[English] 日本語
Yorodumi
- PDB-5bk8: Cancer-associated SHP2/T507K mutant -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5bk8
TitleCancer-associated SHP2/T507K mutant
ComponentsTyrosine-protein phosphatase non-receptor type 11
KeywordsHYDROLASE / Phosphatase / SHP2 / PTPN11 / T507K
Function / homology
Function and homology information


atrioventricular canal development / genitalia development / STAT5 Activation / Co-inhibition by BTLA / Netrin mediated repulsion signals / negative regulation of neutrophil activation / negative regulation of chondrocyte differentiation / positive regulation of lipopolysaccharide-mediated signaling pathway / Interleukin-37 signaling / face morphogenesis ...atrioventricular canal development / genitalia development / STAT5 Activation / Co-inhibition by BTLA / Netrin mediated repulsion signals / negative regulation of neutrophil activation / negative regulation of chondrocyte differentiation / positive regulation of lipopolysaccharide-mediated signaling pathway / Interleukin-37 signaling / face morphogenesis / Signaling by Leptin / negative regulation of cell adhesion mediated by integrin / positive regulation of ossification / MET activates PTPN11 / Regulation of RUNX1 Expression and Activity / Signal regulatory protein family interactions / ERBB signaling pathway / Interleukin-20 family signaling / Interleukin-6 signaling / Co-inhibition by CTLA4 / PI-3K cascade:FGFR3 / STAT5 activation downstream of FLT3 ITD mutants / Platelet sensitization by LDL / negative regulation of T cell activation / inner ear development / PI-3K cascade:FGFR2 / fibroblast growth factor receptor signaling pathway / PI-3K cascade:FGFR4 / peptide hormone receptor binding / negative regulation of type I interferon production / MAPK3 (ERK1) activation / PI-3K cascade:FGFR1 / regulation of type I interferon-mediated signaling pathway / MAPK1 (ERK2) activation / Prolactin receptor signaling / PECAM1 interactions / peptidyl-tyrosine dephosphorylation / non-membrane spanning protein tyrosine phosphatase activity / Regulation of IFNA/IFNB signaling / positive regulation of intracellular signal transduction / RET signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / Co-inhibition by PD-1 / PI3K Cascade / ephrin receptor signaling pathway / regulation of protein-containing complex assembly / positive regulation of insulin receptor signaling pathway / negative regulation of T cell receptor signaling pathway / negative regulation of T cell proliferation / Regulation of IFNG signaling / GAB1 signalosome / T cell costimulation / Activated NTRK2 signals through FRS2 and FRS3 / GPVI-mediated activation cascade / Signaling by CSF3 (G-CSF) / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / phosphotyrosine residue binding / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / phosphoprotein phosphatase activity / protein-tyrosine-phosphatase / FRS-mediated FGFR1 signaling / Tie2 Signaling / FLT3 Signaling / protein tyrosine phosphatase activity / cell adhesion molecule binding / positive regulation of interferon-beta production / Downstream signal transduction / cellular response to epidermal growth factor stimulus / protein tyrosine kinase binding / positive regulation of D-glucose import across plasma membrane / insulin receptor binding / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / brain development / Negative regulation of FGFR3 signaling / cellular response to mechanical stimulus / Negative regulation of FGFR2 signaling / Negative regulation of FGFR4 signaling / Negative regulation of FGFR1 signaling / Signaling by SCF-KIT / Spry regulation of FGF signaling / receptor tyrosine kinase binding / vasodilation / epidermal growth factor receptor signaling pathway / cytokine-mediated signaling pathway / Constitutive Signaling by Aberrant PI3K in Cancer / heart development / Signaling by CSF1 (M-CSF) in myeloid cells / Interferon alpha/beta signaling / positive regulation of tumor necrosis factor production / PIP3 activates AKT signaling / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / signaling receptor complex adaptor activity / molecular adaptor activity / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of ERK1 and ERK2 cascade / cadherin binding / focal adhesion / nucleolus
Similarity search - Function
Protein-tyrosine phosphatase, non-receptor type-6, -11 / SH2 domain / SHC Adaptor Protein / Protein tyrosine phosphatase superfamily / Protein-Tyrosine Phosphatase; Chain A / Protein tyrosine phosphatase, catalytic domain / PTP type protein phosphatase domain profile. / Protein-tyrosine phosphatase / Tyrosine-specific protein phosphatase, PTPase domain / Protein-tyrosine phosphatase, catalytic ...Protein-tyrosine phosphatase, non-receptor type-6, -11 / SH2 domain / SHC Adaptor Protein / Protein tyrosine phosphatase superfamily / Protein-Tyrosine Phosphatase; Chain A / Protein tyrosine phosphatase, catalytic domain / PTP type protein phosphatase domain profile. / Protein-tyrosine phosphatase / Tyrosine-specific protein phosphatase, PTPase domain / Protein-tyrosine phosphatase, catalytic / Protein tyrosine phosphatase, catalytic domain motif / Tyrosine specific protein phosphatases active site. / Protein-tyrosine phosphatase, active site / Tyrosine specific protein phosphatases domain profile. / Tyrosine-specific protein phosphatases domain / Protein-tyrosine phosphatase-like / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Alpha-Beta Complex / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Tyrosine-protein phosphatase non-receptor type 11
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.25 Å
AuthorsYu, Z.H. / Zhang, R.Y. / Zhang, Z.Y.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)RO1 CA69202 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)RO1 CA207288 United States
CitationJournal: J.Biol.Chem. / Year: 2020
Title: Mechanistic insights explain the transforming potential of the T507K substitution in the protein-tyrosine phosphatase SHP2.
Authors: Zhang, R.Y. / Yu, Z.H. / Chen, L. / Walls, C.D. / Zhang, S. / Wu, L. / Zhang, Z.Y.
History
DepositionJun 1, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 8, 2020Provider: repository / Type: Initial release
Revision 1.1May 13, 2020Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title
Revision 1.2Sep 27, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Tyrosine-protein phosphatase non-receptor type 11


Theoretical massNumber of molelcules
Total (without water)61,7901
Polymers61,7901
Non-polymers00
Water4,161231
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area22690 Å2
Unit cell
Length a, b, c (Å)54.699, 203.176, 44.366
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212

-
Components

#1: Protein Tyrosine-protein phosphatase non-receptor type 11 / Protein-tyrosine phosphatase 1D / PTP-1D / Protein-tyrosine phosphatase 2C / PTP-2C / SH-PTP2 / Shp2 / SH-PTP3


Mass: 61789.719 Da / Num. of mol.: 1 / Mutation: T507K
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTPN11, PTP2C, SHPTP2
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
References: UniProt: Q06124, protein-tyrosine-phosphatase
#2: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 231 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 1.99 Å3/Da / Density % sol: 38.34 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 16% PEG3350, 200 mM LiCl

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.97857 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Apr 1, 2011
Diffraction measurementDetails: 1.00 degrees, 11.0 sec, detector distance 327.42 mm
Method: \w scans
RadiationMonochromator: SI(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97857 Å / Relative weight: 1
ReflectionAv R equivalents: 0.14 / Number: 105858
ReflectionResolution: 2.25→50 Å / Num. obs: 23674 / % possible obs: 95.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 4.5 % / Rmerge(I) obs: 0.14 / Rsym value: 0.14 / Net I/av σ(I): 12.744 / Net I/σ(I): 12.66 / Num. measured all: 105858
Reflection shellResolution: 2.25→2.29 Å / Redundancy: 4 % / Rmerge(I) obs: 0.811 / Mean I/σ(I) obs: 1.487 / Num. unique obs: 1139 / Rsym value: 0.811 / % possible all: 93.8
Cell measurementReflection used: 105858

-
Processing

Software
NameVersionClassification
HKL-3000data reduction
SCALEPACKdata scaling
PHENIX1.10.1_2155refinement
PDB_EXTRACT3.25data extraction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4DGP

4dgp


Resolution: 2.25→40.658 Å / SU ML: 0.3 / Cross valid method: THROUGHOUT / σ(F): 1.44 / Phase error: 25.69
RfactorNum. reflection% reflection
Rfree0.262 1168 5.01 %
Rwork0.1982 --
obs0.2014 23297 95.44 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 90.43 Å2 / Biso mean: 31.3359 Å2 / Biso min: 10.66 Å2
Refinement stepCycle: final / Resolution: 2.25→40.658 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4028 0 0 231 4259
Biso mean---32.35 -
Num. residues----498
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0084111
X-RAY DIFFRACTIONf_angle_d1.0055540
X-RAY DIFFRACTIONf_chiral_restr0.056594
X-RAY DIFFRACTIONf_plane_restr0.006718
X-RAY DIFFRACTIONf_dihedral_angle_d15.682469
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 8

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.25-2.35240.33351430.24472654279792
2.3524-2.47640.32081470.2282737288497
2.4764-2.63150.31091440.23042731287597
2.6315-2.83470.32361450.22082755290097
2.8347-3.11980.28441430.21612760290396
3.1198-3.57110.2641480.19032751289995
3.5711-4.49820.23281410.16542780292194
4.4982-40.66440.20931570.18632961311896

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more