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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
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