AC T00930
XX
ID T00930
XX
DT 15.06.1993 (created); ewi.
DT 23.09.2013 (updated); spk.
CO Copyright (C), QIAGEN.
XX
FA LEF-1
XX
SY LEF 1; LEF-1L; lymphocyte enhancer binding factor 1; lymphoid enhancer binding factor 1.
XX
OS mouse, Mus musculus
OC eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; rodentia; myomorpha; muridae; murinae
XX
GE G013561 Lef1.
XX
CL C0015; HMG; 4.1.3.0.4.1.
XX
SZ 397 AA; 44.1 kDa (cDNA) (calc.), 54KDa (SDS)
XX
SQ MPQLSGGGGGGDPELCATDEMIPFKDEGDPQKEKIFAEISHPEEEGDLADIKSSLVNESE
SQ IIPASNGHEVVRQAPSSQEPYHDKAREHPDEGKHPDGGLYNKGPSYSSYSGYIMMPNMNS
SQ DPYMSNGSLSPPIPRTSNKVPVVQPSHAVHPLTPLITYSDEHFSPGSHPSHIPSDVNSKQ
SQ GMSRHPPAPEIPTFYPLSPGGVGQITPPIGWQGQPVYPITGGFRQPYPSSLSGDTSMSRF
SQ SHHMIPGPPGPHTTGIPHPAIVTPQVKQEHPHTDSDLMHVKPQHEQRKEQEPKRPHIKKP
SQ LNAFMLYMKEMRANVVAECTLKESAAINQILGRRWHALSREEQAKYYELARKERQLHMQL
SQ YPGWSARDNYGKKKKRKREKLQESTSGTGPRMTAAYI
XX
SC Swiss-Prot#P27782-1
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FT 12 50 
acidic region (14/36) [1].
FT 75 271 
proline-rich region (37/197) [1].
FT 99 217 
context-dependent activation domain CAD [9].
FT 296 366 
SM00398; hmgende2.
FT 297 365 
PF00505; HMG (high mobility group) box.
FT 297 365 
PS50118; HMG_BOX_2.
FT 372 380 
B box (essential for nuclear transposition) [15].
FT 387 397 
LEF-1N tail [22].
XX
SF DNA binding affinity of the monomer: KD = 1 nM [3];
SF contacts DNA from one side [3];
SF induces a bend of about 117-130 degree [4] [7];
SF widens and binds the minor groove of DNA [4] [7];
SF the L-shape HMG domain also binds across the narrowed major groove [7];
SF expression can be activated by BMP-4, which suggests a regulatory role of LEF-1 in BMP-mediated inductive tissue interaction [13];
SF LEF-1 translocates beta-Catenin to the nucleus [19] [9];
SF truncated LEF-1 (missing the beta-Catenin binding domain) is present in the nucleus but cannot translocate beta-Catenin to the nucleus [9];
SF gene located on chromosome 3 [3];
SF interaction with beta-Catenin and Plakoglobin [19];
SF N terminally deleted LEF-1 is no longer able to interact with beta-Catenin but still binds to specific DNA fragments [19];
SF alanine substitution mutagenesis and EMSA shows that AA 25-27 and 32-34 are not necessary for beta-Catenin binding [21];
SF for the interaction of beta-catenin and LEF-1 the HMG domain of LEF-1 is not essential [9];
SF circular permutation analysis of DNA bending induced by LEF-1 or the beta-catenin/ LEF-1 complex showed that beta-catenin decreased the extent of LEF-1 induced DNA bending (from about 120� to about 80�) [9];
XX
CP pre-B cells, T lymphocytes [1]; during embryogenesis: neural crest, mesencephalon, tooth germs, whisker follicles [11]; (embr.<10.5) limb buds, neural crest, pharyngeal arches, nasal process; (embr. < 15.5): lung, urogenital system, tooth buds, thymus and choroid plexus, tail prevertebrae, brain and inner ear [10] [10] [11] [1].
XX
FF potent activator when bound in the right context, e. g. with an adjacently binding TCF-2 [5];
FF activator, possibly by augmenting an optimal chromatin architecture which facilitates other factors to assemble to a transcription complex [4] [24];
FF for expression in teeth, see [23];
FF for regulation of inductive tissue interactions in tooth and hair development see [13];
FF LEF-1 HMG domain binds to irregular DNA structures although with a roughly 2-fold lower affinity than a specific duplex binding site and induces negative supercoils (about half a helical turn per HMG box);
FF regulation of the TCF alpha enhancer is dependent on the wild-type LEF-1 binding site which induces a bending angle of 130� into the DNA;
FF a mutated LEF-1 binding site leads to a lower bending angle and to lower activity of the TCF alpha enhancer [14];
FF upon Wnt-1 signaling combined with beta-Catenin binding to LEF-1 the transcriptional activity rises;
FF taken together LEF-1 can exert two different roles: in association with beta-Catenin it can mediate transcriptional activation in a context-independent manner, whereas it regulates - together with ALY - transcription in a context specific way [21];
FF interacts with CBP [20];
XX
IN T02977 armadillo; fruit fly, Drosophila melanogaster.
IN T02872 beta-catenin; human, Homo sapiens.
IN T02984 beta-catenin; mouse, Mus musculus.
IN T03236 CBP; fruit fly, Drosophila melanogaster.
IN T25615 NICD1; human, Homo sapiens.
IN T04096 Smad3-isoform1; human, Homo sapiens.
IN T04292 Smad4; human, Homo sapiens.
XX
MX M00978 V$LEF1TCF1_Q4.
MX M02878 V$LEF1_03.
MX M02774 V$LEF1_04.
MX M00805 V$LEF1_Q2.
MX M01022 V$LEF1_Q2_01.
MX M07046 V$LEF1_Q3.
MX M07605 V$LEF1_Q4.
MX M02019 V$LEF1_Q5.
MX M03794 V$LEF1_Q5_01.
MX M08902 V$TCF7RELATED_Q4.
XX
BS R08636.
BS R56947.
BS R56949.
BS R56950.
BS R56951.
BS R03576.
BS R30769.
BS R04450.
BS R08631.
BS R08823.
BS R08824.
BS R56953.
BS R56954.
BS R56956.
BS R56957.
BS R03470.
BS R08809.
BS R38307.
BS R38308.
BS R16083.
BS R08816.
BS R02248.
BS R08649.
BS R08633.
BS R08634.
BS R13042.
XX
DR TRANSPATH: MO000018859.
DR TRANSCOMPEL: C00194.
DR EMBL: X58636; MMLEF1.
DR UniProtKB: P27782-1;
XX
RN [1]; RE0000695.
RX PUBMED: 1827423.
RA Travis A., Amsterdam A., Belanger C., Grosschedl R.
RT LEF-1, a gene encoding a lymphoid-specific with protein, an HMG domain, regulates T-cell receptor alpha enhancer function
RL Genes Dev. 5:880-894 (1991).
RN [2]; RE0002106.
RX PUBMED: 1861981.
RA Aronheim A., Ohlsson H., Park C. W., Edlund T., Walker M. D.
RT Distribution and characterization of helix-loop-helix enhancer-binding proteins from pancreatic beta cells and lymphocytes
RL Nucleic Acids Res. 19:3893-3899 (1991).
RN [3]; RE0004363.
RX PUBMED: 1752444.
RA Giese K., Amsterdam A., Grosschedl R.
RT DNA-binding properties of the HMG domain of the lymphoid-specific transcriptional regulator LEF-1
RL Genes Dev. 5:2567-2578 (1991).
RN [4]; RE0004364.
RX PUBMED: 1555239.
RA Giese K., Cox J., Grosschedl R.
RT The HMG domain of lymphoid enhancer factor 1 bends DNA and facilitates assembly of functional nucleoprotein structures
RL Cell 69:185-195 (1992).
RN [5]; RE0004365.
RX PUBMED: 8253387.
RA Carlsson P., Waterman M. L., Jones K. A.
RT The hLEF/TCF-1alpha HMG protein contains a context-dependent transcriptional activation domain that induces the TCRalpha enhancer in T cells
RL Genes Dev. 7:2418-2430 (1993).
RN [6]; RE0004367.
RX PUBMED: 8346022.
RA Read C. M., Cary P. D., Crane-Robinson C., Driscoll P. C., Norman D. G.
RT Solution structure of a DNA-binding domain from HMG1
RL Nucleic Acids Res. 21:3427-3436 (1993).
RN [7]; RE0004369.
RX PUBMED: 7651541.
RA Love J. J., Li X., Case D. A., Giese K., Grosschedl R., Wright P. E.
RT Structural basis for DNA bending by the architectural transcription factor LEF-1
RL Nature 376:791-795 (1995).
RN [8]; RE0004382.
RX PUBMED: 8467791.
RA Weir H. M., Kraulis P. J., Hill C. S., Raine A. R. C., Laue E. D., Thomas J. O.
RT Structure of the HMG box motif in the B-domain of HMG1
RL EMBO J. 12:1311-1319 (1993).
RN [9]; RE0006108.
RX PUBMED: 8757136.
RA Behrens J., von Kries J. P., Kuehl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W.
RT Functional interaction of beta-catenin with the transcription factor LEF -1
RL Nature 382:638-642 (1996).
RN [10]; RE0006815.
RX PUBMED: 8223271.
RA Oosterwegel M., van de Wetering M., Timmerman J., Kruisbeek A., Destree O., Meijlink F., Clevers H.
RT Differential expression of the HMG box factors TCF-1 and LEF-1 during murine embryogenesis
RL Development 118:439-448 (1993).
RN [11]; RE0009773.
RX PUBMED: 7958926.
RA van Genderen C., Okamura R. M., Farinas I., Quo R.-G., Parslow T. G., Bruhn L., Grosschedl R.
RT Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice
RL Genes Dev. 8:2691- 2703 (1994).
RN [12]; RE0010385.
RX PUBMED: 7537238.
RA Zhou P., Byrne C., Jacobs J., Fuchs E.
RT Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate
RL Genes Dev. 9:700-713 (1995).
RN [13]; RE0012617.
RX PUBMED: 8647435.
RA Kratochwil K., Dull M., Farinas I., Galceran J., Grosschedl R.
RT Lef1 expression is activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development
RL Genes Dev. 10:1382-1394 (1996).
RN [14]; RE0014048.
RX PUBMED: 9371763.
RA Giese K., Pagel J., Grosschedl R.
RT Functional analysis of DNA bending and unwinding by the high mobility group domain of LEF-1
RL Proc. Natl. Acad. Sci. USA 94:12845-12850 (1997).
RN [15]; RE0014054.
RX PUBMED: 8631802.
RA Prieve M. G., Guttridge K. L., Munguia J. E., Waterman M. L.
RT The nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differentially expressed Srp1-nuclear localization sequence receptor proteins
RL J. Biol. Chem. 271:7654-7658 (1996).
RN [16]; RE0014090.
RX PUBMED: 9441678.
RA McKendry R., Hsu S.-C., Harland R. M., Grosschedl R.
RT LEF-1/TCF proteins mediate Wnt-inducible transcription from Xenopus nodal-related 3 promoter
RL Dev. Biol. 192:420-431 (1997).
RN [17]; RE0014091.
RX PUBMED: 9118221.
RA Riese J., Yu X., Munnerlyn A., Eresh S., Hsu S.-C., Grosschedl R., Bienz M.
RT LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic
RL Cell 88:777-787 (1997).
RN [18]; RE0014099.
RX PUBMED: 10409747.
RA Gradl D., Kuhl M., Wedlich D.
RT The Wnt/Wg signal transducer beta-catenin controls fibronectin expression
RL Mol. Cell. Biol. 19:5576-5587 (1999).
RN [19]; RE0014185.
RX PUBMED: 8892228.
RA Huber O., Korn R., McLaughlin J., Ohsugi M., Herrmann B. G., Kemler R.
RT Nuclear localization of beta-catenin by interaction with transcription factor LEF-1
RL Mech. Dev. 59:3-10 (1996).
RN [20]; RE0014226.
RX PUBMED: 9774110.
RA Waltzer L., Bienz M.
RT Drosophila CBP represses the transcription factor TCF to antagonize Wingless signalling
RL Nature 395:521-525 (1998).
RN [21]; RE0014336.
RX PUBMED: 9671490.
RA Hsu S.-C., Galceran J., Grosschedl R.
RT Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with beta-catenin
RL Mol. Cell. Biol. 18:4807-4818 (1998).
RN [22]; RE0014765.
RX PUBMED: 10756202.
RA Hovanes K., Li T. W. H., Waterman M. L.
RT The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing
RL Nucleic Acids Res. 28:1994-2003 (2000).
RN [23]; RE0014810.
RA Pekkanen M., Nieminen P., Sahlberg C., Aberg T., Thesleff I.
RT Gene expression in tooth (WWW database); URL: http://bite-it.helsinki.fi/LEF1.htm
RL Internet : (1996).
RN [24]; RE0016625.
RX PUBMED: 7774816.
RA Giese K., Kingsley C., Kirshner J. R., Grosschedl R.
RT Assembly and function of a TCR alpha enhancer complex id dependent on LEF-1-induced DNA bending and multiple protein-protein interactions.
RL Genes Dev. 9:995-1008 (1995).
XX
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