Summary

Name EGLN3
Full Name Prolyl hydroxylase EGLN3
Synonyms Egl nine homolog 3, 1.14.11.29, HPH-1, Hypoxia-inducible factor prolyl hydroxylase 3, HIF-PH3, HIF-prolyl hydroxylase 3, HPH-3, Prolyl hydroxylase domain-containing protein 3, PHD3 |
Primary ID Q9H6Z9
Links - -
Type protein
Relations 13
Inhibitors dimethyloxalylglycine
Function Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as PKM, TELO2, ATF4 and HIF1A (PubMed:19584355, PubMed:21620138, PubMed:21483450, PubMed:22797300, PubMed:20978507, PubMed:21575608). 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 (PubMed:11595184, PubMed:12181324). 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:12181324). Also hydroxylates HIF2A (PubMed:11595184, PubMed:12181324). Has a preference for the CODD site for both HIF1A and HIF2A (PubMed:11595184, PubMed:12181324). Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site (PubMed:11595184, PubMed:12181324). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:11595184, PubMed:12181324). 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:12181324). ELGN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis (PubMed:21620138, PubMed:21483450). Under normoxia, hydroxylates and regulates the stability of ADRB2 (PubMed:19584355). Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex (PubMed:20849813). In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity (PubMed:16098468). Also essential for hypoxic regulation of neutrophilic inflammation (PubMed:21317538). Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway (PubMed:22797300). Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4 (Probable).

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ EGLN3up-regulates quantity by stabilization img/direct-activation.png hydroxylation ADRB2 0.323
Publications: 2 Organism: Homo Sapiens
+ EGLN3up-regulates activity img/direct-activation.png hydroxylation PKM 0.447
Publications: 2 Organism: Homo Sapiens
+ EGLN3up-regulates quantity by stabilization img/direct-activation.png hydroxylation BCL2L11 (isoform 1) 0.257
Publications: 2 Organism: Homo Sapiens
+ EGLN3up-regulates activity img/direct-activation.png hydroxylation PK 0.447
Publications: 3 Organism: Homo Sapiens
+ dimethyloxalylglycinedown-regulates activity img/direct_inhibition.png chemical inhibition EGLN3 0.8
Publications: 1 Organism: Homo Sapiens
+ Hypoxiadown-regulates img/indirect_inhibition.png EGLN3 0.7
Publications: 1 Organism: Homo Sapiens
+ EGLN3down-regulates quantity by destabilization img/direct_inhibition.png hydroxylation HIF1A 0.79
Publications: 1 Organism: Homo Sapiens
+ EGLN3down-regulates activity img/direct_inhibition.png binding IKBKG 0.331
Publications: 1 Organism: Homo Sapiens