SASDC46: PH - Pleckstrin-homology domain of Bcr-Abl tyrosine kinase p210

基本情報

• 登録情報: データベース: SASBDB / ID: SASDC46

試料

PH - Pleckstrin-homology domain of Bcr-Abl tyrosine kinase p210

• BCR-ABL p210 fusion protein (PH domain) (protein), Homo sapiens

機能・相同性

分子機能:

negative regulation of respiratory burst / negative regulation of cellular extravasation / negative regulation of macrophage migration / neutrophil degranulation / negative regulation of blood vessel remodeling / negative regulation of neutrophil degranulation / macrophage migration / intracellular protein transmembrane transport / renal system process / regulation of vascular permeability / regulation of Rho protein signal transduction / focal adhesion assembly / activation of GTPase activity / Signaling by cytosolic FGFR1 fusion mutants / definitive hemopoiesis / regulation of small GTPase mediated signal transduction / inner ear morphogenesis / RHOB GTPase cycle / small GTPase-mediated signal transduction / RHOC GTPase cycle / negative regulation of reactive oxygen species metabolic process / neuromuscular process controlling balance / CDC42 GTPase cycle / homeostasis of number of cells / RHOA GTPase cycle / RAC2 GTPase cycle / RAC3 GTPase cycle / phagocytosis / positive regulation of phagocytosis / keratinocyte differentiation / RAC1 GTPase cycle / Signaling by FGFR1 in disease / GTPase activator activity / guanyl-nucleotide exchange factor activity / modulation of chemical synaptic transmission / brain development / Schaffer collateral - CA1 synapse / negative regulation of inflammatory response / actin cytoskeleton organization / cellular response to lipopolysaccharide / protein tyrosine kinase activity / dendritic spine / eukaryotic translation initiation factor 2alpha kinase activity / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity / histone H3T45 kinase activity / non-specific serine/threonine protein kinase / regulation of cell cycle / postsynaptic density / protein phosphorylation / axon / protein serine kinase activity / protein serine/threonine kinase activity / glutamatergic synapse / signal transduction / protein-containing complex / extracellular exosome / ATP binding / membrane / plasma membrane / cytosol

ドメイン・相同性:

Bcr-Abl oncoprotein oligomerisation / Bcr-Abl oncoprotein oligomerisation domain superfamily / Abr/Bcr / Bcr-Abl oncoprotein oligomerisation domain / PH domain / Guanine-nucleotide dissociation stimulator, CDC24, conserved site / Dbl homology (DH) domain signature. / Rho GTPase-activating protein domain / RhoGAP domain / Rho GTPase-activating proteins domain profile. / GTPase-activator protein for Rho-like GTPases / Rho GTPase activation protein / Dbl homology (DH) domain superfamily / RhoGEF domain / Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases / Dbl homology (DH) domain / Dbl homology (DH) domain profile. / Protein kinase C conserved region 2 (CalB) / C2 domain / C2 domain / C2 domain profile. / C2 domain superfamily / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / PH-like domain superfamily

構成要素:

Breakpoint cluster region protein

• 生物種: Homo sapiens (ヒト)
• 引用: ジャーナル: Nat Commun / 年: 2017; タイトル: Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase.; 著者: Sina Reckel / Charlotte Gehin / Delphine Tardivon / Sandrine Georgeon / Tim Kükenshöner / Frank Löhr / Akiko Koide / Lena Buchner / Alejandro Panjkovich / Aline Reynaud / Sara Pinho / Barbara Gerig / Dmitri Svergun / Florence Pojer / Peter Güntert / Volker Dötsch / Shohei Koide / Anne-Claude Gavin / Oliver Hantschel / ; 要旨: The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study the Dbl-homology (DH) and Pleckstrin-homology (PH) domains of Bcr-Abl p210, which constitute the only structural differences to p190. Here we report high-resolution structures of the DH and PH domains and characterize conformations of the DH-PH unit in solution. Our structural and functional analyses show no evidence that the DH domain acts as a guanine nucleotide exchange factor, whereas the PH domain binds to various phosphatidylinositol-phosphates. PH-domain mutants alter subcellular localization and result in decreased interactions with p210-selective interaction partners. Hence, the PH domain, but not the DH domain, plays an important role in the formation of the differential p210 and p190 Bcr-Abl signaling networks.

登録者

• Alejandro Panjkovich (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

モデル

• モデル #1387: ; タイプ: atomic / ソフトウェア: (2.8.1) / ダミー原子の半径: 1.90 A / カイ2乗値: 1.062; 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: PH - Pleckstrin-homology domain of Bcr-Abl tyrosine kinase p210; 試料濃度: 1.00-9.14
• バッファ: 名称: 25 mM Tris-HCl, 150 mM NaCl, 5% Glycerol, 1 mM DTT / pH: 7.5

要素 #740

タイプ: protein / 記述: BCR-ABL p210 fusion protein (PH domain) / 分子量: 22.413 / 分子数: 1 / 由来: Homo sapiens / 参照: UniProt: P11274
配列:

GAMGEHRQLL KDSFMVELVE GARKLRHVFL FTDLLLCTKL KKQSGGKTQQ YDCKWYIPLT DLSFQMVDEL EAVPNIPLVP DEELDALKIK ISQIKNDIQR EKRANKGSKA TERLKKKLSE QESLLLLMSP SMAFRVHSRN GKSYTFLISS DYERAEWREN IREQQKKCFR SFSLTSVELQ MLTNSCVKLQ TVH

実験情報

• ビーム: 設備名称: PETRA III P12 / 地域: Hamburg / 国: Germany / 線源: X-ray synchrotron / 波長: 0.124 Å / スペクトロメータ・検出器間距離: 3 mm
• 検出器: 名称: Pilatus 2M

スキャン

タイトル: PH - Pleckstrin-homology domain of Bcr-Abl tyrosine kinase p210
測定日: 2016年11月10日 / 保管温度: 10 °C / セル温度: 10 °C / 照射時間: 0.045 sec. / フレーム数: 20 / 単位: 1/A /

	Min	Max
Q	0.0021	0.379

距離分布関数 P(R)

ソフトウェア P(R): GNOM 5.0 / ポイント数: 1500 /

	Min	Max
Q	0.0071425	0.319587
P(R) point	1	1500
R	0	67

結果

カーブのタイプ: merged
コメント: The homology model is derived from PDB ID: 2z0q. The PDB entry for BCR-ABL p210 fusion protein PH domain is 5oc7 (has an internal deletion).

	実験値	Standard	Standard error	Porod
分子量	23 kDa	16 kDa	3	23 kDa
体積	-	-	-	38 nm3

	P(R)	P(R) error	Guinier	Guinier error
前方散乱 I0	2074	9	2071.9	9.84
慣性半径, Rg	2.07 nm	0.02	2.04 nm	0.03

	Min	Max	Error
D	-	6.6	0.3
Guinier point	26	296	-