EGLN3, a member of the EGLN family of prolyl hydroxylases, has been shown to catalyze hydroxylation of the α subunit of hypoxia-inducible factor-α, which targets hypoxia-inducible factor-α for ubiquitination by a ubiquitin ligase complex containing the von Hippel-Lindau (VHL) tumor suppressor. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia.