EPOR

Erythropoietin receptor ;
EPO-R ;

disease:Defects in EPOR are the cause of erythrocytosis familial type 1 (ECYT1) [MIM:133100]. ECYT1 is an autosomal dominant disorder characterized by increased serum red blood cell mass , elevated hemoglobin and hematocrit , hypersensitivity of erythroid progenitors to erythropoietin , erythropoietin low serum levels , and no increase in platelets nor leukocytes. It has a relatively benign course and does not progress to leukemia. ,domain:Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM) . This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. ,domain:The box 1 motif is required for JAK interaction and/or activation. ,domain:The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. ,function:Isoform EPOR-T , missing the cytoplasmic tail , acts as a dominant-negative receptor of EPOR-mediated signaling. ,function:Receptor for erythropoietin. Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation , EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In some cell types , can also activate STAT1 and STAT3. May also activate the LYN tyrosine kinase. ,PTM:On EPO stimulation , phosphorylated on C-terminal tyrosine residues by JAK2. The phosphotyrosine motifs are also recruitment sites for several SH2-containing proteins and adapter proteins which mediate cell proliferation. Phosphorylation on Tyr-454 is required for PTPN6 interaction , Tyr-426 for PTPN11. Tyr-426 is also required for SOCS3 binding , but Tyr-454/Tyr-456 motif is the preferred binding site. ,PTM:Ubiquitinated by NOSIP; appears to be either multi-monoubiquitinated or polyubiquitinated. Ubiquitination mediates proliferation and survival of EPO-dependent cells. ,similarity:Belongs to the type I cytokine receptor family. Type 1 subfamily. ,similarity:Contains 1 fibronectin type-III domain. ,similarity:Contains 1 Ras-GEF domain. ,subcellular location:Secreted and located to the cell surface. ,subunit:Forms homodimers on EPO stimulation. The tyrosine-phosphorylated form interacts with several SH2 domain-containing proteins including LYN (By similarity) , the adapter protein APS , PTPN6 (By similarity) , PTPN11 , JAK2 , PI3 kinases , STAT5A/B , SOCS3 , CRKL (By similarity) . Interacts with INPP5D/SHIP1 (By similarity) . The N-terminal SH2 domain of PTPN6 binds Tyr-454 and inhibits signaling through dephosphorylation of JAK2 (By similarity) . APS binding also inhibits the JAK-STAT signaling. Binding to PTPN11 , preferentially through the N-terminal SH2 domain , promotes mitogenesis and phosphorylation of PTPN11 (By similarity) . Binding of JAK2 (through its N-terminal) promotes cell-surface expression (By similarity) . Interaction with the ubiquitin ligase NOSIP mediates EPO-induced cell proliferation. Interacts with ATXN2L. ,tissue specificity:Erythroid cells and erythroid progenitor cells. Isoform EPOR-F is the most abundant form in EPO-dependent erythroleukemia cells and in late-stage erythroid progenitors. Isoform EPOR-S and isoform EPOR-T are the predominant forms in bone marrow. Isoform EPOR-T is the most abundant from in early-stage erythroid progenitor cells. ,

placenta development , maternal placenta development , reproductive developmental process , cellular ion homeostasis ,cellular calcium ion homeostasis , cellular metal ion homeostasis , elevation of cytosolic calcium ion concentration ,intracellular signaling cascade , small GTPase mediated signal transduction , heart development , female pregnancy ,cellular homeostasis , cellular cation homeostasis , cellular di- , tri-valent inorganic cation homeostasis , homeostatic process , decidualization , chemical homeostasis , ion homeostasis , cytosolic calcium ion homeostasis , metal ion homeostasis , di- , tri-valent inorganic cation homeostasis , calcium ion homeostasis , cation homeostasis , cellular chemical homeostasis ,

Cell membrane; Single-pass type I membrane protein.; [Isoform EPOR-S]: Secreted . Secreted and located to the cell surface.