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| | <StructureSection load='2ql2' size='340' side='right'caption='[[2ql2]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='2ql2' size='340' side='right'caption='[[2ql2]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ql2]] is a 8 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=2QL2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QL2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ql2]] is a 8 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=2QL2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QL2 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tcf3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Neurod1, Neurod ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 2.5Å</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=2ql2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ql2 OCA], [https://pdbe.org/2ql2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ql2 RCSB], [https://www.ebi.ac.uk/pdbsum/2ql2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ql2 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=2ql2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ql2 OCA], [https://pdbe.org/2ql2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ql2 RCSB], [https://www.ebi.ac.uk/pdbsum/2ql2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ql2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NDF1_MOUSE NDF1_MOUSE]] Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5'-CANNTG-3'. Associates with the p300/CBP transcription coactivator complex to stimulate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor CDKN1A. Contributes to the regulation of several cell differentiation pathways, like those that promote the formation of early retinal ganglion cells, inner ear sensory neurons, granule cells forming either the cerebellum or the dentate gyrus cell layer of the hippocampus, endocrine islet cells of the pancreas and enteroendocrine cells of the small intestine. Together with PAX6 or SIX3, is required for the regulation of amacrine cell fate specification. Also required for dendrite morphogenesis and maintenance in the cerebellar cortex. Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis.<ref>PMID:9308961</ref> <ref>PMID:9512516</ref> <ref>PMID:10398678</ref> <ref>PMID:10639171</ref> <ref>PMID:11152640</ref> <ref>PMID:11861467</ref> <ref>PMID:11970861</ref> <ref>PMID:12810726</ref> <ref>PMID:14697366</ref> <ref>PMID:15797719</ref> <ref>PMID:18007592</ref> <ref>PMID:18339630</ref> <ref>PMID:19200230</ref> <ref>PMID:19759004</ref> <ref>PMID:21593321</ref>
| + | [https://www.uniprot.org/uniprot/TFE2_MOUSE TFE2_MOUSE] Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition (PubMed:15226298, PubMed:18214987). Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation (PubMed:18214987). Together with TCF15, required for the mesenchymal to epithelial transition (PubMed:11309385, PubMed:15226298). Dimers bind DNA on E-box motifs: 5'-CANNTG-3' (PubMed:15226298, PubMed:18214987, PubMed:30426815). Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer (By similarity). Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region (PubMed:2181401).[UniProtKB:P15923]<ref>PMID:11309385</ref> <ref>PMID:15226298</ref> <ref>PMID:18214987</ref> <ref>PMID:2181401</ref> Facilitates ATOH7 binding to DNA at the consensus sequence 5'-CAGGTG-3', and positively regulates transcriptional activity.[UniProtKB:P15923] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Guanga, G P]] | + | [[Category: Guanga GP]] |
| - | [[Category: Longo, A]] | + | [[Category: Longo A]] |
| - | [[Category: Rose, R B]] | + | [[Category: Rose RB]] |
| - | [[Category: Activator]]
| + | |
| - | [[Category: Basic-helix-loop-helix]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Developmental protein]]
| + | |
| - | [[Category: Differentiation]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Heterodimer]]
| + | |
| - | [[Category: Neurogenesis]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Protein-dna complex]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Transcription-dna complex]]
| + | |
| Structural highlights
Function
TFE2_MOUSE Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition (PubMed:15226298, PubMed:18214987). Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation (PubMed:18214987). Together with TCF15, required for the mesenchymal to epithelial transition (PubMed:11309385, PubMed:15226298). Dimers bind DNA on E-box motifs: 5'-CANNTG-3' (PubMed:15226298, PubMed:18214987, PubMed:30426815). Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer (By similarity). Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region (PubMed:2181401).[UniProtKB:P15923][1] [2] [3] [4] Facilitates ATOH7 binding to DNA at the consensus sequence 5'-CAGGTG-3', and positively regulates transcriptional activity.[UniProtKB:P15923]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The ubiquitous class I basic helix-loop-helix (bHLH) factor E47 forms heterodimers with multiple tissue specific class II bHLH proteins to regulate distinct differentiation pathways. In order to define how class I- class II heterodimer partners are selected, we determined the crystal structure of the E47-NeuroD1-bHLH dimer in complex with the insulin promoter E-box sequence. Purification of the bHLH domain of E47-NeuroD1 indicates that E47 heterodimers are stable in solution. The interactions between E47 and NeuroD1 in the heterodimer are comparable to the interactions between E47 monomers in the homodimer, including hydrogen bonding, buried hydrophobic surface, and packing interactions. This is consistent with a model in which E47-NeuroD1 heterodimers are favored due to the instability of NeuroD1 homodimers. Although E47-NeuroD1 is oriented uniquely on the E-box sequence (CATCTG) within the promoter of the insulin gene, no direct contacts are observed with the central base pairs within this E-box sequence. We propose that concerted domain motions allow E47 to form specific base contacts in solution. NeuroD1 is restrained from adopting the same base contacts by an additional phosphate backbone interaction by the neurogenic-specific residue His115. Orienting E47-NeuroD1 on promoters may foster protein-protein contacts essential to initiate transcription.
Crystal structure of E47-NeuroD1/beta2 bHLH domain-DNA complex: heterodimer selectivity and DNA recognition.,Longo A, Guanga GP, Rose RB Biochemistry. 2008 Jan 8;47(1):218-29. Epub 2007 Dec 11. PMID:18069799[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Perez-Moreno MA, Locascio A, Rodrigo I, Dhondt G, Portillo F, Nieto MA, Cano A. A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions. J Biol Chem. 2001 Jul 20;276(29):27424-31. PMID:11309385 doi:10.1074/jbc.M100827200
- ↑ Wilson-Rawls J, Rhee JM, Rawls A. Paraxis is a basic helix-loop-helix protein that positively regulates transcription through binding to specific E-box elements. J Biol Chem. 2004 Sep 3;279(36):37685-92. PMID:15226298 doi:10.1074/jbc.M401319200
- ↑ Ravanpay AC, Olson JM. E protein dosage influences brain development more than family member identity. J Neurosci Res. 2008 May 15;86(7):1472-81. PMID:18214987 doi:10.1002/jnr.21615
- ↑ Walker MD, Park CW, Rosen A, Aronheim A. A cDNA from a mouse pancreatic beta cell encoding a putative transcription factor of the insulin gene. Nucleic Acids Res. 1990 Mar 11;18(5):1159-66. PMID:2181401 doi:10.1093/nar/18.5.1159
- ↑ Longo A, Guanga GP, Rose RB. Crystal structure of E47-NeuroD1/beta2 bHLH domain-DNA complex: heterodimer selectivity and DNA recognition. Biochemistry. 2008 Jan 8;47(1):218-29. Epub 2007 Dec 11. PMID:18069799 doi:http://dx.doi.org/10.1021/bi701527r
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