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P27782

- LEF1_MOUSE

UniProt

P27782 - LEF1_MOUSE

Protein

Lymphoid enhancer-binding factor 1

Gene

Lef1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 148 (01 Oct 2014)
      Sequence version 1 (01 Aug 1992)
      Previous versions | rss
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    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: RefGenome
    2. beta-catenin binding Source: RefGenome
    3. chromatin binding Source: MGI
    4. cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: Ensembl
    5. DNA binding Source: UniProtKB
    6. DNA binding, bending Source: UniProtKB
    7. enhancer binding Source: RefGenome
    8. estrogen receptor activity Source: Ensembl
    9. estrogen receptor binding Source: RefGenome
    10. gamma-catenin binding Source: RefGenome
    11. protein binding Source: UniProtKB
    12. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
    13. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
    14. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: MGI
    15. sequence-specific DNA binding Source: MGI
    16. sequence-specific DNA binding transcription factor activity Source: MGI
    17. transcription factor binding Source: MGI
    18. 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: RefGenome
    8. cell chemotaxis Source: Ensembl
    9. cell development Source: MGI
    10. cellular response to interleukin-4 Source: Ensembl
    11. chorio-allantoic fusion Source: MGI
    12. dentate gyrus development Source: MGI
    13. embryonic limb morphogenesis Source: MGI
    14. epithelial to mesenchymal transition Source: BHF-UCL
    15. eye pigmentation Source: RefGenome
    16. face morphogenesis Source: MGI
    17. forebrain neuroblast division Source: MGI
    18. forebrain neuron differentiation Source: RefGenome
    19. forebrain radial glial cell differentiation Source: MGI
    20. formation of radial glial scaffolds Source: MGI
    21. hippocampus development Source: MGI
    22. histone H3 acetylation Source: Ensembl
    23. histone H4 acetylation Source: Ensembl
    24. hypothalamus development Source: RefGenome
    25. mammary gland development Source: MGI
    26. muscle fiber development Source: RefGenome
    27. negative regulation of apoptotic process in bone marrow Source: RefGenome
    28. negative regulation of canonical Wnt signaling pathway Source: Ensembl
    29. negative regulation of cell-cell adhesion Source: Ensembl
    30. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: RefGenome
    31. negative regulation of DNA binding Source: Ensembl
    32. negative regulation of estrogen receptor binding Source: Ensembl
    33. negative regulation of interleukin-13 production Source: RefGenome
    34. negative regulation of interleukin-4 production Source: RefGenome
    35. negative regulation of interleukin-5 production Source: RefGenome
    36. negative regulation of striated muscle tissue development Source: MGI
    37. negative regulation of transcription, DNA-templated Source: MGI
    38. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    39. neural crest cell migration Source: RefGenome
    40. neutrophil differentiation Source: RefGenome
    41. odontoblast differentiation Source: RefGenome
    42. odontogenesis of dentin-containing tooth Source: MGI
    43. osteoblast differentiation Source: RefGenome
    44. palate development Source: BHF-UCL
    45. paraxial mesoderm formation Source: MGI
    46. patterning of blood vessels Source: MGI
    47. positive regulation by host of viral transcription Source: Ensembl
    48. positive regulation of cell-cell adhesion Source: Ensembl
    49. positive regulation of cell cycle process Source: Ensembl
    50. positive regulation of cell growth Source: Ensembl
    51. positive regulation of cell migration Source: Ensembl
    52. positive regulation of cell proliferation in bone marrow Source: RefGenome
    53. positive regulation of epithelial to mesenchymal transition Source: Ensembl
    54. positive regulation of granulocyte differentiation Source: Ensembl
    55. positive regulation of transcription, DNA-templated Source: MGI
    56. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
    57. regulation of cell-cell adhesion Source: MGI
    58. regulation of transcription from RNA polymerase II promoter Source: MGI
    59. regulation of Wnt signaling pathway Source: MGI
    60. sensory perception of taste Source: MGI
    61. somitogenesis Source: MGI
    62. sprouting angiogenesis Source: MGI
    63. T cell receptor V(D)J recombination Source: MGI
    64. T-helper 1 cell differentiation Source: UniProtKB
    65. tongue development Source: MGI
    66. trachea gland development Source: MGI
    67. vasculature development Source: MGI
    68. Wnt signaling pathway Source: MGI

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation, Wnt signaling pathway

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_216539. formation of the beta-catenin:TCF transactivating complex.
    REACT_219771. deactivation of the beta-catenin transactivating complex.
    REACT_221970. Ca2+ pathway.

    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: 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: Ensembl
    4. transcription factor complex Source: MGI

    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

    ArrayExpressiP27782.
    BgeeiP27782.
    CleanExiMM_LEF1.
    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 – 164
    Beta strandi32 – 343
    Helixi48 – 5811
    Helixi303 – 31816
    Helixi324 – 33512
    Helixi340 – 36021
    Turni370 – 3723

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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. Align

    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

    MPQLSGGGGG GDPELCATDE MIPFKDEGDP QKEKIFAEIS HPEEEGDLAD    50
    IKSSLVNESE IIPASNGHEV VRQAPSSQEP YHDKAREHPD EGKHPDGGLY 100
    NKGPSYSSYS GYIMMPNMNS DPYMSNGSLS PPIPRTSNKV PVVQPSHAVH 150
    PLTPLITYSD EHFSPGSHPS HIPSDVNSKQ GMSRHPPAPE IPTFYPLSPG 200
    GVGQITPPIG WQGQPVYPIT GGFRQPYPSS LSGDTSMSRF SHHMIPGPPG 250
    PHTTGIPHPA IVTPQVKQEH PHTDSDLMHV KPQHEQRKEQ EPKRPHIKKP 300
    LNAFMLYMKE MRANVVAECT LKESAAINQI LGRRWHALSR EEQAKYYELA 350
    RKERQLHMQL YPGWSARDNY GKKKKRKREK LQESTSGTGP RMTAAYI 397
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X58636 mRNA. Translation: CAA41493.1 .
    D16503 mRNA. Translation: BAA03954.1 .
    CCDSi CCDS17842.1. [P27782-1 ]
    PIRi A39565.
    RefSeqi NP_034833.2. NM_010703.4. [P27782-1 ]
    UniGenei Mm.255219.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2LEF NMR - A 296-380 [» ]
    3OUW X-ray 2.91 B 1-63 [» ]
    3OUX X-ray 2.40 B 1-63 [» ]
    ProteinModelPortali P27782.
    SMRi P27782. Positions 11-60, 296-371.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201137. 13 interactions.
    DIPi DIP-35132N.
    IntActi P27782. 6 interactions.
    MINTi MINT-8177749.

    PTM databases

    PhosphoSitei P27782.

    Proteomic databases

    PRIDEi P27782.

    Protocols and materials databases

    DNASUi 16842.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000029611 ; ENSMUSP00000029611 ; ENSMUSG00000027985 . [P27782-1 ]
    GeneIDi 16842.
    KEGGi mmu:16842.
    UCSCi uc008rjf.1. mouse. [P27782-1 ]

    Organism-specific databases

    CTDi 51176.
    MGIi MGI:96770. Lef1.

    Phylogenomic databases

    eggNOGi NOG299161.
    HOGENOMi HOG000116032.
    HOVERGENi HBG000419.
    InParanoidi P27782.
    KOi K04492.
    OMAi GYSGYIM.
    OrthoDBi EOG7QNVMG.
    PhylomeDBi P27782.
    TreeFami TF318448.

    Enzyme and pathway databases

    Reactomei REACT_216539. formation of the beta-catenin:TCF transactivating complex.
    REACT_219771. deactivation of the beta-catenin transactivating complex.
    REACT_221970. Ca2+ pathway.

    Miscellaneous databases

    ChiTaRSi LEF1. mouse.
    EvolutionaryTracei P27782.
    NextBioi 290768.
    PROi P27782.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P27782.
    Bgeei P27782.
    CleanExi MM_LEF1.
    Genevestigatori P27782.

    Family and domain databases

    Gene3Di 1.10.30.10. 1 hit.
    4.10.900.10. 1 hit.
    InterProi IPR027397. Catenin_binding_dom.
    IPR013558. CTNNB1-bd_N.
    IPR009071. HMG_box_dom.
    IPR024940. TCF/LEF.
    [Graphical view ]
    PANTHERi PTHR10373. PTHR10373. 1 hit.
    Pfami PF08347. CTNNB1_binding. 1 hit.
    PF00505. HMG_box. 1 hit.
    [Graphical view ]
    SMARTi SM00398. HMG. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47095. SSF47095. 1 hit.
    PROSITEi PS50118. HMG_BOX_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    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: October 1, 2014
    This is version 148 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