Lymphoid enhancer-binding factor 1

LEF1

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
2LEF, 3OUW, 3OUX

Identifiers

Aliases

LEF1, LEF-1, TCF10, TCF1ALPHA, TCF7L3, lymphoid enhancer binding factor 1

External IDs

MGI: 96770 HomoloGene: 7813 GeneCards: LEF1

Genetically Related Diseases

chronic lymphocytic leukemia, systemic lupus erythematosus^[1]

Gene ontology
Molecular function	• transcription factor activity, sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • histone deacetylase binding • enhancer binding • armadillo repeat domain binding • transcription regulatory region DNA binding • estrogen receptor binding • RNA polymerase II regulatory region sequence-specific DNA binding • transcription factor binding • estrogen receptor activity • RNA polymerase II core promoter proximal region sequence-specific DNA binding • beta-catenin binding • gamma-catenin binding • histone binding • C2H2 zinc finger domain binding • chromatin binding • cysteine-type endopeptidase inhibitor activity involved in apoptotic process • protein binding • DNA binding, bending • DNA binding • sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
Cellular component	• cytoplasm • nucleus • transcription factor complex • beta-catenin-TCF complex • nucleoplasm • protein-DNA complex
Biological process	• somitogenesis • tongue development • paraxial mesoderm formation • regulation of transcription from RNA polymerase II promoter • negative regulation of DNA binding • T cell receptor V(D)J recombination • transcription from RNA polymerase II promoter • cellular response to cytokine stimulus • mammary gland development • negative regulation of interleukin-13 production • odontogenesis of dentin-containing tooth • muscle fiber development • apoptotic process involved in blood vessel morphogenesis • cell chemotaxis • negative regulation of canonical Wnt signaling pathway • face morphogenesis • neutrophil differentiation • negative regulation of interleukin-5 production • regulation of transcription, DNA-templated • dentate gyrus development • apoptotic process involved in morphogenesis • transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of cell growth • regulation of Wnt signaling pathway • embryonic limb morphogenesis • hypothalamus development • branching involved in blood vessel morphogenesis • trachea gland development • regulation of striated muscle tissue development • palate development • positive regulation of cell-cell adhesion • forebrain neuroblast division • eye pigmentation • negative regulation of apoptotic process • sprouting angiogenesis • negative regulation of transcription from RNA polymerase II promoter • positive regulation of epithelial to mesenchymal transition • BMP signaling pathway • positive regulation of cell cycle process • osteoblast differentiation • histone H3 acetylation • regulation of cell-cell adhesion • formation of radial glial scaffolds • positive regulation of granulocyte differentiation • alpha-beta T cell differentiation • canonical Wnt signaling pathway • negative regulation of transcription, DNA-templated • positive regulation by host of viral transcription • sensory perception of taste • cellular response to interleukin-4 • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • cell development • negative regulation of cell-cell adhesion • negative regulation of interleukin-4 production • negative regulation of striated muscle tissue development • positive regulation of cell migration • Wnt signaling pathway • T-helper 1 cell differentiation • positive regulation of cell proliferation in bone marrow • anatomical structure regression • chorio-allantoic fusion • negative regulation of apoptotic process in bone marrow • B cell proliferation • positive regulation of gene expression • vasculature development • forebrain radial glial cell differentiation • neural crest cell migration • positive regulation of cell proliferation • forebrain neuron differentiation • histone H4 acetylation • hippocampus development • negative regulation of estrogen receptor binding • positive regulation of transcription from RNA polymerase II promoter • Wnt signaling pathway, calcium modulating pathway • steroid hormone mediated signaling pathway • odontoblast differentiation • beta-catenin-TCF complex assembly • epithelial to mesenchymal transition
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


51176


16842

Ensembl


ENSG00000138795


ENSMUSG00000027985

UniProt


Q9UJU2


P27782

RefSeq (mRNA)


NM_001130713 NM_001130714 NM_001166119 NM_016269


NM_001276402 NM_001276403 NM_010703

RefSeq (protein)


NP_001124185.1 NP_001124186.1 NP_001159591.1 NP_057353.1 NP_057353.1


NP_034833.2

Location (UCSC)

Chr 4: 108.05 – 108.17 Mb

Chr 3: 131.11 – 131.22 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/Edit Mouse

Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the LEF1 gene.^[4]

Function

Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nuclear protein that is expressed in pre-B and T cells. It binds to a functionally important site in the T-cell receptor-alpha (TCRA) enhancer and confers maximal enhancer activity. LEF1 belongs to a family of regulatory proteins that share homology with high mobility group protein-1 (HMG1).^[5]

Clinical significance

LEF1 is highly overexpressed and associated with disease progression and poor prognosis in B-cell chronic lymphocytic leukemia.^[6] It is also a promising potential drug target.^[7]

Interactions

Lymphoid enhancer-binding factor 1 has been shown to interact with:

References

↑ "Diseases that are genetically associated with LEF1 view/edit references on wikidata".
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Milatovich A, Travis A, Grosschedl R, Francke U (Mar 1992). "Gene for lymphoid enhancer-binding factor 1 (LEF1) mapped to human chromosome 4 (q23-q25) and mouse chromosome 3 near Egf". Genomics. 11 (4): 1040–8. doi:10.1016/0888-7543(91)90030-I. PMID 1783375.
↑ "Entrez Gene: LEF1 lymphoid enhancer-binding factor 1".
↑ Erdfelder F, Hertweck M, Filipovich A, Uhrmacher S, Kreuzer KA (2010). "High lymphoid enhancer- binding factor-1 expression is associated with disease progression and poor prognosis in chronic lymphocytic leukemia". Hematology Reports. 2 (1). doi:10.4081/hr.2010.e3.
↑ Gandhirajan RK, Staib PA, Minke K, Gehrke I, Plickert G, Schlösser A, Schmitt EK, Hallek M, Kreuzer KA (April 2010). "Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo". Neoplasia. 12 (4): 326–35. PMC 2847740. PMID 20360943.
↑ Boras K, Hamel PA (January 2002). "Alx4 binding to LEF-1 regulates N-CAM promoter activity". J. Biol. Chem. 277 (2): 1120–7. doi:10.1074/jbc.M109912200. PMID 11696550.
↑ Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E, Hiebert SW (January 2000). "A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia". J. Biol. Chem. 275 (1): 651–6. doi:10.1074/jbc.275.1.651. PMID 10617663.
↑ Edlund S, Lee SY, Grimsby S, Zhang S, Aspenström P, Heldin CH, Landström M (February 2005). "Interaction between Smad7 and beta-catenin: importance for transforming growth factor beta-induced apoptosis". Mol. Cell. Biol. 25 (4): 1475–88. doi:10.1128/MCB.25.4.1475-1488.2005. PMC 548008. PMID 15684397.
↑ Grueneberg DA, Pablo L, Hu KQ, August P, Weng Z, Papkoff J (June 2003). "A functional screen in human cells identifies UBF2 as an RNA polymerase II transcription factor that enhances the beta-catenin signaling pathway". Mol. Cell. Biol. 23 (11): 3936–50. doi:10.1128/MCB.23.11.3936-3950.2003. PMC 155208. PMID 12748295.
↑ Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W (August 1996). "Functional interaction of beta-catenin with the transcription factor LEF-1". Nature. 382 (6592): 638–42. doi:10.1038/382638a0. PMID 8757136.
1 2 3 Labbé E, Letamendia A, Attisano L (July 2000). "Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways". Proc. Natl. Acad. Sci. U.S.A. 97 (15): 8358–63. doi:10.1073/pnas.150152697. PMC 26952. PMID 10890911.
↑ Hecht A, Stemmler MP (February 2003). "Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4". J. Biol. Chem. 278 (6): 3776–85. doi:10.1074/jbc.M210081200. PMID 12446687.
↑ Yasumoto K, Takeda K, Saito H, Watanabe K, Takahashi K, Shibahara S (June 2002). "Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling". EMBO J. 21 (11): 2703–14. doi:10.1093/emboj/21.11.2703. PMC 126018. PMID 12032083.
↑ Sachdev S, Bruhn L, Sieber H, Pichler A, Melchior F, Grosschedl R (December 2001). "PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies". Genes Dev. 15 (23): 3088–103. doi:10.1101/gad.944801. PMC 312834. PMID 11731474.

External links

LEF1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

PDB gallery

2lef: LEF1 HMG DOMAIN (FROM MOUSE), COMPLEXED WITH DNA (15BP), NMR, 12 STRUCTURES

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1

(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2

(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)

(1.5) RF-X	RFX 1 2 3 4 5 6 ANK

(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR

subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX

subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ

subfamily 4	NUR NGFIB NOR1 NURR1

subfamily 5	LRH-1 SF1

subfamily 6	GCNF

subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2

(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX

(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4

(3.4) Heat shock factors	HSF 1 2 4

(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5

(4.2) STAT	STAT 1 2 3 4 5 6

(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63

(4.4) MADS box	Mef2 A B C D SRF

(4.6) TATA-binding proteins	TBP TBPL1

(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA YBX1

(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1

(0.3) Pocket domain	Rb RBL1 RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3

(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

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