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Schematic representation of the JAK2 domain structure. Seven Janus homology domains (JH1–JH7) constitute the N-terminal FERM and SH2 domain associating with the intracellular domains of cell surface receptors as well as the C-terminal pseudokinase and kinase domain of JAK2. The JAK2 V617F mutation locates to the pseudokinase domain, interfering with the basal inhibitory effect of the pseudokinase on the kinase domain, leading to constitutive JAK2 activation.
