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| | ==Solution Structure of HBP1 SID-mSin3A PAH2 Complex== | | ==Solution Structure of HBP1 SID-mSin3A PAH2 Complex== |
| - | <StructureSection load='1s5r' size='340' side='right' caption='[[1s5r]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1s5r' size='340' side='right'caption='[[1s5r]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1s5r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S5R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1S5R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1s5r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S5R FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1s5q|1s5q]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sin3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=1s5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s5r OCA], [https://pdbe.org/1s5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s5r RCSB], [https://www.ebi.ac.uk/pdbsum/1s5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s5r 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=1s5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s5r OCA], [http://pdbe.org/1s5r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1s5r RCSB], [http://www.ebi.ac.uk/pdbsum/1s5r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1s5r ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HBP1_MOUSE HBP1_MOUSE]] Transcriptional repressor that binds to the promoter region of target genes. Plays a role in the regulation of the cell cycle and of the Wnt pathway. Binds preferentially to the sequence 5'-TTCATTCATTCA-3'. Binding to the H1F0 promoter is enhanced by interaction with RB1. Disrupts the interaction between DNA and TCF4 (By similarity).<ref>PMID:9178770</ref> [[http://www.uniprot.org/uniprot/SIN3A_MOUSE SIN3A_MOUSE]] Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation.<ref>PMID:8649810</ref> <ref>PMID:7889570</ref> <ref>PMID:10734093</ref> | + | [https://www.uniprot.org/uniprot/HBP1_MOUSE HBP1_MOUSE] Transcriptional repressor that binds to the promoter region of target genes. Plays a role in the regulation of the cell cycle and of the Wnt pathway. Binds preferentially to the sequence 5'-TTCATTCATTCA-3'. Binding to the H1F0 promoter is enhanced by interaction with RB1. Disrupts the interaction between DNA and TCF4 (By similarity).<ref>PMID:9178770</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Cowley, S M]] | + | [[Category: Mus musculus]] |
| - | [[Category: Eisenman, R N]] | + | [[Category: Cowley SM]] |
| - | [[Category: Huang, K]] | + | [[Category: Eisenman RN]] |
| - | [[Category: Kang, R S]] | + | [[Category: Huang K]] |
| - | [[Category: Knoepfler, P S]] | + | [[Category: Kang RS]] |
| - | [[Category: Laherty, C D]] | + | [[Category: Knoepfler PS]] |
| - | [[Category: Radhakrishnan, I]] | + | [[Category: Laherty CD]] |
| - | [[Category: Swanson, K A]] | + | [[Category: Radhakrishnan I]] |
| - | [[Category: Amphipathic helix motif]]
| + | [[Category: Swanson KA]] |
| - | [[Category: Four-helix bundle]]
| + | |
| - | [[Category: Protein-peptide complex]]
| + | |
| - | [[Category: Repressor-corepressor complex]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Function
HBP1_MOUSE Transcriptional repressor that binds to the promoter region of target genes. Plays a role in the regulation of the cell cycle and of the Wnt pathway. Binds preferentially to the sequence 5'-TTCATTCATTCA-3'. Binding to the H1F0 promoter is enhanced by interaction with RB1. Disrupts the interaction between DNA and TCF4 (By similarity).[1]
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
Recruitment of the histone deacetylase (HDAC)-associated Sin3 corepressor is an obligatory step in many eukaryotic gene silencing pathways. Here we show that HBP1, a cell cycle inhibitor and regulator of differentiation, represses transcription in a HDAC/Sin3-dependent manner by targeting the mammalian Sin3A (mSin3A) PAH2 domain. HBP1 is unrelated to the Mad1 repressor for which high-resolution structures in complex with PAH2 have been described. We show that like Mad1, the HBP1 transrepression domain binds through a helical structure to the hydrophobic cleft of mSin3A PAH2. Notably, the HBP1 helix binds PAH2 in a reversed orientation relative to Mad1 and, equally unexpectedly, this is correlated with a chain reversal of the minimal Sin3 interaction motifs. These results not only provide insights into how multiple, unrelated transcription factors recruit the same coregulator, but also have implications for how sequence similarity searches are conducted.
HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations.,Swanson KA, Knoepfler PS, Huang K, Kang RS, Cowley SM, Laherty CD, Eisenman RN, Radhakrishnan I Nat Struct Mol Biol. 2004 Aug;11(8):738-46. Epub 2004 Jul 4. PMID:15235594[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lavender P, Vandel L, Bannister AJ, Kouzarides T. The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A. Oncogene. 1997 Jun 5;14(22):2721-8. PMID:9178770 doi:http://dx.doi.org/10.1038/sj.onc.1201243
- ↑ Swanson KA, Knoepfler PS, Huang K, Kang RS, Cowley SM, Laherty CD, Eisenman RN, Radhakrishnan I. HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations. Nat Struct Mol Biol. 2004 Aug;11(8):738-46. Epub 2004 Jul 4. PMID:15235594 doi:10.1038/nsmb798
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