Browse EGLN3

Summary
SymbolEGLN3
Nameegl-9 family hypoxia-inducible factor 3
Aliases PHD3; HIFPH3; HIF prolyl hydroxylase 3; EGL nine (C.elegans) homolog 3; egl nine homolog 3 (C. elegans); HIF ......
Chromosomal Location14q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Nucleus. Cytoplasm. Note=Colocalizes with WDR83 in the cytoplasm.
Domain PF13640 2OG-Fe(II) oxygenase superfamily
Function

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.

> Gene Ontology
 
Biological Process GO:0001666 response to hypoxia
GO:0006575 cellular modified amino acid metabolic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0010950 positive regulation of endopeptidase activity
GO:0010952 positive regulation of peptidase activity
GO:0018126 protein hydroxylation
GO:0018208 peptidyl-proline modification
GO:0018401 peptidyl-proline hydroxylation to 4-hydroxy-L-proline
GO:0019471 4-hydroxyproline metabolic process
GO:0019511 peptidyl-proline hydroxylation
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043523 regulation of neuron apoptotic process
GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress
GO:0043620 regulation of DNA-templated transcription in response to stress
GO:0045862 positive regulation of proteolysis
GO:0051402 neuron apoptotic process
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0070482 response to oxygen levels
GO:0070997 neuron death
GO:0071453 cellular response to oxygen levels
GO:0071456 cellular response to hypoxia
GO:1901214 regulation of neuron death
GO:1901605 alpha-amino acid metabolic process
GO:2000116 regulation of cysteine-type endopeptidase activity
GO:2001056 positive regulation of cysteine-type endopeptidase activity
Molecular Function GO:0005506 iron ion binding
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
GO:0016706 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors
GO:0019842 vitamin binding
GO:0031406 carboxylic acid binding
GO:0031418 L-ascorbic acid binding
GO:0031543 peptidyl-proline dioxygenase activity
GO:0031545 peptidyl-proline 4-dioxygenase activity
GO:0043168 anion binding
GO:0051213 dioxygenase activity
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04066 HIF-1 signaling pathway
Reactome R-HSA-2262749: Cellular response to hypoxia
R-HSA-2262752: Cellular responses to stress
R-HSA-1234176: Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1234174: Regulation of Hypoxia-inducible Factor (HIF) by oxygen
Summary
SymbolEGLN3
Nameegl-9 family hypoxia-inducible factor 3
Aliases PHD3; HIFPH3; HIF prolyl hydroxylase 3; EGL nine (C.elegans) homolog 3; egl nine homolog 3 (C. elegans); HIF ......
Chromosomal Location14q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between EGLN3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between EGLN3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
18980986Renal Cell CarcinomaPromote immunityHIFPH3 was overexpressed in many RCC cell lines and primary RCC tissues, whereas it was not detectable in normal adult tissues by reverse transcription-PCR. Furthermore, HIFPH3-8 peptide-specific CTLs showed cytotoxicity against HIFPH3(+) RCC cell lines in a HLA-A24-restricted manner. HIFPH3 may be a target antigen in immunotherapy for RCC and HIFPH3-8 peptide could be used as a peptide vaccine for HLA-A*2402(+)/HIFPH3(+) RCC patients.
Summary
SymbolEGLN3
Nameegl-9 family hypoxia-inducible factor 3
Aliases PHD3; HIFPH3; HIF prolyl hydroxylase 3; EGL nine (C.elegans) homolog 3; egl nine homolog 3 (C. elegans); HIF ......
Chromosomal Location14q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of EGLN3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolEGLN3
Nameegl-9 family hypoxia-inducible factor 3
Aliases PHD3; HIFPH3; HIF prolyl hydroxylase 3; EGL nine (C.elegans) homolog 3; egl nine homolog 3 (C. elegans); HIF ......
Chromosomal Location14q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of EGLN3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1370.76
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.0130.396
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.5020.591
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0270.958
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.510.77
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.5880.778
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.1630.714
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.690.541
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-1.0920.369
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.0910.968
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4920.885
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0870.681
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of EGLN3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277304.1-4.10.561
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275905.1-5.10.549
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolEGLN3
Nameegl-9 family hypoxia-inducible factor 3
Aliases PHD3; HIFPH3; HIF prolyl hydroxylase 3; EGL nine (C.elegans) homolog 3; egl nine homolog 3 (C. elegans); HIF ......
Chromosomal Location14q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of EGLN3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolEGLN3
Nameegl-9 family hypoxia-inducible factor 3
Aliases PHD3; HIFPH3; HIF prolyl hydroxylase 3; EGL nine (C.elegans) homolog 3; egl nine homolog 3 (C. elegans); HIF ......
Chromosomal Location14q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of EGLN3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by EGLN3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolEGLN3
Nameegl-9 family hypoxia-inducible factor 3
Aliases PHD3; HIFPH3; HIF prolyl hydroxylase 3; EGL nine (C.elegans) homolog 3; egl nine homolog 3 (C. elegans); HIF ......
Chromosomal Location14q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of EGLN3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolEGLN3
Nameegl-9 family hypoxia-inducible factor 3
Aliases PHD3; HIFPH3; HIF prolyl hydroxylase 3; EGL nine (C.elegans) homolog 3; egl nine homolog 3 (C. elegans); HIF ......
Chromosomal Location14q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of EGLN3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolEGLN3
Nameegl-9 family hypoxia-inducible factor 3
Aliases PHD3; HIFPH3; HIF prolyl hydroxylase 3; EGL nine (C.elegans) homolog 3; egl nine homolog 3 (C. elegans); HIF ......
Chromosomal Location14q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between EGLN3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolEGLN3
Nameegl-9 family hypoxia-inducible factor 3
Aliases PHD3; HIFPH3; HIF prolyl hydroxylase 3; EGL nine (C.elegans) homolog 3; egl nine homolog 3 (C. elegans); HIF ......
Chromosomal Location14q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting EGLN3 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting EGLN3.
ID Name Drug Type Targets #Targets
DB00126Vitamin CSmall MoleculeALKBH2, ALKBH3, BBOX1, DBH, EGLN1, EGLN2, EGLN3, KDM5D, LCT, OGFOD ......23
DB04847RoxadustatSmall MoleculeEGLN1, EGLN2, EGLN33