EGLN3 [The Human Chemical-Genetic Interaction Map Project]

This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong.
======= EGLN3 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: EGLN3
  * **<color #00a2e8>Official Name</color>**: egl-9 family hypoxia inducible factor 3
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=112399|112399]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9H6Z9|Q9H6Z9]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=EGLN3&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20EGLN3|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/606426|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|2OG-FeII Oxy|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|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|
|carboxylic acid metabolic process|
|apoptotic process|
|oxidation-reduction process|
|oxoacid metabolic process|
|organic acid metabolic process|
|programmed cell death|
|cell death|
|response to abiotic stimulus|
|regulation of hydrolase activity|
|positive regulation of catalytic activity|
|regulation of apoptotic process|
|regulation of programmed cell death|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|regulation of cell death|
|cellular response to stress|
|positive regulation of protein metabolic process|
|small molecule metabolic process|
|positive regulation of molecular function|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp218|A-395 10μM R05 exp218]]|1.71|
|[[:results:exp449|Arsenic trioxide 60μM R08 exp449]]|1.9|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 6476
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -0.64 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='EGLN3 Expression in NALM6 Cells: -0.64'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>