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FLASH GENE
Symbol EPOR contributors: mct - updated : 17-01-2018
HGNC name erythropoietin receptor
HGNC id 3416
Corresponding disease
ECYT1 erythrocytosis, familial, 1
Location 19p13.2      Physical location : 11.487.880 - 11.495.018
Synonym symbol(s) EPO-R, MGC138358
DNA
TYPE functioning gene
STRUCTURE 7.14 kb     8 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure
  • TAL1 binds to the EPOR promoter to activate EPOR expression , suggesting a potential link to elevated EPOR expression leading to hypersensitivity to erythropoietin and the resultant excessive erythrocytosis
  • MAPPING cloned Y linked Y status confirmed
    Map pter - D19S177 - D19S24 - LDLR LDLR - EPOR - cen - D19S7 - D19S49 - APOC2 APOC2 - qter
    Authors Sistonen (93)
    regionally located tightly linked to a full size LTR of human endogenous retroviruses HERV-K
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - - 27 - - 2010 20169072
  • soluble form of EPOR
  • higher serum sEPOR levels correlate with increased erythropoietin requirements
  • sEPOR levels may contribute to erythropoietin resistance in end stage renal disease, and its production may be mediated by pro-inflammatory cytokines
  • 8 - 2459 - 508 - 2011 21291419
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinner    Homo sapiens
    Nervousbrain     Homo sapiens
    Reproductivefemale systemuterus   
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningendometrium  
    Muscularstriatumcardiac   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticerythroid Homo sapiens
    Cardiovascularendothelial cell Homo sapiens
    Muscularmyocyte Homo sapiens
    Nervousneuron Homo sapiens
    Visualamacrine cell Homo sapiens
    VisualMuller cell Homo sapiens
    Visualrod photoreceptor Homo sapiens
    cell lineage
    cell lines erythroleukemia cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text liver
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • cytokine receptor like domains containing cysteine residues
  • a conserved WSXWS motif
  • a 160 AA sequence that is the minimal essential domain of EPOR for intracellular signaling of chemically inducible erythropoiesis
  • a cytoplasmic C terminal
  • four tyrosine phosphorylation sites involved in the EPO induced calcium influx negative regulatory domain
  • C-terminal EPOR region acts as a negative growth-regulatory domain affecting receptor processing and degradation
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY signaling cytokine , receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    intracellular,cytoplasm,cytosolic
    text
  • TFR2 and EPOR are synchronously coexpressed during the differentiation of erythroid progenitors
  • basic FUNCTION
  • may be playing a role in the mechanism of erythropoietin-induced erythroblast proliferation and differentiation
  • EPOR signaling regulates both erythropoiesis and megakaryopoiesis
  • crucial role for EPOR in glioma stem cells maintenance
  • on glioma stem cells promotes tumor growth and may explain the poor survival of cancer patients treated with EPO
  • its activation by nitric oxide mediates hypoxia preconditioning
  • drives survival, proliferation and differentiation of erythroid progenitor cells via binding of its ligand EPO
  • EPOR cytosolic lysine residues enhance receptor function, most probably through ubiquitination and/or other post-translational modifications
  • vascular EPO/EPOR system plays an important protective role against hypoxia/ischemia
  • EPOR expression is modulated during lymphocyte activation, which may be important for the cells function
  • EPOR can mediate neuroreparative effects
  • EPOR and/or JAK2 deliver signals crucial to EPO-dependent proliferation, differentiation, and cell survival
  • expression of soluble EPOR in the retina may modulate endogenous EPO-EPOR signaling
  • EPOR-deficient macrophages exhibited impaired apoptotic cell phagocytosis
  • several biological roles for erythropoietin and its receptor (EPO and EPOR), unrelated to erythropoiesis, including angiogenesis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • JAK2 and STAT5, STAT3, STAT1 binding (for activation)
  • TFR2 is a component of the EPOR complex
  • GATA4 is novel regulator of EPOR transcription in cardiomyocytes
  • EPO binds to EPOR, initiating signaling that stimulates growth, inhibits apoptosis, and induces the differentiation of erythroid progenitors to increase red blood cell mass
  • interaction between SH2B1 and EPOR (SH2B1 becomes phosphorylated in response to EPO and acts as a negative regulator of signaling downstream of the EPOR)
  • forced TAL1 expression increases EPOR and erythropoietin hypersensitivity in erythroid progenitors
  • TAL1 can recruit GATA1 and increase GATA1 binding to the EPOR promoter region to stimulate gene expression
  • SP1 may significantly affect the number of EPOR molecules present on the surface of activated CD4(+) lymphocytes
  • EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR
  • CBL ubiquitination of PIK3R1 is essential for EPO-induced EPOR endocytosis
  • VEGFA activates EPOR and enhances VEGFR2-mediated pathological angiogenesis
  • EPO binds to the EPOR homodimer on the surface of erythroid progenitors and erythroblasts, and positions the intracellular domains of the homodimer to be in close proximity with each other
  • CSF2RB colocalized and interacted with EPO receptor (EPOR) in macrophages
  • EPO had enhanced carcinogenesis through increase of EPOR and FLT1 expression, and thereby contributed to tumor development
  • EPOR regulates development of blood cells, and its full activation normally requires the cytokine erythropoietin EPO
  • EPO mediates its erythropoietic function through a homodimeric EPO receptor (EPOR) that is also widely expressed in the nervous system
  • cell & other
    REGULATION
    activated by hypoxia
    inhibited by inhibited by SOCS3 binding
    ASSOCIATED DISORDERS
    corresponding disease(s) ECYT1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    activated cell proliferation pathways in melanoma cells and resulted in increased cell proliferation and resistance to hypoxia and cisplatin treatment
    Susceptibility
    Variant & Polymorphism
    Candidate gene unlikely involved in Diamond-Blackfan anemia
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquired 
    EPO/EPOR is a novel therapeutic target in cardiovascular disease
    ANIMAL & CELL MODELS
  • macrophage-specific Epor(-/-) mice developed lupus-like symptoms, and interference in EPO signaling ameliorated the disease progression in lupus-like mice