Tchem LEF1 Lymphoid enhancer-binding factor 1

Protein Summary

Description

Participates in the Wnt signaling pathway. Activates transcription of target genes in the presence of CTNNB1 and EP300. May play a role in hair cell differentiation and follicle morphogenesis. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by LEF1 and CTNNB1. Regulates T-cell receptor alpha enhancer function. Binds DNA in a sequence-specific manner. PIAG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1 (By similarity). Isoform 3 lacks the CTNNB1 interaction domain and may 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. Isoform 1 transcriptionally activates MYC and CCND1 expression and enhances proliferation of pancreatic tumor cells. This gene encodes a transcription factor belonging to a family of proteins that share homology with the high mobility group protein-1. The protein encoded by this gene can bind to a functionally important site in the T-cell receptor-alpha enhancer, thereby conferring maximal enhancer activity. This transcription factor is involved in the Wnt signaling pathway, and it may function in hair cell differentiation and follicle morphogenesis. Mutations in this gene have been found in somatic sebaceous tumors. This gene has also been linked to other cancers, including androgen-independent prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Uniprot Accession IDs

• Q9UJU2
• B4DG38
• B7Z8E2
• E9PDK3
• Q3ZCU4
• Q9HAZ0
• LEF-1

Gene Name

• LEF1

Ensembl ID

• ENST00000265165
• ENSP00000265165
• ENSG00000138795
• ENST00000379951
• ENSP00000369284
• ENST00000438313
• ENSP00000406176
• ENST00000506680
• ENSP00000422334
• ENST00000510624
• ENSP00000422840

Symbol

• LEF-1
• TCF10
• TCF7L3
• TCF1ALPHA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
molecular function	1
PubMedID	0.98
hub protein	0.85
transcription factor	0.83

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 552.85   (req: < 5)

Gene RIFs: 126   (req: <= 3)

Antibodies: 722   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 552.85   (req: >= 5)

Gene RIFs: 126   (req: > 3)

Antibodies: 722   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 89

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (1)

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1 – 1 of 1

Lefmycin-2

LEF1Tchem TF

pIC50 : 6.82

Protein-Protein Interactions (312)

Explore Interacting Targets

1 – 10 of 312

• See Interactions on String-DB

PRMT6

Tchem

Family:  Epigenetic

Novelty:  0.01734208

p_int:  0.901663692

p_ni:  0.0983363

p_wrong:  7e-9

Score:  0.288

Data Source:  BioPlex,STRINGDB

CTNNB1

Tchem

Novelty:  0.0000744

Score:  0.999

Data Source:  Reactome,STRINGDB

AXIN2

Tchem

Novelty:  0.00273189

Score:  0.988

Data Source:  STRINGDB

NLK

Tchem

Family:  Kinase

Novelty:  0.01512201

Score:  0.986

Data Source:  Reactome,STRINGDB

PITX2

Tbio

Family:  TF

Novelty:  0.00216568

Score:  0.982

Data Source:  STRINGDB

MYC

Tchem

Family:  TF

Novelty:  0.00005734

Score:  0.981

Data Source:  STRINGDB

EP300

Tchem

Family:  Epigenetic

Novelty:  0.00055009

Score:  0.978

Data Source:  Reactome,STRINGDB

TLE1

Tbio

Novelty:  0.00594261

Score:  0.975

Data Source:  Reactome,STRINGDB

CCND1

Tchem

Novelty:  0.0001186

Score:  0.969

Data Source:  STRINGDB

HDAC1

Tclin

Family:  Epigenetic

Novelty:  0.00065244

Score:  0.968

Data Source:  Reactome,STRINGDB

Nearest Tclin Targets (9)

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Upstream (2)

Downstream (7)

1 – 2 of 2

GSK3B

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  12

1: Gastric cancer

2: Cushing syndrome

3: Breast cancer

4: Basal cell carcinoma

more:  8 more common pathways

RARA

Tclin

Family:  Nuclear Receptor

KEGG Distance:  2

Common Pathways:  2

1: Acute myeloid leukemia

2: Pathways in cancer

Pathways (83)

Reactome (17)

KEGG (16)

PathwayCommons (28)

WikiPathways (22)

Beta-catenin independent WNT signaling (R-HSA-3858494)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Beta-catenin independent WNT signaling	146 targets	R-HSA-3858494
Reactome	Binding of TCF/LEF:CTNNB1 to target gene promoters	8 targets	R-HSA-4411364
Reactome	Ca2+ pathway	61 targets	R-HSA-4086398
Reactome	Deactivation of the beta-catenin transactivating complex	42 targets	R-HSA-3769402
Reactome	Degradation of beta-catenin by the destruction complex	85 targets	R-HSA-195253

Name	Explore in Pharos	Explore in Source
Beta-catenin independent WNT signaling	146 targets	R-HSA-3858494
Binding of TCF/LEF:CTNNB1 to target gene promoters	8 targets	R-HSA-4411364
Ca2+ pathway	61 targets	R-HSA-4086398
Deactivation of the beta-catenin transactivating complex	42 targets	R-HSA-3769402
Degradation of beta-catenin by the destruction complex	85 targets	R-HSA-195253

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (95)

Functions (22)

Components (6)

Processes (67)

Find Similar Targets

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1 – 10 of 22

GO Term	Evidence	Assigned by
beta-catenin binding	Inferred from Direct Assay (IDA)	BHF-UCL
DNA-binding transcription factor activity	Inferred from Direct Assay (IDA)	BHF-UCL
enhancer binding	Inferred from Direct Assay (IDA)	UniProtKB
estrogen receptor activity	Inferred from Direct Assay (IDA)	UniProtKB
estrogen receptor binding	Inferred from Direct Assay (IDA)	UniProtKB
RNA polymerase II regulatory region sequence-specific DNA binding	Inferred from Direct Assay (IDA)	BHF-UCL
sequence-specific DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
transcription regulatory region DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
armadillo repeat domain binding	Inferred from Physical Interaction (IPI)	BHF-UCL
C2H2 zinc finger domain binding	Inferred from Physical Interaction (IPI)	UniProtKB

Disease Associations ()

No disease associations found

GWAS Traits (6)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
hair color	EFO_0003924	1	2	0	1.2	75.7
testosterone measurement	EFO_0004908	2	1	2		71.9
chronic lymphocytic leukemia	EFO_0000095	2	2	0	1.2	53.1
multiple sclerosis	EFO_0003885	1	1	0	1.1	49.5
heel bone mineral density	EFO_0009270	1	1	1		31.4

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
hair color	EFO_0003924	0	1.2	75.7
testosterone measurement	EFO_0004908	2		71.9
chronic lymphocytic leukemia	EFO_0000095	0	1.2	53.1
multiple sclerosis	EFO_0003885	0	1.1	49.5
heel bone mineral density	EFO_0009270	1		31.4

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UniProt Keyword Find Similar Targets

No Header	No Header
Activator
Alternative promoter usage
Alternative splicing
Complete proteome
Direct protein sequencing
DNA-binding
Isopeptide bond
Nucleus
Phosphoprotein
Polymorphism

GWAS Trait Find Similar Targets

No Header	No Header
Calcium channel blocker use measurement
chronic lymphocytic leukemia
hair color
heel bone mineral density
multiple sclerosis
testosterone measurement

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
integument phenotype
mortality/aging
muscle phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	lymphoid enhancer binding factor 1	VGNC:6477	461425
Macaque	lymphoid enhancer binding factor 1		695776
Mouse	lymphoid enhancer binding factor 1	MGI:96770	16842
Rat	lymphoid enhancer binding factor 1	RGD:620241	161452
Dog	lymphoid enhancer binding factor 1	VGNC:42630	478507

Species	Name	OMA	EggNOG	Inparanoid
Chimp	lymphoid enhancer binding factor 1
Macaque	lymphoid enhancer binding factor 1
Mouse	lymphoid enhancer binding factor 1
Rat	lymphoid enhancer binding factor 1
Dog	lymphoid enhancer binding factor 1

Publication Statistics

PubMed Score 552.85

PubMed score by year

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PubTator Score 365.50

PubTator score by year

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Related Publications

Text Mined References (186)

GeneRif Annotations (126)

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PMID	Year	Title