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Protein

Transducin-like enhancer protein 1

Gene

TLE1

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 NF-kappa-B-regulated gene expression. Inhibits the transcriptional activation mediated by FOXA2, 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. Unusual function as coactivator for ESRRG.1 Publication

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • RNA polymerase II transcription corepressor activity Source: BHF-UCL
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • animal organ morphogenesis Source: ProtInc
  • beta-catenin-TCF complex assembly Source: Reactome
  • multicellular organism development Source: ProtInc
  • negative regulation of anoikis Source: UniProtKB
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • positive regulation of gene expression 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:G66-31494-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.
SignaLinkiQ04724.
SIGNORiQ04724.

Names & Taxonomyi

Protein namesi
Recommended name:
Transducin-like enhancer protein 1
Alternative name(s):
E(Sp1) homolog
Enhancer of split groucho-like protein 1
Short name:
ESG1
Gene namesi
Name:TLE1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:11837. TLE1.

Subcellular locationi

  • Nucleus 1 Publication

  • Note: Nuclear and chromatin-associated, depending on isoforms and phosphorylation status. Hyperphosphorylation decreases the affinity for nuclear components.

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: UniProtKB
  • nucleolus Source: HPA
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi486V → S: Abolishes HESX1 binding. 1 Publication1
Mutagenesisi532Y → H: Abolishes HESX1 binding. 1 Publication1
Mutagenesisi702L → S: Abolishes HESX1 binding. 1 Publication1
Mutagenesisi715S → P: Abolishes HESX1 binding. 1 Publication1

Organism-specific databases

DisGeNETi7088.
OpenTargetsiENSG00000196781.
PharmGKBiPA36539.

Polymorphism and mutation databases

BioMutaiTLE1.
DMDMi29840816.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000512761 – 770Transducin-like enhancer protein 1Add BLAST770

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei239PhosphoserineCombined sources1
Modified residuei259Phosphoserine; by CDK1Sequence analysis1
Modified residuei263Phosphoserine; by CDK1Sequence analysis1
Modified residuei267Phosphoserine; by CDK1Sequence analysis1
Modified residuei286PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated, probably by CDK1. The degree of phosphorylation varies throughout the cell cycle, and is highest at the G2/M transition. Becomes hyperphosphorylated in response to cell differentiation and interaction with HES1 or RUNX1.
Ubiquitinated by XIAP/BIRC4.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ04724.
MaxQBiQ04724.
PaxDbiQ04724.
PeptideAtlasiQ04724.
PRIDEiQ04724.

PTM databases

iPTMnetiQ04724.
PhosphoSitePlusiQ04724.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000196781.
CleanExiHS_TLE1.
ExpressionAtlasiQ04724. baseline and differential.
GenevisibleiQ04724. HS.

Organism-specific databases

HPAiCAB011482.
HPA055160.

Interactioni

Subunit structurei

Homooligomer and heterooligomer with other family members. Binds LEF1, RUNX1, RUNX3, FOXA2, KDM6A, UTY, histone H3, HESX1, ESRRG and the NF-kappa-B subunit RELA. Interacts with HES1 (via WRPW motif). Interacts with SIX3. Interacts with EFNB1.12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-711424,EBI-711424
HIST2H4BP628056EBI-711424,EBI-302023
NOD2Q9HC292EBI-711424,EBI-7445625
RUNX1Q01196-14EBI-711424,EBI-925940
RUNX1Q01196-23EBI-711424,EBI-925944
RUNX3Q137613EBI-711424,EBI-925990
SIRT1Q96EB64EBI-711424,EBI-1802965
SYT-SSX2A4PIW011EBI-711424,EBI-6050533

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112943. 112 interactors.
DIPiDIP-36665N.
IntActiQ04724. 68 interactors.
MINTiMINT-190700.
STRINGi9606.ENSP00000365682.

Structurei

Secondary structure

1770
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi22 – 92Combined sources71
Helixi93 – 95Combined sources3
Helixi98 – 111Combined sources14
Helixi116 – 133Combined sources18
Beta strandi447 – 450Combined sources4
Beta strandi452 – 454Combined sources3
Beta strandi456 – 458Combined sources3
Beta strandi465 – 468Combined sources4
Beta strandi473 – 481Combined sources9
Beta strandi489 – 492Combined sources4
Beta strandi494 – 502Combined sources9
Beta strandi504 – 511Combined sources8
Beta strandi521 – 525Combined sources5
Beta strandi531 – 538Combined sources8
Beta strandi542 – 558Combined sources17
Beta strandi560 – 563Combined sources4
Beta strandi565 – 571Combined sources7
Beta strandi573 – 575Combined sources3
Beta strandi577 – 582Combined sources6
Beta strandi586 – 593Combined sources8
Beta strandi598 – 602Combined sources5
Turni603 – 606Combined sources4
Beta strandi607 – 612Combined sources6
Beta strandi619 – 624Combined sources6
Beta strandi628 – 635Combined sources8
Beta strandi638 – 644Combined sources7
Turni645 – 648Combined sources4
Beta strandi649 – 655Combined sources7
Beta strandi660 – 665Combined sources6
Beta strandi669 – 676Combined sources8
Beta strandi681 – 685Combined sources5
Beta strandi691 – 694Combined sources4
Beta strandi701 – 706Combined sources6
Beta strandi710 – 717Combined sources8
Beta strandi720 – 726Combined sources7
Turni727 – 729Combined sources3
Beta strandi732 – 737Combined sources6
Beta strandi742 – 747Combined sources6
Beta strandi753 – 758Combined sources6
Beta strandi763 – 769Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GXRX-ray1.65A/B443-770[»]
2CE8X-ray2.03A/B/C/D443-770[»]
2CE9X-ray2.12A/B/C/D443-770[»]
4OM2X-ray4.00A/B/C/D1-156[»]
4OM3X-ray2.86A/B/C/D15-156[»]
ProteinModelPortaliQ04724.
SMRiQ04724.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ04724.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati470 – 501WD 1Add BLAST32
Repeati528 – 558WD 2Add BLAST31
Repeati572 – 602WD 3Add BLAST31
Repeati614 – 644WD 4Add BLAST31
Repeati696 – 726WD 5Add BLAST31
Repeati737 – 767WD 6Add BLAST31

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 131Q domain1 PublicationAdd BLAST131
Regioni132 – 199GP domain1 PublicationAdd BLAST68
Regioni200 – 268CcN domain1 PublicationAdd BLAST69
Regioni269 – 450SP domain1 PublicationAdd BLAST182

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 6 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0639. Eukaryota.
ENOG410XPX3. LUCA.
GeneTreeiENSGT00550000074465.
HOGENOMiHOG000293211.
HOVERGENiHBG004689.
InParanoidiQ04724.
OMAiPPSMEIP.
OrthoDBiEOG091G181Y.
PhylomeDBiQ04724.
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]

Sequencei

Sequence statusi: Complete.

Q04724-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFPQSRHPTP HQAAGQPFKF TIPESLDRIK EEFQFLQAQY HSLKLECEKL
60 70 80 90 100
ASEKTEMQRH YVMYYEMSYG LNIEMHKQTE IAKRLNTICA QVIPFLSQEH
110 120 130 140 150
QQQVAQAVER AKQVTMAELN AIIGQQQLQA QHLSHGHGPP VPLTPHPSGL
160 170 180 190 200
QPPGIPPLGG SAGLLALSSA LSGQSHLAIK DDKKHHDAEH HRDREPGTSN
210 220 230 240 250
SLLVPDSLRG TDKRRNGPEF SNDIKKRKVD DKDSSHYDSD GDKSDDNLVV
260 270 280 290 300
DVSNEDPSSP RASPAHSPRE NGIDKNRLLK KDASSSPAST ASSASSTSLK
310 320 330 340 350
SKEMSLHEKA STPVLKSSTP TPRSDMPTPG TSATPGLRPG LGKPPAIDPL
360 370 380 390 400
VNQAAAGLRT PLAVPGPYPA PFGMVPHAGM NGELTSPGAA YASLHNMSPQ
410 420 430 440 450
MSAAAAAAAV VAYGRSPMVG FDPPPHMRVP TIPPNLAGIP GGKPAYSFHV
460 470 480 490 500
TADGQMQPVP FPPDALIGPG IPRHARQINT LNHGEVVCAV TISNPTRHVY
510 520 530 540 550
TGGKGCVKVW DISHPGNKSP VSQLDCLNRD NYIRSCKLLP DGCTLIVGGE
560 570 580 590 600
ASTLSIWDLA APTPRIKAEL TSSAPACYAL AISPDSKVCF SCCSDGNIAV
610 620 630 640 650
WDLHNQTLVR QFQGHTDGAS CIDISNDGTK LWTGGLDNTV RSWDLREGRQ
660 670 680 690 700
LQQHDFTSQI FSLGYCPTGE WLAVGMESSN VEVLHVNKPD KYQLHLHESC
710 720 730 740 750
VLSLKFAYCG KWFVSTGKDN LLNAWRTPYG ASIFQSKESS SVLSCDISVD
760 770
DKYIVTGSGD KKATVYEVIY
Length:770
Mass (Da):83,201
Last modified:March 25, 2003 - v2
Checksum:i695FD1A37410EFE5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti407 – 412AAAVVA → RGRRGR in AAA61192 (PubMed:1303260).Curated6
Sequence conflicti464 – 465DA → TP in AAA61192 (PubMed:1303260).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M99435 mRNA. Translation: AAA61192.1.
AK290860 mRNA. Translation: BAF83549.1.
AL365190, AL353682 Genomic DNA. Translation: CAI14977.1.
AL353682, AL365190 Genomic DNA. Translation: CAI12595.1.
CH471089 Genomic DNA. Translation: EAW62636.1.
BC010100 mRNA. Translation: AAH10100.1.
BC015747 mRNA. Translation: AAH15747.1.
CCDSiCCDS6661.1.
PIRiB56695.
RefSeqiNP_001290032.1. NM_001303103.1.
NP_001290033.1. NM_001303104.1.
NP_005068.2. NM_005077.4.
UniGeneiHs.197320.
Hs.689805.

Genome annotation databases

EnsembliENST00000376499; ENSP00000365682; ENSG00000196781.
GeneIDi7088.
KEGGihsa:7088.
UCSCiuc004aly.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M99435 mRNA. Translation: AAA61192.1.
AK290860 mRNA. Translation: BAF83549.1.
AL365190, AL353682 Genomic DNA. Translation: CAI14977.1.
AL353682, AL365190 Genomic DNA. Translation: CAI12595.1.
CH471089 Genomic DNA. Translation: EAW62636.1.
BC010100 mRNA. Translation: AAH10100.1.
BC015747 mRNA. Translation: AAH15747.1.
CCDSiCCDS6661.1.
PIRiB56695.
RefSeqiNP_001290032.1. NM_001303103.1.
NP_001290033.1. NM_001303104.1.
NP_005068.2. NM_005077.4.
UniGeneiHs.197320.
Hs.689805.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GXRX-ray1.65A/B443-770[»]
2CE8X-ray2.03A/B/C/D443-770[»]
2CE9X-ray2.12A/B/C/D443-770[»]
4OM2X-ray4.00A/B/C/D1-156[»]
4OM3X-ray2.86A/B/C/D15-156[»]
ProteinModelPortaliQ04724.
SMRiQ04724.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112943. 112 interactors.
DIPiDIP-36665N.
IntActiQ04724. 68 interactors.
MINTiMINT-190700.
STRINGi9606.ENSP00000365682.

PTM databases

iPTMnetiQ04724.
PhosphoSitePlusiQ04724.

Polymorphism and mutation databases

BioMutaiTLE1.
DMDMi29840816.

Proteomic databases

EPDiQ04724.
MaxQBiQ04724.
PaxDbiQ04724.
PeptideAtlasiQ04724.
PRIDEiQ04724.

Protocols and materials databases

DNASUi7088.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000376499; ENSP00000365682; ENSG00000196781.
GeneIDi7088.
KEGGihsa:7088.
UCSCiuc004aly.4. human.

Organism-specific databases

CTDi7088.
DisGeNETi7088.
GeneCardsiTLE1.
HGNCiHGNC:11837. TLE1.
HPAiCAB011482.
HPA055160.
MIMi600189. gene.
neXtProtiNX_Q04724.
OpenTargetsiENSG00000196781.
PharmGKBiPA36539.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0639. Eukaryota.
ENOG410XPX3. LUCA.
GeneTreeiENSGT00550000074465.
HOGENOMiHOG000293211.
HOVERGENiHBG004689.
InParanoidiQ04724.
OMAiPPSMEIP.
OrthoDBiEOG091G181Y.
PhylomeDBiQ04724.
TreeFamiTF314167.

Enzyme and pathway databases

BioCyciZFISH:G66-31494-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.
SignaLinkiQ04724.
SIGNORiQ04724.

Miscellaneous databases

ChiTaRSiTLE1. human.
EvolutionaryTraceiQ04724.
GeneWikiiTLE1.
GenomeRNAii7088.
PROiQ04724.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196781.
CleanExiHS_TLE1.
ExpressionAtlasiQ04724. baseline and differential.
GenevisibleiQ04724. 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 nameiTLE1_HUMAN
AccessioniPrimary (citable) accession number: Q04724
Secondary accession number(s): A8K495, Q5T3G4, Q969V9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: March 25, 2003
Last modified: November 2, 2016
This is version 177 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

3D-structure, Complete proteome, Direct protein sequencing, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.