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FLASH GENE
Symbol EGLN1 contributors: mct - updated : 15-05-2014
HGNC name egl nine homolog 1 (C. elegans)
HGNC id 1232
Corresponding disease
ECYT3 erythrocytosis/polycythemia, familial, 3
Location 1q42.2      Physical location : 231.499.496 - 231.560.790
Synonym name
  • chromosome 1 open reading frame 12
  • HIF prolyl hydroxylase 2
  • prolyl hydroxylase domain-containing protein 2
  • hypoxia-inducible factor prolyl hydroxylase 2
  • zinc finger MYND domain-containing protein 6
    • Synonym symbol(s) HIFPH2, C1orf12, PHD2, SM20, ZMYND6, DKFZp761F179, ECYT3, HPH2
    EC.number 1.14.11.29
    DNA
    TYPE functioning gene
    STRUCTURE 61.29 kb     5 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    regionally located 400 kb centromeric to the t(1;11)(q42.1;q14.3) translocation
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 7102 46 426 - 2001 11574160
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
    Visualeyeretina   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Muscularsmooth   
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • contained a region as essential for nuclear export in their N-terminal region
  • a zinc finger MYND type
  • a PKHD (prolyl/lysyl hydroxylase) domain
  • a catalytic domain with potential to react with nitric oxide both at its Fe(II) and at cysteine residues
    • HOMOLOGY
    interspecies ortholog to C.elegans egl9
    homolog to murine Egln1
    Homologene
    FAMILY
  • 2OG-Fe(II) oxygenase superfamily
    • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text able to shuttle between the cytoplasm and the nucleus
    basic FUNCTION
  • catalyzing the posttranslational formation of 4- hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins
  • regulator of hypoxia-inducible factor HIF alpha 1 subunit by prolylhydroxylation and targeting it to proteasome degradation
  • important mediator of neurotrophin withdrawal- mediated cell death
  • contributing in a non-redundant manner to the regulation of both HIF-1alpha and HIF-2alpha subunits
  • its regulation is an effective pathway for the control of the hypoxic response
  • enzyme mostly responsible for oxygen-induced degradation of HIF-A proteins
  • may function as a tumor suppressor gene in pancreatic cancer
  • serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage
  • regulates arteriogenesis and artery homeostasis by controlling a specific differentiation state in macrophages
  • oxygen/redox-sensitive enzyme that induces cellular adaptations to stress conditions
  • plays a pivotal role in the HIF pathway and has emerged as one of the most intriguing genes with respect to physiology at HA (high altitude)
  • EGLN3 with EGLN1, EGLN2 are cellular oxygen sensors that can mark HIF1A for von Hippel-Lindau protein-mediated proteasomal destruction
    • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • iron and ascorbate
    • protein
  • HIF1A
  • ING4
  • interacting with FKBP8
  • can modulate the rate of ADRB2 internalization through interactions with ARRB2
  • ATF4 is a protein interacting with EGLN2 as well as EGLN3, but not with EGLN1
  • regulation of ATP13A2 via EGLN1-HIF1A signaling is critical for cellular iron homeostasis
    • cell & other
    REGULATION
    inhibited by may be inhibited by ING4
    Other FKBP8-bound protein is constantly degraded whereas cytoplasmic EGLN1 is stable and able to function as an active prolyl-4-hydroxylase
    ASSOCIATED DISORDERS
    corresponding disease(s) ECYT3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   translocation    
    translocation t(1;11)(q42.1;q14.3) in major mental illness
    tumoral   LOH    
    suppressed tumor invasion, intravasation, and metastasis, but not affect tumor vessel density or lumen size, and normalized the endothelial lining and vessel maturation
    tumoral       loss of function
    in endothelial cells normalizes tumor vessels and enhances perfusion
    Susceptibility
    Variant & Polymorphism SNP
  • significant association between rs186996510 and hemoglobin levels in Tibetans, suggesting that EGLN1 contributes to the adaptively low hemoglobin level of Tibetans compared to acclimatized lowlanders at high altitude
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    inhibition of EGLN1 may offer alternative therapeutic opportunities for anticancer therapy
    cardiovascularatheroma 
    new treatment options for ischaemic disorders
    cancerendocrinepancreas
    potential target for the treatment of pancreatic cancer
    neurosensorialvisualdegenerative
    may be a promising therapeutic target to prevent oxygen-induced retinopathy
    ANIMAL & CELL MODELS
  • haplodeficient (Phd2(+/-) mice displayed preformed collateral arteries that preserved limb perfusion and prevented tissue necrosis in ischaemia