[English] 日本語
Yorodumi
- PDB-2uzr: A transforming mutation in the pleckstrin homology domain of AKT1... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2uzr
TitleA transforming mutation in the pleckstrin homology domain of AKT1 in cancer (AKT1-PH_E17K)
ComponentsRAC-alpha serine/threonine-protein kinase
KeywordsTRANSFERASE / GLYCOGEN BIOSYNTHESIS / TRANSLATION REGULATION / NUCLEOTIDE- BINDING / GLYCOGEN METABOLISM / ATP-BINDING / SUGAR TRANSPORT / NUCLEAR PROTEIN / SERINE/THREONINE-PROTEIN KINASE / TRANSPORT / CARBOHYDRATE METABOLISM / KINASE / APOPTOSIS / PHOSPHORYLATION / GLUCOSE METABOLISM
Function / homology
Function and homology information


regulation of tRNA methylation / negative regulation of protein maturation / mammalian oogenesis stage / response to insulin-like growth factor stimulus / negative regulation of fatty acid beta-oxidation / regulation of glycogen biosynthetic process / positive regulation of protein localization to endoplasmic reticulum / negative regulation of lymphocyte migration / negative regulation of protein localization to lysosome / cellular response to decreased oxygen levels ...regulation of tRNA methylation / negative regulation of protein maturation / mammalian oogenesis stage / response to insulin-like growth factor stimulus / negative regulation of fatty acid beta-oxidation / regulation of glycogen biosynthetic process / positive regulation of protein localization to endoplasmic reticulum / negative regulation of lymphocyte migration / negative regulation of protein localization to lysosome / cellular response to decreased oxygen levels / cellular response to rapamycin / maintenance of protein location in mitochondrion / AKT-mediated inactivation of FOXO1A / negative regulation of long-chain fatty acid import across plasma membrane / Negative regulation of the PI3K/AKT network / regulation of type B pancreatic cell development / maternal placenta development / establishment of protein localization to mitochondrion / activation-induced cell death of T cells / potassium channel activator activity / AKT phosphorylates targets in the nucleus / cellular response to oxidised low-density lipoprotein particle stimulus / negative regulation of cilium assembly / negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway / Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA / positive regulation of glucose metabolic process / cellular response to peptide / positive regulation of TORC2 signaling / RUNX2 regulates genes involved in cell migration / positive regulation of organ growth / interleukin-18-mediated signaling pathway / mammary gland epithelial cell differentiation / positive regulation of sodium ion transport / MTOR signalling / fibroblast migration / response to fluid shear stress / response to growth factor / cellular response to granulocyte macrophage colony-stimulating factor stimulus / RAB GEFs exchange GTP for GDP on RABs / complement receptor mediated signaling pathway / negative regulation of leukocyte cell-cell adhesion / glycogen biosynthetic process / peripheral nervous system myelin maintenance / phosphatidylinositol-3,4-bisphosphate binding / positive regulation of protein localization to cell surface / positive regulation of endodeoxyribonuclease activity / sphingosine-1-phosphate receptor signaling pathway / phosphorylation / cell migration involved in sprouting angiogenesis / response to growth hormone / regulation of postsynapse organization / anoikis / AKT phosphorylates targets in the cytosol / TORC2 complex binding / positive regulation of fibroblast migration / labyrinthine layer blood vessel development / regulation of myelination / Regulation of TP53 Activity through Association with Co-factors / response to UV-A / execution phase of apoptosis / KSRP (KHSRP) binds and destabilizes mRNA / Mechanical load activates signaling by PIEZO1 and integrins in osteocytes / response to food / Co-inhibition by CTLA4 / negative regulation of cGAS/STING signaling pathway / negative regulation of macroautophagy / cellular response to stress / negative regulation of release of cytochrome c from mitochondria / regulation of neuron projection development / Constitutive Signaling by AKT1 E17K in Cancer / negative regulation of PERK-mediated unfolded protein response / positive regulation of protein metabolic process / apoptotic mitochondrial changes / phosphatidylinositol-3,4,5-trisphosphate binding / TOR signaling / behavioral response to pain / Regulation of localization of FOXO transcription factors / peptidyl-threonine phosphorylation / protein serine/threonine kinase inhibitor activity / cellular response to vascular endothelial growth factor stimulus / negative regulation of Notch signaling pathway / CD28 dependent PI3K/Akt signaling / positive regulation of peptidyl-serine phosphorylation / positive regulation of blood vessel endothelial cell migration / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / Activation of BAD and translocation to mitochondria / positive regulation of glycogen biosynthetic process / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / Mitochondrial unfolded protein response (UPRmt) / positive regulation of G1/S transition of mitotic cell cycle / positive regulation of fat cell differentiation / vascular endothelial cell response to laminar fluid shear stress / positive regulation of lipid biosynthetic process / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / Cyclin E associated events during G1/S transition / Cyclin A:Cdk2-associated events at S phase entry / T cell costimulation / nitric oxide metabolic process / Regulation of TP53 Activity through Acetylation
Similarity search - Function
Protein kinase B alpha, catalytic domain / Protein Kinase B, pleckstrin homology domain / Protein kinase, C-terminal / Protein kinase C terminal domain / Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB) / PH-domain like / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / PH domain ...Protein kinase B alpha, catalytic domain / Protein Kinase B, pleckstrin homology domain / Protein kinase, C-terminal / Protein kinase C terminal domain / Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB) / PH-domain like / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / PH domain / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / PH-like domain superfamily / Roll / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Mainly Beta
Similarity search - Domain/homology
RAC-alpha serine/threonine-protein kinase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.94 Å
AuthorsCarpten, J.D. / Faber, A.L. / Horn, C. / Donoho, G.P. / Briggs, S.L. / Robbins, C.M. / Hostetter, G. / Boguslawski, S. / Moses, T.Y. / Savage, S. ...Carpten, J.D. / Faber, A.L. / Horn, C. / Donoho, G.P. / Briggs, S.L. / Robbins, C.M. / Hostetter, G. / Boguslawski, S. / Moses, T.Y. / Savage, S. / Uhlik, M. / Lin, A. / Du, J. / Qian, Y.W. / Zeckner, D.J. / Tucker-Kellogg, G. / Touchman, J. / Patel, K. / Mousses, S. / Bittner, M. / Schevitz, R. / Lai, M.H. / Blanchard, K.L. / Thomas, J.E.
CitationJournal: Nature / Year: 2007
Title: A transforming mutation in the pleckstrin homology domain of AKT1 in cancer.
Authors: Carpten, J.D. / Faber, A.L. / Horn, C. / Donoho, G.P. / Briggs, S.L. / Robbins, C.M. / Hostetter, G. / Boguslawski, S. / Moses, T.Y. / Savage, S. / Uhlik, M. / Lin, A. / Du, J. / Qian, Y.W. ...Authors: Carpten, J.D. / Faber, A.L. / Horn, C. / Donoho, G.P. / Briggs, S.L. / Robbins, C.M. / Hostetter, G. / Boguslawski, S. / Moses, T.Y. / Savage, S. / Uhlik, M. / Lin, A. / Du, J. / Qian, Y.W. / Zeckner, D.J. / Tucker-Kellogg, G. / Touchman, J. / Patel, K. / Mousses, S. / Bittner, M. / Schevitz, R. / Lai, M.H. / Blanchard, K.L. / Thomas, J.E.
History
DepositionMay 1, 2007Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 17, 2007Provider: repository / Type: Initial release
Revision 1.1May 8, 2011Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Sep 19, 2018Group: Data collection / Database references ...Data collection / Database references / Source and taxonomy / Structure summary
Category: citation / entity ...citation / entity / entity_name_com / entity_src_gen / entity_src_nat / struct_ref / struct_ref_seq / struct_ref_seq_dif
Item: _citation.journal_id_ISSN / _citation.page_last ..._citation.journal_id_ISSN / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.title / _entity.pdbx_description / _entity.src_method / _entity_name_com.name
Revision 1.4Oct 16, 2019Group: Data collection / Experimental preparation / Other
Category: exptl_crystal_grow / pdbx_database_status / reflns_shell
Item: _exptl_crystal_grow.method / _pdbx_database_status.status_code_sf ..._exptl_crystal_grow.method / _pdbx_database_status.status_code_sf / _reflns_shell.Rmerge_I_obs / _reflns_shell.meanI_over_sigI_obs
Revision 1.5Dec 13, 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
Revision 1.6Oct 16, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: RAC-alpha serine/threonine-protein kinase


Theoretical massNumber of molelcules
Total (without water)14,7741
Polymers14,7741
Non-polymers00
Water72140
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPQS
Unit cell
Length a, b, c (Å)83.886, 32.811, 42.160
Angle α, β, γ (deg.)90.00, 119.11, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein RAC-alpha serine/threonine-protein kinase / Protein kinase B / PKB / Protein kinase B alpha / PKB alpha / Proto-oncogene c-Akt / RAC-PK-alpha


Mass: 14773.732 Da / Num. of mol.: 1 / Fragment: RESIDUES 1-123 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: AKT1, PKB, RAC / Cell line (production host): HEK293T / Production host: Homo sapiens (human)
References: UniProt: P31749, non-specific serine/threonine protein kinase
#2: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 40 / Source method: isolated from a natural source / Formula: H2O
Compound detailsENGINEERED RESIDUE IN CHAIN A, GLU 17 TO LYS
Has protein modificationY
Sequence detailsMUTATED E17K

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 1.7 Å3/Da / Density % sol: 28.27 %
Crystal growMethod: vapor diffusion, hanging drop / pH: 7.5
Details: 0.1 M HEPES PH 7.5 AND 1.4 M SODIUM CITRATE, OR 0.1 M SODIUM ACETATE PH 4.6, 0.2 M AMMONIUM ACETATE AND 15%-30% PEG 3350,

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1
DetectorType: ADSC CCD / Detector: CCD / Date: Jul 17, 2006 / Details: MIRRORS
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.94→36.64 Å / Num. obs: 7529 / % possible obs: 97.1 % / Observed criterion σ(I): 2 / Redundancy: 4 % / Rmerge(I) obs: 0.06 / Net I/σ(I): 4.9
Reflection shellResolution: 1.95→2.02 Å / Redundancy: 2 % / Rmerge(I) obs: 0.139 / Mean I/σ(I) obs: 2.11 / % possible all: 86.4

-
Processing

Software
NameVersionClassification
REFMAC5.2.0019refinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1UNQ

1unq


Resolution: 1.94→36.64 Å / Cor.coef. Fo:Fc: 0.928 / Cor.coef. Fo:Fc free: 0.915 / SU B: 4.931 / SU ML: 0.146 / Cross valid method: THROUGHOUT / ESU R: 0.276 / ESU R Free: 0.194 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. RESIDUES 43-47 ARE DISORDERED.
RfactorNum. reflection% reflectionSelection details
Rfree0.257 367 5 %RANDOM
Rwork0.238 ---
obs0.239 6956 97.1 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 30.96 Å2
Baniso -1Baniso -2Baniso -3
1--0.12 Å20 Å20.02 Å2
2--0.17 Å20 Å2
3----0.02 Å2
Refinement stepCycle: LAST / Resolution: 1.94→36.64 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms956 0 0 40 996
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0050.022980
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg0.8771.9411323
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.0065111
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.35923.26952
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.21515181
X-RAY DIFFRACTIONr_dihedral_angle_4_deg7.5271510
X-RAY DIFFRACTIONr_chiral_restr0.0690.2139
X-RAY DIFFRACTIONr_gen_planes_refined0.0020.02744
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined0.1830.2377
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined0.30.2651
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.3750.259
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1970.264
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1320.219
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.4581.5583
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it0.812920
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it0.6743460
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it1.0984.5403
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.94→2 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.316 25
Rwork0.275 414

+
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