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P27782 (LEF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lymphoid enhancer-binding factor 1

Short name=LEF-1
Gene names
Name:Lef1
Synonyms:Lef-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length397 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Regulates T-cell receptor alpha enhancer function. Binds DNA in a sequence-specific manner. PIASG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1. Ref.5

Subunit structure

Binds the armadillo repeat of CTNNB1 and forms a stable complex. Binds TLE1, ALYREF/THOC4, MDFI and MDFIC By similarity. Interacts with NLK By similarity. Interacts with EP300 and PIASG. Ref.4 Ref.6 Ref.7

Subcellular location

Nucleus. Note: Found in nuclear bodies upon PIASG binding.

Tissue specificity

Lymphocytes. Found in distinct epithelial cell compartments of the skin and is abundant in the hair-producing progenitors of the follicle. Ref.3

Developmental stage

Detected throughout the basal layer, in ectodermal placodes and the underlying dermal condensates in embryonic skin, and in epithelium and mesenchyme from early hair germs. At birth expression decreases in the basal level of the epidermis and increases in hair bulbs, in particular in matrix and precortex. At day 6-9 expression is concentrated in follicle bulbs and in the hair shaft in a concentric ring of hair-keratin-expressing cells derived from the precortex. Detected in dermal papilla throughout the hair cycle, and in a subset of cells emanating from the bulge to form the secondary hair germ.

Domain

Proline-rich and acidic regions are implicated in the activation functions of RNA polymerase II transcription factors.

Post-translational modification

Phosphorylated at Thr-153 and/or Ser-164 by NLK. Phosphorylation by NLK at these sites represses LEF1-mediated transcriptional activation of target genes of the canonical Wnt signaling pathway By similarity.

Sequence similarities

Belongs to the TCF/LEF family.

Contains 1 HMG box DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Wnt signaling pathway
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   LigandDNA-binding
   Molecular functionActivator
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell proliferation

Inferred from mutant phenotype PubMed 10933391. Source: MGI

BMP signaling pathway

Inferred from direct assay PubMed 9769173. Source: MGI

T cell receptor V(D)J recombination

Inferred from genetic interaction PubMed 9462507. Source: MGI

T-helper 1 cell differentiation

Inferred from direct assay PubMed 18579517. Source: UniProtKB

Wnt signaling pathway

Inferred from direct assay PubMed 9769173. Source: MGI

alpha-beta T cell differentiation

Inferred from genetic interaction PubMed 9462507. Source: MGI

anatomical structure regression

Inferred from mutant phenotype PubMed 16163358. Source: MGI

apoptotic process involved in morphogenesis

Inferred from mutant phenotype PubMed 15649466. Source: MGI

apoptotic process involved in patterning of blood vessels

Inferred from mutant phenotype PubMed 16163358. Source: MGI

canonical Wnt signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell chemotaxis

Inferred from electronic annotation. Source: Ensembl

cell development

Inferred from genetic interaction PubMed 15729346. Source: MGI

cellular response to interleukin-4

Inferred from electronic annotation. Source: Ensembl

chorio-allantoic fusion

Inferred from genetic interaction PubMed 10090727. Source: MGI

dentate gyrus development

Inferred from mutant phenotype PubMed 10631168. Source: MGI

embryonic limb morphogenesis

Inferred from genetic interaction PubMed 10090727. Source: MGI

epithelial to mesenchymal transition

Inferred from mutant phenotype PubMed 14691138. Source: BHF-UCL

eye pigmentation

Inferred from Biological aspect of Ancestor. Source: RefGenome

face morphogenesis

Inferred from genetic interaction PubMed 17699607. Source: MGI

forebrain neuroblast division

Inferred from genetic interaction PubMed 14715945. Source: MGI

forebrain neuron differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

forebrain radial glial cell differentiation

Inferred from genetic interaction PubMed 14715945. Source: MGI

formation of radial glial scaffolds

Inferred from genetic interaction PubMed 14715945. Source: MGI

hippocampus development

Inferred from mutant phenotype PubMed 10631168. Source: MGI

histone H3 acetylation

Inferred from electronic annotation. Source: Ensembl

histone H4 acetylation

Inferred from electronic annotation. Source: Ensembl

hypothalamus development

Inferred from Biological aspect of Ancestor. Source: RefGenome

mammary gland development

Inferred from mutant phenotype PubMed 16678815. Source: MGI

muscle fiber development

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of DNA binding

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process in bone marrow

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of estrogen receptor binding

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-13 production

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of interleukin-4 production

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of interleukin-5 production

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of striated muscle tissue development

Inferred from direct assay PubMed 16936075. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16678101PubMed 19056892. Source: MGI

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12551949. Source: MGI

neural crest cell migration

Inferred from Biological aspect of Ancestor. Source: RefGenome

neutrophil differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

odontoblast differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

odontogenesis of dentin-containing tooth

Inferred from mutant phenotype PubMed 12502739PubMed 15649466. Source: MGI

osteoblast differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

palate development

Inferred from mutant phenotype PubMed 14691138. Source: BHF-UCL

paraxial mesoderm formation

Inferred from genetic interaction PubMed 10090727. Source: MGI

patterning of blood vessels

Inferred from mutant phenotype PubMed 19154719. Source: MGI

positive regulation by host of viral transcription

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell cycle process

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation in bone marrow

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial to mesenchymal transition

Inferred from electronic annotation. Source: Ensembl

positive regulation of granulocyte differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12475749PubMed 15545629. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 10631168. Source: MGI

regulation of Wnt signaling pathway

Inferred from genetic interaction PubMed 10090727. Source: MGI

regulation of cell-cell adhesion

Inferred from mutant phenotype PubMed 19154719. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 11696550. Source: MGI

sensory perception of taste

Inferred from mutant phenotype PubMed 17284610. Source: MGI

somitogenesis

Inferred from mutant phenotype PubMed 15545629. Source: MGI

sprouting angiogenesis

Inferred from mutant phenotype PubMed 19154719. Source: MGI

tongue development

Inferred from mutant phenotype PubMed 17284610. Source: MGI

trachea gland development

Inferred from mutant phenotype PubMed 10498680. Source: MGI

vasculature development

Inferred from mutant phenotype PubMed 16163358. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 14623238. Source: MGI

nucleus

Inferred from direct assay PubMed 18579517. Source: UniProtKB

protein-DNA complex

Inferred from electronic annotation. Source: Ensembl

transcription factor complex

Inferred from physical interaction PubMed 11696550. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 7774816. Source: UniProtKB

DNA binding, bending

Inferred from direct assay PubMed 7774816. Source: UniProtKB

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from genetic interaction PubMed 15729346. Source: MGI

RNA polymerase II regulatory region sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

armadillo repeat domain binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

beta-catenin binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

chromatin binding

Inferred from direct assay PubMed 15024079PubMed 16678101PubMed 16818445PubMed 18202148. Source: MGI

cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

enhancer binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

estrogen receptor activity

Inferred from electronic annotation. Source: Ensembl

estrogen receptor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

gamma-catenin binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein binding

Inferred from physical interaction PubMed 20802155. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 21750544PubMed 22235033. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 11696550PubMed 15545629PubMed 16936075. Source: MGI

transcription factor binding

Inferred from physical interaction PubMed 12551949. Source: MGI

transcription regulatory region DNA binding

Inferred from direct assay PubMed 12551949PubMed 19056892PubMed 7537238. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Ctnnb1Q022486EBI-984464,EBI-397872
JRKO755643EBI-984464,EBI-8607681From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P27782-1)

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.
Isoform 2 (identifier: P27782-2)

Also known as: LEF-1S;

The sequence of this isoform differs from the canonical sequence as follows:
     1-113: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 397397Lymphoid enhancer-binding factor 1
PRO_0000048596

Regions

DNA binding297 – 36569HMG box
Region1 – 6060CTNNB1-binding
Compositional bias6 – 116Poly-Gly
Compositional bias12 – 5039Asp/Glu-rich (acidic)
Compositional bias75 – 271197Pro-rich
Compositional bias372 – 3776Poly-Lys

Amino acid modifications

Modified residue1301Phosphoserine By similarity
Modified residue1531Phosphothreonine; by NLK By similarity
Modified residue1641Phosphoserine; by NLK By similarity
Cross-link25Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Cross-link267Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

Natural variations

Alternative sequence1 – 113113Missing in isoform 2.
VSP_006983

Experimental info

Mutagenesis191D → A: Strongly diminishes CTNNB1 binding and transactivation. Prevents nuclear translocation of CTNNB1. Ref.4
Mutagenesis201E → A: Prevents nuclear translocation of CTNNB1. Ref.4
Mutagenesis241F → A: Strongly diminishes CTNNB1 binding and transactivation. Prevents nuclear translocation of CTNNB1. Ref.4
Mutagenesis261D → A: Prevents nuclear translocation of CTNNB1. Ref.4
Mutagenesis271E → A: Prevents nuclear translocation of CTNNB1. Ref.4

Secondary structure

............... 397
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: 0CA01B6C528FD7FA

FASTA39744,059
        10         20         30         40         50         60 
MPQLSGGGGG GDPELCATDE MIPFKDEGDP QKEKIFAEIS HPEEEGDLAD IKSSLVNESE 

        70         80         90        100        110        120 
IIPASNGHEV VRQAPSSQEP YHDKAREHPD EGKHPDGGLY NKGPSYSSYS GYIMMPNMNS 

       130        140        150        160        170        180 
DPYMSNGSLS PPIPRTSNKV PVVQPSHAVH PLTPLITYSD EHFSPGSHPS HIPSDVNSKQ 

       190        200        210        220        230        240 
GMSRHPPAPE IPTFYPLSPG GVGQITPPIG WQGQPVYPIT GGFRQPYPSS LSGDTSMSRF 

       250        260        270        280        290        300 
SHHMIPGPPG PHTTGIPHPA IVTPQVKQEH PHTDSDLMHV KPQHEQRKEQ EPKRPHIKKP 

       310        320        330        340        350        360 
LNAFMLYMKE MRANVVAECT LKESAAINQI LGRRWHALSR EEQAKYYELA RKERQLHMQL 

       370        380        390 
YPGWSARDNY GKKKKRKREK LQESTSGTGP RMTAAYI 

« Hide

Isoform 2 (LEF-1S) [UniParc].

Checksum: 86E7EBEA4B85F890
Show »

FASTA28431,894

References

[1]"LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function."
Travis A., Amsterdam A., Belanger C., Grosschedl R.
Genes Dev. 5:880-894(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: C57BL/6 X DBA.
[2]"Nucleotide sequence of a cDNA encoding an alternative form of LEF-1."
Fujimoto S., Morita K., Kanaitsuka T., Germeraad W.T., Mazda O., Katsura Y.
Nucleic Acids Res. 21:4403-4403(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: C57BL/6.
[3]"Multiple roles for activated LEF/TCF transcription complexes during hair follicle development and differentiation."
DasGupta R., Fuchs E.
Development 126:4557-4568(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[4]"Hot spots in beta-catenin for interactions with LEF-1, conductin and APC."
von Kries J.P., Winbeck G., Asbrand C., Schwarz-Romond T., Sochnikova N., Dell'Oro A., Behrens J., Birchmeier W.
Nat. Struct. Biol. 7:800-807(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CTNNB1, MUTAGENESIS OF ASP-19; GLU-20; PHE-24; ASP-26 AND GLU-27.
[5]"Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin."
Merrill B.J., Gat U., DasGupta R., Fuchs E.
Genes Dev. 15:1688-1705(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN HAIR DEVELOPMENT.
[6]"PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies."
Sachdev S., Bruhn L., Sieber H., Pichler A., Melchior F., Grosschedl R.
Genes Dev. 15:3088-3103(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION, INTERACTION WITH PIASG, LOCATION IN NUCLEAR BODIES.
[7]"Identification of a promoter-specific transcriptional activation domain at the C-terminus of the Wnt effector protein T-cell factor 4."
Hecht A., Stemmler M.P.
J. Biol. Chem. 278:3776-3785(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EP300.
[8]"Structural basis for DNA bending by the architectural transcription factor LEF-1."
Love J.J., Li X., Case D.A., Glese K., Grosschedl P., Wright P.E.
Nature 376:791-795(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 296-380.
[9]"High resolution NMR structure of the LEF-1 HMG domain complexed with its cognate DNA."
Li X., Love J.J., Case D.A., Wright P.E.
Submitted (OCT-1998) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 296-380.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X58636 mRNA. Translation: CAA41493.1.
D16503 mRNA. Translation: BAA03954.1.
CCDSCCDS17842.1. [P27782-1]
PIRA39565.
RefSeqNP_034833.2. NM_010703.4. [P27782-1]
UniGeneMm.255219.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LEFNMR-A296-380[»]
3OUWX-ray2.91B1-63[»]
3OUXX-ray2.40B1-63[»]
ProteinModelPortalP27782.
SMRP27782. Positions 11-60, 296-371.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201137. 13 interactions.
DIPDIP-35132N.
IntActP27782. 6 interactions.
MINTMINT-8177749.

PTM databases

PhosphoSiteP27782.

Proteomic databases

PRIDEP27782.

Protocols and materials databases

DNASU16842.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000029611; ENSMUSP00000029611; ENSMUSG00000027985. [P27782-1]
GeneID16842.
KEGGmmu:16842.
UCSCuc008rjf.1. mouse. [P27782-1]

Organism-specific databases

CTD51176.
MGIMGI:96770. Lef1.

Phylogenomic databases

eggNOGNOG299161.
HOGENOMHOG000116032.
HOVERGENHBG000419.
InParanoidP27782.
KOK04492.
OMAGYSGYIM.
OrthoDBEOG7QNVMG.
PhylomeDBP27782.
TreeFamTF318448.

Gene expression databases

ArrayExpressP27782.
BgeeP27782.
CleanExMM_LEF1.
GenevestigatorP27782.

Family and domain databases

Gene3D1.10.30.10. 1 hit.
4.10.900.10. 1 hit.
InterProIPR027397. Catenin_binding_dom.
IPR013558. CTNNB1-bd_N.
IPR009071. HMG_box_dom.
IPR024940. TCF/LEF.
[Graphical view]
PANTHERPTHR10373. PTHR10373. 1 hit.
PfamPF08347. CTNNB1_binding. 1 hit.
PF00505. HMG_box. 1 hit.
[Graphical view]
SMARTSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMSSF47095. SSF47095. 1 hit.
PROSITEPS50118. HMG_BOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLEF1. mouse.
EvolutionaryTraceP27782.
NextBio290768.
PROP27782.
SOURCESearch...

Entry information

Entry nameLEF1_MOUSE
AccessionPrimary (citable) accession number: P27782
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: July 9, 2014
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot