Diagram of oxygen-sensing pathway.
 In normoxic conditions PHD2 hydroxylates HIF-2α which binds VHL. The proteins are then ubiquitinated and degraded in the proteasome. In hypoxic conditions HIF-2α associates with HIF-β, binds to the transcription enhancer element of the EPO gene, which leads to gene transcription and protein production including production of EPO, which drives red cell production.