FIGURE 4.

Known EPAS1 variants mapped to the structure of the DNA binding and dimerization domain of HIF-2α in various species. (Top) “Top” view of HIF-2α structure (PDB ID 4ZPK). (Middle) “Side” view of HIF-2α. Spheres representing locations of interest are mapped onto HIF-2α with magenta representing sites of ubiquitylation in humans (K186, K191, K291, and K299) (Akimov et al., 2018), yellow representing phosphorylation sites (S10, S12, T182, and T324), and green representing the locations of identified variants from genetic studies. The species, variation, and publication are listed in Table 1. (Bottom) “Side” view of HIF-2α bound to ARNT and DNA (PDB ID 4ZPK). HIF-2α is shown in gray. ARNT is shown in blue. The DNA double helix is shown in Orange. Note: Tyr333 in chickens maps to residue Tyr342 in humans.