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Aliases for EGLN3 Gene

Aliases for EGLN3 Gene

  • Egl-9 Family Hypoxia-Inducible Factor 3 2 3 5
  • Prolyl Hydroxylase Domain-Containing Protein 3 3 4
  • Hypoxia-Inducible Factor Prolyl Hydroxylase 3 3 4
  • HIF Prolyl Hydroxylase 3 2 3
  • HIF-Prolyl Hydroxylase 3 3 4
  • HIF-PH3 3 4
  • HPH-1 3 4
  • HPH-3 3 4
  • PHD3 3 4
  • Egl Nine Homolog 3 (C. Elegans) 2
  • Egl Nine-Like Protein 3 Isoform 3
  • EGL Nine (C.Elegans) Homolog 3 2
  • EC 1.14.11.29 4
  • EC 1.14.11 63
  • HIFP4H3 3
  • HIFPH3 3

External Ids for EGLN3 Gene

Previous GeneCards Identifiers for EGLN3 Gene

  • GC14M031770
  • GC14M028180
  • GC14M032383
  • GC14M033463
  • GC14M034393
  • GC14M014510

Summaries for EGLN3 Gene

GeneCards Summary for EGLN3 Gene

EGLN3 (Egl-9 Family Hypoxia-Inducible Factor 3) is a Protein Coding gene. Diseases associated with EGLN3 include Hypoxia and Renal Cell Carcinoma. Among its related pathways are Pathways in cancer and HIF Repressor Pathways. GO annotations related to this gene include oxidoreductase activity and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen. An important paralog of this gene is ENSG00000268797.

UniProtKB/Swiss-Prot for EGLN3 Gene

  • 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 Wiki entry for EGLN3 Gene

No data available for Entrez Gene Summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EGLN3 Gene

Genomics for EGLN3 Gene

Regulatory Elements for EGLN3 Gene

Enhancers for EGLN3 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around EGLN3 on UCSC Golden Path with GeneCards custom track

Promoters for EGLN3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around EGLN3 on UCSC Golden Path with GeneCards custom track

Genomic Location for EGLN3 Gene

Chromosome:
14
Start:
33,924,215 bp from pter
End:
34,462,774 bp from pter
Size:
538,560 bases
Orientation:
Minus strand

Genomic View for EGLN3 Gene

Genes around EGLN3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EGLN3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EGLN3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EGLN3 Gene

Proteins for EGLN3 Gene

  • Protein details for EGLN3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9H6Z9-EGLN3_HUMAN
    Recommended name:
    Egl nine homolog 3
    Protein Accession:
    Q9H6Z9
    Secondary Accessions:
    • Q2TA79
    • Q3B8N4
    • Q6P1R2

    Protein attributes for EGLN3 Gene

    Size:
    239 amino acids
    Molecular mass:
    27261 Da
    Cofactor:
    Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
    Cofactor:
    Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
    Quaternary structure:
    • Interacts with WDR83; the interaction leads to almost complete elimination of HIF-mediated reporter activity (By similarity). Interacts with BCL2 (via its BH4 domain); the interaction disrupts the BAX-BCL4 complex inhibiting the anti-apoptotic activity of BCL2. Interacts with ADRB2; the interaction hydroxylates ADRB2 facilitating its ubiquitination by the VHL-E3 ligase complex. Interacts with PAX2; the interaction targets PAX2 for destruction. Interacts with PKM; the interaction hydroxylates PKM in hypoxia.

neXtProt entry for EGLN3 Gene

Proteomics data for EGLN3 Gene at MOPED

Selected DME Specific Peptides for EGLN3 Gene

Post-translational modifications for EGLN3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for EGLN3 Gene

Antibody Products

  • Abcam antibodies for PHD3

Domains & Families for EGLN3 Gene

Protein Domains for EGLN3 Gene

Suggested Antigen Peptide Sequences for EGLN3 Gene

Graphical View of Domain Structure for InterPro Entry

Q9H6Z9

UniProtKB/Swiss-Prot:

EGLN3_HUMAN :
  • The Beta(2)beta(3) finger-like loop domain is important for substrate (HIFs CODD/NODD) selectivity.
Domain:
  • The Beta(2)beta(3) finger-like loop domain is important for substrate (HIFs CODD/NODD) selectivity.
  • Contains 1 Fe2OG dioxygenase domain.
genes like me logo Genes that share domains with EGLN3: view

No data available for Gene Families for EGLN3 Gene

Function for EGLN3 Gene

Molecular function for EGLN3 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Hypoxia-inducible factor-L-proline + 2-oxoglutarate + O(2) = hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO(2).
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated in cardiovascular cells and Hela cells following exposure to hypoxia. Inhibited by polynitrogen compounds probably by chelation to Fe(2+) ions.
UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction:
Induced by hypoxia in a number of cells including neutrophils and certain cancer cell lines. Up-regulated 10-fold in pancreatic cancers.

Enzyme Numbers (IUBMB) for EGLN3 Gene

Gene Ontology (GO) - Molecular Function for EGLN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen IEA --
genes like me logo Genes that share ontologies with EGLN3: view
genes like me logo Genes that share phenotypes with EGLN3: view

Animal Models for EGLN3 Gene

MGI Knock Outs for EGLN3:

Animal Model Products

  • Taconic Biosciences Mouse Models for EGLN3

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for EGLN3 Gene

Localization for EGLN3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EGLN3 Gene

Nucleus. Cytoplasm. Note=Colocalizes with WDR83 in the cytoplasm. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for EGLN3 Gene COMPARTMENTS Subcellular localization image for EGLN3 gene
Compartment Confidence
cytosol 5
nucleus 5
extracellular 2
mitochondrion 1

No data available for Gene Ontology (GO) - Cellular Components for EGLN3 Gene

Pathways & Interactions for EGLN3 Gene

genes like me logo Genes that share pathways with EGLN3: view

Gene Ontology (GO) - Biological Process for EGLN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEP 20978507
GO:0006915 apoptotic process IEP 20978507
GO:0018126 protein hydroxylation IDA 19584355
GO:0018401 peptidyl-proline hydroxylation to 4-hydroxy-L-proline IDA 11598268
GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia TAS --
genes like me logo Genes that share ontologies with EGLN3: view

No data available for SIGNOR curated interactions for EGLN3 Gene

Drugs & Compounds for EGLN3 Gene

(7) Drugs for EGLN3 Gene - From: DrugBank, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Vitamin C Approved Nutra Target 471,471
hydroxyproline Approved, Experimental Pharma 0
L-Proline Approved Nutra 0
Succinic acid Approved Nutra Full agonist, Agonist 0
FG-4592 Investigational Pharma inhibitor, Target 0

(4) Additional Compounds for EGLN3 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
oxygen
  • Dioxygen
  • Molecular oxygen
  • O2
  • Oxygen
  • Oxygen molecule
7782-44-7
Oxoglutaric acid
  • 2-Ketoglutarate
  • 2-Ketoglutaric acid
  • 2-Oxo-1,5-pentanedioate
  • 2-Oxo-1,5-pentanedioic acid
  • 2-Oxoglutarate
328-50-7
genes like me logo Genes that share compounds with EGLN3: view

Transcripts for EGLN3 Gene

Unigene Clusters for EGLN3 Gene

Egl nine homolog 3 (C. elegans):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for EGLN3 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b · 5c
SP1: -
SP2: - -
SP3:

Relevant External Links for EGLN3 Gene

GeneLoc Exon Structure for
EGLN3
ECgene alternative splicing isoforms for
EGLN3

Expression for EGLN3 Gene

mRNA expression in normal human tissues for EGLN3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for EGLN3 Gene

This gene is overexpressed in Heart - Left Ventricle (x6.6), Skin - Not Sun Exposed (Suprapubic) (x5.3), Skin - Sun Exposed (Lower leg) (x4.8), and Heart - Atrial Appendage (x4.4).

Protein differential expression in normal tissues from HIPED for EGLN3 Gene

This gene is overexpressed in Urinary Bladder (22.5), Heart (13.6), Gallbladder (10.9), Ovary (9.0), and Peripheral blood mononuclear cells (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for EGLN3 Gene



SOURCE GeneReport for Unigene cluster for EGLN3 Gene Hs.135507

mRNA Expression by UniProt/SwissProt for EGLN3 Gene

Q9H6Z9-EGLN3_HUMAN
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. Localized to pancreatic acini and islet cells.
genes like me logo Genes that share expression patterns with EGLN3: view

Protein tissue co-expression partners for EGLN3 Gene

Primer Products

Orthologs for EGLN3 Gene

This gene was present in the common ancestor of animals.

Orthologs for EGLN3 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia EGLN3 35
  • 92.61 (n)
  • 97.49 (a)
EGLN3 36
  • 97 (a)
OneToOne
dog
(Canis familiaris)
Mammalia EGLN3 35
  • 94.14 (n)
  • 99.16 (a)
EGLN3 36
  • 78 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Egln3 35
  • 91.91 (n)
  • 96.65 (a)
Egln3 16
Egln3 36
  • 97 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia EGLN3 35
  • 99.86 (n)
  • 100 (a)
EGLN3 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Egln3 35
  • 91.49 (n)
  • 96.65 (a)
oppossum
(Monodelphis domestica)
Mammalia EGLN3 36
  • 93 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia EGLN3 36
  • 90 (a)
OneToOne
chicken
(Gallus gallus)
Aves EGLN3 35
  • 82.71 (n)
  • 89.54 (a)
EGLN3 36
  • 88 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia EGLN3 36
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia egln3 35
  • 69.32 (n)
  • 72.8 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.16140 35
zebrafish
(Danio rerio)
Actinopterygii egln3 35
  • 66.22 (n)
  • 66.52 (a)
wufj78a08 35
egln3 36
  • 60 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8898 35
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003523 35
  • 59.97 (n)
  • 58.82 (a)
fruit fly
(Drosophila melanogaster)
Insecta Hph 36
  • 22 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea egl-9 36
  • 13 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 30 (a)
OneToMany
Species with no ortholog for EGLN3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for EGLN3 Gene

ENSEMBL:
Gene Tree for EGLN3 (if available)
TreeFam:
Gene Tree for EGLN3 (if available)

Paralogs for EGLN3 Gene

Paralogs for EGLN3 Gene

(2) SIMAP similar genes for EGLN3 Gene using alignment to 6 proteins:

Pseudogenes.org Pseudogenes for EGLN3 Gene

genes like me logo Genes that share paralogs with EGLN3: view

Variants for EGLN3 Gene

Sequence variations from dbSNP and Humsavar for EGLN3 Gene

SNP ID Clin Chr 14 pos Sequence Context AA Info Type
rs17102002 - 33,931,167(+) GTCCA(C/G)GTGGC reference, missense
rs17101995 - 33,925,911(+) GGCAG(A/T)TTCAG reference, missense
rs1384372 -- 33,945,516(-) CAGCC(C/T)TTAGT intron-variant
rs1384373 -- 33,925,271(-) ATTTT(C/T)TGCCT utr-variant-3-prime
rs1384374 -- 33,925,207(-) TTTTT(C/T)TCCAT utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for EGLN3 Gene

Variant ID Type Subtype PubMed ID
esv34070 CNV Loss 18971310
nsv832768 CNV Gain 17160897
nsv832769 CNV Loss 17160897

Variation tolerance for EGLN3 Gene

Residual Variation Intolerance Score: 24% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.88; 18.40% of all genes are more intolerant (likely to be disease-causing)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Relevant External Links for EGLN3 Gene

Disorders for EGLN3 Gene

MalaCards: The human disease database

(4) MalaCards diseases for EGLN3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
hypoxia
renal cell carcinoma
  • renal cell carcinoma, clear cell, somatic
chronic mountain sickness
phaeochromocytoma
  • pheochromocytoma
- elite association - COSMIC cancer census association via MalaCards
Search EGLN3 in MalaCards View complete list of genes associated with diseases

Relevant External Links for EGLN3

Genetic Association Database (GAD)
EGLN3
Human Genome Epidemiology (HuGE) Navigator
EGLN3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
EGLN3
genes like me logo Genes that share disorders with EGLN3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for EGLN3 Gene

Publications for EGLN3 Gene

  1. Differential regulation of HIF-1alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells. (PMID: 12670503) Cioffi C.L. … Bowen B.R. (Biochem. Biophys. Res. Commun. 2003) 3 4 23 67
  2. Prolyl hydroxylase-3 is down-regulated in colorectal cancer cells and inhibits IKKbeta independent of hydroxylase activity. (PMID: 19786027) Xue J. … Fang J. (Gastroenterology 2010) 3 23
  3. Prolyl hydroxylases 2 and 3 act in gliomas as protective negative feedback regulators of hypoxia-inducible factors. (PMID: 20028863) Henze A.T. … Acker T. (Cancer Res. 2010) 3 23
  4. Role of the intracellular localization of HIF-prolyl hydroxylases. (PMID: 19339211) Yasumoto K. … Sogawa K. (Biochim. Biophys. Acta 2009) 3 23
  5. Interferon-gamma induces prolyl hydroxylase (PHD)3 through a STAT1-dependent mechanism in human endothelial cells. (PMID: 19574556) Gerber S.A. … Pober J.S. (Arterioscler. Thromb. Vasc. Biol. 2009) 3 23

Products for EGLN3 Gene

Sources for EGLN3 Gene

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