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| | ==NMR structure of SRA1p C-terminal domain== | | ==NMR structure of SRA1p C-terminal domain== |
| - | <StructureSection load='2mgx' size='340' side='right' caption='[[2mgx]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='2mgx' size='340' side='right'caption='[[2mgx]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mgx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MGX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MGX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mgx]] 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=2MGX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MGX FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SRA1, PP7684 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mgx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mgx RCSB], [http://www.ebi.ac.uk/pdbsum/2mgx 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=2mgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mgx OCA], [https://pdbe.org/2mgx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mgx RCSB], [https://www.ebi.ac.uk/pdbsum/2mgx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mgx ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SRA1_HUMAN SRA1_HUMAN] Functional RNA which acts as a transcriptional coactivator that selectively enhances steroid receptor-mediated transactivation ligand-independently through a mechanism involving the modulating N-terminal domain (AF-1) of steroid receptors. Also mediates transcriptional coactivation of steroid receptors ligand-dependently through the steroid-binding domain (AF-2). Enhances cellular proliferation and differentiation and promotes apoptosis in vivo. May play a role in tumorigenesis.<ref>PMID:10199399</ref> <ref>PMID:12943696</ref> <ref>PMID:14517287</ref> <ref>PMID:15351741</ref> <ref>PMID:15147866</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | The C-Terminal Domain of SRA1p Has a Fold More Similar to PRP18 than to an RRM and Does Not Directly Bind to the SRA1 RNA STR7 Region.,Bilinovich SM, Davis CM, Morris DL, Ray LA, Prokop JW, Buchan GJ, Leeper TC J Mol Biol. 2014 Apr 17;426(8):1753-65. doi: 10.1016/j.jmb.2014.01.007. Epub 2014, Jan 29. PMID:24486611<ref>PMID:24486611</ref> | | The C-Terminal Domain of SRA1p Has a Fold More Similar to PRP18 than to an RRM and Does Not Directly Bind to the SRA1 RNA STR7 Region.,Bilinovich SM, Davis CM, Morris DL, Ray LA, Prokop JW, Buchan GJ, Leeper TC J Mol Biol. 2014 Apr 17;426(8):1753-65. doi: 10.1016/j.jmb.2014.01.007. Epub 2014, Jan 29. PMID:24486611<ref>PMID:24486611</ref> |
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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 2mgx" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bilinovich, S M.]] | + | [[Category: Large Structures]] |
| - | [[Category: Buchan, G J.]] | + | [[Category: Bilinovich SM]] |
| - | [[Category: Davis, C M.]] | + | [[Category: Buchan GJ]] |
| - | [[Category: Leeper, T C.]] | + | [[Category: Davis CM]] |
| - | [[Category: Morris, D L.]] | + | [[Category: Leeper TC]] |
| - | [[Category: Prokop, J W.]] | + | [[Category: Morris DL]] |
| - | [[Category: Ray, L A.]] | + | [[Category: Prokop JW]] |
| - | [[Category: Unknown function]] | + | [[Category: Ray LA]] |
| Structural highlights
Function
SRA1_HUMAN Functional RNA which acts as a transcriptional coactivator that selectively enhances steroid receptor-mediated transactivation ligand-independently through a mechanism involving the modulating N-terminal domain (AF-1) of steroid receptors. Also mediates transcriptional coactivation of steroid receptors ligand-dependently through the steroid-binding domain (AF-2). Enhances cellular proliferation and differentiation and promotes apoptosis in vivo. May play a role in tumorigenesis.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Steroid receptor activator RNA protein (SRA1p) is the translation product of the bi-functional long non-coding RNA steroid receptor activator RNA 1 (SRA1) that is part of the steroid receptor coactivator-1 acetyltransferase complex and is indicated to be an epigenetic regulatory component. Previously, the SRA1p protein was suggested to contain an RNA recognition motif (RRM) domain. We have determined the solution structure of the C-terminal domain of human SRA1p by NMR spectroscopy. Our structure along with sequence comparisons among SRA1p orthologs and against authentic RRM proteins indicates that it is not an RRM domain but rather an all-helical protein with a fold more similar to the PRP18 splicing factor. NMR spectroscopy on the full SRA1p protein suggests that this structure is relevant to the native full-length context. Furthermore, molecular modeling indicates that this fold is well conserved among vertebrates. Amino acid variations in this protein seen across sequenced human genomes, including those in tumor cells, indicate that mutations that disrupt the fold occur vary rarely and highlight that its function is well conserved. SRA1p had previously been suggested to bind to the SRA1 RNA, but NMR spectra of SRA1p in the presence of its 80-nt RNA target suggest otherwise and indicate that this protein must be part of a multi-protein complex in order to recognize its proposed RNA recognition element.
The C-Terminal Domain of SRA1p Has a Fold More Similar to PRP18 than to an RRM and Does Not Directly Bind to the SRA1 RNA STR7 Region.,Bilinovich SM, Davis CM, Morris DL, Ray LA, Prokop JW, Buchan GJ, Leeper TC J Mol Biol. 2014 Apr 17;426(8):1753-65. doi: 10.1016/j.jmb.2014.01.007. Epub 2014, Jan 29. PMID:24486611[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, Tsai MJ, O'Malley BW. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell. 1999 Apr 2;97(1):17-27. PMID:10199399
- ↑ Deblois G, Giguere V. Ligand-independent coactivation of ERalpha AF-1 by steroid receptor RNA activator (SRA) via MAPK activation. J Steroid Biochem Mol Biol. 2003 Jun;85(2-5):123-31. PMID:12943696
- ↑ Lanz RB, Chua SS, Barron N, Soder BM, DeMayo F, O'Malley BW. Steroid receptor RNA activator stimulates proliferation as well as apoptosis in vivo. Mol Cell Biol. 2003 Oct;23(20):7163-76. PMID:14517287
- ↑ Coleman KM, Lam V, Jaber BM, Lanz RB, Smith CL. SRA coactivation of estrogen receptor-alpha is phosphorylation-independent, and enhances 4-hydroxytamoxifen agonist activity. Biochem Biophys Res Commun. 2004 Oct 8;323(1):332-8. PMID:15351741 doi:http://dx.doi.org/10.1016/j.bbrc.2004.08.090
- ↑ Chooniedass-Kothari S, Emberley E, Hamedani MK, Troup S, Wang X, Czosnek A, Hube F, Mutawe M, Watson PH, Leygue E. The steroid receptor RNA activator is the first functional RNA encoding a protein. FEBS Lett. 2004 May 21;566(1-3):43-7. PMID:15147866 doi:http://dx.doi.org/10.1016/j.febslet.2004.03.104
- ↑ Bilinovich SM, Davis CM, Morris DL, Ray LA, Prokop JW, Buchan GJ, Leeper TC. The C-Terminal Domain of SRA1p Has a Fold More Similar to PRP18 than to an RRM and Does Not Directly Bind to the SRA1 RNA STR7 Region. J Mol Biol. 2014 Apr 17;426(8):1753-65. doi: 10.1016/j.jmb.2014.01.007. Epub 2014, Jan 29. PMID:24486611 doi:http://dx.doi.org/10.1016/j.jmb.2014.01.007
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