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| | <StructureSection load='3ouw' size='340' side='right'caption='[[3ouw]], [[Resolution|resolution]] 2.91Å' scene=''> | | <StructureSection load='3ouw' size='340' side='right'caption='[[3ouw]], [[Resolution|resolution]] 2.91Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ouw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OUW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ouw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OUW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OUW FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3oux|3oux]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.91Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ctnnb1, Catnb ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Lef1, Lef-1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ouw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ouw OCA], [https://pdbe.org/3ouw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ouw RCSB], [https://www.ebi.ac.uk/pdbsum/3ouw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ouw ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ouw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ouw OCA], [https://pdbe.org/3ouw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ouw RCSB], [https://www.ebi.ac.uk/pdbsum/3ouw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ouw ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CTNB1_MOUSE CTNB1_MOUSE]] Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (By similarity). [[https://www.uniprot.org/uniprot/LEF1_MOUSE LEF1_MOUSE]] 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>PMID:11445543</ref>
| + | [https://www.uniprot.org/uniprot/CTNB1_MOUSE CTNB1_MOUSE] Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Sun, J]] | + | [[Category: Sun J]] |
| - | [[Category: Weis, W I]] | + | [[Category: Weis WI]] |
| - | [[Category: Lef]]
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| - | [[Category: Phosphorylation]]
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| - | [[Category: Protein binding]]
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| - | [[Category: Tcf]]
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| - | [[Category: Transcription factor]]
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| - | [[Category: Wnt/beta-catenin signaling pathway]]
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| Structural highlights
Function
CTNB1_MOUSE Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2 (By similarity).
Publication Abstract from PubMed
In the Wnt/beta-catenin signaling pathway, beta-catenin activates target genes through its interactions with the T-cell factor/lymphoid enhancer-binding factor (TCF/Lef) family of transcription factors. The crystal structures of complexes between the beta-catenin armadillo domain and the Lef-1 N-terminal domain show that the overall conformation and many of the interactions are similar to other published structures of TCFs bound to beta-catenin. However, a second salt bridge in other TCF-beta-catenin structures is absent in the structure of beta-catenin-Lef-1 complex, indicating that this feature is not obligatory for beta-catenin binding. Casein kinase II (CK2) has been shown to act as a positive regulator of Wnt signaling, and Lef-1 is a substrate of CK2. In vitro phosphorylation of purified Lef-1 was used to examine the effect of CK2 on the interaction of Lef-1 with beta-catenin. Mass spectrometry data show that CK2 phosphorylation of Lef-1 N-terminal domain results in a single phosphorylation site at Ser40. Isothermal titration calorimetry revealed that beta-catenin binds to nonphosphorylated or CK2-phosphorylated Lef-1 with the same affinity, which is consistent with the absence of phospho-Ser40 interactions in the crystal structure of phosphorylated Lef-1 N-terminal domain bound to beta-catenin. These data indicate that the effect of CK2 on the Wnt/beta-catenin pathway does not appear to be at the level of the Lef-1-beta-catenin interaction.
Biochemical and structural characterization of beta-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1.,Sun J, Weis WI J Mol Biol. 2011 Jan 14;405(2):519-30. doi: 10.1016/j.jmb.2010.11.010. Epub 2010 , Nov 12. PMID:21075118[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sun J, Weis WI. Biochemical and structural characterization of beta-catenin interactions with nonphosphorylated and CK2-phosphorylated Lef-1. J Mol Biol. 2011 Jan 14;405(2):519-30. doi: 10.1016/j.jmb.2010.11.010. Epub 2010 , Nov 12. PMID:21075118 doi:http://dx.doi.org/10.1016/j.jmb.2010.11.010
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