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- PDB-9uw4: The complex of human pMEK1 and uERK1 (ANP)(from pY204ERK1) -

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Basic information

Entry
Database: PDB / ID: 9uw4
TitleThe complex of human pMEK1 and uERK1 (ANP)(from pY204ERK1)
Components
  • Dual specificity mitogen-activated protein kinase kinase 1
  • Mitogen-activated protein kinase 3
KeywordsTRANSFERASE / MEK1. ERK1 / Complex / Kinase / MAPK pathway
Function / homology
Function and homology information


negative regulation of cholesterol efflux / negative regulation of homotypic cell-cell adhesion / epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / positive regulation of xenophagy / xenophagy / regulation of vascular associated smooth muscle contraction / mitogen-activated protein kinase kinase / negative regulation of T cell mediated immune response to tumor cell ...negative regulation of cholesterol efflux / negative regulation of homotypic cell-cell adhesion / epithelial cell proliferation involved in lung morphogenesis / positive regulation of endodermal cell differentiation / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / positive regulation of xenophagy / xenophagy / regulation of vascular associated smooth muscle contraction / mitogen-activated protein kinase kinase / negative regulation of T cell mediated immune response to tumor cell / positive regulation of muscle contraction / Golgi inheritance / placenta blood vessel development / MAP kinase scaffold activity / RAF-independent MAPK1/3 activation / Suppression of apoptosis / regulation of axon regeneration / cerebellar cortex formation / labyrinthine layer development / Gastrin-CREB signalling pathway via PKC and MAPK / Signaling by Activin / melanosome transport / cardiac neural crest cell development involved in heart development / interleukin-34-mediated signaling pathway / caveolin-mediated endocytosis / peptidyl-tyrosine autophosphorylation / response to epidermal growth factor / Signaling by NODAL / Signaling by MAP2K mutants / RSK activation / ERKs are inactivated / positive regulation of cyclase activity / phosphorylation / type B pancreatic cell proliferation / Regulation of the apoptosome activity / Golgi Cisternae Pericentriolar Stack Reorganization / positive regulation of macrophage proliferation / central nervous system neuron differentiation / cartilage development / outer ear morphogenesis / vesicle transport along microtubule / positive regulation of Ras protein signal transduction / : / Signaling by LTK in cancer / regulation of Golgi inheritance / mitogen-activated protein kinase kinase kinase binding / interleukin-1-mediated signaling pathway / positive regulation of axonogenesis / trachea formation / triglyceride homeostasis / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / IFNG signaling activates MAPKs / regulation of stress-activated MAPK cascade / positive regulation of neuroinflammatory response / Frs2-mediated activation / MAPK3 (ERK1) activation / ERBB2-ERBB3 signaling pathway / Activation of the AP-1 family of transcription factors / RUNX2 regulates osteoblast differentiation / response to exogenous dsRNA / ERK/MAPK targets / positive regulation of macrophage chemotaxis / regulation of cytoskeleton organization / face development / endodermal cell differentiation / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / MAP kinase kinase activity / Bergmann glial cell differentiation / positive regulation of protein serine/threonine kinase activity / lung morphogenesis / thyroid gland development / pseudopodium / positive regulation of telomere maintenance / positive regulation of ATP biosynthetic process / Advanced glycosylation endproduct receptor signaling / Uptake and function of anthrax toxins / MAP kinase activity / regulation of ossification / mitogen-activated protein kinase / Regulation of HSF1-mediated heat shock response / RHO GTPases Activate NADPH Oxidases / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / RHO GTPases Activate WASPs and WAVEs / protein kinase activator activity / Signal attenuation / BMP signaling pathway / Growth hormone receptor signaling / Schwann cell development / response to axon injury / stress-activated MAPK cascade / phosphatase binding / keratinocyte differentiation / neuron projection morphogenesis / ERK1 and ERK2 cascade / NPAS4 regulates expression of target genes / signal transduction in response to DNA damage / Nuclear events stimulated by ALK signaling in cancer / phosphotyrosine residue binding / myelination
Similarity search - Function
: / Mitogen-activated protein (MAP) kinase, ERK1/2 / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / 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 ...: / Mitogen-activated protein (MAP) kinase, ERK1/2 / Mitogen-activated protein (MAP) kinase, conserved site / MAP kinase signature. / : / 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
Similarity search - Domain/homology
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / Mitogen-activated protein kinase 3 / Dual specificity mitogen-activated protein kinase kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsPeng, C. / Sun, Y. / Liu, S. / Zhou, F. / Hu, Q.
Funding support China, 1items
OrganizationGrant numberCountry
Other government2023C03109 China
CitationJournal: Biorxiv / Year: 2026
Title: Mechanistic insight into the phosphorylation of ERK by MEK
Authors: Sun, Y. / Peng, C. / Liu, S. / Zhou, F. / Huang, G. / Wang, J. / Hu, Q.
History
DepositionMay 12, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Apr 1, 2026Provider: repository / Type: Initial release
Revision 1.0Apr 1, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Apr 1, 2026Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Apr 1, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 1, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Apr 1, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Apr 1, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
B: Mitogen-activated protein kinase 3
A: Dual specificity mitogen-activated protein kinase kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)90,4385
Polymers89,4012
Non-polymers1,0373
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Mitogen-activated protein kinase 3 / MAP kinase 3 / MAPK 3 / ERT2 / Extracellular signal-regulated kinase 1 / ERK-1 / Insulin-stimulated ...MAP kinase 3 / MAPK 3 / ERT2 / Extracellular signal-regulated kinase 1 / ERK-1 / Insulin-stimulated MAP2 kinase / MAP kinase isoform p44 / p44-MAPK / Microtubule-associated protein 2 kinase / p44-ERK1


Mass: 44399.773 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Recombinant human ERK1 with additional C-terminal His-tag expressed in E. coli
Source: (gene. exp.) Homo sapiens (human) / Gene: MAPK3, ERK1, PRKM3 / Production host: Escherichia coli (E. coli)
References: UniProt: P27361, mitogen-activated protein kinase
#2: Protein Dual specificity mitogen-activated protein kinase kinase 1 / MAP kinase kinase 1 / MAPKK 1 / MKK1 / ERK activator kinase 1 / MAPK/ERK kinase 1 / MEK 1


Mass: 45001.320 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: Recombinant human MEK1 with additional C-terminal His-tag expressed in E. coli, with phosphorylation sites on S218 and S222.
Source: (gene. exp.) Homo sapiens (human) / Gene: MAP2K1, MEK1, PRKMK1 / Production host: Escherichia coli (E. coli)
References: UniProt: Q02750, mitogen-activated protein kinase kinase
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-ANP / PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER


Mass: 506.196 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H17N6O12P3 / Feature type: SUBJECT OF INVESTIGATION / Comment: AMP-PNP, energy-carrying molecule analogue*YM
Has ligand of interestY
Has protein modificationY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: The complex of human pMEK1 and uERK1 (from pY204) at the presence of AMPPNP
Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli (E. coli)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 1100 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameCategory
7Cootmodel fitting
8UCSF ChimeraXmodel fitting
9PHENIXmodel fitting
11PHENIXmodel refinement
12Cootmodel refinement
13UCSF ChimeraXmodel refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 235273 / Symmetry type: POINT
Atomic model buildingSource name: AlphaFold / Type: in silico model
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0025386
ELECTRON MICROSCOPYf_angle_d0.6147295
ELECTRON MICROSCOPYf_dihedral_angle_d11.708738
ELECTRON MICROSCOPYf_chiral_restr0.04801
ELECTRON MICROSCOPYf_plane_restr0.004924

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