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| <StructureSection load='5acy' size='340' side='right'caption='[[5acy]], [[Resolution|resolution]] 2.01Å' scene=''> | | <StructureSection load='5acy' size='340' side='right'caption='[[5acy]], [[Resolution|resolution]] 2.01Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[5acy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ACY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ACY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5acy]] 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=5ACY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ACY FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9S3:1-[(2S,4R)-2-METHYL-4-(PHENYLAMINO)-6-[4-(PIPERIDIN-1-YLMETHYL)PHENYL]-3,4-DIHYDROQUINOLIN-1(2H)-YL]ETHANONE'>9S3</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9S3:1-[(2S,4R)-2-METHYL-4-(PHENYLAMINO)-6-[4-(PIPERIDIN-1-YLMETHYL)PHENYL]-3,4-DIHYDROQUINOLIN-1(2H)-YL]ETHANONE'>9S3</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=5acy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5acy OCA], [http://pdbe.org/5acy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5acy RCSB], [http://www.ebi.ac.uk/pdbsum/5acy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5acy 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=5acy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5acy OCA], [https://pdbe.org/5acy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5acy RCSB], [https://www.ebi.ac.uk/pdbsum/5acy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5acy 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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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
- | [[Category: Chung, C]] | + | [[Category: Chung C]] |
- | [[Category: Antagonist]]
| + | |
- | [[Category: Brd4]]
| + | |
- | [[Category: Bromodomain]]
| + | |
- | [[Category: Bromodomain containing protein 4]]
| + | |
- | [[Category: Epigenetic reader]]
| + | |
- | [[Category: Histone]]
| + | |
- | [[Category: Inhibitor]]
| + | |
- | [[Category: Transcription]]
| + | |
| 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
Studies investigating the causes of autism spectrum disorder (ASD) point to genetic, as well as epigenetic, mechanisms of the disease. Identification of epigenetic processes that contribute to ASD development and progression is of major importance and may lead to the development of novel therapeutic strategies. Here, we identify the bromodomain and extraterminal domain-containing proteins (BETs) as epigenetic regulators of genes involved in ASD-like behaviors in mice. We found that the pharmacological suppression of BET proteins in the brain of young mice, by the novel, highly specific, brain-permeable inhibitor I-BET858 leads to selective suppression of neuronal gene expression followed by the development of an autism-like syndrome. Many of the I-BET858-affected genes have been linked to ASD in humans, thus suggesting the key role of the BET-controlled gene network in the disorder. Our studies suggest that environmental factors controlling BET proteins or their target genes may contribute to the epigenetic mechanism of ASD.
Autism-like syndrome is induced by pharmacological suppression of BET proteins in young mice.,Sullivan JM, Badimon A, Schaefer U, Ayata P, Gray J, Chung CW, von Schimmelmann M, Zhang F, Garton N, Smithers N, Lewis H, Tarakhovsky A, Prinjha RK, Schaefer A J Exp Med. 2015 Sep 21. pii: jem.20151271. PMID:26392221[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Sullivan JM, Badimon A, Schaefer U, Ayata P, Gray J, Chung CW, von Schimmelmann M, Zhang F, Garton N, Smithers N, Lewis H, Tarakhovsky A, Prinjha RK, Schaefer A. Autism-like syndrome is induced by pharmacological suppression of BET proteins in young mice. J Exp Med. 2015 Sep 21. pii: jem.20151271. PMID:26392221 doi:http://dx.doi.org/10.1084/jem.20151271
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