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

Basic information

• Entry: Database: SASBDB / ID: SASDC46

Sample

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

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

Function / homology

Function:

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 / Signaling by cytosolic FGFR1 fusion mutants / definitive hemopoiesis / activation of GTPase activity / regulation of small GTPase mediated signal transduction / inner ear morphogenesis / small GTPase-mediated signal transduction / RHOB GTPase cycle / RHOC GTPase cycle / CDC42 GTPase cycle / neuromuscular process controlling balance / homeostasis of number of cells / RHOA GTPase cycle / negative regulation of reactive oxygen species metabolic process / 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 / brain development / modulation of chemical synaptic transmission / Schaffer collateral - CA1 synapse / negative regulation of inflammatory response / actin cytoskeleton organization / protein tyrosine kinase activity / cellular response to lipopolysaccharide / dendritic spine / postsynaptic density / non-specific serine/threonine protein kinase / regulation of cell cycle / 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

Domain/homology:

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

Component:

Breakpoint cluster region protein

• Biological species: Homo sapiens (human)
• Citation: Journal: Nat Commun / Year: 2017; Title: Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase.; Authors: 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 / ; Abstract: 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.

Contact author

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

Models

• Model #1387: ; Type: atomic / Software: (2.8.1) / Radius of dummy atoms: 1.90 A / Chi-square value: 1.062; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: PH - Pleckstrin-homology domain of Bcr-Abl tyrosine kinase p210; Specimen concentration: 1.00-9.14
• Buffer: Name: 25 mM Tris-HCl, 150 mM NaCl, 5% Glycerol, 1 mM DTT / pH: 7.5

Entity #740

Type: protein / Description: BCR-ABL p210 fusion protein (PH domain) / Formula weight: 22.413 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: P11274
Sequence:

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

Experimental information

• Beam: Instrument name: PETRA III P12 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotron / Wavelength: 0.124 Å / Dist. spec. to detc.: 3 mm
• Detector: Name: Pilatus 2M

Scan

Title: PH - Pleckstrin-homology domain of Bcr-Abl tyrosine kinase p210
Measurement date: Nov 10, 2016 / Storage temperature: 10 °C / Cell temperature: 10 °C / Exposure time: 0.045 sec. / Number of frames: 20 / Unit: 1/A /

	Min	Max
Q	0.0021	0.379

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 1500 /

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

Result

Type of curve: merged
Comments: 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).

	Experimental	Standard	Standard error	Porod
MW	23 kDa	16 kDa	3	23 kDa
Volume	-	-	-	38 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	2074	9	2071.9	9.84
Radius of gyration, Rg	2.07 nm	0.02	2.04 nm	0.03

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