Details of the Target

General Information of Target

Target ID LDTP13397
Target Name Lymphoid enhancer-binding factor 1 (LEF1)
Gene Name LEF1
Gene ID 51176
Synonyms
Lymphoid enhancer-binding factor 1; LEF-1; T cell-specific transcription factor 1-alpha; TCF1-alpha
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGANNGKQYGSEGKGSSSISSDVSSSTDHTPTKAQKNVATSEDSDLSMRTLSTPSPALIC
PPNLPGFQNGRGSSTSSSSITGETVAMVHSPPPTRLTHPLIRLASRPQKEQASIDRLPDH
SMVQIFSFLPTNQLCRCARVCRRWYNLAWDPRLWRTIRLTGETINVDRALKVLTRRLCQD
TPNVCLMLETVTVSGCRRLTDRGLYTIAQCCPELRRLEVSGCYNISNEAVFDVVSLCPNL
EHLDVSGCSKVTCISLTREASIKLSPLHGKQISIRYLDMTDCFVLEDEGLHTIAAHCTQL
THLYLRRCVRLTDEGLRYLVIYCASIKELSVSDCRFVSDFGLREIAKLESRLRYLSIAHC
GRVTDVGIRYVAKYCSKLRYLNARGCEGITDHGVEYLAKNCTKLKSLDIGKCPLVSDTGL
ECLALNCFNLKRLSLKSCESITGQGLQIVAANCFDLQTLNVQDCEVSVEALRFVKRHCKR
CVIEHTNPAFF
Target Bioclass
Transcription factor
Family
TCF/LEF family
Subcellular location
Nucleus
Function
Transcription factor that binds DNA in a sequence-specific manner. Participates in the Wnt signaling pathway. Activates transcription of target genes in the presence of CTNNB1 and EP300. PIAG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by LEF1 and CTNNB1. Regulates T-cell receptor alpha enhancer function. Required for IL17A expressing gamma-delta T-cell maturation and development, via binding to regulator loci of BLK to modulate expression. Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling. May play a role in hair cell differentiation and follicle morphogenesis.; [Isoform 1]: Transcriptionally activates MYC and CCND1 expression and enhances proliferation of pancreatic tumor cells.; [Isoform 3]: Lacks the CTNNB1 interaction domain and may therefore be an antagonist for Wnt signaling.; [Isoform 5]: Transcriptionally activates the fibronectin promoter, binds to and represses transcription from the E-cadherin promoter in a CTNNB1-independent manner, and is involved in reducing cellular aggregation and increasing cell migration of pancreatic cancer cells.
Uniprot ID
Q9UJU2
Ensemble ID
ENST00000265165.6
HGNC ID
HGNC:6551
ChEMBL ID
CHEMBL3217392

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CCK81 Deletion: p.D14TfsTer10 .
CORL23 SNV: p.G168R .
HT SNV: p.P302L .
Ishikawa (Heraklio) 02 ER Insertion: p.R296KfsTer5 .
MEWO SNV: p.S231F .
NCIH2172 SNV: p.P156S .
PANC0403 Deletion: p.E381RfsTer14 .
RKO Insertion: p.D14GfsTer39 .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 7 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C321(6.97)  LDD0209  [1]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [2]
IA-alkyne
 Probe Info  		N.A.  LDD0036  [2]
Lodoacetamide azide
 Probe Info  		N.A.  LDD0037  [2]
Compound 10
 Probe Info  		N.A.  LDD2216  [3]
Compound 11
 Probe Info  		N.A.  LDD2213  [3]
IPM
 Probe Info  		N.A.  LDD2156  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0625  F8 Ramos C321(1.00)  LDD2187  [5]
 LDCM0572  Fragment10 Ramos C321(1.00)  LDD2189  [5]
 LDCM0573  Fragment11 Ramos C18(7.56)  LDD2190  [5]
 LDCM0574  Fragment12 Ramos C321(0.82); C18(0.67)  LDD2191  [5]
 LDCM0575  Fragment13 Ramos C321(1.01)  LDD2192  [5]
 LDCM0576  Fragment14 Ramos C321(1.15); C18(0.79)  LDD2193  [5]
 LDCM0579  Fragment20 Ramos C321(0.81); C18(0.37)  LDD2194  [5]
 LDCM0580  Fragment21 Ramos C321(0.85); C18(1.56)  LDD2195  [5]
 LDCM0582  Fragment23 Ramos C321(1.02)  LDD2196  [5]
 LDCM0578  Fragment27 Ramos C321(0.57)  LDD2197  [5]
 LDCM0586  Fragment28 Ramos C321(0.75); C18(0.80)  LDD2198  [5]
 LDCM0588  Fragment30 Ramos C321(1.02)  LDD2199  [5]
 LDCM0589  Fragment31 Ramos C321(0.83); C18(2.00)  LDD2200  [5]
 LDCM0590  Fragment32 Ramos C321(0.87)  LDD2201  [5]
 LDCM0468  Fragment33 Ramos C321(0.77); C18(1.23)  LDD2202  [5]
 LDCM0596  Fragment38 Ramos C321(0.68); C18(0.52)  LDD2203  [5]
 LDCM0566  Fragment4 Ramos C321(0.89)  LDD2184  [5]
 LDCM0610  Fragment52 Ramos C321(1.04)  LDD2204  [5]
 LDCM0614  Fragment56 Ramos C321(1.05)  LDD2205  [5]
 LDCM0569  Fragment7 Ramos C321(1.22)  LDD2186  [5]
 LDCM0571  Fragment9 Ramos C321(0.94); C18(1.10)  LDD2188  [5]
 LDCM0022  KB02 HEK-293T C321(0.98)  LDD1492  [6]
 LDCM0023  KB03 Jurkat C321(6.97)  LDD0209  [1]
 LDCM0024  KB05 PF-382 C321(3.60); C18(0.75)  LDD3397  [7]
 LDCM0131  RA190 MM1.R C321(2.10)  LDD0304  [8]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Insulin-like growth factor 1 receptor (IGF1R) Tyr protein kinase family P08069
Bis(5'-adenosyl)-triphosphatase (FHIT) . P49789
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Nuclear factor erythroid 2-related factor 2 (NFE2L2) BZIP family Q16236
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Catenin beta-1 (CTNNB1) Beta-catenin family P35222

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Etacrynic Acid Small molecular drug DB00903

References

1 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.
2 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
3 Multiplexed CuAAC Suzuki-Miyaura Labeling for Tandem Activity-Based Chemoproteomic Profiling. Anal Chem. 2021 Feb 2;93(4):2610-2618. doi: 10.1021/acs.analchem.0c04726. Epub 2021 Jan 20.
Mass spectrometry data entry: PXD022279
4 Benchmarking Cleavable Biotin Tags for Peptide-Centric Chemoproteomics. J Proteome Res. 2022 May 6;21(5):1349-1358. doi: 10.1021/acs.jproteome.2c00174. Epub 2022 Apr 25.
Mass spectrometry data entry: PXD031019
5 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
6 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402
7 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
8 Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190. Cell Chem Biol. 2020 Nov 19;27(11):1371-1382.e6. doi: 10.1016/j.chembiol.2020.08.007. Epub 2020 Aug 27.