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

基本情報

• 登録情報: データベース: SASBDB / ID: SASDCR2

試料

Bromodomain-containing protein 4 (BRD4) tandem bromodomains

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

機能・相同性

分子機能:

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 / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / lysine-acetylated histone binding / p53 binding / 染色体 / regulation of inflammatory response / positive regulation of canonical NF-kappaB signal transduction / Potential therapeutics for SARS / transcription coactivator activity / transcription cis-regulatory region binding / クロマチンリモデリング / 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 / 核質 / 細胞核

ドメイン・相同性:

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. / ブロモドメイン / Bromodomain profile. / bromo domain / ブロモドメイン / Bromodomain-like superfamily

構成要素:

BRD4

• 生物種: Homo sapiens (ヒト)
• 引用: ジャーナル: Mol Cell / 年: 2019; タイトル: Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.; 著者: 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 / ; 要旨: 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.

登録者

• Joseph Newman (University of Oxford, Oxford, UK)

モデル

• モデル #1183: ; タイプ: dummy / ダミー原子の半径: 3.75 A / カイ2乗値: 1.047 / P-value: 0.027000; Omokage検索でこの集合体の類似形状データを探す (詳細)

試料

• 試料: 名称: Bromodomain-containing protein 4 (BRD4) tandem bromodomains; 試料濃度: 13 mg/ml
• バッファ: 名称: 20 mM HEPES, 150 mM NaCl, 2% glycerol, 0.5 mM TCEP / pH: 7.5

要素 #617

名称: BRD4 / タイプ: protein / 記述: Bromodomain-containing protein 4BRD4 / 分子量: 47.243 / 分子数: 1 / 由来: Homo sapiens / 参照: UniProt: O60885
配列:

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

実験情報

• ビーム: 設備名称: Diamond Light Source B21 / 地域: Oxfordshire / 国: UK / 形状: 1 x 5 mm / 線源: X-ray synchrotronシンクロトロン / 波長: 0.1 Å / スペクトロメータ・検出器間距離: 3.929 mm
• 検出器: 名称: Pilatus 2M

スキャン

タイトル: Bromodomain-containing protein 4 (BRD4) tandem bromodomains
測定日: 2017年1月13日 / 保管温度: 10 °C / セル温度: 10 °C / 照射時間: 10 sec. / フレーム数: 12 / 単位: 1/A /

	Min	Max
Q	0.004	0.4398

距離分布関数 P(R)

ソフトウェア P(R): GNOM 4.6 / ポイント数: 452 /

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

結果

カーブのタイプ: single_conc

	実験値	Porod	Estimated	Estimated method
分子量	47.2 kDa	41 kDa	-	-
体積	-	251.43 nm3	88	DAMMIN

	P(R)	P(R) error	Guinier	Guinier error
前方散乱 I0	0.1053	0.000777	0.103524	0.00095
慣性半径, Rg	6.79 nm	0.061	6.319 nm	0.12

	Min	Max
D	-	22
Guinier point	18	69