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Symbol EPAS1 contributors: mct/npt/pgu - updated : 08-09-2014
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
    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
    Physical map
    D2LIC 2p25.1-p24.1 dynein 2 light intermediate chain ABCG5 2p21 ATP-binding cassette, sub-family G (WHITE), member 5 (sterolin 1) ABCG8 2p21 ATP-binding cassette, sub-family G (WHITE), member 8 (sterolin 2) LRPPRC 2p21 leucine-rich PPR-motif containing PPM1B 2p22,1 protein phosphatase 1B (formerly 2C), magnesium-dependent, beta isoform LOC391371 2 similar to 60S RIBOSOMAL PROTEIN L12 SLC3A1 2p16.3 solute carrier family 3 (cystine, dibasic and neutral amino acid transporters, activator of cystine, dibasic and neutral amino acid transport), member 1 FLJ23451 2p22.1 hypothetical protein FLJ23451 SIX3 2p21-p16 sine oculis homeobox homolog 3 (Drosophila) LOC388944 2 LOC388944 SIX2 2p16-p15 sine oculis homeobox homolog 2 (Drosophila) LOC151111 2p21 hypothetical LOC151111 FLJ10379 2p21 hypothetical protein FLJ10379 PRKCE 2p21 protein kinase C, epsilon EPAS1 2p21-p26 endothelial PAS domain protein 1 LOC388945 2 LOC388945 LOC388946 2 LOC388946 ATP6V1E2 2p21 ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E isoform 2 ARHQ 2p21 ras homolog gene family, member Q PIGF 2p16 phosphatidylinositol glycan, class F CRIPT 2p21 phosphatidylinositol glycan, class F LOC388947 2 LOC388947 SOCS5 2p21 suppressor of cytokine signaling 5 LOC388948 2 hypothetical gene supported by BC062774 MCFD2 TTC7 2p21 tetratricopeptide repeat domain 7 FLJ40172 2p21 hypothetical protein FLJ40172 CALM2 2p21.3-p21.1 calmodulin 2 (phosphorylase kinase, delta) TACSTD1 2p21 tumor-associated calcium signal transducer 1 MSH2 2p22-p21 mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) KCNK12 2p22-p21 potassium channel, subfamily K, member 12 LOC285053 2p21 similar to ribosomal protein L18a; 60S ribosomal protein L18a LOC391372 2 similar to Nucleoside diphosphate kinase B (NDK B) (NDP kinase B) (P18) MSH6 2p16 mutS homolog 6 (E. coli) FBXO11 2p21-p16 F-box only protein 11 HTLF 2p21 human T-cell leukemia virus enhancer factor LOC129285 2p21 smooth muscle myosin heavy chain 11 isoform SM1-like SALF 2p16.3 smooth muscle myosin heavy chain 11 isoform SM1-like SBLF 2p16.3 stoned B-like factor ALF 2p16.3 stoned B-like factor LHCGR 2p21 luteinizing hormone/choriogonadotropin receptor
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 5184 96.3 870 - 2000 10823831
    Type widely
       expressed in (based on citations)
    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
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, pregnancy
    Text endothelial cells, placenta
  • two PAS (per-arnt-sim) dimerization domains
  • C-terminal PAS domains form heterodimer with ARNT subunits of the HIF2 transcription factor
    intraspecies homolog to HIF1A
  • basic helix-loop-helix (BHLH) family of transcription factors
  • CATEGORY RNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    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
    text vascular remodeling
    metabolism aminoacid
    catecholamine homeostasis
    a component
    small molecule
  • 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
  • cell & other
    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
    corresponding disease(s) ECYT4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in renal cell carcinoma
  • 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
    Therapy target new and promising therapeutic target for cartilage repair
    new and promising therapeutic target for cartilage repair