EGLN2(redirected from Prolyl hydroxylase domain-containing protein 1)
EGLN2A gene on chromosome 19q13.2 that encodes a cellular oxygen sensor which catalyses, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. It is involved in regulating hypoxia tolerance, susceptibility to normoxic oxidative neuronal death and apoptosis in cardiac and skeletal muscle.
EGLN2 hydroxylates a specific proline found in each oxygen-dependent degradation (ODD) domains—N-terminal (NODD) and C-terminal (CODD)—of HIF1A; hydroxylated HIFs are then targeted for proteasomal degradation by the von Hippel-Lindau ubiquitination complex. During hypoxia, the hydroxylation reaction is attenuated, allowing HIFs to escape degradation, resulting in translocation to the nucleus, heterodimerisation with HIF1B and increased expression of hypoxy-inducible genes.