Scheme and in silico modeling of the JAK2 mutants. (A) Scheme and location of germ-line JAK2 mutations. (B) Superimposition of the crystal structures of the active JH1 kinase and JH2 pseudokinase domains of JAK2 wild type (WT) based on 2 radiograph crystal structure studies.^20,21  On the left in blue: coordinate of active JH1 (protein data bank [PDB] code: 2B7A). On the right in green: coordinate of active JH2 (PDB code: 4FVQ). Two of the mutations, R938Q and R867Q, are located in the JH1, whereas the S755R mutation is located in the JH2 (pink residues). The germ-line JAK2 S755R/R938Q mutant therefore contains mutations in both JH2 and JH1. The activation loop is represented in red in both JH1 and JH2. The glycine-rich loop is in yellow, and the catalytic loop is in orange. The salt bridge between D869 and R867 is only formed in the inactive JH1, which is the coordinate represented on the small square on the left. The coordinate of inactive JH1 is PDB code 3UGC. The salt bridge between K752 and D635 is formed in active JH2 (WT and V617F). The coordinate shown here in the small square on the right is the active JH2 WT (PDB code: 4FVQ).