Egl nine homolog 1

Egl nine homolog 1 (EGLN1) is a cellular oxygen sensor that catalyzes the post-translational hydroxylation of hypoxia-inducible factor (HIF) alpha proteins under normoxic conditions (UniProt: Q9GZT9). This modification targets HIFs for proteasomal degradation via the von Hippel-Lindau ubiquitination complex, thereby regulating hypoxia-responsive gene expression and processes including angiogenesis and cardiac function. EGLN1 is the predominant isozyme under normal oxygen conditions.

EGLN1 operates in cellular oxygen-sensing pathways critical to vascular and metabolic homeostasis. UniProt identifies a disease association with familial erythrocytosis type 3 (ECYT3), an autosomal dominant disorder characterized by elevated hemoglobin and hematocrit.

EGLN1 is upregulated in Alzheimer's disease brain tissue (Chaparral AD proteomics). Proteomic analysis of post-mortem AD brain compared to age-matched controls using TMT-labeled, subcellular-fraction tandem mass spectrometry shows EGLN1 elevated with a mean log2 fold-change of +0.39 (ad:direction:up). This upregulation suggests altered hypoxic signaling or oxygen-sensing dysfunction may contribute to AD pathology, though the functional significance requires further investigation.