Lymphoid enhancer-binding factor 1 - Homo sapiens (Human)

Contribute

Send feedback

Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot Q9UJU2 (LEF1_HUMAN)

Last modified February 9, 2010. Version 92. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

Third-party data |

Customize display

text xml rdf/xml gff fasta

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Hide | Top

Names and origin

Protein names

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 names

Name:

LEF1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Hide | Top

Protein attributes

Sequence length	399 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

Hide | Top

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. 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. Ref.1 Ref.9
Subunit structure	Binds the armadillo repeat of CTNNB1 and forms a stable complex. Interacts with EP300, TLE1 and PIASG By similarity. Binds THOC4, MDFI and MDFIC. Ref.9 Ref.5 Ref.6 Ref.7 Ref.10
Subcellular location	Nucleus By similarity. Note: Found in nuclear bodies upon PIASG binding By similarity.
Tissue specificity	Detected in thymus. Not detected in normal colon, but highly expressed in colon cancer biopsies and colon cancer cell lines.
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.

Hide | Top

Ontologies

Keywords
Biological process	Transcription Transcription regulation Wnt signaling pathway
Cellular component	Nucleus
Coding sequence diversity	Alternative promoter usage Alternative splicing Polymorphism
Ligand	DNA-binding
Molecular function	Activator
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from direct assay. Source: UniProtKB epithelial to mesenchymal transition Inferred from sequence or structural similarity. Source: UniProtKB palate development Inferred from sequence or structural similarity. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: HPA
Molecular function	DNA bending activity Inferred from sequence or structural similarity. Source: UniProtKB protein binding Ref.7 Ref.10 Inferred from physical interaction. Source: UniProtKB sequence-specific DNA binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Hide | Top

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TLE1	Q04724	1	EBI-926131,EBI-711424

Hide | Top

Alternative products

This entry describes 4 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select] Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q9UJU2-1) 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.
Note: Produced by alternative promoter usage.

Isoform 2 (identifier: Q9UJU2-2) 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.

Isoform 3 (identifier: Q9UJU2-3) 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.

Isoform 4 (identifier: Q9UJU2-4) 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.

Hide | Top

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 399

399

Lymphoid enhancer-binding factor 1

PRO_0000048595

Regions

DNA binding

299 – 367

HMG box

Region

1 – 62

CTNNB1-binding By similarity

Compositional bias

6 – 13

Poly-Gly

Compositional bias

14 – 52

Asp/Glu-rich (acidic)

Compositional bias

77 – 273

197

Pro-rich

Compositional bias

374 – 379

Poly-Lys

Amino acid modifications

Modified residue

N6-acetyllysine Ref.13

Modified residue

132

Phosphoserine Ref.12

Cross-link

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

Cross-link

269

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

Natural variations

Alternative sequence

1 – 115

115

Missing in isoform 3 and isoform 4.

VSP_007022

Alternative sequence

283 – 399

117

KPQHE…TAAYI → CSAFLLPHPFLIPSTPSPNH HHHHLLGSLSMNRERSRSQK DLTLRSL in isoform 2 and isoform 4.

VSP_002188

Natural variant

113

G → R in a colorectal cancer sample; somatic mutation. Ref.14

VAR_035935

Hide | Top

Sequences

Sequence		Length	Mass (Da)
Isoform 1 (A) [UniParc]. Last modified May 1, 2000. Version 1. Checksum: D480D440698EEFE3 Show »	FASTA	399	44,201
10 20 30 40 50 60 MPQLSGGGGG GGGDPELCAT DEMIPFKDEG DPQKEKIFAE ISHPEEEGDL ADIKSSLVNE 70 80 90 100 110 120 SEIIPASNGH EVARQAQTSQ EPYHDKAREH PDDGKHPDGG LYNKGPSYSS YSGYIMMPNM 130 140 150 160 170 180 NNDPYMSNGS LSPPIPRTSN KVPVVQPSHA VHPLTPLITY SDEHFSPGSH PSHIPSDVNS 190 200 210 220 230 240 KQGMSRHPPA PDIPTFYPLS PGGVGQITPP LGWQGQPVYP ITGGFRQPYP SSLSVDTSMS 250 260 270 280 290 300 RFSHHMIPGP PGPHTTGIPH PAIVTPQVKQ EHPHTDSDLM HVKPQHEQRK EQEPKRPHIK 310 320 330 340 350 360 KPLNAFMLYM KEMRANVVAE CTLKESAAIN QILGRRWHAL SREEQAKYYE LARKERQLHM 370 380 390 QLYPGWSARD NYGKKKKRKR EKLQESASGT GPRMTAAYI « Hide
Isoform 2 (B) (8A). Checksum: 3632325D440CA5DD Show »	FASTA	329	35,672
10 20 30 40 50 60 MPQLSGGGGG GGGDPELCAT DEMIPFKDEG DPQKEKIFAE ISHPEEEGDL ADIKSSLVNE 70 80 90 100 110 120 SEIIPASNGH EVARQAQTSQ EPYHDKAREH PDDGKHPDGG LYNKGPSYSS YSGYIMMPNM 130 140 150 160 170 180 NNDPYMSNGS LSPPIPRTSN KVPVVQPSHA VHPLTPLITY SDEHFSPGSH PSHIPSDVNS 190 200 210 220 230 240 KQGMSRHPPA PDIPTFYPLS PGGVGQITPP LGWQGQPVYP ITGGFRQPYP SSLSVDTSMS 250 260 270 280 290 300 RFSHHMIPGP PGPHTTGIPH PAIVTPQVKQ EHPHTDSDLM HVCSAFLLPH PFLIPSTPSP 310 320 NHHHHHLLGS LSMNRERSRS QKDLTLRSL « Hide
Isoform 3 (LEF-1-DN). Checksum: 22320A1A195401ED Show »	FASTA	284	31,919
10 20 30 40 50 60 MMPNMNNDPY MSNGSLSPPI PRTSNKVPVV QPSHAVHPLT PLITYSDEHF SPGSHPSHIP 70 80 90 100 110 120 SDVNSKQGMS RHPPAPDIPT FYPLSPGGVG QITPPLGWQG QPVYPITGGF RQPYPSSLSV 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 SASGTGPRMT AAYI « Hide
Isoform 4. Checksum: DDBF9358A5E8944C Show »	FASTA	214	23,390
10 20 30 40 50 60 MMPNMNNDPY MSNGSLSPPI PRTSNKVPVV QPSHAVHPLT PLITYSDEHF SPGSHPSHIP 70 80 90 100 110 120 SDVNSKQGMS RHPPAPDIPT FYPLSPGGVG QITPPLGWQG QPVYPITGGF RQPYPSSLSV 130 140 150 160 170 180 DTSMSRFSHH MIPGPPGPHT TGIPHPAIVT PQVKQEHPHT DSDLMHVCSA FLLPHPFLIP 190 200 210 STPSPNHHHH HLLGSLSMNR ERSRSQKDLT LRSL « Hide

Hide | Top

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer." Waterman M.L., Fischer W.H., Jones K.A. Genes Dev. 5:656-669(1991) [PubMed: 2010090] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, FUNCTION.
[2]	"The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing." Hovanes K., Li T.W., Waterman M.L. Nucleic Acids Res. 28:1994-2003(2000) [PubMed: 10756202] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
[3]	"New transcript isoform of the human LEF-1 devoid of HMG domain, derived from alternative splicing of exon 8." Kobielak A., Kobielak K., Trzeciak W.H. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Skin.
[5]	"ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function." Bruhn L., Munnerlyn A., Grosschedl R. Genes Dev. 11:640-653(1997) [PubMed: 9119228] [Abstract] Cited for: INTERACTION WITH THOC4.
[6]	"Two members of the Tcf family implicated in Wnt/b-catenin signaling during embryogenesis in the mouse." Korinek V., Barker N., Willert K., Molenaar M., Roose J., Wagenaar G., Markman M., Lamers W., Destree O., Clevers H. Mol. Cell. Biol. 18:1248-1256(1998) [PubMed: 9488439] [Abstract] Cited for: INTERACTION WITH CTNNB1.
[7]	"Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors." Levanon D., Goldstein R.E., Bernstein Y., Tang H., Goldenberg D., Stifani S., Paroush Z., Groner Y. Proc. Natl. Acad. Sci. U.S.A. 95:11590-11595(1998) [PubMed: 9751710] [Abstract] Cited for: INTERACTION WITH TLE1, INHIBITION OF TRANSCRIPTIONAL ACTIVATION BY TLE1.
[8]	"Beta-catenin-sensitive isoforms of lymphoid enhancer factor-1 are selectively expressed in colon cancer." Hovanes K., Li T.W.H., Munguia J.E., Truong T., Milovanovic T., Lawrence Marsh J., Holcombe R.F., Waterman M.L. Nat. Genet. 28:53-57(2001) [PubMed: 11326276] [Abstract] Cited for: IDENTIFICATION (ISOFORM 3), EXPRESSION IN COLON CANCER.
[9]	"All Tcf HMG box transcription factors interact with Groucho-related co-repressors." Brantjes H., Roose J., van De Wetering M., Clevers H. Nucleic Acids Res. 29:1410-1419(2001) [PubMed: 11266540] [Abstract] Cited for: FUNCTIONAL INTERACTION WITH TLE1; TLE2; TLE3 AND TLE4.
[10]	"I-mfa domain proteins interact with Axin and affect its regulation of the Wnt and c-Jun N-terminal kinase signaling pathways." Kusano S., Raab-Traub N. Mol. Cell. Biol. 22:6393-6405(2002) [PubMed: 12192039] [Abstract] Cited for: INTERACTION WITH MDFI AND MDFIC.
[11]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[12]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132, MASS SPECTROMETRY. Tissue: T-cell.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-95, MASS SPECTROMETRY.
[14]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-113.
+	Additional computationally mapped references.

Hide | Top

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF288571 mRNA. Translation: AAG01022.1. AF198532 mRNA. Translation: AAF13268.1. AF294627 mRNA. Translation: AAG26886.1. BC050632 mRNA. Translation: AAH50632.1.
IPI	IPI00007156. IPI00220455. IPI00220456. IPI00220457.
PIR	A39625.
RefSeq	NP_001124185.1. NP_001124186.1. NP_001159591.1. NP_057353.1.
3D structure databases
SMR	Q9UJU2. Positions 2-61, 298-373.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29946N.
IntAct	Q9UJU2. 2 interactions.
STRING	Q9UJU2.
PTM databases
PhosphoSite	Q9UJU2.
Proteomic databases
PRIDE	Q9UJU2.
Genome annotation databases
Ensembl	ENST00000265165; ENSP00000265165; ENSG00000138795; Homo sapiens. [Genome view]
GeneID	51176.
UCSC	uc003hyt.1. human.
Organism-specific databases
CTD	51176.
GeneCards	GC04M109188.
H-InvDB	HIX0004430. HIX0031436.
HGNC	HGNC:6551. LEF1.
HPA	CAB019405. HPA002087.
MIM	153245. gene.
PharmGKB	PA30331.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG714960.
HOVERGEN	Q9UJU2.
InParanoid	Q9UJU2.
OMA	GYSGYIM.
PhylomeDB	Q9UJU2.
Enzyme and pathway databases
Pathway_Interaction_DB	wnt_canonical_pathway. Canonical Wnt signaling pathway.
Gene expression databases
ArrayExpress	Q9UJU2.
Bgee	Q9UJU2.
CleanEx	HS_LEF1.
Genevestigator	Q9UJU2.
GermOnline	ENSG00000138795. Homo sapiens.
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	54133.
SOURCE	Search...

Hide | Top

Entry information

Entry name

LEF1_HUMAN

Accession

Primary (citable) accession number: Q9UJU2
Secondary accession number(s): Q9HAZ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 2000
Last modified:	February 9, 2010
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.

Hide | Top

Relevant documents

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents