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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

  1. armadillo repeat domain binding Source: MGI
  2. beta-catenin binding Source: MGI
  3. C2H2 zinc finger domain binding Source: MGI
  4. chromatin binding Source: MGI
  5. cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: MGI
  6. DNA binding Source: UniProtKB
  7. DNA binding, bending Source: UniProtKB
  8. enhancer binding Source: MGI
  9. estrogen receptor activity Source: MGI
  10. estrogen receptor binding Source: MGI
  11. gamma-catenin binding Source: MGI
  12. histone binding Source: MGI
  13. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  14. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
  15. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: MGI
  16. RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  17. RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: MGI
  18. sequence-specific DNA binding Source: MGI
  19. sequence-specific DNA binding transcription factor activity Source: MGI
  20. transcription factor binding Source: MGI
  21. transcription regulatory region DNA binding Source: MGI

GO - Biological processi

  1. alpha-beta T cell differentiation Source: MGI
  2. anatomical structure regression Source: MGI
  3. apoptotic process involved in morphogenesis Source: MGI
  4. apoptotic process involved in patterning of blood vessels Source: MGI
  5. B cell proliferation Source: MGI
  6. BMP signaling pathway Source: MGI
  7. canonical Wnt signaling pathway Source: MGI
  8. cell chemotaxis Source: MGI
  9. cell development Source: MGI
  10. cellular response to cytokine stimulus Source: MGI
  11. cellular response to interleukin-4 Source: MGI
  12. chorio-allantoic fusion Source: MGI
  13. dentate gyrus development Source: MGI
  14. embryonic limb morphogenesis Source: MGI
  15. epithelial to mesenchymal transition Source: BHF-UCL
  16. eye pigmentation Source: GO_Central
  17. face morphogenesis Source: MGI
  18. forebrain neuroblast division Source: MGI
  19. forebrain neuron differentiation Source: GO_Central
  20. forebrain radial glial cell differentiation Source: MGI
  21. formation of radial glial scaffolds Source: MGI
  22. hippocampus development Source: MGI
  23. histone H3 acetylation Source: MGI
  24. histone H4 acetylation Source: MGI
  25. hypothalamus development Source: GO_Central
  26. mammary gland development Source: MGI
  27. muscle fiber development Source: GO_Central
  28. negative regulation of apoptotic process Source: MGI
  29. negative regulation of apoptotic process in bone marrow Source: MGI
  30. negative regulation of canonical Wnt signaling pathway Source: MGI
  31. negative regulation of cell-cell adhesion Source: MGI
  32. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  33. negative regulation of DNA binding Source: MGI
  34. negative regulation of estrogen receptor binding Source: MGI
  35. negative regulation of interleukin-13 production Source: MGI
  36. negative regulation of interleukin-4 production Source: MGI
  37. negative regulation of interleukin-5 production Source: MGI
  38. negative regulation of striated muscle tissue development Source: MGI
  39. negative regulation of transcription, DNA-templated Source: MGI
  40. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  41. neural crest cell migration Source: GO_Central
  42. neutrophil differentiation Source: MGI
  43. odontoblast differentiation Source: GO_Central
  44. odontogenesis of dentin-containing tooth Source: MGI
  45. osteoblast differentiation Source: GO_Central
  46. palate development Source: BHF-UCL
  47. paraxial mesoderm formation Source: MGI
  48. patterning of blood vessels Source: MGI
  49. positive regulation by host of viral transcription Source: MGI
  50. positive regulation of cell-cell adhesion Source: MGI
  51. positive regulation of cell cycle process Source: MGI
  52. positive regulation of cell growth Source: MGI
  53. positive regulation of cell migration Source: MGI
  54. positive regulation of cell proliferation Source: MGI
  55. positive regulation of cell proliferation in bone marrow Source: MGI
  56. positive regulation of epithelial to mesenchymal transition Source: MGI
  57. positive regulation of gene expression Source: MGI
  58. positive regulation of granulocyte differentiation Source: MGI
  59. positive regulation of transcription, DNA-templated Source: MGI
  60. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  61. regulation of cell-cell adhesion Source: MGI
  62. regulation of transcription from RNA polymerase II promoter Source: MGI
  63. regulation of Wnt signaling pathway Source: MGI
  64. sensory perception of taste Source: MGI
  65. somitogenesis Source: MGI
  66. sprouting angiogenesis Source: MGI
  67. steroid hormone mediated signaling pathway Source: MGI
  68. T cell receptor V(D)J recombination Source: MGI
  69. T-helper 1 cell differentiation Source: UniProtKB
  70. tongue development Source: MGI
  71. trachea gland development Source: MGI
  72. transcription from RNA polymerase II promoter Source: MGI
  73. vasculature development Source: MGI
  74. 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

  1. cytoplasm Source: MGI
  2. nucleus Source: UniProtKB
  3. protein-DNA complex Source: MGI
  4. 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.
GenevestigatoriP27782.

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.

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:July 31, 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.

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.
GenevestigatoriP27782.

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(1990) [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(1992) [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(1998) [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(2000) [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(2000) [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(2002) [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(1994) [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 (SEP-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: July 31, 1992
Last sequence update: July 31, 1992
Last modified: March 31, 2015
This is version 154 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.