 300
DDNLVVDVSN EDPSSPRGSP AHSPRENGLD KTRLLKKDAP ISPASVASSS
310 320 330 340 350
STPSSKSKEL SLNEKSTTPV SKSNTPTPRT DAPTPGSNST PGLRPVPGKP
360 370 380 390 400
PGVDPLASSL RTPMAVPCPY PTPFGIVPHA GMNGELTSPG AAYAGLHNIS
410 420 430 440 450
PQMSAAAAAA AAAAAYGRSP VVGFDPHHHM RVPAIPPNLT GIPGGKPAYS
460 470 480 490 500
FHVSADGQMQ PVPFPPDALI GPGIPRHARQ INTLNHGEVV CAVTISNPTR
510 520 530 540 550
HVYTGGKGCV KVWDISHPGN KSPVSQLDCL NRDNYIRSCR LLPDGRTLIV
560 570 580 590 600
GGEASTLSIW DLAAPTPRIK AELTSSAPAC YALAISPDSK VCFSCCSDGN
610 620 630 640 650
IAVWDLHNQT LVRQFQGHTD GASCIDISND GTKLWTGGLD NTVRSWDLRE
660 670 680 690 700
GRQLQQHDFT SQIFSLGYCP TGEWLAVGME NSNVEVLHVT KPDKYQLHLH
710 720 730 740 750
ESCVLSLKFA HCGKWFVSTG KDNLLNAWRT PYGASIFQSK ESSSVLSCDI
760 770
SVDDKYIVTG SGDKKATVYE VIY
Length:773
Mass (Da):83,787
Last modified:September 11, 2007 - v4
Checksum:i5A0090789774CACC
GO

Sequence cautioni

The sequence AAF43203.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti197 – 1993RDR → QTN in AAC97070 (PubMed:8892234).Curated
Sequence conflicti405 – 4051A → R in AAC97070 (PubMed:8892234).Curated
Sequence conflicti454 – 4552SA → RS in AAC97070 (PubMed:8892234).Curated
Sequence conflicti608 – 6092NQ → KE in AAC97070 (PubMed:8892234).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF229633 mRNA. Translation: AAF43203.1. Different initiation.
U61363 mRNA. Translation: AAC97070.1.
CCDSiCCDS50399.1.
RefSeqiNP_035730.2. NM_011600.3.
UniGeneiMm.103638.

Genome annotation databases

EnsembliENSMUST00000052011; ENSMUSP00000057527; ENSMUSG00000024642.
GeneIDi21888.
KEGGimmu:21888.
UCSCiuc008gwk.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF229633 mRNA. Translation: AAF43203.1. Different initiation.
U61363 mRNA. Translation: AAC97070.1.
CCDSiCCDS50399.1.
RefSeqiNP_035730.2. NM_011600.3.
UniGeneiMm.103638.

3D structure databases

ProteinModelPortaliQ62441.
SMRiQ62441. Positions 27-132, 441-773.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204219. 9 interactions.
IntActiQ62441. 3 interactions.
STRINGi10090.ENSMUSP00000057527.

PTM databases

iPTMnetiQ62441.
PhosphoSiteiQ62441.

Proteomic databases

EPDiQ62441.
MaxQBiQ62441.
PaxDbiQ62441.
PRIDEiQ62441.

Protocols and materials databases

DNASUi21888.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000052011; ENSMUSP00000057527; ENSMUSG00000024642.
GeneIDi21888.
KEGGimmu:21888.
UCSCiuc008gwk.2. mouse.

Organism-specific databases

CTDi7091.
MGIiMGI:104633. Tle4.

Phylogenomic databases

eggNOGiKOG0639. Eukaryota.
ENOG410XPX3. LUCA.
GeneTreeiENSGT00550000074465.
HOVERGENiHBG004689.
InParanoidiQ62441.
OMAiCPYPAPF.
OrthoDBiEOG7HQNC3.
PhylomeDBiQ62441.
TreeFamiTF314167.

Enzyme and pathway databases

ReactomeiR-MMU-201722. Formation of the beta-catenin:TCF transactivating complex.
R-MMU-3769402. Deactivation of the beta-catenin transactivating complex.
R-MMU-4641265. Repression of WNT target genes.

Miscellaneous databases

PROiQ62441.
SOURCEiSearch...

Gene expression databases

BgeeiQ62441.
ExpressionAtlasiQ62441. baseline and differential.
GenevisibleiQ62441. MM.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR005617. Groucho/TLE_N.
IPR009146. Groucho_enhance.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF03920. TLE_N. 1 hit.
PF00400. WD40. 2 hits.
[Graphical view]
PRINTSiPR01850. GROUCHOFAMLY.
SMARTiSM00320. WD40. 7 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 3 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Transcriptional repression by Pax5 (BSAP) through interaction with corepressors of the Groucho family."
    Eberhard D., Jimenez G., Heavey B., Busslinger M.
    EMBO J. 19:2292-2303(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION, INTERACTION WITH PAX5.
    Tissue: Embryo.
  2. "Transcripts of Grg4, a murine groucho-related gene, are detected in adjacent tissues to other murine neurogenic gene homologues during embryonic development."
    Koop K.E., Macdonald L.M., Lobe C.G.
    Mech. Dev. 59:73-87(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 197-773.
  3. Lobe C.G., Koop K.E., Macdonald L.M.
    Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION.
  4. "All Tcf HMG box transcription factors interact with Groucho-related co-repressors."
    Brantjes H., Roose J., van De Wetering M., Clevers H.
    Nucleic Acids Res. 29:1410-1419(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LEF1; TCF7; TCF7L1 AND TCF7L2.
  5. "Six3-mediated auto repression and eye development requires its interaction with members of the Groucho-related family of co-repressors."
    Zhu C.C., Dyer M.A., Uchikawa M., Kondoh H., Lagutin O.V., Oliver G.
    Development 129:2835-2849(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SIX3 AND SIX6.
  6. "The Groucho/TLE/Grg family of transcriptional co-repressors."
    Jennings B.H., Ish-Horowicz D.
    Genome Biol. 9:R205.1-R205.7(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-292; THR-318; SER-321 AND THR-325, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain and Testis.
  8. "Zeppo1 is a novel metastasis promoter that represses E-cadherin expression and regulates p120-catenin isoform expression and localization."
    Slorach E.M., Chou J., Werb Z.
    Genes Dev. 25:471-484(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ZNF703.

Entry informationi

Entry nameiTLE4_MOUSE
AccessioniPrimary (citable) accession number: Q62441
Secondary accession number(s): Q9JKQ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 11, 2007
Last modified: July 6, 2016
This is version 138 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

It is uncertain whether Met-1 or Met-8 is the initiator.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.