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FLASH GENE
Symbol EGLN3 contributors: mct - updated : 27-09-2023
HGNC name egl nine homolog 3 (C. elegans)
HGNC id 14661
Location 14q13.1      Physical location : 34.393.422 - 34.420.284
Synonym name
  • hypoxia-inducible factor prolyl hydroxylase 3
  • HIF-prolyl hydroxylase 3
  • egl nine-like protein 3 isoform
  • prolyl hydroxylase domain-containing protein 3
  • hydroxylase 3
  • Synonym symbol(s) PHD3, HIFPH3, FLJ21620, MGC125998, MGC125999, HPH-1
    EC.number 1.14.11.29
    DNA
    TYPE functioning gene
    STRUCTURE 26.86 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text other, rare, alternatively spliced transcripts with/without intron retention
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2722 - 239 - 2009 19339211
    - - 1710 - 239 - 2009 19339211
    5 - 2424 - 145 - 2009 19339211
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinelarge intestinecolon  
    Reproductivefemale systemovary  highly
     female systemplacenta  highly
     female systemuterus  highly
    Urinarybladder    
    Visualeyeuvea   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective    
    Epithelial    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal zinc finger domain, MYND-type
  • PKHD (prolyl/lysyl hydroxylase) domain
  • HOMOLOGY
    interspecies ortholog to C.elegans egl9
    ortholog to rattus sm_20
    Homologene
    FAMILY
  • 2OG-Fe(II) oxygenase superfamily
  • EGLN family of prolyl hydroxylases
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • acting as a regulator of hypoxia-inducible factor HIF, alpha-1 subunit by prolylhydroxylation and targeting it to proteasome degradation
  • playing a role during the differentiation (when is overexpressed)
  • contributing in a non-redundant manner to the regulation of both HIF-1alpha and HIF-2alpha subunits
  • catalyzing hydroxylation of the alpha subunit of hypoxia-inducible factor-alpha
  • stabilizing myogenin protein
  • playing a role in regulating skeletal muscle differentiation
  • central regulator of the molecular responses to oxygen availability (Rantanen 2008)
  • expressed in response to hypoxia and causes apoptosis in oxygenated conditions in neural cells (Rantanen 2008)
  • may hydroxylate divergent substrates and/or connect divergent cellular responses with HIF (Hopfer 2006)
  • plays an important role in neuronal apoptosis (Schlisio 2008)
  • negative regulator of NFKappaB, potentiating myogenic differentiation (Fu 2010)
  • EGLN2, EGLN3 control the transactivation activity of ATF4
  • is a critical determinant of glioma formation and tumor vascular functionality
  • with EGLN1, EGLN2 are cellular oxygen sensors that can mark HIF1A for von Hippel-Lindau protein-mediated proteasomal destruction
  • under normoxia, has been shown to be proapoptotic, but under hypoxia, it can have cell survival or proliferation-supporting functions
  • negative regulator of the NFKB pathway
  • negatively regulates the canonical NFKB1 pathway
  • important role for EGLN1, EGLN3 as mediators of islet insulin secretion
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    text oxygen homeostasis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • iron and ascorbate
  • protein
  • HIG1A
  • interacting with myogenin protein
  • intreacting with MORG1 (decreased by Morg1 and reduced to basal levels when MORG1 is co-expressed with EGLN3 (Hopfer 2006)
  • PRPF19 interacts with prolyl-hydroxylase EGLN3 and inhibits cell death in hypoxia
  • ATF4 is a protein interacting with EGLN2 as well as EGLN3, but not with EGLN1
  • SQSTM1 is a critical regulator of the hypoxia response and EGLN3 activity, by inducing EGLN3 aggregation and degradation under normoxia
  • interacts with and inhibits K63-linked ubiquitination of IKBKG (interaction with IKBKG is required for the ability of EGLN3 to inhibit IKBKG ubiquitination and IKK-NFKB signaling)
  • regulates EGFR internalization and signalling in tumours
  • EGLN3 interferes with the association between RIPK1 and BIRC2, and attenuates RIPK1-induced NFKB1 activation
  • TP53 is a EGLN33 substrate and hydroxylation by PHD3 regulates TP53 protein stability through modulation of ubiquitination
  • positive correlation of EGLN3 and EPAS1 mRNA expression in clear cell renal cell carcinomas (ccRCCs)
  • prolyl hydroxylase activity of EGLN3 is dispensable for its ability to stabilize TP53
  • EGLN3 catalyzes the hydroxylation of extracellular signal-regulated kinase 3 (ERK3), a potent driver of cancers
  • TFAM is hydroxylated by EGLN3 and subsequently bound by VHL, which stabilizes TFAM by preventing mitochondrial proteolysis
  • cell & other
    REGULATION
    activated by in cardiovascular cells following exposure to hypoxia
    Other regulated by SIAH2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in melanoma
    tumoral     --over  
    associated with early tumor stage and well differentiation in non-small cell lung cancer.
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    manipulating EGLN3 activity holds promise for cancer treatment
    ANIMAL & CELL MODELS
  • macrophages from PHD3-/- mice showed, however, a dampened inflammatory reaction in the affected skeletal muscle tissues compared to WT controls