Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif.
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Protein Aliases: Egl nine homolog 1; Egl nine homolog 2; egl nine-like protein 1; egl-9 family hypoxia-inducible factor 1; egl-9 family hypoxia-inducible factor 2; EIT-6; Estrogen-induced tag 6; Falkor; HIF prolyl hydroxylase 2; HIF-1alpha prolyl-4-hydroxylase-1; HIF-PH1; HIF-PH2; HIF-prolyl hydroxylase 1; HIF-prolyl hydroxylase 2; HPH-1; HPH-3; Hypoxia-inducible factor prolyl hydroxylase 1; Hypoxia-inducible factor prolyl hydroxylase 2; immediate early response 4; PHD1; PHD2; Prolyl hydroxylase domain-containing protein 1; Prolyl hydroxylase domain-containing protein 2; SM-20; zinc finger MYND domain-containing protein 6
Gene Aliases: 0610011A13Rik; AI503754; C1orf12; C85656; ECYT3; EGLN1; EGLN2; EIT6; HALAH; Hif-p4h-1; Hif-p4h-2; HIF-PH1; HIF-PH2; HIFPH1; HIFPH2; HPH-1; HPH-2; HPH-3; HPH2; Ier4; ORF13; PHD-1; PHD-2; PHD1; PHD2; PNAS-118; PNAS-137; SM-20; SM20; ZMYND6