Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as ATF4, IKBKB, CEP192 and HIF1A . Target proteins are preferentially recognized via a LXXLAP motif . 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 HIF2A . 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 . EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle . Also regulates susceptibility to normoxic oxidative neuronal death . Links oxygen sensing to cell cycle and primary cilia formation by hydroxylating the critical centrosome component CEP192 which promotes its ubiquitination and subsequent proteasomal degradation . Hydroxylates IKBKB, mediating NF-kappa-B activation in hypoxic conditions . Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (By similarity).
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