SASDCU2: Bromodomain testis-specific protein (BRDT) tandem bromodomains

Basic information

• Entry: Database: SASBDB / ID: SASDCU2

Sample

Bromodomain testis-specific protein (BRDT) tandem bromodomains

• Bromodomain testis-specific protein (protein), BRDT, Homo sapiens

Function / homology

Function:

sperm DNA condensation / male meiotic nuclear division / regulation of RNA splicing / male meiosis I / histone reader activity / RNA splicing / lysine-acetylated histone binding / mRNA processing / histone binding / transcription coactivator activity / chromatin remodeling / protein serine/threonine kinase activity / positive regulation of gene expression / chromatin binding / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / chromatin / nucleus

Domain/homology:

Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / Brdt, bromodomain, repeat I / Brdt, bromodomain, repeat II / NET domain superfamily / NET domain profile. / : / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily

Component:

Bromodomain testis-specific protein

• 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 #1187: ; Type: dummy / Radius of dummy atoms: 3.75 A / Chi-square value: 1.270 / P-value: 0.000410; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Bromodomain testis-specific protein (BRDT) 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 #620

Name: BRDT / Type: protein / Description: Bromodomain testis-specific protein / Formula weight: 42.59 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: Q58F21
Sequence:

SMAIIVNPPP PEYINTKKNG RLTNQLQYLQ KVVLKDLWKH SFSWPFQRPV DAVKLQLPDY YTIIKNPMDL NTIKKRLENK YYAKASECIE DFNTMFSNCY LYNKPGDDIV LMAQALEKLF MQKLSQMPQE EQVVGVKERI KKGTQQNIAV SSAKEKSSPS ATEKVFKQQE IPSVFPKTSI SPLNVVQGAS VNSSSQTAAQ VTKGVKRKAD TTTPATSAVK ASSEFSPTFT EKSVALPPIK ENMPKNVLPD SQQQYNVVKT VKVTEQLRHC SEILKEMLAK KHFSYAWPFY NPVDVNALGL HNYYDVVKNP MDLGTIKEKM DNQEYKDAYK FAADVRLMFM NCYKYNPPDH EVVTMARMLQ DVFETHFSKI PIE

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

Scan

Title: Bromodomain testis-specific protein (BRDT) 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	200

Result

Type of curve: single_conc

	Experimental	Porod	Estimated	Estimated method
MW	42 kDa	39 kDa	-	-
Volume	-	200 nm3	80	DAMMIN

	P(R)	Guinier	Guinier error	P(R) error
Forward scattering, I0	0.0853	0.083	0.0008	-
Radius of gyration, Rg	5.55 nm	5.13 nm	0.09	0.06

	Min	Max
D	-	20
Guinier point	26	80