3.0
Summary
| Name |  EGLN2View Modifications |
| Full Name | Prolyl hydroxylase EGLN2 |
| Synonyms | 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 | EIT6 |
| Primary ID | Q96KS0 |
| Links |  -  -  |
| Type | protein |
| Relations | 9 |
| Inhibitors | dimethyloxalylglycine |
| Function | Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as ATF4, IKBKB, CEP192 and HIF1A (PubMed:11595184, PubMed:12039559, PubMed:15925519, PubMed:16509823, PubMed:17114296, PubMed:23932902). Target proteins are preferentially recognized via a LXXLAP motif (PubMed:11595184, PubMed:12039559, PubMed:15925519). Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519, PubMed:19339211). Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (PubMed:11595184, PubMed:12039559, PubMed:12181324, PubMed:15925519). Also hydroxylates HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519). Has a preference for the CODD site for both HIF1A and HIF2A (PubMed:11595184, PubMed:12039559, PubMed:15925519). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:11595184, PubMed:12039559, PubMed: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 (PubMed:11595184, PubMed:12039559, PubMed:15925519). EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle (PubMed:11595184, PubMed:12039559, PubMed:15925519). Also regulates susceptibility to normoxic oxidative neuronal death (PubMed:11595184, PubMed:12039559, PubMed: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 (PubMed:23932902). Hydroxylates IKBKB, mediating NF-kappa-B activation in hypoxic conditions (PubMed:17114296). Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (By similarity). |
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Modifications Tables
Relations
| Regulator | Mechanism | target | score ℹ | |
|---|---|---|---|---|
| + | EGLN2 | up-regulates activity 
hydroxylation
|
ADSL | 0.2 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | PRKCA | down-regulates 
phosphorylation
|
EGLN2 | 0.34 |
| Publications: | 2 | Organism: | Homo Sapiens | |
| + | EGLN2 | down-regulates activity
hydroxylation
|
FOXO3 | 0.292 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | SPOP | down-regulates quantity by destabilization
ubiquitination
|
EGLN2 | 0.353 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | FBXW7 | down-regulates quantity by destabilization
ubiquitination
|
EGLN2 | 0.355 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | dimethyloxalylglycine | down-regulates activity
chemical inhibition
|
EGLN2 | 0.8 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | Hypoxia | down-regulates 
|
EGLN2 | 0.7 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | EGLN2 | down-regulates quantity by destabilization
hydroxylation
|
HIF1A | 0.851 |
| Publications: | 1 | Organism: | Homo Sapiens | |