Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Lymphoid enhancer-binding factor 1

Gene

LEF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Regulates T-cell receptor alpha enhancer function. Binds DNA in a sequence-specific manner. PIAG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1 (By similarity). Isoform 3 lacks the CTNNB1 interaction domain and may 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. Isoform 1 transcriptionally activates MYC and CCND1 expression and enhances proliferation of pancreatic tumor cells.By similarity3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi299 – 367HMG boxPROSITE-ProRule annotationAdd BLAST69

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201722 Formation of the beta-catenin:TCF transactivating complex
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex
R-HSA-4086398 Ca2+ pathway
R-HSA-4411364 Binding of TCF/LEF:CTNNB1 to target gene promoters
R-HSA-4641265 Repression of WNT target genes
R-HSA-8951430 RUNX3 regulates WNT signaling
SignaLinkiQ9UJU2
SIGNORiQ9UJU2

Names & Taxonomyi

Protein namesi
Recommended name:
Lymphoid enhancer-binding factor 1
Short name:
LEF-1
Alternative name(s):
T cell-specific transcription factor 1-alpha
Short name:
TCF1-alpha
Gene namesi
Name:LEF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000138795.9
HGNCiHGNC:6551 LEF1
MIMi153245 gene
neXtProtiNX_Q9UJU2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi155T → A: Reduced phosphorylation by NLK; when associated with A-166. 1 Publication1
Mutagenesisi166S → A: Reduced phosphorylation by NLK; when associated with A-155. 1 Publication1

Organism-specific databases

DisGeNETi51176
OpenTargetsiENSG00000138795
PharmGKBiPA30331

Chemistry databases

ChEMBLiCHEMBL3217392

Polymorphism and mutation databases

BioMutaiLEF1
DMDMi8928194

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000485951 – 399Lymphoid enhancer-binding factor 1Add BLAST399

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki27Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei132PhosphoserineCombined sources1
Modified residuei155Phosphothreonine; by NLK1 Publication1
Modified residuei166Phosphoserine; by NLK1 Publication1
Cross-linki269Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

Phosphorylated at Thr-155 and/or Ser-166 by NLK. Phosphorylation by NLK at these sites represses LEF1-mediated transcriptional activation of target genes of the canonical Wnt signaling pathway.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9UJU2
PeptideAtlasiQ9UJU2
PRIDEiQ9UJU2
ProteomicsDBi84650
84651 [Q9UJU2-2]
84652 [Q9UJU2-3]
84653 [Q9UJU2-4]
84654 [Q9UJU2-5]
84655 [Q9UJU2-6]
TopDownProteomicsiQ9UJU2-2 [Q9UJU2-2]

PTM databases

iPTMnetiQ9UJU2
PhosphoSitePlusiQ9UJU2

Expressioni

Tissue specificityi

Detected in thymus. Not detected in normal colon, but highly expressed in colon cancer biopsies and colon cancer cell lines. Expressed in several pancreatic tumors and weakly expressed in normal pancreatic tissue. Isoforms 1 and 5 are detected in several pancreatic cell lines.1 Publication

Gene expression databases

BgeeiENSG00000138795 Expressed in 202 organ(s), highest expression level in female gonad
CleanExiHS_LEF1
ExpressionAtlasiQ9UJU2 baseline and differential
GenevisibleiQ9UJU2 HS

Organism-specific databases

HPAiCAB019405
HPA002087

Interactioni

Subunit structurei

Binds the armadillo repeat of CTNNB1 and forms a stable complex. Interacts with EP300, TLE1 and PIASG (By similarity). Binds ALYREF/THOC4, MDFI and MDFIC. Interacts with NLK.By similarity5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi119354, 40 interactors
ComplexPortaliCPX-316 beta1-catenin - LEF1 complex
DIPiDIP-29946N
IntActiQ9UJU2, 23 interactors
MINTiQ9UJU2
STRINGi9606.ENSP00000265165

Structurei

3D structure databases

ProteinModelPortaliQ9UJU2
SMRiQ9UJU2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 62CTNNB1-bindingBy similarityAdd BLAST62

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi6 – 13Poly-Gly8
Compositional biasi14 – 52Asp/Glu-rich (acidic)Add BLAST39
Compositional biasi77 – 273Pro-richAdd BLAST197
Compositional biasi374 – 379Poly-Lys6

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

Phylogenomic databases

eggNOGiKOG3248 Eukaryota
ENOG41109RU LUCA
GeneTreeiENSGT00390000009964
HOGENOMiHOG000116032
HOVERGENiHBG000419
InParanoidiQ9UJU2
KOiK04492
OMAiGYSGYIM
OrthoDBiEOG091G0705
PhylomeDBiQ9UJU2
TreeFamiTF318448

Family and domain databases

Gene3Di1.10.30.10, 1 hit
4.10.900.10, 1 hit
InterProiView protein in InterPro
IPR027397 Catenin_binding_dom_sf
IPR013558 CTNNB1-bd_N
IPR009071 HMG_box_dom
IPR036910 HMG_box_dom_sf
IPR028769 LEF1
IPR024940 TCF/LEF
PANTHERiPTHR10373 PTHR10373, 1 hit
PTHR10373:SF11 PTHR10373:SF11, 1 hit
PfamiView protein in Pfam
PF08347 CTNNB1_binding, 1 hit
PF00505 HMG_box, 1 hit
SMARTiView protein in SMART
SM00398 HMG, 1 hit
SUPFAMiSSF47095 SSF47095, 1 hit
PROSITEiView protein in PROSITE
PS50118 HMG_BOX_2, 1 hit

Sequences (7+)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket
Note: Additional isoforms seem to exist.

This entry has 7 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9UJU2-1) [UniParc]FASTAAdd to basket
Also known as: A

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 GGGDPELCAT DEMIPFKDEG DPQKEKIFAE ISHPEEEGDL
60 70 80 90 100
ADIKSSLVNE SEIIPASNGH EVARQAQTSQ EPYHDKAREH PDDGKHPDGG
110 120 130 140 150
LYNKGPSYSS YSGYIMMPNM NNDPYMSNGS LSPPIPRTSN KVPVVQPSHA
160 170 180 190 200
VHPLTPLITY SDEHFSPGSH PSHIPSDVNS KQGMSRHPPA PDIPTFYPLS
210 220 230 240 250
PGGVGQITPP LGWQGQPVYP ITGGFRQPYP SSLSVDTSMS RFSHHMIPGP
260 270 280 290 300
PGPHTTGIPH PAIVTPQVKQ EHPHTDSDLM HVKPQHEQRK EQEPKRPHIK
310 320 330 340 350
KPLNAFMLYM KEMRANVVAE CTLKESAAIN QILGRRWHAL SREEQAKYYE
360 370 380 390
LARKERQLHM QLYPGWSARD NYGKKKKRKR EKLQESASGT GPRMTAAYI
Note: Produced by alternative promoter usage.
Length:399
Mass (Da):44,201
Last modified:May 1, 2000 - v1
Checksum:iD480D440698EEFE3
GO
Isoform 2 (identifier: Q9UJU2-2) [UniParc]FASTAAdd to basket
Also known as: B, 8A

The sequence of this isoform differs from the canonical sequence as follows:
     283-399: KPQHEQRKEQ...TGPRMTAAYI → CSAFLLPHPF...SQKDLTLRSL

Note: Produced by alternative splicing of isoform 1. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:329
Mass (Da):35,672
Checksum:i3632325D440CA5DD
GO
Isoform 3 (identifier: Q9UJU2-3) [UniParc]FASTAAdd to basket
Also known as: LEF-1-DN

The sequence of this isoform differs from the canonical sequence as follows:
     1-115: Missing.

Note: Produced by alternative promoter usage. Acts as dominant negative mutant.
Show »
Length:284
Mass (Da):31,919
Checksum:i22320A1A195401ED
GO
Isoform 4 (identifier: Q9UJU2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-115: Missing.
     283-399: KPQHEQRKEQ...TGPRMTAAYI → CSAFLLPHPF...SQKDLTLRSL

Note: Produced by alternative splicing of isoform 3.
Show »
Length:214
Mass (Da):23,390
Checksum:iDDBF9358A5E8944C
GO
Isoform 5 (identifier: Q9UJU2-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     214-241: Missing.

Note: Produced by alternative splicing of isoform 1.
Show »
Length:371
Mass (Da):41,162
Checksum:iF929C8679F4EC1A3
GO
Isoform 6 (identifier: Q9UJU2-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     214-241: Missing.
     390-399: TGPRMTAAYI → GKRSSFPTCKAKAATPGPLLEMEAC

Note: Produced by alternative splicing of isoform 1. No experimental confirmation available.
Show »
Length:386
Mass (Da):42,676
Checksum:i918B4201D718A485
GO
Isoform 7 (identifier: Q9UJU2-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: MPQLSGGGGGGGGDPELCATDEMIPFKDEGDPQKEKIFAEISHPEEEGDLADIKSSLVNESEIIPASNGH → MA
     214-241: Missing.

Note: No experimental confirmation available.
Show »
Length:303
Mass (Da):34,103
Checksum:i38F7331074A62A79
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RIV1D6RIV1_HUMAN
Lymphoid enhancer-binding factor 1
LEF1
145Annotation score:
D6RAB1D6RAB1_HUMAN
Lymphoid enhancer-binding factor 1
LEF1
173Annotation score:
D6RID7D6RID7_HUMAN
Lymphoid enhancer-binding factor 1
LEF1
133Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti146Q → R in BAH13928 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035935113G → R in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs369649181Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0070221 – 115Missing in isoform 3 and isoform 4. 1 PublicationAdd BLAST115
Alternative sequenceiVSP_0448771 – 70MPQLS…ASNGH → MA in isoform 7. 1 PublicationAdd BLAST70
Alternative sequenceiVSP_040068214 – 241Missing in isoform 5, isoform 6 and isoform 7. 3 PublicationsAdd BLAST28
Alternative sequenceiVSP_002188283 – 399KPQHE…TAAYI → CSAFLLPHPFLIPSTPSPNH HHHHLLGSLSMNRERSRSQK DLTLRSL in isoform 2 and isoform 4. 1 PublicationAdd BLAST117
Alternative sequenceiVSP_040069390 – 399TGPRMTAAYI → GKRSSFPTCKAKAATPGPLL EMEAC in isoform 6. 1 Publication10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF288571 mRNA Translation: AAG01022.1
AF198532 mRNA Translation: AAF13268.1
AF294627 mRNA Translation: AAG26886.1
AK294395 mRNA Translation: BAG57649.1
AK303272 mRNA Translation: BAH13928.1
AC092539 Genomic DNA No translation available.
AC097067 Genomic DNA No translation available.
AC118062 Genomic DNA No translation available.
AC123576 Genomic DNA No translation available.
CH471057 Genomic DNA Translation: EAX06223.1
CH471057 Genomic DNA Translation: EAX06225.1
BC040559 mRNA Translation: AAH40559.1
BC050632 mRNA Translation: AAH50632.1
CCDSiCCDS3679.1 [Q9UJU2-1]
CCDS47122.1 [Q9UJU2-6]
CCDS47123.1 [Q9UJU2-5]
CCDS54791.1 [Q9UJU2-7]
PIRiA39625
RefSeqiNP_001124185.1, NM_001130713.2 [Q9UJU2-5]
NP_001124186.1, NM_001130714.2 [Q9UJU2-6]
NP_001159591.1, NM_001166119.1 [Q9UJU2-7]
NP_057353.1, NM_016269.4 [Q9UJU2-1]
UniGeneiHs.743478

Genome annotation databases

EnsembliENST00000265165; ENSP00000265165; ENSG00000138795 [Q9UJU2-1]
ENST00000379951; ENSP00000369284; ENSG00000138795 [Q9UJU2-6]
ENST00000438313; ENSP00000406176; ENSG00000138795 [Q9UJU2-5]
ENST00000506680; ENSP00000422334; ENSG00000138795 [Q9UJU2-2]
ENST00000510624; ENSP00000422840; ENSG00000138795 [Q9UJU2-7]
GeneIDi51176
KEGGihsa:51176
UCSCiuc003hyt.3 human [Q9UJU2-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF288571 mRNA Translation: AAG01022.1
AF198532 mRNA Translation: AAF13268.1
AF294627 mRNA Translation: AAG26886.1
AK294395 mRNA Translation: BAG57649.1
AK303272 mRNA Translation: BAH13928.1
AC092539 Genomic DNA No translation available.
AC097067 Genomic DNA No translation available.
AC118062 Genomic DNA No translation available.
AC123576 Genomic DNA No translation available.
CH471057 Genomic DNA Translation: EAX06223.1
CH471057 Genomic DNA Translation: EAX06225.1
BC040559 mRNA Translation: AAH40559.1
BC050632 mRNA Translation: AAH50632.1
CCDSiCCDS3679.1 [Q9UJU2-1]
CCDS47122.1 [Q9UJU2-6]
CCDS47123.1 [Q9UJU2-5]
CCDS54791.1 [Q9UJU2-7]
PIRiA39625
RefSeqiNP_001124185.1, NM_001130713.2 [Q9UJU2-5]
NP_001124186.1, NM_001130714.2 [Q9UJU2-6]
NP_001159591.1, NM_001166119.1 [Q9UJU2-7]
NP_057353.1, NM_016269.4 [Q9UJU2-1]
UniGeneiHs.743478

3D structure databases

ProteinModelPortaliQ9UJU2
SMRiQ9UJU2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119354, 40 interactors
ComplexPortaliCPX-316 beta1-catenin - LEF1 complex
DIPiDIP-29946N
IntActiQ9UJU2, 23 interactors
MINTiQ9UJU2
STRINGi9606.ENSP00000265165

Chemistry databases

ChEMBLiCHEMBL3217392

PTM databases

iPTMnetiQ9UJU2
PhosphoSitePlusiQ9UJU2

Polymorphism and mutation databases

BioMutaiLEF1
DMDMi8928194

Proteomic databases

PaxDbiQ9UJU2
PeptideAtlasiQ9UJU2
PRIDEiQ9UJU2
ProteomicsDBi84650
84651 [Q9UJU2-2]
84652 [Q9UJU2-3]
84653 [Q9UJU2-4]
84654 [Q9UJU2-5]
84655 [Q9UJU2-6]
TopDownProteomicsiQ9UJU2-2 [Q9UJU2-2]

Protocols and materials databases

DNASUi51176
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265165; ENSP00000265165; ENSG00000138795 [Q9UJU2-1]
ENST00000379951; ENSP00000369284; ENSG00000138795 [Q9UJU2-6]
ENST00000438313; ENSP00000406176; ENSG00000138795 [Q9UJU2-5]
ENST00000506680; ENSP00000422334; ENSG00000138795 [Q9UJU2-2]
ENST00000510624; ENSP00000422840; ENSG00000138795 [Q9UJU2-7]
GeneIDi51176
KEGGihsa:51176
UCSCiuc003hyt.3 human [Q9UJU2-1]

Organism-specific databases

CTDi51176
DisGeNETi51176
EuPathDBiHostDB:ENSG00000138795.9
GeneCardsiLEF1
HGNCiHGNC:6551 LEF1
HPAiCAB019405
HPA002087
MIMi153245 gene
neXtProtiNX_Q9UJU2
OpenTargetsiENSG00000138795
PharmGKBiPA30331
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3248 Eukaryota
ENOG41109RU LUCA
GeneTreeiENSGT00390000009964
HOGENOMiHOG000116032
HOVERGENiHBG000419
InParanoidiQ9UJU2
KOiK04492
OMAiGYSGYIM
OrthoDBiEOG091G0705
PhylomeDBiQ9UJU2
TreeFamiTF318448

Enzyme and pathway databases

ReactomeiR-HSA-201722 Formation of the beta-catenin:TCF transactivating complex
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex
R-HSA-4086398 Ca2+ pathway
R-HSA-4411364 Binding of TCF/LEF:CTNNB1 to target gene promoters
R-HSA-4641265 Repression of WNT target genes
R-HSA-8951430 RUNX3 regulates WNT signaling
SignaLinkiQ9UJU2
SIGNORiQ9UJU2

Miscellaneous databases

ChiTaRSiLEF1 human
GeneWikiiLymphoid_enhancer-binding_factor_1
GenomeRNAii51176
PROiPR:Q9UJU2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138795 Expressed in 202 organ(s), highest expression level in female gonad
CleanExiHS_LEF1
ExpressionAtlasiQ9UJU2 baseline and differential
GenevisibleiQ9UJU2 HS

Family and domain databases

Gene3Di1.10.30.10, 1 hit
4.10.900.10, 1 hit
InterProiView protein in InterPro
IPR027397 Catenin_binding_dom_sf
IPR013558 CTNNB1-bd_N
IPR009071 HMG_box_dom
IPR036910 HMG_box_dom_sf
IPR028769 LEF1
IPR024940 TCF/LEF
PANTHERiPTHR10373 PTHR10373, 1 hit
PTHR10373:SF11 PTHR10373:SF11, 1 hit
PfamiView protein in Pfam
PF08347 CTNNB1_binding, 1 hit
PF00505 HMG_box, 1 hit
SMARTiView protein in SMART
SM00398 HMG, 1 hit
SUPFAMiSSF47095 SSF47095, 1 hit
PROSITEiView protein in PROSITE
PS50118 HMG_BOX_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiLEF1_HUMAN
AccessioniPrimary (citable) accession number: Q9UJU2
Secondary accession number(s): B4DG38
, B7Z8E2, E9PDK3, Q3ZCU4, Q9HAZ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 180 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again