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- PDB-9t1u: JAK2-ruxolitinib complex with a phosphorylated activation loop -

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Basic information

Entry
Database: PDB / ID: 9t1u
TitleJAK2-ruxolitinib complex with a phosphorylated activation loop
ComponentsTyrosine-protein kinase JAK2
KeywordsTRANSFERASE / Janus kinase / JAK2 / JH1
Function / homology
Function and homology information


nuclear receptor-mediated mineralocorticoid signaling pathway / response to interleukin-12 / histone H3Y41 kinase activity / mammary gland epithelium development / symbiont-induced defense-related programmed cell death / positive regulation of growth hormone receptor signaling pathway / interleukin-35-mediated signaling pathway / positive regulation of growth factor dependent skeletal muscle satellite cell proliferation / granulocyte macrophage colony-stimulating factor receptor complex / regulation of postsynapse to nucleus signaling pathway ...nuclear receptor-mediated mineralocorticoid signaling pathway / response to interleukin-12 / histone H3Y41 kinase activity / mammary gland epithelium development / symbiont-induced defense-related programmed cell death / positive regulation of growth hormone receptor signaling pathway / interleukin-35-mediated signaling pathway / positive regulation of growth factor dependent skeletal muscle satellite cell proliferation / granulocyte macrophage colony-stimulating factor receptor complex / regulation of postsynapse to nucleus signaling pathway / granulocyte-macrophage colony-stimulating factor signaling pathway / thrombopoietin-mediated signaling pathway / interleukin-12 receptor complex / Signaling by Erythropoietin / interleukin-23 receptor complex / Erythropoietin activates STAT5 / collagen-activated signaling pathway / interleukin-12 receptor binding / activation of Janus kinase activity / Erythropoietin activates Phospholipase C gamma (PLCG) / post-embryonic hemopoiesis / positive regulation of NK T cell proliferation / type 1 angiotensin receptor binding / positive regulation of T-helper 17 type immune response / positive regulation of MHC class II biosynthetic process / erythropoietin-mediated signaling pathway / Interleukin-23 signaling / positive regulation of cell-substrate adhesion / interleukin-12-mediated signaling pathway / positive regulation of leukocyte proliferation / positive regulation of platelet activation / positive regulation of natural killer cell proliferation / interleukin-23-mediated signaling pathway / intrinsic apoptotic signaling pathway in response to oxidative stress / interleukin-3-mediated signaling pathway / positive regulation of epithelial cell apoptotic process / interleukin-5-mediated signaling pathway / Interleukin-12 signaling / acetylcholine receptor binding / cellular response to interleukin-3 / positive regulation of platelet aggregation / Signaling by Leptin / IL-6-type cytokine receptor ligand interactions / Interleukin-27 signaling / Interleukin-35 Signalling / growth hormone receptor binding / axon regeneration / regulation of nitric oxide biosynthetic process / response to hydroperoxide / negative regulation of cell-cell adhesion / growth hormone receptor signaling pathway / extrinsic component of plasma membrane / regulation of receptor signaling pathway via JAK-STAT / Interleukin-20 family signaling / platelet-derived growth factor receptor signaling pathway / extrinsic component of cytoplasmic side of plasma membrane / Interleukin-6 signaling / IFNG signaling activates MAPKs / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / enzyme-linked receptor protein signaling pathway / interleukin-6-mediated signaling pathway / positive regulation of tyrosine phosphorylation of STAT protein / peptide hormone receptor binding / MAPK3 (ERK1) activation / positive regulation of interleukin-17 production / MAPK1 (ERK2) activation / Prolactin receptor signaling / cellular response to dexamethasone stimulus / mesoderm development / negative regulation of cardiac muscle cell apoptotic process / signaling receptor activator activity / positive regulation of SMAD protein signal transduction / Interleukin-3, Interleukin-5 and GM-CSF signaling / growth hormone receptor signaling pathway via JAK-STAT / insulin receptor substrate binding / response to tumor necrosis factor / Interleukin receptor SHC signaling / Regulation of IFNG signaling / type II interferon-mediated signaling pathway / Growth hormone receptor signaling / extrinsic apoptotic signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / cell surface receptor signaling pathway via JAK-STAT / phosphatidylinositol 3-kinase binding / Erythropoietin activates RAS / Signaling by CSF3 (G-CSF) / lipopolysaccharide-mediated signaling pathway / actin filament polymerization / positive regulation of T cell proliferation / negative regulation of cytokine production involved in inflammatory response / negative regulation of protein localization to chromatin / post-translational protein modification / SH2 domain binding / positive regulation of apoptotic signaling pathway / erythrocyte differentiation / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / endosome lumen / tumor necrosis factor-mediated signaling pathway / positive regulation of interleukin-1 beta production / positive regulation of receptor signaling pathway via JAK-STAT
Similarity search - Function
Tyrosine-protein kinase, non-receptor Jak2 / Janus kinase 2, pseudokinase domain / Janus kinase 2, catalytic domain / Tyrosine-protein kinase JAK2, SH2 domain / JAK2, FERM domain C-lobe / Tyrosine-protein kinase, non-receptor Jak/Tyk2 / JAK, FERM F2 lobe domain / FERM F1 lobe ubiquitin-like domain / JAK1-3/TYK2, pleckstrin homology-like domain / : ...Tyrosine-protein kinase, non-receptor Jak2 / Janus kinase 2, pseudokinase domain / Janus kinase 2, catalytic domain / Tyrosine-protein kinase JAK2, SH2 domain / JAK2, FERM domain C-lobe / Tyrosine-protein kinase, non-receptor Jak/Tyk2 / JAK, FERM F2 lobe domain / FERM F1 lobe ubiquitin-like domain / JAK1-3/TYK2, pleckstrin homology-like domain / : / Jak1 pleckstrin homology-like domain / FERM F2 acyl-CoA binding protein-like domain / FERM F1 ubiquitin-like domain / SH2 domain / FERM central domain / FERM superfamily, second domain / FERM domain / FERM domain profile. / Band 4.1 domain / Band 4.1 homologues / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH2 domain superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / PH-like domain superfamily / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, 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
MALONATE ION / Chem-RXT / Tyrosine-protein kinase JAK2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.65 Å
AuthorsMiao, Y. / Haikarainen, T.
Funding support Finland, 1items
OrganizationGrant numberCountry
Academy of Finland Finland
CitationJournal: Int.J.Biol.Macromol. / Year: 2026
Title: Janus kinase 2 activation loop as a regulator of catalysis and trans-activation.
Authors: Miao, Y. / Mykuliak, V.V. / Hubbard, S.R. / Silvennoinen, O. / Hytonen, V. / Haikarainen, T.
History
DepositionOct 22, 2025Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 29, 2026Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Tyrosine-protein kinase JAK2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)37,7235
Polymers37,2681
Non-polymers4544
Water2,864159
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: homology
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area450 Å2
ΔGint-12 kcal/mol
Surface area15100 Å2
MethodPISA
Unit cell
Length a, b, c (Å)107.654, 68.974, 49.721
Angle α, β, γ (deg.)90.000, 99.621, 90.000
Int Tables number5
Space group name H-MC121
Space group name HallC2y
Symmetry operation#1: x,y,z
#2: -x,y,-z
#3: x+1/2,y+1/2,z
#4: -x+1/2,y+1/2,-z
Components on special symmetry positions
IDModelComponents
11A-1417-

HOH

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Components

#1: Protein Tyrosine-protein kinase JAK2 / Janus kinase 2 / JAK-2


Mass: 37268.285 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: JAK2 / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: O60674, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-RXT / (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile / Ruxolitinib


Mass: 306.365 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H18N6
#3: Chemical ChemComp-MLI / MALONATE ION


Mass: 102.046 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H2O4
#4: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Na
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 159 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.44 Å3/Da / Density % sol: 49.63 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop / pH: 8.2 / Details: 0.1 M Gly-Gly pH 8.2, 1.6 M Na-malonate

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97625 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Dec 11, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97625 Å / Relative weight: 1
ReflectionResolution: 1.65→57.84 Å / Num. obs: 42816 / % possible obs: 99.2 % / Redundancy: 7 % / Biso Wilson estimate: 13.76 Å2 / CC1/2: 0.999 / Net I/σ(I): 17.3
Reflection shellResolution: 1.65→1.68 Å / Redundancy: 6.6 % / Num. unique obs: 2040 / CC1/2: 0.55 / % possible all: 96.7

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Processing

Software
NameVersionClassification
PHENIX1.21.1_5286refinement
XDSdata reduction
Aimlessdata scaling
PHENIXphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 1.65→49.02 Å / SU ML: 0.1821 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 17.8353
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.1926 2117 4.95 %
Rwork0.1655 40672 -
obs0.1668 42789 99.08 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 22.77 Å2
Refinement stepCycle: LAST / Resolution: 1.65→49.02 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2466 0 32 159 2657
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01242602
X-RAY DIFFRACTIONf_angle_d1.20953525
X-RAY DIFFRACTIONf_chiral_restr0.0644370
X-RAY DIFFRACTIONf_plane_restr0.013457
X-RAY DIFFRACTIONf_dihedral_angle_d14.29131014
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.65-1.690.2891370.28272627X-RAY DIFFRACTION97.02
1.69-1.730.27291380.26612716X-RAY DIFFRACTION98.75
1.73-1.780.29271250.22832696X-RAY DIFFRACTION98.95
1.78-1.830.24841490.22982677X-RAY DIFFRACTION99.05
1.83-1.890.23521420.20092710X-RAY DIFFRACTION99.13
1.89-1.960.2191530.17642664X-RAY DIFFRACTION99.19
1.96-2.030.18991310.16272726X-RAY DIFFRACTION99.13
2.03-2.130.18821410.14662728X-RAY DIFFRACTION99.58
2.13-2.240.15341640.14322692X-RAY DIFFRACTION99.37
2.24-2.380.1931620.14312661X-RAY DIFFRACTION98.05
2.38-2.560.16581390.14292744X-RAY DIFFRACTION99.83
2.56-2.820.1711320.14712724X-RAY DIFFRACTION99.93
2.82-3.230.16541420.14932751X-RAY DIFFRACTION99.86
3.23-4.070.18091370.13472770X-RAY DIFFRACTION99.97
4.07-49.020.18021250.16982786X-RAY DIFFRACTION98.44

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