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| - | [[Image:1ow1.gif|left|200px]] | |
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| - | {{Structure
| + | ==Crystal structure of the SPOC domain of the human transcriptional corepressor, SHARP.== |
| - | |PDB= 1ow1 |SIZE=350|CAPTION= <scene name='initialview01'>1ow1</scene>, resolution 1.80Å
| + | <StructureSection load='1ow1' size='340' side='right'caption='[[1ow1]], [[Resolution|resolution]] 1.80Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <table><tr><td colspan='2'>[[1ow1]] is a 1 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=1OW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OW1 FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | |GENE=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ow1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ow1 OCA], [https://pdbe.org/1ow1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ow1 RCSB], [https://www.ebi.ac.uk/pdbsum/1ow1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ow1 ProSAT]</span></td></tr> |
| - | }}
| + | </table> |
| - | | + | == Function == |
| - | '''Crystal structure of the SPOC domain of the human transcriptional corepressor, SHARP.''' | + | [https://www.uniprot.org/uniprot/MINT_HUMAN MINT_HUMAN] May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA.<ref>PMID:11331609</ref> <ref>PMID:12374742</ref> |
| - | | + | == Evolutionary Conservation == |
| - | | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | ==Overview== | + | Check<jmol> |
| - | Spen proteins regulate the expression of key transcriptional effectors in diverse signaling pathways. They are large proteins characterized by N-terminal RNA-binding motifs and a highly conserved C-terminal SPOC domain. The specific biological role of the SPOC domain (Spen paralog and ortholog C-terminal domain), and hence, the common function of Spen proteins, has been unclear to date. The Spen protein, SHARP (SMRT/HDAC1-associated repressor protein), was identified as a component of transcriptional repression complexes in both nuclear receptor and Notch/RBP-Jkappa signaling pathways. We have determined the 1.8 A crystal structure of the SPOC domain from SHARP. This structure shows that essentially all of the conserved surface residues map to a positively charged patch. Structure-based mutational analysis indicates that this conserved region is responsible for the interaction between SHARP and the universal transcriptional corepressor SMRT/NCoR (silencing mediator for retinoid and thyroid receptors/nuclear receptor corepressor. We demonstrate that this interaction involves a highly conserved acidic motif at the C terminus of SMRT/NCoR. These findings suggest that the conserved function of the SPOC domain is to mediate interaction with SMRT/NCoR corepressors, and that Spen proteins play an essential role in the repression complex.
| + | <jmolCheckbox> |
| - | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ow/1ow1_consurf.spt"</scriptWhenChecked> |
| - | ==Disease== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | Known disease associated with this structure: Megakaryoblastic leukemia, acute OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606077 606077]]
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | | + | </jmolCheckbox> |
| - | ==About this Structure==
| + | </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=1ow1 ConSurf]. |
| - | 1OW1 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OW1 OCA].
| + | <div style="clear:both"></div> |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling., Ariyoshi M, Schwabe JW, Genes Dev. 2003 Aug 1;17(15):1909-20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12897056 12897056]
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Ariyoshi, M.]] | + | [[Category: Ariyoshi M]] |
| - | [[Category: Schwabe, J W.]] | + | [[Category: Schwabe JW]] |
| - | [[Category: beta-alpha-barrel]]
| + | |
| - | [[Category: spoc domain]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:16:21 2008''
| + | |
| Structural highlights
Function
MINT_HUMAN May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, Hon M, Evans RM. Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. Genes Dev. 2001 May 1;15(9):1140-51. PMID:11331609 doi:http://dx.doi.org/10.1101/gad.871201
- ↑ Oswald F, Kostezka U, Astrahantseff K, Bourteele S, Dillinger K, Zechner U, Ludwig L, Wilda M, Hameister H, Knochel W, Liptay S, Schmid RM. SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. EMBO J. 2002 Oct 15;21(20):5417-26. PMID:12374742
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