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Protein

Transducin-like enhancer protein 2

Gene

TLE2

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 - Molecular functioni

  • transcription corepressor activity Source: UniProtKB

GO - Biological processi

  • animal organ morphogenesis Source: ProtInc
  • beta-catenin-TCF complex assembly Source: Reactome
  • negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • 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:ENSG00000065717-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.
SignaLinkiQ04725.
SIGNORiQ04725.

Names & Taxonomyi

Protein namesi
Recommended name:
Transducin-like enhancer protein 2
Alternative name(s):
Enhancer of split groucho-like protein 2
Short name:
ESG2
Gene namesi
Name:TLE2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:11838. TLE2.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: UniProtKB
  • focal adhesion Source: HPA
  • nucleoplasm Source: Reactome
  • nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi7089.
OpenTargetsiENSG00000065717.
PharmGKBiPA36540.

Polymorphism and mutation databases

BioMutaiTLE2.
DMDMi20532416.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000512781 – 743Transducin-like enhancer protein 2Add BLAST743

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei228Phosphoserine; by CK2Sequence analysis1
Modified residuei249Phosphoserine; by CDK1Sequence analysis1
Modified residuei253Phosphothreonine; by CDK1Sequence analysis1
Modified residuei281PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated by XIAP/BIRC4.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ04725.
MaxQBiQ04725.
PaxDbiQ04725.
PeptideAtlasiQ04725.
PRIDEiQ04725.

PTM databases

iPTMnetiQ04725.
PhosphoSitePlusiQ04725.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000065717.
CleanExiHS_TLE2.
ExpressionAtlasiQ04725. baseline and differential.
GenevisibleiQ04725. HS.

Organism-specific databases

HPAiHPA049103.

Interactioni

Subunit structurei

Homooligomer and heterooligomer with other family members. Binds LEF1, TCF7, TCF7L1, TCF7L2, UTY, HES1 and HES5.

Binary interactionsi

WithEntry#Exp.IntActNotes
DDB1Q165312EBI-1176061,EBI-350322

Protein-protein interaction databases

BioGridi112944. 22 interactors.
IntActiQ04725. 3 interactors.
STRINGi9606.ENSP00000262953.

Structurei

3D structure databases

ProteinModelPortaliQ04725.
SMRiQ04725.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati455 – 493WD 1Add BLAST39
Repeati501 – 540WD 2Add BLAST40
Repeati545 – 584WD 3Add BLAST40
Repeati587 – 626WD 4Add BLAST40
Repeati669 – 708WD 5Add BLAST40
Repeati710 – 742WD 6Add BLAST33

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 127Q domainBy similarityAdd BLAST127
Regioni128 – 191GP domainBy similarityAdd BLAST64
Regioni192 – 254CcN domainBy similarityAdd BLAST63
Regioni255 – 423SP domainBy similarityAdd BLAST169

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi214 – 217Nuclear 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 6 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0639. Eukaryota.
ENOG410XPX3. LUCA.
GeneTreeiENSGT00550000074465.
HOGENOMiHOG000293211.
HOVERGENiHBG004689.
InParanoidiQ04725.
PhylomeDBiQ04725.
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. 3 hits.
[Graphical view]
PRINTSiPR01850. GROUCHOFAMLY.
SMARTiSM00320. WD40. 7 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 3 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q04725-1) [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
MYPQGRHPTP LQSGQPFKFS ILEICDRIKE EFQFLQAQYH SLKLECEKLA
60 70 80 90 100
SEKTEMQRHY VMYYEMSYGL NIEMHKQAEI VKRLSGICAQ IIPFLTQEHQ
110 120 130 140 150
QQVLQAVERA KQVTVGELNS LIGQQLQPLS HHAPPVPLTP RPAGLVGGSA
160 170 180 190 200
TGLLALSGAL AAQAQLAAAV KEDRAGVEAE GSRVERAPSR SASPSPPESL
210 220 230 240 250
VEEERPSGPG GGGKQRADEK EPSGPYESDE DKSDYNLVVD EDQPSEPPSP
260 270 280 290 300
ATTPCGKVPI CIPARRDLVD SPASLASSLG SPLPRAKELI LNDLPASTPA
310 320 330 340 350
SKSCDSSPPQ DASTPGPSSA SHLCQLAAKP APSTDSVALR SPLTLSSPFT
360 370 380 390 400
TSFSLGSHST LNGDLSVPSS YVSLHLSPQV SSSVVYGRSP VMAFESHPHL
410 420 430 440 450
RGSSVSSSLP SIPGGKPAYS FHVSADGQMQ PVPFPSDALV GAGIPRHARQ
460 470 480 490 500
LHTLAHGEVV CAVTISGSTQ HVYTGGKGCV KVWDVGQPGA KTPVAQLDCL
510 520 530 540 550
NRDNYIRSCK LLPDGRSLIV GGEASTLSIW DLAAPTPRIK AELTSSAPAC
560 570 580 590 600
YALAVSPDAK VCFSCCSDGN IVVWDLQNQT MVRQFQGHTD GASCIDISDY
610 620 630 640 650
GTRLWTGGLD NTVRCWDLRE GRQLQQHDFS SQIFSLGHCP NQDWLAVGME
660 670 680 690 700
SSNVEILHVR KPEKYQLHLH ESCVLSLKFA SCGRWFVSTG KDNLLNAWRT
710 720 730 740
PYGASIFQSK ESSSVLSCDI SRNNKYIVTG SGDKKATVYE VVY
Length:743
Mass (Da):79,841
Last modified:May 10, 2002 - v2
Checksum:i5E3DBFAB67278219
GO
Isoform 2 (identifier: Q04725-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: Missing.
     124-190: Missing.

Note: No experimental confirmation available.
Show »
Length:621
Mass (Da):66,678
Checksum:iF5100FF0B0FECFBA
GO
Isoform 3 (identifier: Q04725-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MYPQGRHP → MVQSRLTATSASQDSPASGLQ
     124-124: Q → QQ
     683-743: GRWFVSTGKDNLLNAWRTPYGASIFQSKESSSVLSCDISRNNKYIVTGSGDKKATVYEVVY → VQGVVLSPEL

Note: No experimental confirmation available.
Show »
Length:706
Mass (Da):75,364
Checksum:i71A2BA068112A6AE
GO

Sequence cautioni

The sequence AK308137 differs from that shown. Reason: Frameshift at position 537.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti280G → R in AAA61193 (PubMed:1303260).Curated1
Sequence conflicti328A → L in AAA61193 (PubMed:1303260).Curated1
Sequence conflicti441G → D in AAA61193 (PubMed:1303260).Curated1
Sequence conflicti495A → R in AAA61193 (PubMed:1303260).Curated1
Sequence conflicti636 – 637LG → PC in AAA61193 (PubMed:1303260).Curated2
Sequence conflicti660R → G in AAA61193 (PubMed:1303260).Curated1
Sequence conflicti681S → P in AAA61193 (PubMed:1303260).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069063381S → G.1 PublicationCorresponds to variant rs199788562dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0456931 – 55Missing in isoform 2. 1 PublicationAdd BLAST55
Alternative sequenceiVSP_0461621 – 8MYPQGRHP → MVQSRLTATSASQDSPASGL Q in isoform 3. 1 Publication8
Alternative sequenceiVSP_045694124 – 190Missing in isoform 2. 1 PublicationAdd BLAST67
Alternative sequenceiVSP_046163124Q → QQ in isoform 3. 1 Publication1
Alternative sequenceiVSP_046164683 – 743GRWFV…YEVVY → VQGVVLSPEL in isoform 3. 1 PublicationAdd BLAST61

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M99436 mRNA. Translation: AAA61193.1.
AK293407 mRNA. Translation: BAG56914.1.
AK308137 mRNA. No translation available.
AC007766 Genomic DNA. Translation: AAD38075.1.
AC011549 Genomic DNA. No translation available.
AC093053 Genomic DNA. No translation available.
BC017364 mRNA. Translation: AAH17364.1.
CCDSiCCDS45911.1. [Q04725-1]
CCDS45912.1. [Q04725-2]
CCDS45913.1. [Q04725-3]
PIRiC56695.
RefSeqiNP_001138233.1. NM_001144761.1. [Q04725-3]
NP_001138234.1. NM_001144762.1. [Q04725-2]
NP_001287775.1. NM_001300846.1.
NP_003251.2. NM_003260.4. [Q04725-1]
UniGeneiHs.332173.

Genome annotation databases

EnsembliENST00000262953; ENSP00000262953; ENSG00000065717. [Q04725-1]
ENST00000426948; ENSP00000392869; ENSG00000065717. [Q04725-3]
ENST00000443826; ENSP00000392427; ENSG00000065717. [Q04725-2]
ENST00000455444; ENSP00000413107; ENSG00000065717. [Q04725-2]
ENST00000591529; ENSP00000468279; ENSG00000065717. [Q04725-3]
GeneIDi7089.
KEGGihsa:7089.
UCSCiuc002lww.3. human. [Q04725-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M99436 mRNA. Translation: AAA61193.1.
AK293407 mRNA. Translation: BAG56914.1.
AK308137 mRNA. No translation available.
AC007766 Genomic DNA. Translation: AAD38075.1.
AC011549 Genomic DNA. No translation available.
AC093053 Genomic DNA. No translation available.
BC017364 mRNA. Translation: AAH17364.1.
CCDSiCCDS45911.1. [Q04725-1]
CCDS45912.1. [Q04725-2]
CCDS45913.1. [Q04725-3]
PIRiC56695.
RefSeqiNP_001138233.1. NM_001144761.1. [Q04725-3]
NP_001138234.1. NM_001144762.1. [Q04725-2]
NP_001287775.1. NM_001300846.1.
NP_003251.2. NM_003260.4. [Q04725-1]
UniGeneiHs.332173.

3D structure databases

ProteinModelPortaliQ04725.
SMRiQ04725.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112944. 22 interactors.
IntActiQ04725. 3 interactors.
STRINGi9606.ENSP00000262953.

PTM databases

iPTMnetiQ04725.
PhosphoSitePlusiQ04725.

Polymorphism and mutation databases

BioMutaiTLE2.
DMDMi20532416.

Proteomic databases

EPDiQ04725.
MaxQBiQ04725.
PaxDbiQ04725.
PeptideAtlasiQ04725.
PRIDEiQ04725.

Protocols and materials databases

DNASUi7089.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262953; ENSP00000262953; ENSG00000065717. [Q04725-1]
ENST00000426948; ENSP00000392869; ENSG00000065717. [Q04725-3]
ENST00000443826; ENSP00000392427; ENSG00000065717. [Q04725-2]
ENST00000455444; ENSP00000413107; ENSG00000065717. [Q04725-2]
ENST00000591529; ENSP00000468279; ENSG00000065717. [Q04725-3]
GeneIDi7089.
KEGGihsa:7089.
UCSCiuc002lww.3. human. [Q04725-1]

Organism-specific databases

CTDi7089.
DisGeNETi7089.
GeneCardsiTLE2.
HGNCiHGNC:11838. TLE2.
HPAiHPA049103.
MIMi601041. gene.
neXtProtiNX_Q04725.
OpenTargetsiENSG00000065717.
PharmGKBiPA36540.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0639. Eukaryota.
ENOG410XPX3. LUCA.
GeneTreeiENSGT00550000074465.
HOGENOMiHOG000293211.
HOVERGENiHBG004689.
InParanoidiQ04725.
PhylomeDBiQ04725.
TreeFamiTF314167.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000065717-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.
SignaLinkiQ04725.
SIGNORiQ04725.

Miscellaneous databases

ChiTaRSiTLE2. human.
GeneWikiiTLE2.
GenomeRNAii7089.
PROiQ04725.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000065717.
CleanExiHS_TLE2.
ExpressionAtlasiQ04725. baseline and differential.
GenevisibleiQ04725. 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. 3 hits.
[Graphical view]
PRINTSiPR01850. GROUCHOFAMLY.
SMARTiSM00320. WD40. 7 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 3 hits.
PS50294. WD_REPEATS_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTLE2_HUMAN
AccessioniPrimary (citable) accession number: Q04725
Secondary accession number(s): B4DE03
, E9PEV7, F8WCH2, Q8WVY0, Q9Y6S0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 10, 2002
Last modified: November 2, 2016
This is version 159 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, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: 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.