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Beschreibung

Erythropoietin receptor (UniProt: P19235, also known as EPO-R) is encoded by the EPOR gene (Gene ID: 2057) in human. EPO-R is a single-pass type I membrane protein that serves as a receptor for erythropoietin. It mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPO-R dimerizes triggering the JAK2/STAT5 signaling cascade. EPO-R has an extracellular domain (aa 25-250), a transmembrane domain (aa 251-273), and a cytoplasmic domain (aa 274-508). It is synthesized with a signal peptide (aa 1-24) that is cleaved to generate mature EPO-R. Upon stimulation following Erythropoietin (EPO) binding, EPO-R is 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 Tyrosine 454 is shown to be essential for PTPN6 interaction, and on Tyrosine 426 for PTPN11 interaction. Tyrosine 426 is also required for SOCS3 binding, however, Tyr-454/Tyr-456 motif is reported to be the preferred binding site. Ubiquitination of EPO-R at Lysine 81 is required for receptor internalization, whereas ubiquitination at Lysine 453 promotes trafficking of activated receptors to the lysosomes for degradation. Defects in EPOR gene are linked to familial erythrocytosis which is characterized by increased serum red blood cell mass, elevated hemoglobin and hematocrit, and hypersensitivity of erythroid progenitors to erythropoietin.