P27782 (LEF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lymphoid enhancer-binding factor 1
Short name=LEF-1

Gene names

Name:	Lef1
Synonyms:	Lef-1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	397 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Transcription Transcription regulation Wnt signaling pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Activator
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B 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 anatomical structure regression Inferred from mutant phenotype PubMed 16163358. Source: MGI apoptotic process involved in morphogenesis Inferred from mutant phenotype PubMed 15649466. Source: MGI canonical Wnt receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome cell chemotaxis Inferred from electronic annotation. Source: Compara cellular response to interleukin-4 Inferred from electronic annotation. Source: Compara 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 histone H3 acetylation Inferred from electronic annotation. Source: Compara histone H4 acetylation Inferred from electronic annotation. Source: Compara hypothalamus development Inferred from Biological aspect of Ancestor. Source: RefGenome induction of apoptosis Inferred from mutant phenotype PubMed 16163358. Source: MGI intracellular estrogen receptor signaling pathway 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: Compara negative regulation of apoptotic process in bone marrow Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of cell-cell adhesion Inferred from electronic annotation. Source: Compara 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: Compara 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 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: Compara positive regulation of cell cycle process Inferred from electronic annotation. Source: Compara positive regulation of cell growth Inferred from electronic annotation. Source: Compara positive regulation of cell migration Inferred from electronic annotation. Source: Compara 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: Compara positive regulation of epithelial to mesenchymal transition Inferred from electronic annotation. Source: Compara positive regulation of granulocyte differentiation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 12475749PubMed 15545629. Source: MGI regulation of Wnt receptor signaling pathway Inferred from genetic interaction PubMed 10090727. Source: MGI regulation of cell-cell adhesion Inferred from mutant phenotype PubMed 19154719. 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
Cellular_component	cytoplasm Inferred from direct assay PubMed 14623238. Source: MGI protein-DNA complex Inferred from electronic annotation. Source: Compara transcription factor complex Inferred from physical interaction PubMed 11696550. Source: MGI
Molecular_function	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 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: Compara enhancer binding Inferred from Biological aspect of Ancestor. Source: RefGenome estrogen receptor activity Inferred from electronic annotation. Source: Compara estrogen receptor binding Inferred from Biological aspect of Ancestor. Source: RefGenome gamma-catenin binding Inferred from Biological aspect of Ancestor. Source: RefGenome sequence-specific DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ctnnb1	Q02248	6	EBI-984464,EBI-397872

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 397

397

Lymphoid enhancer-binding factor 1

PRO_0000048596

Regions

DNA binding

297 – 365

69

HMG box

Region

1 – 60

60

CTNNB1-binding

Compositional bias

6 – 11

6

Poly-Gly

Compositional bias

12 – 50

39

Asp/Glu-rich (acidic)

Compositional bias

75 – 271

197

Pro-rich

Compositional bias

372 – 377

6

Poly-Lys

Amino acid modifications

Modified residue

130

1

Phosphoserine By similarity

Modified residue

153

1

Phosphothreonine; by NLK By similarity

Modified residue

164

1

Phosphoserine; by NLK By similarity

Cross-link

25

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

Cross-link

267

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

Natural variations

Alternative sequence

1 – 113

113

Missing in isoform 2.

VSP_006983

Experimental info

Mutagenesis

19

1

D → A: Strongly diminishes CTNNB1 binding and transactivation. Prevents nuclear translocation of CTNNB1. Ref.4

Mutagenesis

20

1

E → A: Prevents nuclear translocation of CTNNB1. Ref.4

Mutagenesis

24

1

F → A: Strongly diminishes CTNNB1 binding and transactivation. Prevents nuclear translocation of CTNNB1. Ref.4

Mutagenesis

26

1

D → A: Prevents nuclear translocation of CTNNB1. Ref.4

Mutagenesis

27

1

E → A: Prevents nuclear translocation of CTNNB1. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

397

Helix Strand Turn

Details...

Turn

13 – 16

4

Beta strand

32 – 34

3

Helix

48 – 58

11

Helix

303 – 318

16

Helix

324 – 335

12

Helix

340 – 360

21

Turn

370 – 372

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 0CA01B6C528FD7FA	FASTA	397	44,059
	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
	Isoform 2 (LEF-1S) [UniParc]. Checksum: 86E7EBEA4B85F890	FASTA	284	31,894
	10 20 30 40 50 60 MMPNMNSDPY MSNGSLSPPI PRTSNKVPVV QPSHAVHPLT PLITYSDEHF SPGSHPSHIP 70 80 90 100 110 120 SDVNSKQGMS RHPPAPEIPT FYPLSPGGVG QITPPIGWQG QPVYPITGGF RQPYPSSLSG 130 140 150 160 170 180 DTSMSRFSHH MIPGPPGPHT TGIPHPAIVT PQVKQEHPHT DSDLMHVKPQ HEQRKEQEPK 190 200 210 220 230 240 RPHIKKPLNA FMLYMKEMRA NVVAECTLKE SAAINQILGR RWHALSREEQ AKYYELARKE 250 260 270 280 RQLHMQLYPG WSARDNYGKK KKRKREKLQE STSGTGPRMT AAYI

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.

IPI

IPI00119934.
IPI00230713.

PIR

A39565.

RefSeq

NP_034833.2. NM_010703.4.

UniGene

Mm.255219.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P27782.

SMR

P27782. Positions 11-60, 296-371.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35132N.

IntAct

P27782. 3 interactions.

PTM databases

PhosphoSite

P27782.

Proteomic databases

PRIDE

P27782.

Protocols and materials databases

DNASU

16842.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000029611; ENSMUSP00000029611; ENSMUSG00000027985.

GeneID

16842.

KEGG

mmu:16842.

Organism-specific databases

CTD

51176.

MGI

MGI:96770. Lef1.

Phylogenomic databases

eggNOG

NOG299161.

HOGENOM

HOG000116032.

HOVERGEN

HBG000419.

InParanoid

P27782.

KO

K04492.

OMA

GYSGYIM.

OrthoDB

EOG480HWS.

Gene expression databases

ArrayExpress

P27782.

Bgee

P27782.

CleanEx

MM_LEF1.

Genevestigator

P27782.

GermOnline

ENSMUSG00000027985. Mus musculus.

Family and domain databases

Gene3D

1.10.30.10. 1 hit.

InterPro

IPR013558. CTNNB1-bd_N.
IPR009071. HMG_box_dom.
IPR024940. TCF/LEF.
[Graphical view]

PANTHER

PTHR10373. PTHR10373. 1 hit.

Pfam

PF08347. CTNNB1_binding. 1 hit.
PF00505. HMG_box. 1 hit.
[Graphical view]

SMART

SM00398. HMG. 1 hit.
[Graphical view]

SUPFAM

SSF47095. HMG-box. 1 hit.

PROSITE

PS50118. HMG_BOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

LEF1. mouse.

EvolutionaryTrace

P27782.

NextBio

290768.

SOURCE

Search...

Entry information

Entry name

LEF1_MOUSE

Accession

Primary (citable) accession number: P27782

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	May 1, 2013
This is version 133 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program