Recombinant Human Egl nine homolog 3 (EGLN3)

Uniprot Id

Q9H6Z9

Target Species

Human

Target Name

EGLN3

Target Full Name

Prolyl hydroxylase EGLN3

Target Function

Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as PKM, TELO2, ATF4 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. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. 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. ELGN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. 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. Also mediates hydroxylation of ATF4, leading to decreased protein stability of ATF4.

Target Subcellular Location

Nucleus. Cytoplasm.

Target Tissue Specificity

Widely expressed at low levels. Expressed at higher levels in adult heart (cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle), lung and placenta, and in fetal spleen, heart and skeletal muscle. Also expressed in pancreas. Locali

Target Research Area

Cancer

Target Synonyms

Egl 9 family hypoxia inducible factor 3; Egl nine homolog 3 (C. elegans); Egl nine homolog 3; Egl nine like protein 3 isoform; EGL9 homolog of C. elegans 3; EGLN3; EGLN3_HUMAN; Factor responsive smooth muscle protein; HIF Prolyl Hydroxylase 3; HIF-PH3; HIF-prolyl hydroxylase 3; HIFP4H3; HIFPH3; HPH-1; HPH-3; Hypoxia-inducible factor prolyl hydroxylase 3; P4H3; PHD3; Prolyl Hydroxylase Domain Containing Protein 3; Prolyl hydroxylase domain-containing protein 3; SM20

Target Background

Enables peptidyl-proline 4-dioxygenase activity. Involved in several processes, including activation of cysteine-type endopeptidase activity involved in apoptotic process; peptidyl-proline hydroxylation to 4-hydroxy-L-proline; and response to hypoxia. Located in cytosol and nucleus. Implicated in renal cell carcinoma. Biomarker of clear cell renal cell carcinoma.