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- SASDCT2: Bromodomain-containing protein 2 (BRD2) tandem bromodomains -

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Basic information

Entry
Database: SASBDB / ID: SASDCT2
SampleBromodomain-containing protein 2 (BRD2) tandem bromodomains
  • Bromodomain-containing protein 2BRD2 (protein), BRD2, Homo sapiens
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
NET domain superfamily / NET domain profile. / Brdt, bromodomain, repeat II / Brdt, bromodomain, repeat I / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. ...NET domain superfamily / NET domain profile. / Brdt, bromodomain, repeat II / Brdt, bromodomain, repeat I / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily
Similarity search - Domain/homology
Bromodomain-containing protein 2
Similarity search - Component
Biological speciesHomo sapiens (human)
CitationJournal: 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
  • Joseph Newman (University of Oxford, Oxford, UK)

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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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

SampleName: Bromodomain-containing protein 2 (BRD2) tandem bromodomains
Specimen concentration: 13 mg/ml
BufferName: 20 mM HEPES, 150 mM NaCl, 2% glycerol, 0.5 mM TCEP / pH: 7.5
Entity #619Name: 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

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Experimental information

BeamInstrument name: Diamond Light Source B21 / City: Oxfordshire / : UK / Shape: 1 x 5 mm / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.1 Å / Dist. spec. to detc.: 3.92 mm
DetectorName: 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 /
MinMax
Q0.004 0.4398
Distance distribution function P(R)
Sofotware P(R): GNOM 4.6 / Number of points: 452 /
MinMax
Q0.006044 0.4396
P(R) point8 459
R0 210
Result
Type of curve: single_conc
ExperimentalPorodEstimatedEstimated method
MW43.4 kDa39 kDa--
Volume-220 nm381 DAMMIN

P(R)P(R) errorGuinierGuinier error
Forward scattering, I00.0975 0.0007 0.09 0.0014
Radius of gyration, Rg6.24 nm0.055 5.71 nm0.72

MinMax
D-21
Guinier point33 77

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