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Protein

Transducin-like enhancer protein 4

Gene

TLE4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (By similarity).By similarity

Caution

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionRepressor
Biological processTranscription, Transcription regulation, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201722 Formation of the beta-catenin:TCF transactivating complex
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex
R-HSA-4641265 Repression of WNT target genes
SignaLinkiQ04727
SIGNORiQ04727

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, KIAA1261
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000106829.18
HGNCiHGNC:11840 TLE4
MIMi605132 gene
neXtProtiNX_Q04727

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi7091
OpenTargetsiENSG00000106829
PharmGKBiPA36542

Polymorphism and mutation databases

DMDMi158518541

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000512831 – 773Transducin-like enhancer protein 4Add BLAST773

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei208PhosphoserineCombined sources1
Modified residuei212PhosphoserineBy similarity1
Modified residuei222PhosphoserineBy similarity1
Modified residuei237N6-acetyllysineCombined sources1
Modified residuei245PhosphoserineBy similarity1
Modified residuei250PhosphoserineCombined sources1
Modified residuei269PhosphoserineCombined sources1
Modified residuei273PhosphoserineBy similarity1
Modified residuei281N6-acetyllysineCombined sources1
Modified residuei292PhosphoserineCombined sources1
Modified residuei318PhosphothreonineBy similarity1
Modified residuei321PhosphoserineBy similarity1
Modified residuei323PhosphoserineBy similarity1
Modified residuei325PhosphothreonineBy similarity1
Modified residuei327PhosphothreonineBy similarity1
Modified residuei334PhosphothreonineBy similarity1
Modified residuei340PhosphothreonineBy similarity1
Modified residuei419PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ04727
PaxDbiQ04727
PeptideAtlasiQ04727
PRIDEiQ04727

PTM databases

iPTMnetiQ04727
PhosphoSitePlusiQ04727

Expressioni

Tissue specificityi

In all tissues examined, mostly in brain, and muscle.

Gene expression databases

BgeeiENSG00000106829
ExpressionAtlasiQ04727 baseline and differential
GenevisibleiQ04727 HS

Organism-specific databases

HPAiHPA065357

Interactioni

Subunit structurei

Homooligomer and heterooligomer with other family members. Binds PAX5, LEF1, TCF7, TCF7L1 and TCF7L2. Interacts with ZNF703; TLE4 may mediate ZNF703 transcriptional repression. Interacts with SIX3 and SIX6 (By similarity). Interacts with PAX2.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112946, 36 interactors
CORUMiQ04727
IntActiQ04727, 5 interactors
MINTiQ04727
STRINGi9606.ENSP00000365735

Structurei

3D structure databases

ProteinModelPortaliQ04727
SMRiQ04727
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati485 – 523WD 1Add BLAST39
Repeati531 – 570WD 2Add BLAST40
Repeati575 – 614WD 3Add BLAST40
Repeati617 – 656WD 4Add BLAST40
Repeati658 – 697WD 5Add BLAST40
Repeati699 – 738WD 6Add BLAST40
Repeati740 – 773WD 7Add BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 136Q domain1 PublicationAdd BLAST136
Regioni137 – 204GP domain1 PublicationAdd BLAST68
Regioni205 – 274CcN domain1 PublicationAdd BLAST70
Regioni275 – 452SP domain1 PublicationAdd BLAST178

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

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0639 Eukaryota
ENOG410XPX3 LUCA
GeneTreeiENSGT00550000074465
HOVERGENiHBG004689
InParanoidiQ04727
OMAiWFMNEKS
OrthoDBiEOG091G181Y
PhylomeDBiQ04727
TreeFamiTF314167

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR005617 Groucho/TLE_N
IPR009146 Groucho_enhance
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF03920 TLE_N, 1 hit
PF00400 WD40, 2 hits
PRINTSiPR01850 GROUCHOFAMLY
SMARTiView protein in SMART
SM00320 WD40, 7 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 2 hits
PS50082 WD_REPEATS_2, 3 hits
PS50294 WD_REPEATS_REGION, 2 hits

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q04727-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 ASFRGAEKHR NSADYSSESK KQKTEEKEIA ARYDSDGEKS
260 270 280 290 300
DDNLVVDVSN EDPSSPRGSP AHSPRENGLD KTRLLKKDAP ISPASIASSS
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):83,755
Last modified:September 11, 2007 - v3
Checksum:iDA138F1DA29E81B6
GO
Isoform 2 (identifier: Q04727-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     244-312: Missing.

Note: No experimental confirmation available.
Show »
Length:704
Mass (Da):76,581
Checksum:iEF8F211B53D9CD3C
GO
Isoform 3 (identifier: Q04727-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     312-312: L → LKRDMGKLSETRLSEDEQCTLGLQRWFCRLWFM

Note: No experimental confirmation available.
Show »
Length:805
Mass (Da):87,702
Checksum:i7301C1C49E992219
GO
Isoform 4 (identifier: Q04727-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     106-130: Missing.

Show »
Length:748
Mass (Da):81,011
Checksum:i2402704F8D17A77E
GO

Sequence cautioni

The sequence BAA86575 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAC22598 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAC22599 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI13644 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI13734 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAI41315 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti131Q → QQ in CAB82397 (PubMed:17974005).Curated1
Sequence conflicti468A → P in AAA61195 (PubMed:1303260).Curated1
Sequence conflicti509C → A in AAA61195 (PubMed:1303260).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_055169106 – 130Missing in isoform 4. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_030497244 – 312Missing in isoform 2. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_030498312L → LKRDMGKLSETRLSEDEQCT LGLQRWFCRLWFM in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB033087 mRNA Translation: BAA86575.1 Different initiation.
AK296342 mRNA Translation: BAG59027.1
AL358975 Genomic DNA Translation: CAC22598.1 Sequence problems.
AL358975 Genomic DNA Translation: CAC22599.1 Sequence problems.
AL445252, AL353813, AL358975 Genomic DNA Translation: CAI13644.1 Sequence problems.
AL353813, AL445252, AL358975 Genomic DNA Translation: CAI41315.1 Sequence problems.
AL358975, AL445252, AL353813 Genomic DNA Translation: CAI13734.1 Sequence problems.
BC045650 mRNA Translation: AAH45650.1
BC059405 mRNA Translation: AAH59405.2
AL162059 mRNA Translation: CAB82397.1
M99439 mRNA Translation: AAA61195.1
CCDSiCCDS43837.1 [Q04727-1]
CCDS65069.1 [Q04727-3]
CCDS65070.1 [Q04727-4]
CCDS75851.1 [Q04727-2]
PIRiT47149
RefSeqiNP_001269677.1, NM_001282748.1 [Q04727-3]
NP_001269678.1, NM_001282749.1 [Q04727-4]
NP_001269682.1, NM_001282753.1 [Q04727-2]
NP_008936.2, NM_007005.4 [Q04727-1]
UniGeneiHs.444213

Genome annotation databases

EnsembliENST00000265284; ENSP00000265284; ENSG00000106829 [Q04727-4]
ENST00000376537; ENSP00000365720; ENSG00000106829 [Q04727-3]
ENST00000376544; ENSP00000365727; ENSG00000106829 [Q04727-2]
ENST00000376552; ENSP00000365735; ENSG00000106829 [Q04727-1]
GeneIDi7091
KEGGihsa:7091
UCSCiuc004alc.5 human [Q04727-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTLE4_HUMAN
AccessioniPrimary (citable) accession number: Q04727
Secondary accession number(s): F8W6T6
, Q3ZCS1, Q5T1Y2, Q6PCB3, Q9BZ07, Q9BZ08, Q9BZ09, Q9NSL3, Q9ULF9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: September 11, 2007
Last modified: March 28, 2018
This is version 187 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health