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FLASH GENE
Symbol EPAS1 contributors: mct/npt/pgu - updated : 08-09-2018
HGNC name endothelial PAS domain protein 1
HGNC id 3374
Corresponding disease
ECYT4 erythrocytosis/polycythemia, familial, 4
Location 2p21      Physical location : 46.524.540 - 46.613.842
Synonym name
  • hypoxia inducible factor 2 alpha subunit
  • HIF-1 alpha-like factor
  • HIF2 alpha
    • Synonym symbol(s) MOP2, HIF2A, PASD2, HLF, bHLHe73, EPAS-1
    DNA
    TYPE functioning gene
    STRUCTURE 89.30 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 5184 96.3 870 - 2000 10823831
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Digestiveintestinesmall intestine    Homo sapiens
    Respiratorylung   highly Homo sapiens
     respiratory tracttrachea  highly
    Urinarykidney     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/lining   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text endothelial cells, placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two PAS (per-arnt-sim) dimerization domains
  • C-terminal PAS domains form heterodimer with ARNT subunits of the HIF2 transcription factor
    • HOMOLOGY
    intraspecies homolog to HIF1A
    Homologene
    FAMILY
  • basic helix-loop-helix (BHLH) family of transcription factors
    • CATEGORY RNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • involved in the induction of oxygen regulated genes and may be implicated in the development of blood vessels and the tubular system of lung
  • playing a role in the adaptation of the cardiac myocytes during heart failure as well as in the regulation of gene expression by hypoxia
  • involved in complex oxygen sensing, and influencing the relative contribution of aerobic and anaerobic metabolism and hence the maximum sustainable metabolic power for a given event duration
  • differentially binds and regulates transcription under hypoxia
  • EPAS1 acts downstream of PPARGC1A as a key regulator of a muscle fiber-type program and the adaptive response to exercise
  • regulated CD82 gene expression by binding to its HRE consensus sequence located within its first intron
  • is required to induce CD82 expression under hypoxia
  • HIF1A and EPAS1 play a critical role in cellular response to hypoxia
  • important role in the regulation of tumor progression under chronic hypoxia
  • opposite roles of HIF1A and EPAS1 in the regulation of IL8 expression in endothelial cells
  • key regulator in alveolar maturation and the production of phospholipids by Type II cells
  • role for the EPAS1/ITPR1 axis in regulating Clear cell renal carcinomas cell survival
    • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text vascular remodeling
    PATHWAY
    metabolism aminoacid
    signaling
    catecholamine homeostasis
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with SOX9 (hypoxia, and more specifically EPAS1, promotes both SOX9-dependent and -independent factors important for cartilage homeostasis)
  • interacting with RICTOR (dependent only on the CRTC2 constituent Rictor)
  • regulating intronic hypoxia response elements of TWIST1
  • VHL appears to specifically repress EPAS1 in renal epithelia
  • EPAS1, but not HIF1A, interacted with KLHL20
  • KLHL20 as a EPAS1-interacting protein that increases the expression level of EPAS1 protein
  • potent and functional inducer of CEBPB expression in chondrocytes by the CEBPB promoter assay
  • critical role for CDCP1 as a unique EPAS1 target gene involved in the regulation of cancer metastasis
  • FOXO4 interacts with SREBF2 and EPAS1 to modulate CYP51A1 promoter activity
  • EPAS1 plays an indispensible role in SP1 transcription factor-mediated ZBTB7A induction, and participated in tumor cell survival and proliferation
  • positive correlation of EGLN3 and EPAS1 mRNA expression in clear cell renal cell carcinomas (ccRCCs)
  • TSGA10 could bind EPAS1
    • cell & other
    REGULATION
    activated by hypoxia
    KLHL20, that increases EPAS1 activity through a VHL-independent pathway
    induced by IL-1beta at the transcriptional level
    Other regulated via SUMOylation, reducing its transcriptional activity
    regulated by VHL (regulate HIF-alpha proteolysis by acting as the recognition component of a ubiquitin ligase complex)
    VHL and RNF4 control the levels of sumoylated EPAS1
    ASSOCIATED DISORDERS
    corresponding disease(s) ECYT4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in renal cell carcinoma
    Susceptibility
  • to the endurance phenotype in elite endurance athletes
  • to the development of retinopathy of prematurity (ROP)
    • Variant & Polymorphism SNP
  • influencing the relative contribution of aerobic and anaerobic metabolism and hence the maximum sustainable metabolic power for a given event duration
  • association between SNPs in the EPAS1 gene and the development of ROP
    • Candidate gene
    Marker
    Therapy target new and promising therapeutic target for cartilage repair
    SystemTypeDisorderPubmed
    osteoarticular  
    new and promising therapeutic target for cartilage repair
    ANIMAL & CELL MODELS