EGLN3(redirected from HIFPH3)
EGLN3A gene on chromosome 14q13.1 that encodes a cellular oxygen sensor that catalyses, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. EGLN3 limits physiologic activation of HIF during hypoxia and hydroxylates PKM2, limiting glycolysis. Under normoxia, EGLN3: hydroxylates and regulates the stability of ADRB2; regulates cardiomyocyte and neuronal apoptosis; inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex in cardiac myocytes; has an NGF-induced pro-apoptotic effect on neurons by regulating CASP3 activity; and is essential for hypoxic regulation of neutrophilic inflammation.
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.