LEF1 (lymphoid enhancer binding factor 1)

Gene

• Entrez ID: 51176
• Gene name: Lymphoid enhancer binding factor 1
• Gene symbol: LEF1
• Synonyms: LEF-1, TCF10, TCF1ALPHA, TCF7L3
• Chromosome: 4
• Chromosome location: 4q25
• Summary: 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]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016343	hsa-miR-193b-3p	Microarray	20304954
MIRT025380	hsa-miR-34a-5p	Reporter assay;Proteomics	21566225
MIRT025380	hsa-miR-34a-5p	Luciferase reporter assay, Western blot, Microarray	25587085
MIRT025380	hsa-miR-34a-5p	qRT-PCR, Western blot	28098757
MIRT053004	hsa-miR-218-5p	Luciferase reporter assay, Western blot	22766851
MIRT053005	hsa-miR-449a	Luciferase reporter assay, qRT-PCR, Western blot	22769578
MIRT054053	hsa-miR-34c-3p	Luciferase reporter assay, Western blot	22421157
MIRT437781	hsa-miR-452-5p	Immunofluorescence, Western blot	23695168

Transcription factors

Transcription factor	Regulation	Reference
AES	Activation	20676368
LMO2	Repression	22517897
PAX5	Activation	9545244
PITX2	Activation	17785445
ZBTB16	Unknown	19723763

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	23001182
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	7657162, 16344550, 17063141, 18579517, 19351848, 20128911, 20363964
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	23001182
GO:0001569	Process	Branching involved in blood vessel morphogenesis	IEA
GO:0001649	Process	Osteoblast differentiation	IEP	20128911
GO:0001756	Process	Somitogenesis	IEA
GO:0001837	Process	Epithelial to mesenchymal transition	ISS
GO:0002040	Process	Sprouting angiogenesis	IEA
GO:0003677	Function	DNA binding	ISS
GO:0003682	Function	Chromatin binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IDA	11751639
GO:0005515	Function	Protein binding	IPI	9751710, 12192039, 17510365, 17517646, 18077326, 18936100, 19460168, 20123964, 21743491, 22261717, 23001182, 29540185, 32911434
GO:0005634	Component	Nucleus	IC
GO:0005634	Component	Nucleus	IDA	17063141, 18579517, 18936100, 23001182
GO:0005654	Component	Nucleoplasm	TAS
GO:0005667	Component	Transcription regulator complex	IDA	11751639, 23001182
GO:0005737	Component	Cytoplasm	IDA	19402906, 23001182
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0007223	Process	Wnt signaling pathway, calcium modulating pathway	TAS
GO:0008013	Function	Beta-catenin binding	IDA	9488439
GO:0008013	Function	Beta-catenin binding	IPI	10825188, 12408825, 18936100, 20123964, 20360943
GO:0008013	Function	Beta-catenin binding	TAS	16344550
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	19351848
GO:0008301	Function	DNA binding, bending	ISS
GO:0010628	Process	Positive regulation of gene expression	IDA	16344550
GO:0010718	Process	Positive regulation of epithelial to mesenchymal transition	IMP	20018240
GO:0021542	Process	Dentate gyrus development	IEA
GO:0021861	Process	Forebrain radial glial cell differentiation	IEA
GO:0021873	Process	Forebrain neuroblast division	IEA
GO:0021943	Process	Formation of radial glial scaffolds	IEA
GO:0030111	Process	Regulation of Wnt signaling pathway	IEA
GO:0030223	Process	Neutrophil differentiation	IMP	17063141
GO:0030284	Function	Estrogen receptor activity	IDA	18794125
GO:0030326	Process	Embryonic limb morphogenesis	IEA
GO:0030331	Function	Estrogen receptor binding	IDA	18794125
GO:0030335	Process	Positive regulation of cell migration	IMP	20018240
GO:0030509	Process	BMP signaling pathway	IEA
GO:0030854	Process	Positive regulation of granulocyte differentiation	IDA	19620402
GO:0030854	Process	Positive regulation of granulocyte differentiation	IMP	23001182
GO:0030879	Process	Mammary gland development	IEA
GO:0032696	Process	Negative regulation of interleukin-13 production	IDA	18445004
GO:0032713	Process	Negative regulation of interleukin-4 production	IDA	18445004
GO:0032714	Process	Negative regulation of interleukin-5 production	IDA	18445004
GO:0032993	Component	Protein-DNA complex	IDA	10825188
GO:0033153	Process	T cell receptor V(D)J recombination	IEA
GO:0042100	Process	B cell proliferation	IEA
GO:0042393	Function	Histone binding	IPI	20363964
GO:0042475	Process	Odontogenesis of dentin-containing tooth	IEA
GO:0042826	Function	Histone deacetylase binding	IPI	18936100
GO:0043066	Process	Negative regulation of apoptotic process	IMP	20360943
GO:0043392	Process	Negative regulation of DNA binding	IDA	18445004
GO:0043401	Process	Steroid hormone mediated signaling pathway	IEA
GO:0043565	Function	Sequence-specific DNA binding	IDA	10825188
GO:0043586	Process	Tongue development	IEA
GO:0043923	Process	Positive regulation by host of viral transcription	IDA	7657162
GO:0043966	Process	Histone H3 acetylation	IMP	20363964
GO:0043967	Process	Histone H4 acetylation	IMP	20363964
GO:0045063	Process	T-helper 1 cell differentiation	ISS
GO:0045295	Function	Gamma-catenin binding	IPI	14661054
GO:0045588	Process	Positive regulation of gamma-delta T cell differentiation	ISS
GO:0045843	Process	Negative regulation of striated muscle tissue development	IEA
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IDA	18794125
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IMP	18579517, 20363964
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	7657162, 10644691, 17063141, 19620402, 20128911
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IMP	19351848
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	11751639, 23001182
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	23001182
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0048341	Process	Paraxial mesoderm formation	IEA
GO:0050909	Process	Sensory perception of taste	IEA
GO:0060033	Process	Anatomical structure regression	IEA
GO:0060070	Process	Canonical Wnt signaling pathway	IBA	21873635
GO:0060070	Process	Canonical Wnt signaling pathway	IDA	10644691, 20123964
GO:0060325	Process	Face morphogenesis	IEA
GO:0060326	Process	Cell chemotaxis	IDA	19576624
GO:0060710	Process	Chorio-allantoic fusion	IEA
GO:0061153	Process	Trachea gland development	IEA
GO:0062009	Process	Secondary palate development	ISS
GO:0070016	Function	Armadillo repeat domain binding	IPI	12408825
GO:0070742	Function	C2H2 zinc finger domain binding	IPI	18445004
GO:0071345	Process	Cellular response to cytokine stimulus	IMP	23001182
GO:0071353	Process	Cellular response to interleukin-4	IDA	18579517
GO:0071864	Process	Positive regulation of cell proliferation in bone marrow	IMP	17063141
GO:0071866	Process	Negative regulation of apoptotic process in bone marrow cell	IMP	17063141
GO:0071899	Process	Negative regulation of estrogen receptor binding	IDA	18794125
GO:1902262	Process	Apoptotic process involved in blood vessel morphogenesis	IEA
GO:1904837	Process	Beta-catenin-TCF complex assembly	TAS
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536
GO:1990907	Component	Beta-catenin-TCF complex	IBA	21873635
GO:1990907	Component	Beta-catenin-TCF complex	IPI	18936100

Other IDs

• MIM: 153245
• HGNC: 6551
• e!Ensembl: ENSG00000138795

Protein

• UniProt ID: Q9UJU2
• Protein name: Lymphoid enhancer-binding factor 1 (LEF-1) (T cell-specific transcription factor 1-alpha) (TCF1-alpha)
• Protein function: Transcription factor that binds DNA in a sequence-specific manner (PubMed:2010090). Participates in the Wnt signaling pathway (By similarity). Activates transcription of target genes in the presence of CTNNB1 and EP300 (By similarity). PIAG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1 (By similarity). TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by LEF1 and CTNNB1 (PubMed:11266540). Regulates T-cell receptor alpha enhancer function (PubMed:19653274). Required for IL17A expressing gamma-delta T-cell maturation and development, via binding to regulator loci of BLK to modulate expression (By similarity). May play a role in hair cell differentiation and follicle morphogenesis (By similarity). ; [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.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08347	CTNNB1_binding	1 → 213	N-terminal CTNNB1 binding	Family
  PF00505	HMG_box	299 → 367	HMG (high mobility group) box	Domain

• Sequence:

  MPQLSGGGGGGGGDPELCATDEMIPFKDEGDPQKEKIFAEISHPEEEGDLADIKSSLVNE
  SEIIPASNGHEVARQAQTSQEPYHDKAREHPDDGKHPDGGLYNKGPSYSSYSGYIMMPNM
  NNDPYMSNGSLSPPIPRTSNKVPVVQPSHAVHPLTPLITYSDEHFSPGSHPSHIPSDVNS
  KQGMSRHPPAPDIPTFYPLSPGGVGQITPPLGWQGQPVYPITGGFRQPYPSSLSVDTSMS
  RFSHHMIPGPPGPHTTGIPHPAIVTPQVKQEHPHTDSDLMHVKPQHEQRKEQEPKRPHIK
  KPLNAFMLYMKEMRANVVAECTLKESAAINQILGRRWHALSREEQAKYYELARKERQLHM
  QLYPGWSARDNYGKKKKRKREKLQESASGTGPRMTAAYI

• Sequence length: 399