Egl nine homolog 2 (PHD1) (PHD1)

Egl nine homolog 2 (EGLN2), also known as Prolyl hydroxylase domain-containing protein 1 (PHD1), is a critical oxygen-sensing enzyme that regulates the cellular response to hypoxia [1, 2]. It belongs to the family of 2-oxoglutarate-dependent dioxygenases and functions by hydroxylating specific proline residues on the alpha subunit of Hypoxia-Inducible Factor (HIF) [3, 6]. Under normoxic conditions, this modification marks HIF for recognition by the von Hippel-Lindau (VHL) protein, leading to its rapid proteasomal degradation [3, 10]. When oxygen levels are low, EGLN2 activity is reduced, allowing HIF to stabilize and activate the transcription of genes involved in erythropoiesis, angiogenesis, and metabolic adaptation [1, 8]. Beyond its role in oxygen sensing, EGLN2 is involved in mitochondrial function, cell cycle regulation, and neuroprotection, often through HIF-independent pathways [5, 9, 11]. It is a significant therapeutic target for treating anemia associated with chronic kidney disease, where inhibitors mimic hypoxia to stimulate red blood cell production [1, 7]. Additionally, EGLN2 is implicated in various cancers and neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), making it a focus for both inhibitory and activatory therapeutic strategies [4, 9, 10].

Other names

PHD1HIFPH1HPH-1HPH-3EIT6Egl-9 family hypoxia-inducible factor 2Prolyl hydroxylase domain-containing protein 1Hypoxia-inducible factor prolyl hydroxylase 1Estrogen-induced tag 6

HIF prolyl hydroxylase inhibition, which prevents the hydroxylation and subsequent degradation of Hypoxia-Inducible Factor (HIF) alpha subunits, leading to the stabilization of HIF and the induction of hypoxia-responsive genes such as erythropoietin [1, 3, 10].