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| | ==Solution structure and backbone dynamics of the DNA-binding domain of FOXP1: Insight into its domain swapping== | | ==Solution structure and backbone dynamics of the DNA-binding domain of FOXP1: Insight into its domain swapping== |
| - | <StructureSection load='2kiu' size='340' side='right' caption='[[2kiu]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kiu' size='340' side='right'caption='[[2kiu]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kiu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KIU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kiu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KIU FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">3p14.1, FOXP1, HSPC215 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kiu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2kiu RCSB], [http://www.ebi.ac.uk/pdbsum/2kiu PDBsum]</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=2kiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kiu OCA], [https://pdbe.org/2kiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kiu RCSB], [https://www.ebi.ac.uk/pdbsum/2kiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kiu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/FOXP1_HUMAN FOXP1_HUMAN]] MALT lymphoma;Precursor B-cell acute lymphoblastic leukemia;Intellectual disability-severe speech delay-mild dysmorphism syndrome. A chromosomal aberration involving FOXP1 is found in acute lymphoblastic leukemia. Translocation t(9;3)(p13;p14.1) with PAX5. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:20950788</ref> | + | [https://www.uniprot.org/uniprot/FOXP1_HUMAN FOXP1_HUMAN] MALT lymphoma;Precursor B-cell acute lymphoblastic leukemia;Intellectual disability-severe speech delay-mild dysmorphism syndrome. A chromosomal aberration involving FOXP1 is found in acute lymphoblastic leukemia. Translocation t(9;3)(p13;p14.1) with PAX5. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:20950788</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FOXP1_HUMAN FOXP1_HUMAN]] Transcriptional repressor. It plays an important role in the specification and differentiation of lung epithelium. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Essential transcriptional regulator of B-cell development (By similarity).<ref>PMID:20950788</ref> | + | [https://www.uniprot.org/uniprot/FOXP1_HUMAN FOXP1_HUMAN] Transcriptional repressor. It plays an important role in the specification and differentiation of lung epithelium. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Essential transcriptional regulator of B-cell development (By similarity).<ref>PMID:20950788</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ki/2kiu_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ki/2kiu_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kiu ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 2kiu" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Forkhead box protein|Forkhead box protein]] | + | *[[FOX 3D structures|FOX 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Chu, Y]] | + | [[Category: Large Structures]] |
| - | [[Category: Chuang, W]] | + | [[Category: Chu Y]] |
| - | [[Category: Dna binding protein]] | + | [[Category: Chuang W]] |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Metal-binding]]
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| - | [[Category: Nucleus]]
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| - | [[Category: Phosphoprotein]]
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| - | [[Category: Repressor]]
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| - | [[Category: Solution structure of the monomeric foxp1]]
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| - | [[Category: Transcription]]
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| - | [[Category: Transcription regulation]]
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| - | [[Category: Zinc-finger]]
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| Structural highlights
Disease
FOXP1_HUMAN MALT lymphoma;Precursor B-cell acute lymphoblastic leukemia;Intellectual disability-severe speech delay-mild dysmorphism syndrome. A chromosomal aberration involving FOXP1 is found in acute lymphoblastic leukemia. Translocation t(9;3)(p13;p14.1) with PAX5. The disease is caused by mutations affecting the gene represented in this entry.[1]
Function
FOXP1_HUMAN Transcriptional repressor. It plays an important role in the specification and differentiation of lung epithelium. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Essential transcriptional regulator of B-cell development (By similarity).[2]
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
FOXP1 belongs to the P-subfamily of forkhead transcription factors and contains a conserved forkhead DNA-binding domain. According to size exclusion chromatography analysis, the forkhead domain of FOXP1 existed as a mixture of monomer and dimer. The dissociation constants of the forkhead domain of wild-type, C61S, and C61Y mutants of FOXP1 were 27.3, 28.8, and 332.0 muM, respectively. In contrast, FOXP1 A39P mutant formed only a monomer. NMR analysis also showed that FOXP1 C61S and C61Y mutants existed as a mixture. The solution structure of FOXP1 A39P/C61Y mutant was similar to the X-ray structure of the FOXP2 monomer. Comparison of backbone dynamics of FOXP1 A39P/C61Y and C61Y mutants showed that the residues preceding helix 3, the hinge region, exhibited the largest conformational exchange in FOXP1 monomer. The A39 residue of FOXP1 dimer has a lower order parameter with internal motion on the ps-ns timescale, suggesting that the dynamics of the hinge region of FOXP1 are important in the formation of the swapped dimer. The analysis also showed that the residues exhibiting the motions on the ps-ns and mus-ms timescales were located at the DNA-binding surface of FOXP1, suggesting the interactions between FOXP1 and DNA may be highly dynamic.
Solution structure and backbone dynamics of the DNA-binding domain of FOXP1: Insight into its domain swapping and DNA binding.,Chu YP, Chang CH, Shiu JH, Chang YT, Chen CY, Chuang WJ Protein Sci. 2011 May;20(5):908-24. doi: 10.1002/pro.626. Epub 2011 Apr, 11. PMID:21416545[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hamdan FF, Daoud H, Rochefort D, Piton A, Gauthier J, Langlois M, Foomani G, Dobrzeniecka S, Krebs MO, Joober R, Lafreniere RG, Lacaille JC, Mottron L, Drapeau P, Beauchamp MH, Phillips MS, Fombonne E, Rouleau GA, Michaud JL. De novo mutations in FOXP1 in cases with intellectual disability, autism, and language impairment. Am J Hum Genet. 2010 Nov 12;87(5):671-8. doi: 10.1016/j.ajhg.2010.09.017. Epub, 2010 Oct 14. PMID:20950788 doi:http://dx.doi.org/10.1016/j.ajhg.2010.09.017
- ↑ Hamdan FF, Daoud H, Rochefort D, Piton A, Gauthier J, Langlois M, Foomani G, Dobrzeniecka S, Krebs MO, Joober R, Lafreniere RG, Lacaille JC, Mottron L, Drapeau P, Beauchamp MH, Phillips MS, Fombonne E, Rouleau GA, Michaud JL. De novo mutations in FOXP1 in cases with intellectual disability, autism, and language impairment. Am J Hum Genet. 2010 Nov 12;87(5):671-8. doi: 10.1016/j.ajhg.2010.09.017. Epub, 2010 Oct 14. PMID:20950788 doi:http://dx.doi.org/10.1016/j.ajhg.2010.09.017
- ↑ Chu YP, Chang CH, Shiu JH, Chang YT, Chen CY, Chuang WJ. Solution structure and backbone dynamics of the DNA-binding domain of FOXP1: Insight into its domain swapping and DNA binding. Protein Sci. 2011 May;20(5):908-24. doi: 10.1002/pro.626. Epub 2011 Apr, 11. PMID:21416545 doi:10.1002/pro.626
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