| Description |
Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as ATF4, IKBKB, CEP192 and HIF1A (PMID:11595184, PMID:12039559, PMID:15925519, PMID:16509823, PMID:17114296, PMID:23932902). Target proteins are preferentially recognized via a LXXLAP motif (PMID:11595184, PMID:12039559, PMID:15925519). Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (PMID:11595184, PMID:12039559, PMID:12181324, PMID:15925519, PMID:19339211). Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (PMID:11595184, PMID:12039559, PMID:12181324, PMID:15925519). Also hydroxylates HIF2A (PMID:11595184, PMID:12039559, PMID:15925519). Has a preference for the CODD site for both HIF1A and HIF2A (PMID:11595184, PMID:12039559, PMID:15925519). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PMID:11595184, PMID:12039559, PMID:15925519). 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 (PMID:11595184, PMID:12039559, PMID:15925519). EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle (PMID:11595184, PMID:12039559, PMID:15925519). Also regulates susceptibility to normoxic oxidative neuronal death (PMID:11595184, PMID:12039559, PMID:15925519). 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 (PMID:23932902). Hydroxylates IKBKB, mediating NF-kappa-B activation in hypoxic conditions (PMID:17114296). Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 . |
| Other names |
Egl nine homolog 2, EC 1.14.11.29, Estrogen-induced tag 6, HPH-3, Hypoxia-inducible factor prolyl hydroxylase 1, HIF-PH1, HIF-prolyl hydroxylase 1, HPH-1, Prolyl hydroxylase domain-containing protein 1, PHD1, EGLN2, EIT6 |
