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| | ==A novel phospho-switch in the linker region of the snail zinc finger protein which regulates 14-3-3 association, DNA binding and epithelial-mesenchymal differentiation== | | ==A novel phospho-switch in the linker region of the snail zinc finger protein which regulates 14-3-3 association, DNA binding and epithelial-mesenchymal differentiation== |
| - | <StructureSection load='4qli' size='340' side='right' caption='[[4qli]], [[Resolution|resolution]] 1.45Å' scene=''> | + | <StructureSection load='4qli' size='340' side='right'caption='[[4qli]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qli]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QLI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QLI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qli]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QLI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QLI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 1.45Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4iea|4iea]], [[4jdd|4jdd]], [[4n7g|4n7g]]</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=4qli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qli OCA], [https://pdbe.org/4qli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qli RCSB], [https://www.ebi.ac.uk/pdbsum/4qli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qli ProSAT]</span></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=4qli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qli OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qli RCSB], [http://www.ebi.ac.uk/pdbsum/4qli PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/1433S_HUMAN 1433S_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). p53-regulated inhibitor of G2/M progression. [[http://www.uniprot.org/uniprot/SNAI1_HUMAN SNAI1_HUMAN]] Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. Binds to 3 E-boxes of the E-cadherin/CDH1 gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription. Associates with EGR1 and SP1 to mediate tetradecanoyl phorbol acetate (TPA)-induced up-regulation of CDKN2B, possibly by binding to the CDKN2B promoter region 5'-TCACA-3. In addition, may also activate the CDKN2B promoter by itself.<ref>PMID:10655587</ref> <ref>PMID:16096638</ref> <ref>PMID:15647282</ref> <ref>PMID:20121949</ref> <ref>PMID:20562920</ref> <ref>PMID:21952048</ref> | + | [https://www.uniprot.org/uniprot/SNAI1_HUMAN SNAI1_HUMAN] Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. Binds to 3 E-boxes of the E-cadherin/CDH1 gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription. Associates with EGR1 and SP1 to mediate tetradecanoyl phorbol acetate (TPA)-induced up-regulation of CDKN2B, possibly by binding to the CDKN2B promoter region 5'-TCACA-3. In addition, may also activate the CDKN2B promoter by itself.<ref>PMID:10655587</ref> <ref>PMID:16096638</ref> <ref>PMID:15647282</ref> <ref>PMID:20121949</ref> <ref>PMID:20562920</ref> <ref>PMID:21952048</ref> |
| | + | |
| | + | ==See Also== |
| | + | *[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bier, D]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Ottmann, C]] | + | [[Category: Large Structures]] |
| - | [[Category: 14-3-3]] | + | [[Category: Bier D]] |
| - | [[Category: Adapter protein]] | + | [[Category: Ottmann C]] |
| - | [[Category: Protein-protein interaction]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
SNAI1_HUMAN Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration. Binds to 3 E-boxes of the E-cadherin/CDH1 gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription. Associates with EGR1 and SP1 to mediate tetradecanoyl phorbol acetate (TPA)-induced up-regulation of CDKN2B, possibly by binding to the CDKN2B promoter region 5'-TCACA-3. In addition, may also activate the CDKN2B promoter by itself.[1] [2] [3] [4] [5] [6]
See Also
References
- ↑ Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia De Herreros A. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol. 2000 Feb;2(2):84-9. PMID:10655587 doi:http://dx.doi.org/10.1038/35000034
- ↑ Peinado H, Del Carmen Iglesias-de la Cruz M, Olmeda D, Csiszar K, Fong KS, Vega S, Nieto MA, Cano A, Portillo F. A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression. EMBO J. 2005 Oct 5;24(19):3446-58. Epub 2005 Aug 18. PMID:16096638 doi:http://dx.doi.org/10.1038/sj.emboj.7600781
- ↑ Yook JI, Li XY, Ota I, Fearon ER, Weiss SJ. Wnt-dependent regulation of the E-cadherin repressor snail. J Biol Chem. 2005 Mar 25;280(12):11740-8. Epub 2005 Jan 11. PMID:15647282 doi:http://dx.doi.org/10.1074/jbc.M413878200
- ↑ Hu CT, Chang TY, Cheng CC, Liu CS, Wu JR, Li MC, Wu WS. Snail associates with EGR-1 and SP-1 to upregulate transcriptional activation of p15INK4b. FEBS J. 2010 Mar;277(5):1202-18. doi: 10.1111/j.1742-4658.2009.07553.x. Epub 2010, Feb 1. PMID:20121949 doi:http://dx.doi.org/10.1111/j.1742-4658.2009.07553.x
- ↑ Lin T, Ponn A, Hu X, Law BK, Lu J. Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition. Oncogene. 2010 Sep 2;29(35):4896-904. doi: 10.1038/onc.2010.234. Epub 2010 Jun, 21. PMID:20562920 doi:http://dx.doi.org/10.1038/onc.2010.234
- ↑ Zhang K, Rodriguez-Aznar E, Yabuta N, Owen RJ, Mingot JM, Nojima H, Nieto MA, Longmore GD. Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation. EMBO J. 2012 Jan 4;31(1):29-43. doi: 10.1038/emboj.2011.357. Epub 2011 Sep 27. PMID:21952048 doi:http://dx.doi.org/10.1038/emboj.2011.357
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