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Protein

Transducin-like enhancer protein 3

Gene

TLE3

Organism
Homo sapiens (Human)
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 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 (By similarity).By similarity

GO - Biological processi

  • animal organ morphogenesis Source: ProtInc
  • beta-catenin-TCF complex assembly Source: Reactome
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • signal transduction Source: ProtInc
  • transcription, DNA-templated Source: UniProtKB-KW
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation, Wnt signaling pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140332-MONOMER.
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.
SignaLinkiQ04726.

Names & Taxonomyi

Protein namesi
Recommended name:
Transducin-like enhancer protein 3
Alternative name(s):
Enhancer of split groucho-like protein 3
Short name:
ESG3
Gene namesi
Name:TLE3
Synonyms:KIAA1547
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:11839. TLE3.

Subcellular locationi

GO - Cellular componenti

  • nucleoplasm Source: Reactome
  • nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi7090.
OpenTargetsiENSG00000140332.
PharmGKBiPA36541.

Polymorphism and mutation databases

DMDMi20532417.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000512801 – 772Transducin-like enhancer protein 3Add BLAST772

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei203PhosphoserineCombined sources1
Modified residuei207PhosphoserineCombined sources1
Modified residuei211PhosphoserineCombined sources1
Modified residuei217PhosphoserineCombined sources1
Modified residuei232N6-acetyllysineBy similarity1
Modified residuei240PhosphoserineCombined sources1
Modified residuei245PhosphoserineCombined sources1
Modified residuei259PhosphothreonineCombined sources1
Modified residuei263PhosphoserineCombined sources1
Modified residuei267PhosphoserineCombined sources1
Modified residuei275N6-acetyllysineBy similarity1
Modified residuei286PhosphoserineCombined sources1
Modified residuei312PhosphothreonineCombined sources1
Modified residuei317PhosphoserineCombined sources1
Modified residuei319PhosphothreonineCombined sources1
Modified residuei321PhosphothreonineCombined sources1
Modified residuei328PhosphothreonineCombined sources1
Modified residuei334PhosphothreonineCombined sources1
Modified residuei413PhosphoserineCombined sources1
Isoform 7 (identifier: Q04726-7)
Modified residuei336N6-acetyllysineCombined sources1
Isoform 3 (identifier: Q04726-3)
Modified residuei343N6-acetyllysineCombined sources1
Isoform 5 (identifier: Q04726-5)
Modified residuei343N6-acetyllysineCombined sources1

Post-translational modificationi

Ubiquitinated by XIAP/BIRC4. This ubiquitination does not affect its stability, nuclear localization, or capacity to tetramerize but inhibits its interaction with TCF7L2/TCF4.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ04726.
MaxQBiQ04726.
PaxDbiQ04726.
PeptideAtlasiQ04726.
PRIDEiQ04726.

PTM databases

iPTMnetiQ04726.
PhosphoSitePlusiQ04726.

Expressioni

Tissue specificityi

Placenta and lung.

Gene expression databases

BgeeiENSG00000140332.
CleanExiHS_TLE3.
ExpressionAtlasiQ04726. baseline and differential.
GenevisibleiQ04726. HS.

Organism-specific databases

HPAiHPA054116.

Interactioni

Subunit structurei

Homotetramer and heterooligomer with other family members. Binds LEF1, TCF7 and TCF7L1 (By similarity). Binds FOXA2. Interacts with XIAP/BIRC4 and TCF7L2/TCF4. Interacts with TBX18 (via engrailed homology 1 repressor motif), leading to decreased of TBX18 transcriptional activity.By similarity3 Publications

Protein-protein interaction databases

BioGridi112945. 71 interactors.
DIPiDIP-36666N.
IntActiQ04726. 17 interactors.
MINTiMINT-2805536.
STRINGi9606.ENSP00000452871.

Structurei

3D structure databases

ProteinModelPortaliQ04726.
SMRiQ04726.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati484 – 522WD 1Add BLAST39
Repeati530 – 569WD 2Add BLAST40
Repeati574 – 613WD 3Add BLAST40
Repeati616 – 655WD 4Add BLAST40
Repeati657 – 696WD 5Add BLAST40
Repeati698 – 737WD 6Add BLAST40
Repeati739 – 771WD 7Add BLAST33

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 131Q domainBy similarityAdd BLAST131
Regioni132 – 199GP domainBy similarityAdd BLAST68
Regioni200 – 268CcN domainBy similarityAdd BLAST69
Regioni269 – 452SP domainBy similarityAdd BLAST184

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi225 – 228Nuclear localization signalSequence analysis4

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.
HOGENOMiHOG000293211.
HOVERGENiHBG004689.
InParanoidiQ04726.
PhylomeDBiQ04726.
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. 2 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q04726-1) [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
MYPQGRHPAP HQPGQPGFKF TVAESCDRIK DEFQFLQAQY HSLKVEYDKL
60 70 80 90 100
ANEKTEMQRH YVMYYEMSYG LNIEMHKQTE IAKRLNTILA QIMPFLSQEH
110 120 130 140 150
QQQVAQAVER AKQVTMTELN AIIGQQQLQA QHLSHATHGP PVQLPPHPSG
160 170 180 190 200
LQPPGIPPVT GSSSGLLALG ALGSQAHLTV KDEKNHHELD HRERESSANN
210 220 230 240 250
SVSPSESLRA SEKHRGSADY SMEAKKRKAE EKDSLSRYDS DGDKSDDLVV
260 270 280 290 300
DVSNEDPATP RVSPAHSPPE NGLDKARSLK KDAPTSPASV ASSSSTPSSK
310 320 330 340 350
TKDLGHNDKS STPGLKSNTP TPRNDAPTPG TSTTPGLRSM PGKPPGMDPI
360 370 380 390 400
GIMASALRTP ISITSSYAAP FAMMSHHEMN GSLTSPGAYA GLHNIPPQMS
410 420 430 440 450
AAAAAAAAAY GRSPMVSFGA VGFDPHPPMR ATGLPSSLAS IPGGKPAYSF
460 470 480 490 500
HVSADGQMQP VPFPHDALAG PGIPRHARQI NTLSHGEVVC AVTISNPTRH
510 520 530 540 550
VYTGGKGCVK IWDISQPGSK SPISQLDCLN RDNYIRSCKL LPDGRTLIVG
560 570 580 590 600
GEASTLTIWD LASPTPRIKA ELTSSAPACY ALAISPDAKV CFSCCSDGNI
610 620 630 640 650
AVWDLHNQTL VRQFQGHTDG ASCIDISHDG TKLWTGGLDN TVRSWDLREG
660 670 680 690 700
RQLQQHDFTS QIFSLGYCPT GEWLAVGMES SNVEVLHHTK PDKYQLHLHE
710 720 730 740 750
SCVLSLKFAY CGKWFVSTGK DNLLNAWRTP YGASIFQSKE SSSVLSCDIS
760 770
ADDKYIVTGS GDKKATVYEV IY
Length:772
Mass (Da):83,417
Last modified:May 10, 2002 - v2
Checksum:iA2A469D73BF04A43
GO
Isoform 2 (identifier: Q04726-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     342-353: Missing.

Show »
Length:760
Mass (Da):82,222
Checksum:i5CA1DDAE26C00E19
GO
Isoform 3 (identifier: Q04726-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     351-353: Missing.
     417-421: Missing.

Show »
Length:764
Mass (Da):82,654
Checksum:iEF5606A1D9C7C2BA
GO
Isoform 4 (identifier: Q04726-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MYPQGRHP → MPPPPPLSCLRGLQ
     127-127: Missing.
     417-421: Missing.

Show »
Length:772
Mass (Da):83,348
Checksum:iF10C1C00DE38D280
GO
Isoform 5 (identifier: Q04726-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     351-353: Missing.

Note: No experimental confirmation available.Combined sources
Show »
Length:769
Mass (Da):83,115
Checksum:i9E7895DE647F9D9E
GO
Isoform 6 (identifier: Q04726-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     416-420: Missing.

Note: No experimental confirmation available.
Show »
Length:767
Mass (Da):82,955
Checksum:i7081DB8CE8BF2EAD
GO
Isoform 7 (identifier: Q04726-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MYPQGRHP → M
     351-353: Missing.

Show »
Length:762
Mass (Da):82,279
Checksum:iE82ECE78C54894E1
GO

Sequence cautioni

The sequence BAB13373 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti358R → C in BAG60692 (PubMed:14702039).Curated1
Sequence conflicti365S → G in BAG60692 (PubMed:14702039).Curated1
Sequence conflicti409A → T in AAH41831 (PubMed:15489334).Curated1
Sequence conflicti487E → G in AAA61194 (PubMed:1303260).Curated1
Sequence conflicti498T → S in AAA61194 (PubMed:1303260).Curated1
Sequence conflicti535I → M in AAA61194 (PubMed:1303260).Curated1
Sequence conflicti541L → H in AAA61194 (PubMed:1303260).Curated1
Sequence conflicti549V → E in BAG60692 (PubMed:14702039).Curated1
Sequence conflicti553A → G in AAA61194 (PubMed:1303260).Curated1
Sequence conflicti692D → H in AAA61194 (PubMed:1303260).Curated1
Sequence conflicti736F → S in AAA61194 (PubMed:1303260).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053421229A → V.1 PublicationCorresponds to variant rs1057864dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0070231 – 8MYPQGRHP → MPPPPPLSCLRGLQ in isoform 4. 1 Publication8
Alternative sequenceiVSP_0551681 – 8MYPQGRHP → M in isoform 7. 1 Publication8
Alternative sequenceiVSP_007024127Missing in isoform 4. 1 Publication1
Alternative sequenceiVSP_006788342 – 353Missing in isoform 2. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_006789351 – 353Missing in isoform 3, isoform 5 and isoform 7. 2 Publications3
Alternative sequenceiVSP_054598416 – 420Missing in isoform 6. 1 Publication5
Alternative sequenceiVSP_006790417 – 421Missing in isoform 3 and isoform 4. 1 Publication5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M99438 mRNA. Translation: AAA61194.1.
AB046767 mRNA. Translation: BAB13373.1. Different initiation.
AK315058 mRNA. No translation available.
AK298482 mRNA. Translation: BAG60692.1.
AC026583 Genomic DNA. No translation available.
AC068327 Genomic DNA. No translation available.
BC015729 mRNA. No translation available.
BC041831 mRNA. Translation: AAH41831.1.
BC043247 mRNA. Translation: AAH43247.1.
CCDSiCCDS45293.1. [Q04726-1]
CCDS45294.1. [Q04726-5]
CCDS58375.1. [Q04726-2]
CCDS61689.1. [Q04726-7]
CCDS61691.1. [Q04726-6]
CCDS61692.1. [Q04726-3]
PIRiD56695.
RefSeqiNP_001098662.1. NM_001105192.2. [Q04726-5]
NP_001269908.1. NM_001282979.1. [Q04726-3]
NP_001269909.1. NM_001282980.1. [Q04726-6]
NP_001269910.1. NM_001282981.1. [Q04726-7]
NP_001269911.1. NM_001282982.1.
NP_005069.2. NM_005078.3. [Q04726-1]
NP_065959.1. NM_020908.2. [Q04726-2]
UniGeneiHs.287362.

Genome annotation databases

EnsembliENST00000317509; ENSP00000319233; ENSG00000140332. [Q04726-2]
ENST00000440567; ENSP00000415057; ENSG00000140332. [Q04726-7]
ENST00000451782; ENSP00000394717; ENSG00000140332. [Q04726-5]
ENST00000557907; ENSP00000453107; ENSG00000140332. [Q04726-3]
ENST00000557997; ENSP00000453083; ENSG00000140332. [Q04726-3]
ENST00000558379; ENSP00000453435; ENSG00000140332. [Q04726-6]
ENST00000558939; ENSP00000452871; ENSG00000140332. [Q04726-1]
ENST00000559048; ENSP00000453760; ENSG00000140332. [Q04726-4]
GeneIDi7090.
KEGGihsa:7090.
UCSCiuc002asl.4. human. [Q04726-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M99438 mRNA. Translation: AAA61194.1.
AB046767 mRNA. Translation: BAB13373.1. Different initiation.
AK315058 mRNA. No translation available.
AK298482 mRNA. Translation: BAG60692.1.
AC026583 Genomic DNA. No translation available.
AC068327 Genomic DNA. No translation available.
BC015729 mRNA. No translation available.
BC041831 mRNA. Translation: AAH41831.1.
BC043247 mRNA. Translation: AAH43247.1.
CCDSiCCDS45293.1. [Q04726-1]
CCDS45294.1. [Q04726-5]
CCDS58375.1. [Q04726-2]
CCDS61689.1. [Q04726-7]
CCDS61691.1. [Q04726-6]
CCDS61692.1. [Q04726-3]
PIRiD56695.
RefSeqiNP_001098662.1. NM_001105192.2. [Q04726-5]
NP_001269908.1. NM_001282979.1. [Q04726-3]
NP_001269909.1. NM_001282980.1. [Q04726-6]
NP_001269910.1. NM_001282981.1. [Q04726-7]
NP_001269911.1. NM_001282982.1.
NP_005069.2. NM_005078.3. [Q04726-1]
NP_065959.1. NM_020908.2. [Q04726-2]
UniGeneiHs.287362.

3D structure databases

ProteinModelPortaliQ04726.
SMRiQ04726.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112945. 71 interactors.
DIPiDIP-36666N.
IntActiQ04726. 17 interactors.
MINTiMINT-2805536.
STRINGi9606.ENSP00000452871.

PTM databases

iPTMnetiQ04726.
PhosphoSitePlusiQ04726.

Polymorphism and mutation databases

DMDMi20532417.

Proteomic databases

EPDiQ04726.
MaxQBiQ04726.
PaxDbiQ04726.
PeptideAtlasiQ04726.
PRIDEiQ04726.

Protocols and materials databases

DNASUi7090.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000317509; ENSP00000319233; ENSG00000140332. [Q04726-2]
ENST00000440567; ENSP00000415057; ENSG00000140332. [Q04726-7]
ENST00000451782; ENSP00000394717; ENSG00000140332. [Q04726-5]
ENST00000557907; ENSP00000453107; ENSG00000140332. [Q04726-3]
ENST00000557997; ENSP00000453083; ENSG00000140332. [Q04726-3]
ENST00000558379; ENSP00000453435; ENSG00000140332. [Q04726-6]
ENST00000558939; ENSP00000452871; ENSG00000140332. [Q04726-1]
ENST00000559048; ENSP00000453760; ENSG00000140332. [Q04726-4]
GeneIDi7090.
KEGGihsa:7090.
UCSCiuc002asl.4. human. [Q04726-1]

Organism-specific databases

CTDi7090.
DisGeNETi7090.
GeneCardsiTLE3.
HGNCiHGNC:11839. TLE3.
HPAiHPA054116.
MIMi600190. gene.
neXtProtiNX_Q04726.
OpenTargetsiENSG00000140332.
PharmGKBiPA36541.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0639. Eukaryota.
ENOG410XPX3. LUCA.
GeneTreeiENSGT00550000074465.
HOGENOMiHOG000293211.
HOVERGENiHBG004689.
InParanoidiQ04726.
PhylomeDBiQ04726.
TreeFamiTF314167.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000140332-MONOMER.
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.
SignaLinkiQ04726.

Miscellaneous databases

ChiTaRSiTLE3. human.
GeneWikiiTLE3.
GenomeRNAii7090.
PROiQ04726.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000140332.
CleanExiHS_TLE3.
ExpressionAtlasiQ04726. baseline and differential.
GenevisibleiQ04726. HS.

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. 2 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTLE3_HUMAN
AccessioniPrimary (citable) accession number: Q04726
Secondary accession number(s): B4DPT0
, E9PD64, F8W964, Q6PI57, Q8IVV6, Q8WVR2, Q9HCM5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 10, 2002
Last modified: November 30, 2016
This is version 174 of the entry and version 2 of the sequence. [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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.