Reviewed, UniProtKB/Swiss-Prot P27782 (LEF1_MOUSE)

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)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › 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, THOC4, MDFI and MDFIC 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. Ref.5
Domain	Proline-rich and acidic regions are implicated in the activation functions of RNA polymerase II transcription factors.
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	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from mutant phenotype. Source: MGI chorio-allantoic fusion Inferred from genetic interaction. Source: MGI dentate gyrus development Inferred from mutant phenotype. Source: MGI embryonic limb morphogenesis Inferred from genetic interaction. Source: MGI epithelial to mesenchymal transition Inferred from mutant phenotype. Source: UniProtKB mammary gland development Inferred from mutant phenotype. Source: MGI negative regulation of striated muscle tissue development Inferred from direct assay. Source: MGI negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: MGI odontogenesis of dentine-containing tooth Inferred from mutant phenotype. Source: MGI palate development Inferred from mutant phenotype. Source: UniProtKB paraxial mesoderm formation Inferred from genetic interaction. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: MGI regulation of Wnt receptor signaling pathway Inferred from genetic interaction. Source: MGI somitogenesis Inferred from mutant phenotype. Source: MGI transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: MGI transcription factor complex Inferred from physical interaction. Source: MGI
Molecular function	DNA bending activity Inferred from direct assay. Source: UniProtKB RNA polymerase II transcription factor activity, enhancer binding Inferred from genetic interaction. Source: MGI chromatin binding Inferred from direct assay. Source: MGI protein binding Inferred from physical interaction. Source: IntAct transcription activator activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ctnnb1	Q02248	2	EBI-984464,EBI-397872
RUNX3	Q13761	1	EBI-984464,EBI-925990	From a different organism.

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

93

1

N6-acetyllysine By similarity

Modified residue

130

1

Phosphoserine 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...

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). 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: 1827423] [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: 8415007] [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: 10498690] [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: 10966653] [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: 11445543] [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: 11731474] [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: 12446687] [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: 7651541] [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.

UniGene

Mm.255219

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LEF	NMR	-	A	296-380	[»]

SMR

P27782. Positions 2-59.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35132N.

IntAct

P27782. 2 interactions.

STRING

P27782.

PTM databases

PhosphoSite

P27782.

Proteomic databases

PRIDE

P27782.

Genome annotation databases

Ensembl

ENSMUST00000029611; ENSMUSP00000029611; ENSMUSG00000027985; Mus musculus. [Genome view]
ENSMUST00000098611; ENSMUSP00000096211; ENSMUSG00000027985; Mus musculus. [Genome view]

GeneID

16842.

KEGG

mmu:16842.

UCSC

uc008rjf.1. mouse.

Organism-specific databases

CTD

16842.

MGI

MGI:96770. Lef1.

Phylogenomic databases

eggNOG

roNOG08331.

HOGENOM

HBG714960.

HOVERGEN

P27782.

InParanoid

P27782.

OMA

GYSGYIM.

OrthoDB

EOG9FN73S.

PhylomeDB

P27782.

Gene expression databases

ArrayExpress

P27782.

Bgee

P27782.

CleanEx

MM_LEF1.

Genevestigator

P27782.

GermOnline

ENSMUSG00000027985. Mus musculus.

Family and domain databases

InterPro

IPR013558. CTNNB1_bd_N.
IPR000910. HMG_HMG1/HMG2.
IPR009071. HMG_superfamily.
[Graphical view]

Gene3D

G3DSA:1.10.30.10. HMG-box. 1 hit.

Pfam

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

SMART

SM00398. HMG. 1 hit.
[Graphical view]

PROSITE

PS50118. HMG_BOX_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

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:	January 19, 2010
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)