Egl nine homologs (EGLN1, EGLN2, EGLN3) (EGLN1/2/3)

EGLN1, EGLN2, and EGLN3 are prolyl hydroxylase enzymes that act as oxygen sensors in human cells. They regulate the stability of hypoxia-inducible factor α (HIF-α) subunits through oxygen-dependent proline hydroxylation, targeting them for degradation under normoxic conditions. EGLN1 (PHD2) is the primary isozyme under normal oxygen levels and is critical for many hypoxia-influenced physiological processes, including erythropoiesis and angiogenesis. Beyond HIF, these enzymes hydroxylate a growing list of other substrates involved in metabolism, signal transduction, and cell fate determination, suggesting roles in cancer, metabolic disease, and immune responses. Targeting these enzymes pharmacologically has therapeutic potential but requires careful management due to the risks related to chronic HIF activation and impacts on non-HIF pathways.

Other names

Prolyl hydroxylase domain-containing protein 2 (PHD2)Prolyl hydroxylase domain-containing protein 1 (PHD1)Prolyl hydroxylase domain-containing protein 3 (PHD3)SM-20

Inhibition of prolyl hydroxylase activity leads to stabilization of HIF-α subunits, promoting adaptive gene expression to hypoxia (increased erythropoietin, improved iron metabolism, angiogenesis).