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Protein

Lymphoid enhancer-binding factor 1

Gene

Lef1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi297 – 36569HMG boxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • alpha-beta T cell differentiation Source: MGI
  • anatomical structure regression Source: MGI
  • apoptotic process involved in morphogenesis Source: MGI
  • apoptotic process involved in patterning of blood vessels Source: MGI
  • B cell proliferation Source: MGI
  • BMP signaling pathway Source: MGI
  • canonical Wnt signaling pathway Source: MGI
  • cell chemotaxis Source: MGI
  • cell development Source: MGI
  • cellular response to cytokine stimulus Source: MGI
  • cellular response to interleukin-4 Source: MGI
  • chorio-allantoic fusion Source: MGI
  • dentate gyrus development Source: MGI
  • embryonic limb morphogenesis Source: MGI
  • epithelial to mesenchymal transition Source: BHF-UCL
  • eye pigmentation Source: GO_Central
  • face morphogenesis Source: MGI
  • forebrain neuroblast division Source: MGI
  • forebrain neuron differentiation Source: GO_Central
  • forebrain radial glial cell differentiation Source: MGI
  • formation of radial glial scaffolds Source: MGI
  • generation of neurons Source: GO_Central
  • hippocampus development Source: MGI
  • histone H3 acetylation Source: MGI
  • histone H4 acetylation Source: MGI
  • hypothalamus development Source: GO_Central
  • mammary gland development Source: MGI
  • muscle fiber development Source: GO_Central
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of apoptotic process in bone marrow Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of cell-cell adhesion Source: MGI
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • negative regulation of DNA binding Source: MGI
  • negative regulation of estrogen receptor binding Source: MGI
  • negative regulation of interleukin-13 production Source: MGI
  • negative regulation of interleukin-4 production Source: MGI
  • negative regulation of interleukin-5 production Source: MGI
  • negative regulation of striated muscle tissue development Source: MGI
  • negative regulation of transcription, DNA-templated Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • neural crest cell migration Source: GO_Central
  • neutrophil differentiation Source: MGI
  • odontoblast differentiation Source: GO_Central
  • odontogenesis of dentin-containing tooth Source: MGI
  • osteoblast differentiation Source: GO_Central
  • palate development Source: BHF-UCL
  • paraxial mesoderm formation Source: MGI
  • patterning of blood vessels Source: MGI
  • positive regulation by host of viral transcription Source: MGI
  • positive regulation of cell-cell adhesion Source: MGI
  • positive regulation of cell cycle process Source: MGI
  • positive regulation of cell growth Source: MGI
  • positive regulation of cell migration Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of cell proliferation in bone marrow Source: MGI
  • positive regulation of epithelial to mesenchymal transition Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of granulocyte differentiation Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • regulation of cell-cell adhesion Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of Wnt signaling pathway Source: MGI
  • sensory perception of taste Source: MGI
  • somitogenesis Source: MGI
  • sprouting angiogenesis Source: MGI
  • steroid hormone mediated signaling pathway Source: MGI
  • T cell receptor V(D)J recombination Source: MGI
  • T-helper 1 cell differentiation Source: UniProtKB
  • tongue development Source: MGI
  • trachea gland development Source: MGI
  • transcription from RNA polymerase II promoter Source: MGI
  • vasculature development Source: MGI
  • Wnt signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation, Wnt signaling pathway

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_325952. formation of the beta-catenin:TCF transactivating complex.
REACT_331940. Ca2+ pathway.
REACT_351655. deactivation of the beta-catenin transactivating complex.

Names & Taxonomyi

Protein namesi
Recommended name:
Lymphoid enhancer-binding factor 1
Short name:
LEF-1
Gene namesi
Name:Lef1
Synonyms:Lef-1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:96770. Lef1.

Subcellular locationi

  • Nucleus

  • Note: Found in nuclear bodies upon PIASG binding.

GO - Cellular componenti

  • cytoplasm Source: MGI
  • nucleus Source: UniProtKB
  • protein-DNA complex Source: MGI
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi19 – 191D → A: Strongly diminishes CTNNB1 binding and transactivation. Prevents nuclear translocation of CTNNB1. 1 Publication
Mutagenesisi20 – 201E → A: Prevents nuclear translocation of CTNNB1. 1 Publication
Mutagenesisi24 – 241F → A: Strongly diminishes CTNNB1 binding and transactivation. Prevents nuclear translocation of CTNNB1. 1 Publication
Mutagenesisi26 – 261D → A: Prevents nuclear translocation of CTNNB1. 1 Publication
Mutagenesisi27 – 271E → A: Prevents nuclear translocation of CTNNB1. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 397397Lymphoid enhancer-binding factor 1PRO_0000048596Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki25 – 25Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Modified residuei130 – 1301PhosphoserineBy similarity
Modified residuei153 – 1531Phosphothreonine; by NLKBy similarity
Modified residuei164 – 1641Phosphoserine; by NLKBy similarity
Cross-linki267 – 267Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

Post-translational modificationi

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).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP27782.

PTM databases

PhosphoSiteiP27782.

Expressioni

Tissue specificityi

Lymphocytes. Found in distinct epithelial cell compartments of the skin and is abundant in the hair-producing progenitors of the follicle.1 Publication

Developmental stagei

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.

Gene expression databases

BgeeiP27782.
CleanExiMM_LEF1.
ExpressionAtlasiP27782. baseline and differential.
GenevisibleiP27782. MM.

Interactioni

Subunit structurei

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.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ctnnb1Q022486EBI-984464,EBI-397872
JRKO755643EBI-984464,EBI-8607681From a different organism.

Protein-protein interaction databases

BioGridi201137. 13 interactions.
DIPiDIP-35132N.
IntActiP27782. 6 interactions.
MINTiMINT-8177749.
STRINGi10090.ENSMUSP00000029611.

Structurei

Secondary structure

1
397
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni13 – 164Combined sources
Beta strandi32 – 343Combined sources
Helixi48 – 5811Combined sources
Helixi303 – 31816Combined sources
Helixi324 – 33512Combined sources
Helixi340 – 36021Combined sources
Turni370 – 3723Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LEFNMR-A296-380[»]
3OUWX-ray2.91B1-63[»]
3OUXX-ray2.40B1-63[»]
ProteinModelPortaliP27782.
SMRiP27782. Positions 11-60, 296-371.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27782.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6060CTNNB1-bindingAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi6 – 116Poly-Gly
Compositional biasi12 – 5039Asp/Glu-rich (acidic)Add
BLAST
Compositional biasi75 – 271197Pro-richAdd
BLAST
Compositional biasi372 – 3776Poly-Lys

Domaini

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

Sequence similaritiesi

Belongs to the TCF/LEF family.Curated
Contains 1 HMG box DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG299161.
HOGENOMiHOG000116032.
HOVERGENiHBG000419.
InParanoidiP27782.
KOiK04492.
OMAiGYSGYIM.
OrthoDBiEOG7QNVMG.
PhylomeDBiP27782.
TreeFamiTF318448.

Family and domain databases

Gene3Di1.10.30.10. 1 hit.
4.10.900.10. 1 hit.
InterProiIPR027397. Catenin_binding_dom.
IPR013558. CTNNB1-bd_N.
IPR009071. HMG_box_dom.
IPR024940. TCF/LEF.
[Graphical view]
PANTHERiPTHR10373. PTHR10373. 1 hit.
PfamiPF08347. CTNNB1_binding. 1 hit.
PF00505. HMG_box. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 1 hit.
PROSITEiPS50118. HMG_BOX_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P27782-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPQLSGGGGG GDPELCATDE MIPFKDEGDP QKEKIFAEIS HPEEEGDLAD
60 70 80 90 100
IKSSLVNESE IIPASNGHEV VRQAPSSQEP YHDKAREHPD EGKHPDGGLY
110 120 130 140 150
NKGPSYSSYS GYIMMPNMNS DPYMSNGSLS PPIPRTSNKV PVVQPSHAVH
160 170 180 190 200
PLTPLITYSD EHFSPGSHPS HIPSDVNSKQ GMSRHPPAPE IPTFYPLSPG
210 220 230 240 250
GVGQITPPIG WQGQPVYPIT GGFRQPYPSS LSGDTSMSRF SHHMIPGPPG
260 270 280 290 300
PHTTGIPHPA IVTPQVKQEH PHTDSDLMHV KPQHEQRKEQ EPKRPHIKKP
310 320 330 340 350
LNAFMLYMKE MRANVVAECT LKESAAINQI LGRRWHALSR EEQAKYYELA
360 370 380 390
RKERQLHMQL YPGWSARDNY GKKKKRKREK LQESTSGTGP RMTAAYI
Length:397
Mass (Da):44,059
Last modified:August 1, 1992 - v1
Checksum:i0CA01B6C528FD7FA
GO
Isoform 2 (identifier: P27782-2) [UniParc]FASTAAdd to basket

Also known as: LEF-1S

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

Show »
Length:284
Mass (Da):31,894
Checksum:i86E7EBEA4B85F890
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 113113Missing in isoform 2. 1 PublicationVSP_006983Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X58636 mRNA. Translation: CAA41493.1.
D16503 mRNA. Translation: BAA03954.1.
CCDSiCCDS17842.1. [P27782-1]
PIRiA39565.
RefSeqiNP_034833.2. NM_010703.4. [P27782-1]
UniGeneiMm.255219.

Genome annotation databases

EnsembliENSMUST00000029611; ENSMUSP00000029611; ENSMUSG00000027985. [P27782-1]
GeneIDi16842.
KEGGimmu:16842.
UCSCiuc008rjf.1. mouse. [P27782-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X58636 mRNA. Translation: CAA41493.1.
D16503 mRNA. Translation: BAA03954.1.
CCDSiCCDS17842.1. [P27782-1]
PIRiA39565.
RefSeqiNP_034833.2. NM_010703.4. [P27782-1]
UniGeneiMm.255219.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2LEFNMR-A296-380[»]
3OUWX-ray2.91B1-63[»]
3OUXX-ray2.40B1-63[»]
ProteinModelPortaliP27782.
SMRiP27782. Positions 11-60, 296-371.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201137. 13 interactions.
DIPiDIP-35132N.
IntActiP27782. 6 interactions.
MINTiMINT-8177749.
STRINGi10090.ENSMUSP00000029611.

PTM databases

PhosphoSiteiP27782.

Proteomic databases

PRIDEiP27782.

Protocols and materials databases

DNASUi16842.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029611; ENSMUSP00000029611; ENSMUSG00000027985. [P27782-1]
GeneIDi16842.
KEGGimmu:16842.
UCSCiuc008rjf.1. mouse. [P27782-1]

Organism-specific databases

CTDi51176.
MGIiMGI:96770. Lef1.

Phylogenomic databases

eggNOGiNOG299161.
HOGENOMiHOG000116032.
HOVERGENiHBG000419.
InParanoidiP27782.
KOiK04492.
OMAiGYSGYIM.
OrthoDBiEOG7QNVMG.
PhylomeDBiP27782.
TreeFamiTF318448.

Enzyme and pathway databases

ReactomeiREACT_325952. formation of the beta-catenin:TCF transactivating complex.
REACT_331940. Ca2+ pathway.
REACT_351655. deactivation of the beta-catenin transactivating complex.

Miscellaneous databases

ChiTaRSiLef1. mouse.
EvolutionaryTraceiP27782.
NextBioi290768.
PROiP27782.
SOURCEiSearch...

Gene expression databases

BgeeiP27782.
CleanExiMM_LEF1.
ExpressionAtlasiP27782. baseline and differential.
GenevisibleiP27782. MM.

Family and domain databases

Gene3Di1.10.30.10. 1 hit.
4.10.900.10. 1 hit.
InterProiIPR027397. Catenin_binding_dom.
IPR013558. CTNNB1-bd_N.
IPR009071. HMG_box_dom.
IPR024940. TCF/LEF.
[Graphical view]
PANTHERiPTHR10373. PTHR10373. 1 hit.
PfamiPF08347. CTNNB1_binding. 1 hit.
PF00505. HMG_box. 1 hit.
[Graphical view]
SMARTiSM00398. HMG. 1 hit.
[Graphical view]
SUPFAMiSSF47095. SSF47095. 1 hit.
PROSITEiPS50118. HMG_BOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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. 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.

Entry informationi

Entry nameiLEF1_MOUSE
AccessioniPrimary (citable) accession number: P27782
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: June 24, 2015
This is version 155 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.