Function
EGLN1 (Egl Nine homolog 1), also known as PHD2 (Prolyl Hydroxylase Domain 2), is a cellular oxygen sensor that plays a critical role in regulating the stability of hypoxia-inducible factors (HIFs). Under normoxic conditions, EGLN1 catalyzes the post-translational hydroxylation of specific proline residues within the oxygen-dependent degradation (ODD) domains of HIFα proteins, such as HIF1A and HIF2A. This hydroxylation event targets HIFα proteins for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Conversely, under hypoxic conditions, EGLN1 activity is attenuated, allowing HIFα proteins to escape degradation and translocate to the nucleus, where they heterodimerize with HIF1B and promote the expression of hypoxia-inducible genes. EGLN1 is the most prominent isozyme responsible for HIF1 stability under normoxic conditions, and it is involved in various hypoxia-influenced processes, including angiogenesis in retinal and cardiac function. EGLN1 preferentially recognizes target proteins via a LXXLAP motif.