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| | ==Solution NMR structures of BRD4 ET domain with LANA peptide== | | ==Solution NMR structures of BRD4 ET domain with LANA peptide== |
| - | <StructureSection load='2nd0' size='340' side='right' caption='[[2nd0]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2nd0' size='340' side='right'caption='[[2nd0]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2nd0]] is a 2 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=2ND0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ND0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2nd0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ND0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ND0 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nd0 OCA], [http://pdbe.org/2nd0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2nd0 RCSB], [http://www.ebi.ac.uk/pdbsum/2nd0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2nd0 ProSAT]</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=2nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nd0 OCA], [https://pdbe.org/2nd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nd0 RCSB], [https://www.ebi.ac.uk/pdbsum/2nd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nd0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref> | + | [[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). | + | [[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Zeng, L]] | | [[Category: Zeng, L]] |
| | [[Category: Zhou, M]] | | [[Category: Zhou, M]] |
| Structural highlights
Disease
[BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.[1] [2]
Function
[BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
Publication Abstract from PubMed
The bromodomains and extra-terminal domain (BET) proteins direct gene transcription in chromatin, and represent new drug targets for cancer and inflammation. Here we report that the ET domain of the BET protein BRD4 recognizes an amphipathic protein sequence motif through establishing a two-strand antiparallel beta sheet anchored on a hydrophobic cleft of the three-helix bundle. This structural mechanism likely explains BRD4 interactions with numerous cellular and viral proteins such as Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen, and NSD3 whose interaction with BRD4 via this ET domain mechanism is essential for acute myeloid leukemia maintenance.
Structural Mechanism of Transcriptional Regulator NSD3 Recognition by the ET Domain of BRD4.,Zhang Q, Zeng L, Shen C, Ju Y, Konuma T, Zhao C, Vakoc CR, Zhou MM Structure. 2016 Jul 6;24(7):1201-8. doi: 10.1016/j.str.2016.04.019. Epub 2016 Jun, 9. PMID:27291650[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
- ↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
- ↑ Zhang Q, Zeng L, Shen C, Ju Y, Konuma T, Zhao C, Vakoc CR, Zhou MM. Structural Mechanism of Transcriptional Regulator NSD3 Recognition by the ET Domain of BRD4. Structure. 2016 Jul 6;24(7):1201-8. doi: 10.1016/j.str.2016.04.019. Epub 2016 Jun, 9. PMID:27291650 doi:http://dx.doi.org/10.1016/j.str.2016.04.019
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