Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

EPOR

contributors: mct - updated : 17-01-2018

HGNC name	erythropoietin receptor
HGNC id	3416

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed sEPOR - - - 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 NM_000121 8 - 2459 NP_000112 - 508 - 2011 21291419

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Hearing/Equilibrium ear inner       Homo sapiens Nervous brain         Homo sapiens Reproductive female system uterus       Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining endometrium     Muscular striatum cardiac     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic erythroid Homo sapiens Cardiovascular endothelial cell Homo sapiens Muscular myocyte Homo sapiens Nervous neuron Homo sapiens Visual amacrine cell Homo sapiens Visual Muller cell Homo sapiens Visual rod 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cardiovascular aquired   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