25 exons spanning roughly 140 kb of genomic DNA; 5402 bp pre-mRNA; 6 different transcripts, putatively encoding 4 different protein isoforms

1132 amino acids; 130,7 kDa; JAK2 contains a central Src homology 2 (SH2) domain, and two C-terminal domains: a tyrosine kinase domain JH1 (also termed PTK or TyrKc domain), and a tyrosine kinase-like domain JH2 (also termed STYKc)

wide

intracellular, possibly membrane associated

protein tyrosine kinase of the non-receptor type that associates with the intracellular domains of cytokine receptors; JAK2 is the predominant JAK kinase activated in response to several growth factors and cytokines such as IL-3, GM-CSF and erythropoietin; it has been found to be constitutively associated with the prolactin receptor and is required for responses to gamma interferon

JAK2 belongs to the janus kinase subfamily; so far four mammalian JAKs have been identified (JAK1, JAK2, JAK3, and TYK2); human JAK2 is > 90% identical to the mouse and the rat JAK2 homologs.

A high proportion (> 50%) of patients with myeloproliferative disorders (MPD; (polycythemia vera, essential thrombocythemia, idiopathic myelofibrosis - see below) carry a dominant gain-of-function V617F mutation in the JH2 kinase-like domain of JAK2. This mutation leads to deregulation of the kinase activity, and thus to constitutive tyrosine phosphorylation activity. The incidence of the V617F mutation in different studies ranges from 65-97% in polycythemia vera, from 41-57% in patients with essential thrombocythemia, and from 23-95% in patients with idiopathic myelofibrosis. In MPD the mutation is heterozygous in most patients and homozygous only in a minor subset. Mitotic recombination probably causes both 9p LOH and the transition from heterozygosity to homozygosity. The same mutation was also found in roughly 20% of Ph-negative atypical CML, in more than 10% of CMML, in about 15% of patients with megakaryocytic AML (AML M7), and 1/5 patients with juvenile myelomonocytic leukemia (JMML). The V617F mutation seems to occur exclusively in hematopietic malignancies of the myeloid lineage.