SASDCR2: Bromodomain-containing protein 4 (BRD4) tandem bromodomains

Basic information

• Entry: Database: SASBDB / ID: SASDCR2

Sample

Bromodomain-containing protein 4 (BRD4) tandem bromodomains

• Bromodomain-containing protein 4BRD4 (protein), BRD4, Homo sapiens

Function / homology

Function:

RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / negative regulation by host of viral transcription / positive regulation of T-helper 17 cell lineage commitment / positive regulation of G2/M transition of mitotic cell cycle / histone reader activity / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome / transcription coregulator activity / positive regulation of transcription elongation by RNA polymerase II / lysine-acetylated histone binding / p53 binding / chromosome / regulation of inflammatory response / positive regulation of canonical NF-kappaB signal transduction / Potential therapeutics for SARS / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / enzyme binding / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus

Domain/homology:

Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / 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

Component:

Bromodomain-containing protein 4

• 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 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, 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)

Models

• Model #1183: ; Type: dummy / Radius of dummy atoms: 3.75 A / Chi-square value: 1.047 / P-value: 0.027000; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Bromodomain-containing protein 4 (BRD4) tandem bromodomains; Specimen concentration: 13 mg/ml
• Buffer: Name: 20 mM HEPES, 150 mM NaCl, 2% glycerol, 0.5 mM TCEP / pH: 7.5

Entity #617

Name: BRD4 / Type: protein / Description: Bromodomain-containing protein 4BRD4 / Formula weight: 47.243 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: O60885
Sequence:

SMNPPPPETS NPNKPKRQTN QLQYLLRVVL KTLWKHQFAW PFQQPVDAVK LNLPDYYKII KTPMDMGTIK KRLENNYYWN AQECIQDFNT MFTNCYIYNK PGDDIVLMAE ALEKLFLQKI NELPTEETEI MIVQAKGRGR GRKETGTAKP GVSTVPNTTQ ASTPPQTQTP QPNPPPVQAT PHPFPAVTPD LIVQTPVMTV VPPQPLQTPP PVPPQPQPPP APAPQPVQSH PPIIAATPQP VKTKKGVKRK ADTTTPTTID PIHEPPSLPP EPKTTKLGQR RESSRPVKPP KKDVPDSQQH PAPEKSSKVS EQLKCCSGIL KEMFAKKHAA YAWPFYKPVD VEALGLHDYC DIIKHPMDMS TIKSKLEARE YRDAQEFGAD VRLMFSNCYK YNPPDHEVVA MARKLQDVFE MRFAKMPDE

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.: 3.929 mm
• Detector: Name: Pilatus 2M

Scan

Title: Bromodomain-containing protein 4 (BRD4) 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 /

	Min	Max
Q	0.004	0.4398

Distance distribution function P(R)

Sofotware P(R): GNOM 4.6 / Number of points: 452 /

	Min	Max
Q	0.006044	0.4396
P(R) point	8	459
R	0	220

Result

Type of curve: single_conc

	Experimental	Porod	Estimated	Estimated method
MW	47.2 kDa	41 kDa	-	-
Volume	-	251.43 nm3	88	DAMMIN

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	0.1053	0.000777	0.103524	0.00095
Radius of gyration, Rg	6.79 nm	0.061	6.319 nm	0.12

	Min	Max
D	-	22
Guinier point	18	69