SASDCS2: Bromodomain-containing protein 3 (BRD3) tandem bromodomains

Basic information

• Entry: Database: SASBDB / ID: SASDCS2

Sample

Bromodomain-containing protein 3 (BRD3) tandem bromodomains

• Bromodomain-containing protein 3 (protein), BRD3, Homo sapiens

Function / homology

Function:

lncRNA binding / endodermal cell differentiation / protein localization to chromatin / molecular condensate scaffold activity / lysine-acetylated histone binding / chromatin remodeling / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / nucleus

Domain/homology:

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 3

• 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 #1184: ; Type: dummy / Radius of dummy atoms: 4.00 A / Chi-square value: 1.277 / P-value: 0.103000; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Bromodomain-containing protein 3 (BRD3) 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 #618

Name: BRD3 / Type: protein / Description: Bromodomain-containing protein 3 / Formula weight: 44.491 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q15059
Sequence:

SMNPPPPEVS NPSKPGRKTN QLQYMQNVVV KTLWKHQFAW PFYQPVDAIK LNLPDYHKII KNPMDMGTIK KRLENNYYWS ASECMQDFNT MFTNCYIYNK PTDDIVLMAQ ALEKIFLQKV AQMPQEEVEL LPPAPKGKGR KPAAGAQSAG TQQVAAVSSV SPATPFQSVP PTVSQTPVIA ATPVPTITAN VTSVPVPPAA APPPPATPIV PVVPPTPPVV KKKGVKRKAD TTTPTTSAIT ASRSESPPPL SDPKQAKVVA RRESGGRPIK PPKKDLEDGE VPQHAGKKGK LSEHLRYCDS ILREMLSKKH AAYAWPFYKP VDAEALELHD YHDIIKHPMD LSTVKRKMDG REYPDAQGFA ADVRLMFSNC YKYNPPDHEV VAMARKLQDV FEMRFAKMPD E

Experimental information

• Beam: Instrument name: Diamond Light Source B21 / City: Oxfordshire / 国: UK / Shape: 1 x 5 mm / Type of source: X-ray synchrotron / Wavelength: 0.1 Å / Dist. spec. to detc.: 3.923 mm
• Detector: Name: Pilatus 2M

Scan

Title: Bromodomain-containing protein 3 (BRD3) 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	0.006285	0.4398
P(R) point	9	460
R	0	215

Result

Type of curve: single_conc

	Experimental	Porod	Estimated	Estimated method
MW	44.49 kDa	36 kDa	-	-
Volume	-	210 nm3	81	DAMMIN

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	0.1035	0.0008	0.1	0.0008
Radius of gyration, Rg	6.55 nm	0.054	6.22 nm	0.92

	Min	Max
D	-	21.5
Guinier point	23	71