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FLASH GENE
Symbol EPO contributors: mct - updated : 27-04-2016
HGNC name erythropoietin
HGNC id 3415
Location 7q22.1      Physical location : 100.318.422 - 100.321.321
Synonym name epoetin
Synonym symbol(s) EP, MGC138142, MVCD2, RhEPO
DNA
TYPE functioning gene
SPECIAL FEATURE opposite orientation, tail to tail
text tail to tail with MPO and LPO
STRUCTURE 2.90 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked Y status confirmed
Map cen - D7S456 - GUSB - D7S186 - ASL ASL - (ABCB1 ,ABCB4 ),GNB2 ,EPO ,ACHE - D7S238 - D7S240 - qter
Authors Scherrer (93)
Text see COL1A2 , MET
Physical map
GATS 7q22.1 opposite strand transcription unit to STAG3 LOC392080 7 similar to opposite strand transcription unit to Stag3; Gats protein PILRB 7q22.1 paired immunoglobin-like type 2 receptor beta PILRA 7q22 paired immunoglobin-like type 2 receptor alpha ZCWPW1 7q22.1 zinc finger, CW-type with PWWP domain 1 FLJ20257 7q22.1 hypothetical protein FLJ20257 MGC22793 7q22.1 hypothetical protein MGC22793 THG-1 7p21-p15 TSC-22-like FLJ37538 7q22.1 hypothetical protein FLJ37538 HRBL 7q22 HIV-1 Rev binding protein-like LOC392081 7 similar to insulin receptor substrate like protein LRRN4 7q22 leucine rich repeat neuronal 4 FBXO24 7q22 F-box only protein 24 PCOLCE 7q22 procollagen C-endopeptidase enhancer AF053356_CDS3 7q22 hypothetical protein AF053356_CDS3 TFR2 7q22 transferrin receptor 2 ACTL6 7q22 actin-like 6 GNB2 7q21.1-q22.2 guanine nucleotide binding protein (G protein), beta polypeptide 2 PERQ1 7q22 PERQ amino acid rich, with GYF domain 1 RPP20 7q22 POP7 (processing of precursor, S. cerevisiae) homolog EPO 7q21.3-q22.1 erythropoietin ZAN 7q22 zonadhesin EPHB4 7q32-q36 EphB4 LOC285995 7q22.1 hypothetical LOC285995 SLC12A9 7q22 solute carrier family 12 (potassium/chloride transporters), member 9 TRIP6 7q22 thyroid hormone receptor interactor 6 ARS2 7q21 arsenate resistance protein ARS2 ACHE 7q22.1 acetylcholinesterase (YT blood group) MUC3B 7q22 mucin 3B LOC219612 7q22.1 hypothetical gene supported by AK025404 MUC17 7q22 mucin 17 TRIM56 7q11.2 tripartite motif-containing 56 SERPINE1 7q21.3-q22.1 serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 AP1S1 7q11.22 adaptor-related protein complex 1, sigma 1 subunit VGF 7q22 VGF nerve growth factor inducible FLJ39237 7q22.1 FLJ39237 protein MGAT3 22q13.1 mannosyl (beta-1,4-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase
regionally located cluster with MPO and LPO
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 1340 18.4 193 - 2000 11154762
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver   lowly
Hearing/Equilibriumear     Homo sapiens
Nervousbrain     Homo sapiens
Urinarykidney   lowly
Visualeyeretina  lowly
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal, neonatal
Text liver, cerebellum, pituitary gland, cortex
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