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FLASH GENE
Symbol EPO contributors: mct - updated : 27-04-2016
HGNC name erythropoietin
HGNC id 3415
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to rattus Epo (81.25 pc)
homolog to murine Epo (79.17 pc)
Homologene
FAMILY
  • mammalian peroxidase family (EPO/TPO family)
    • CATEGORY signaling cytokine , receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • activating a voltage independent calcium channel dependent on tyrosine phosphorylation
  • stimulating cellular differentiation of bone marrow cells at an early stage
  • angioneurin acting as a survival factor for neurons and their progenitors
  • modulating TRPC3 activation
  • IL3 and KITLG have synergistic effects with EPO on the proliferation, differentiation and apoptosis of erythroid progenitors
  • neuroprotective to the photoreceptors in the retinal degeneration
  • has a protective effect on auditory hair cells in the inner ear
  • potential role for EPO signaling in megakaryopoiesis
  • acts through the erythropoietin receptor (EPOR) present in erythroblasts
  • regulates the formation of bone by both direct and indirect pathway
  • brain EPO signaling can stimulate neural cell survival and prevent neuron apoptosis
  • required for erythroid progenitor differentiation
  • EPO and TFR2 are involved in production of GDF15 by erythroid cells
  • exerts protection either by preventing apoptosis of cardiac myocytes, smooth muscle cells, and endothelial cells, or by increasing endothelial production of nitric oxide
  • is the key hormone for erythropoiesis, and also increases nitric oxide (NO) bioavailability in endothelial cells (ECs)
  • may play an integrative role in the EPO signaling-mediated activation of endothelial NO synthase (eNOS) in endothelial cells (ECs)
  • cytokine with antiapoptotic activity and plays a potential neuroprotective and cardioprotective role against ischemia
  • biological effects of EPO on the pancreatic beta cells and potential protective role in diabetes
  • may stimulate angiogenesis and increase survival of melanoma cells under hypoxic condition
  • activates JAK/STAT signaling in hematopoietic stem cells , leading to the production of bone morphogenetic protein 2 (BMP2) and bone formation
  • hematopoietic hormone that acts exclusively in the proliferation and differentiation of erythroid progenitors
  • vascular EPO/EPOR system plays an important protective role against hypoxia/ischemia
  • acts on erythroblasts in the bone marrow (BM) to stimulate the formation of red blood cells
  • enhanced endothelial proliferation and the level of synaptophysin expression in the brain
  • EPOR and/or JAK2 deliver signals crucial to EPO-dependent proliferation, differentiation, and cell survival
  • could induce dysfunction of renal glomerulus through its influence on the function of mesangial cells
  • EPO is involved in both physiological and pathological angiogenesis in the retina
  • cytoprotective in several tissues, including the retina
  • several biological roles for erythropoietin and its receptor (EPO and EPOR), unrelated to erythropoiesis, including angiogenesis
  • EPO could increase T cell suppression in the tumor microenvironments (TMEs) by acting directly on macrophages
  • EPO contributes to beneficial functions in a variety of non-hematopoietic tissues including the nervous system, and protects cells from apoptosis, reduces inflammatory responses
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • EPO combined with CSF3 enhanced MMP2 expression in mesenchymal stem cells (MSCs), promoted MSC motility and activated the ERK1/2 signaling pathway
  • binds to erythropoietin receptors (EPOR), initiating signaling that stimulates growth, inhibits apoptosis, and induces the differentiation of erythroid progenitors to increase red blood cell mass
  • increases NFATC1 expression and decreases cathepsin K expression in an MTOR-independent manner, resulting in an increase of osteoclast numbers and a decrease in resorption activity
  • SH2B1 is responsive to EPO stimulation and becomes phosphorylated, most likely on serines/threonines, in an EPO dose- and time-dependent manner
  • interaction between SH2B1 and EPOR (SH2B1 becomes phosphorylated in response to EPO and acts as a negative regulator of signaling downstream of the EPOR)
  • novel role for GATA4 and TAL1 to affect skeletal myogenic differentiation and EPO response via cross-talk with SIRT1
  • association between EPO and FN1 expression in glomerular mesangial cells
  • EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR
  • 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
  • EPO and CCL3 antagonise their functional properties during neuroinflammation
  • EPO enhanced apoptotic cell clearance through peroxisome proliferator activated receptor-gamma (PPARG)
  • 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
  • macrophages are direct targets of erythropoietin and that erythropoietin treatment enhances the pro-inflammatory activity and function of these cells
    • REGULATION
    activated by hypoxia
    inhibited by
  • IL1A
    • ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD)
    Variant & Polymorphism other
  • loss of function leading to reduced hippocampal neurogenesis
  • polymorphisms increasing the risk of proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD)
    • Candidate gene
  • EPO is increased in the vitreous fluid from ischemic retinal diseases such as proliferative diabetic retinopathy
  • EPO is expressed in the human retina, and it is upregulated in diabetic patients even without retinopathy
    • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquired 
    EPO/EPOR is a novel therapeutic target in cardiovascular disease
    diabete  
    promotion of EPO signaling in beta cells may be a novel therapeutic strategy for diabetes prevention and treatment
    neurologyneurodegenerative 
    EPO administration can be a new promising therapeutic approach in amyotrophic lateral sclerosis
    neurologyneurodegenerativealzheimer
    may be useful for the treatment of AD
    ANIMAL & CELL MODELS
  • deletion of the Epo gene in mice leads to embryonic lethality at days 13 to 15, coincident with the establishment of definitive (adult-type) erythropoiesis and underscoring the absolute necessity of Epo function