+Open data
-Basic information
Entry | Database: SASBDB / ID: SASDCT2 |
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Sample | Bromodomain-containing protein 2 (BRD2) tandem bromodomains
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Function / homology | Function and homology information chromatin looping / acetylation-dependent protein binding / RUNX3 regulates p14-ARF / positive regulation of T-helper 17 cell lineage commitment / protein localization to chromatin / neural tube closure / lysine-acetylated histone binding / nucleosome assembly / spermatogenesis / nuclear speck ...chromatin looping / acetylation-dependent protein binding / RUNX3 regulates p14-ARF / positive regulation of T-helper 17 cell lineage commitment / protein localization to chromatin / neural tube closure / lysine-acetylated histone binding / nucleosome assembly / spermatogenesis / nuclear speck / protein phosphorylation / protein serine/threonine kinase activity / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / nucleoplasm / nucleus / cytoplasm Similarity search - Function |
Biological species | Homo sapiens (human) |
Citation | Journal: Mol Cell / Year: 2019 Title: Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains. Authors: Jean-Philippe Lambert / Sarah Picaud / Takao Fujisawa / Huayun Hou / Pavel Savitsky / Liis Uusküla-Reimand / Gagan D Gupta / Hala Abdouni / Zhen-Yuan Lin / Monika Tucholska / James D R ...Authors: Jean-Philippe Lambert / Sarah Picaud / Takao Fujisawa / Huayun Hou / Pavel Savitsky / Liis Uusküla-Reimand / Gagan D Gupta / Hala Abdouni / Zhen-Yuan Lin / Monika Tucholska / James D R Knight / Beatriz Gonzalez-Badillo / Nicole St-Denis / Joseph A Newman / Manuel Stucki / Laurence Pelletier / Nuno Bandeira / Michael D Wilson / Panagis Filippakopoulos / Anne-Claude Gingras / Abstract: Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, ...Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, BRD3, BRD4, and BRDT following treatment with the pan-BET BRD inhibitor JQ1, revealing broad rewiring of the interaction landscape, with three distinct classes of behavior for the 603 unique interactors identified. A group of proteins associate in a JQ1-sensitive manner with BET BRDs through canonical and new binding modes, while two classes of extra-terminal (ET)-domain binding motifs mediate acetylation-independent interactions. Last, we identify an unexpected increase in several interactions following JQ1 treatment that define negative functions for BRD3 in the regulation of rRNA synthesis and potentially RNAPII-dependent gene expression that result in decreased cell proliferation. Together, our data highlight the contributions of BET protein modules to their interactomes allowing for a better understanding of pharmacological rewiring in response to JQ1. |
Contact author |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Data source
SASBDB page | SASDCT2 |
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-Related structure data
Related structure data | 5nncC 5nndC 5nneC 5nnfC 5nngC 6g0oC 6g0pC 6g0qC 6g0rC 6g0sC C: citing same article (ref.) |
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Similar structure data |
-External links
Related items in Molecule of the Month |
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-Models
Model #1186 | Type: dummy / Radius of dummy atoms: 4.25 A / Chi-square value: 1.152 Search similar-shape structures of this assembly by Omokage search (details) |
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-Sample
Sample | Name: Bromodomain-containing protein 2 (BRD2) tandem bromodomains Specimen concentration: 13 mg/ml |
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Buffer | Name: 20 mM HEPES, 150 mM NaCl, 2% glycerol, 0.5 mM TCEP / pH: 7.5 |
Entity #619 | Name: BRD2 / Type: protein / Description: Bromodomain-containing protein 2BRD2 / Formula weight: 43.431 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: P25440 Sequence: SMKPGRVTNQ LQYLHKVVMK ALWKHQFAWP FRQPVDAVKL GLPDYHKIIK QPMDMGTIKR RLENNYYWAA SECMQDFNTM FTNCYIYNKP TDDIVLMAQT LEKIFLQKVA SMPQEEQELV VTIPKNSHKK GAKLAALQGS VTSAHQVPAV SSVSHTALYT PPPEIPTTVL ...Sequence: SMKPGRVTNQ LQYLHKVVMK ALWKHQFAWP FRQPVDAVKL GLPDYHKIIK QPMDMGTIKR RLENNYYWAA SECMQDFNTM FTNCYIYNKP TDDIVLMAQT LEKIFLQKVA SMPQEEQELV VTIPKNSHKK GAKLAALQGS VTSAHQVPAV SSVSHTALYT PPPEIPTTVL NIPHPSVISS PLLKSLHSAG PPLLAVTAAP PAQPLAKKKG VKRKADTTTP TPTAILAPGS PASPPGSLEP KAARLPPMRR ESGRPIKPPR KDLPDSQQQH QSSKKGKLSE QLKHCNGILK ELLSKKHAAY AWPFYKPVDA SALGLHDYHD IIKHPMDLST VKRKMENRDY RDAQEFAADV RLMFSNCYKY NPPDHDVVAM ARKLQDVFEF RYAKMPD |
-Experimental information
Beam | Instrument name: Diamond Light Source B21 / City: Oxfordshire / 国: UK / Shape: 1 x 5 mm / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.1 Å / Dist. spec. to detc.: 3.92 mm | |||||||||||||||||||||||||||||||||||||||
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Detector | Name: Pilatus 2M | |||||||||||||||||||||||||||||||||||||||
Scan | Title: Bromodomain-containing protein 2 (BRD2) tandem bromodomains Measurement date: Jan 13, 2017 / Storage temperature: 10 °C / Cell temperature: 10 °C / Exposure time: 10 sec. / Number of frames: 12 / Unit: 1/A /
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Distance distribution function P(R) | Sofotware P(R): GNOM 4.6 / Number of points: 452 /
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Result | Type of curve: single_conc
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