EGLN3

Gene Information

Official Symbol: EGLN3
Official Name: egl-9 family hypoxia inducible factor 3
Aliases and Previous Symbols: N/A
Entrez ID: 112399
UniProt: Q9H6Z9
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: N/A
UniProt Summary: 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. EGLN3 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. Target proteins are preferentially recognized via a LXXLAP motif. {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:16098468, ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:20849813, ECO:0000269|PubMed:20978507, ECO:0000269|PubMed:21317538, ECO:0000269|PubMed:21483450, ECO:0000269|PubMed:21575608, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22797300}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Global Fraction of Cell Lines Where Essential: 1/726

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/25
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/15
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/14
ovary	0/26
pancreas	0/24
peripheral nervous system	1/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/7
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 6476
Expression level (log2 read counts): -0.64

Expression Distribution

Screen	Score
A-395 10μM R05 exp218	1.71
Arsenic trioxide 60μM R08 exp449	1.9

peptidyl-proline 4-dioxygenase activity
peptidyl-proline hydroxylation to 4-hydroxy-L-proline
peptidyl-proline hydroxylation
4-hydroxyproline metabolic process
2-oxoglutarate-dependent dioxygenase activity
L-ascorbic acid binding
protein hydroxylation
peptidyl-proline modification
regulation of transcription from RNA polymerase II promoter in response to hypoxia
activation of cysteine-type endopeptidase activity involved in apoptotic process
regulation of transcription from RNA polymerase II promoter in response to stress
regulation of DNA-templated transcription in response to stress
iron ion binding
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of cysteine-type endopeptidase activity
positive regulation of endopeptidase activity
cellular response to hypoxia
positive regulation of peptidase activity
cellular modified amino acid metabolic process
cellular response to decreased oxygen levels
regulation of neuron apoptotic process
alpha-amino acid metabolic process
cellular response to oxygen levels
regulation of cysteine-type endopeptidase activity involved in apoptotic process
regulation of cysteine-type endopeptidase activity
cellular amino acid metabolic process
regulation of neuron death
response to hypoxia
positive regulation of proteolysis
response to decreased oxygen levels
response to oxygen levels
regulation of endopeptidase activity
regulation of peptidase activity
positive regulation of apoptotic process
positive regulation of programmed cell death
positive regulation of cell death
regulation of proteolysis
positive regulation of hydrolase activity
cellular response to DNA damage stimulus
peptidyl-amino acid modification