Prolyl hydroxylase EGLN3 is an oxygen-sensing enzyme that catalyzes the hydroxylation of proline residues in target proteins, including PKM, TELO2, ATF4, and HIF1A. It preferentially recognizes substrates with an LXXLAP motif. Under normoxic conditions, EGLN3 hydroxylates specific prolines in the oxygen-dependent degradation (ODD) domains (NODD and CODD) of hypoxia-inducible factors (HIFs), particularly HIF1A and HIF2A, with a preference for the CODD site. Hydroxylation facilitates HIF ubiquitination by the von Hippel-Lindau (VHL) complex, leading to proteasomal degradation.
In hypoxia, EGLN3 activity is reduced, allowing HIF stabilization, nuclear translocation, and activation of hypoxia-responsive genes. EGLN3 is essential for regulating HIF activity, particularly HIF2A, and hydroxylates PKM under hypoxic conditions to limit glycolysis. Under normoxia, it regulates the stability of ADRB2 through hydroxylation.
EGLN3 also plays roles in apoptosis and inflammation. In cardiomyocytes, it disrupts the BAX-BCL2 complex, inhibiting BCL2’s anti-apoptotic function, while in neurons, it promotes apoptosis via NGF signaling and potential CASP3 regulation. It is crucial in hypoxic regulation of neutrophilic inflammation and DNA damage response (DDR) by hydroxylating TELO2, enabling ATR activation and downstream ATR/CHK1/p53 signaling. EGLN3 also hydroxylates ATF4, reducing its stability, further influencing cellular stress responses. Its diverse functions highlight its critical role in cellular homeostasis and adaptation to stress.
| Product Name | Recombinant Human PHD3 Protein |
| Accession | Q9H6Z9 |
| Host Species | Human |
| Gene | EGLN3 |
| Source | E.coli |
