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Literature summary for 2.7.10.2 extracted from

  • Lucet, I.S.; Fantino, E.; Styles, M.; Bamert, R.; Patel, O.; Broughton, S.E.; Walter, M.; Burns, C.J.; Treutlein, H.; Wilks, A.F.; Rossjohn, J.
    The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor (2006), Blood, 107, 176-183.
    View publication on PubMed

Activating Compound

Activating Compound Comment Organism Structure
additional information JAK2 activation loop structure, residues 994-1023, with phosphorylation sites Y1007 and Y1008, JAK2 switches between active and inactive forms involving the switch motif Asp994-Phe2995-Gly996 proximal to the active site, overview Homo sapiens

Application

Application Comment Organism
drug development JAK2 is a target for drug development, specific inhibitors are of tremendous clinical relevance Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression of JAK2 kinase domain, comprisine residues 835-1132, as GST-fusion protein in Spodoptera frugiperda Sf9 cells using baculovirus transfection system Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
purified recombinant detagged JAK2 kinase domain bound to inhibitor CMP6, hanging drop vapour diffusion method, 20°C, mixing of equal volumes of protein solution, containing 10 mg/ml protein in 20 mM Tris, pH 8.5, 250 mM NaCl, and 1 mM DTT, and reservoir solution, containing 28% PEG 4000, 0.2 M ammonium acetate, and 0.1 M citrate, pH 6.0, 1-3 days, X-ray diffraction structure determination and analysis at 2.0 A Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
CMP6 i.e. 2-tert-butyl-9-fluoro-3,6-dihydro-7H-benz[h]-imidaz[4,5-f]isoquinoline-7-1, specific for JAK2, kinase domain binding structure and mechanism Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens JAK2 is an important intracellular mediator of cytokine signalling, JAK2 deficiency may lead to hematologic cancers, and a number of immune diseases ?
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Organism

Organism UniProt Comment Textmining
Homo sapiens
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Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein activation of JAK2 by phosphorylation at sites Y1007 and Y1008 of the activation loop structure Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
recombinant GST-fusion JAK2 kinase domain from Sf9 insect cells, glutathione affinity chromatography, afterwards the JAK2 protein is treated with inhibitor CMP6 and the GST-tag is cleaved off by thrombin, followed by gel filtration Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information JAK2 is an important intracellular mediator of cytokine signalling, JAK2 deficiency may lead to hematologic cancers, and a number of immune diseases Homo sapiens ?
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?

Synonyms

Synonyms Comment Organism
JAK2
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Homo sapiens
Janus kinase 2
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Homo sapiens
More JAK2 is a member of the Janus kinase family of PTKs Homo sapiens
Protein tyrosine kinase
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Homo sapiens
PTK
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Homo sapiens