EGLN1

Gene Information

Official Symbol: EGLN1
Official Name: egl-9 family hypoxia inducible factor 1
Aliases and Previous Symbols: N/A
Entrez ID: 54583
UniProt: Q9GZT9
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: The protein encoded by this gene catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. This protein functions as a cellular oxygen sensor, and under normal oxygen concentration, modification by prolyl hydroxylation is a key regulatory event that targets HIF subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Mutations in this gene are associated with erythrocytosis familial type 3 (ECYT3). [provided by RefSeq, Nov 2009].
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 HIF1B. 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. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif. {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:12351678, ECO:0000269|PubMed:15897452, ECO:0000269|PubMed:19339211, ECO:0000269|PubMed:21792862, ECO:0000269|PubMed:25129147}.

Pfam Domains GO Terms

CRISPR Data

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

Screen	Score
Dimethyloxaloylglycine 100μM R05 exp229	-3.32
Dimethyloxaloylglycine 11μM R07 exp314	-2.85
ABT-702 5μM plus Dimethyloxaloylglycine 11μM R07 exp319	-2.04
BAY-598 4μM R05 exp220	-1.95
Hypoxia 5%O2 R04 exp191	-1.84
39°C R06 exp303	-1.73
BI-D1870 2μM R04 exp162	-1.72
Hydroxyurea 15μM R06 exp289	-1.72
Salubrinal 20μM R07 exp399	1.74
Doxorubicin 0.02μM R08 exp478	2.11
QNZ 0.01μM R08 exp439	2.21

Global Fraction of Cell Lines Where Essential: 22/726

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

Essentiality in NALM6

Essentiality Rank: 9586
Expression level (log2 read counts): 5.62

Expression Distribution

Gene	Correlation
SCAF8	0.426
ATP5B	0.414
MAML1	0.408
PPP6C	0.406
ID3	0.404
VHL	0.4

zf-MYND
2OG-FeII Oxy

peptidyl-proline dioxygenase activity
peptidyl-proline 4-dioxygenase activity
negative regulation of cyclic-nucleotide phosphodiesterase activity
oxygen homeostasis
peptidyl-proline hydroxylation to 4-hydroxy-L-proline
regulation of cyclic-nucleotide phosphodiesterase activity
gas homeostasis
peptidyl-proline hydroxylation
4-hydroxyproline metabolic process
2-oxoglutarate-dependent dioxygenase activity
response to nitric oxide
L-ascorbic acid binding
protein hydroxylation
ferrous iron binding
response to bronchodilator
peptidyl-proline modification
regulation of transcription from RNA polymerase II promoter in response to hypoxia
regulation of transcription from RNA polymerase II promoter in response to stress
regulation of DNA-templated transcription in response to stress
negative regulation of DNA-binding transcription factor activity
cellular response to hypoxia
response to reactive oxygen species
cellular modified amino acid metabolic process
cellular response to decreased oxygen levels
alpha-amino acid metabolic process
cellular response to oxygen levels
regulation of angiogenesis
cellular amino acid metabolic process
regulation of vasculature development
response to hypoxia
enzyme binding
response to decreased oxygen levels
response to oxygen levels
response to oxidative stress
regulation of DNA-binding transcription factor activity
negative regulation of hydrolase activity
response to inorganic substance
negative regulation of catalytic activity
peptidyl-amino acid modification
carboxylic acid metabolic process