EPOR
entrez
2057
canonical
uniprot
P19235
canonical
ensembl
ENSG00000187266
resolver
ensp
ENSP00000222139
resolver
genesymbol
EPOR
resolver
hgnc
HGNC:3416
resolver
uniprot
B2RCG4
resolver
uniprot
Q15443
resolver
uniprot
Q2M205
resolver
uniprot_entry
EPOR_HUMAN
resolver
uniprot_sec
B2RCG4
resolver
uniprot_sec
Q15443
resolver
uniprot_sec
Q2M205
resolver
amino_acid_sequence
MDHLGASLWPQVGSLCLLLAGAAWAPPPNLPDPKFESKAALLAARGPEELLCFTERLEDLVCFWEEAASAGVGPGNYSFSYQLEDEPWKLCRLHQAPTARGAVRFWCSLPTADTSSFVPLELRVTAASGAPRYHRVIHINEVVLLDAPVGLVARLADESGHVVLRWLPPPETPMTSHIRYEVDVSAGNGAGSVQRVEILEGRTECVLSNLRGRTRYTFAVRARMAEPSFGGFWSAWSEPVSLLTPSDLDPLILTLSLILVVILVLLTVLALLSHRRALKQKIWPGIPSPESEFEGLFTTHKGNFQLWLYQNDGCLWWSPCTPFTEDPPASLEVLSERCWGTMQAVEPGTDDEGPLLEPVGSEHAQDTYLVLDKWLLPRNPPSEDLPGPGGSVDIVAMDEGSEASSCSSALASKPSPEGASAASFEYTILDPSSQLLRPWTLCPELPPTPPHLKYLYLVVSDSGISTDYSSGDSQGAQGGLSDGPYSNPYENSLIPAAEPLPPSYVACS
uniprot
proteins
disease_involvement
DISEASE: Erythrocytosis, familial, 1 (ECYT1) [MIM:133100]: An autosomal dominant disorder characterized by 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. {ECO:0000269|PubMed:8506290, ECO:0000269|PubMed:8608241}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Receptor for erythropoietin, which mediates erythropoietin-induced erythroblast proliferation and differentiation (PubMed:10388848, PubMed:2163695, PubMed:2163696, PubMed:8662939, PubMed:9774108). Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade (By similarity). In some cell types, can also activate STAT1 and STAT3 (PubMed:11756159). May also activate the LYN tyrosine kinase (By similarity). {ECO:0000250|UniProtKB:P14753, ECO:0000269|PubMed:10388848, ECO:0000269|PubMed:11756159, ECO:0000269|PubMed:2163695, ECO:0000269|PubMed:2163696, ECO:0000269|PubMed:8662939, ECO:0000269|PubMed:9774108}.; FUNCTION: [Isoform EPOR-T]: Acts as a dominant-negative receptor of EPOR-mediated signaling. {ECO:0000269|PubMed:1324524}.
uniprot
proteins
mass_dalton
55065
uniprot
proteins
mutagenesis
MUTAGEN 114; /note="T->A: Little effect on EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 115; /note="S->A: Little effect on EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 116; /note="S->A: 10-fold reduction in EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 117; /note="F->A,L: Greatly reduced EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 117; /note="F->W: 60-fold reduction in EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 117; /note="F->Y: 8-fold reduction in EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 118; /note="V->A: 16-fold reduction in EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 120; /note="L->A: Some reduction in EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 121; /note="E->A: Little effect on EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 165; /note="R->A: Little effect on EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 174; /note="M->A: Little effect on EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 176; /note="S->A: 16-fold reduction in EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 177; /note="H->A: Little effect on EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 179; /note="R->A: Little effect on EPO binding."; /evidence="ECO:0000269|PubMed:8662939"; MUTAGEN 426; /note="Y->F: Decreased phosphorylation by JAK2 and association with the ECS(SOCS2) complex."; /evidence="ECO:0000269|PubMed:11781573"; MUTAGEN 454; /note="Y->F: Some loss of SOCS3 binding."; /evidence="ECO:0000269|PubMed:12027890"; MUTAGEN 456; /note="Y->F: Inhibition of STAT1/STAT3 activity. No effect on STAT5 activity. Some loss of SOCS3 binding."; /evidence="ECO:0000269|PubMed:11756159, ECO:0000269|PubMed:12027890"; MUTAGEN 468; /note="Y->F: No effect on STAT1/STAT3 nor STAT5 activity."; /evidence="ECO:0000269|PubMed:11756159
uniprot
proteins
post_translational_modification
PTM: On EPO stimulation, phosphorylated on C-terminal tyrosine residues by JAK2 (PubMed:11781573). The phosphotyrosine motifs are also recruitment sites for several SH2-containing proteins and adapter proteins which mediate cell proliferation (PubMed:10374881). Phosphorylation on Tyr-454 is required for PTPN6 interaction, Tyr-426 for PTPN11 (By similarity). Tyr-426 is also required for SOCS3 binding, but Tyr-454/Tyr-456 motif is the preferred binding site (PubMed:12027890). {ECO:0000250|UniProtKB:P14753, ECO:0000269|PubMed:10374881, ECO:0000269|PubMed:11781573, ECO:0000269|PubMed:12027890}.; PTM: Ubiquitinated by the ECS(SOCS2) complex following ligand-binding and phosphorylation by JAK2, leading to its degradation by the proteasome (PubMed:11781573, PubMed:31182716). Regulation by the ECS(SOCS2) complex acts as a negative feedback loop of erythropoietin-mediated signaling pathway (PubMed:11781573). Ubiquitination at Lys-281 mediates receptor internalization, whereas ubiquitination at Lys-453 promotes trafficking of activated receptors to the lysosomes for degradation (By similarity). Ubiquitinated by NOSIP; appears to be either multi-monoubiquitinated or polyubiquitinated (PubMed:12746455). Ubiquitination mediates proliferation and survival of EPO-dependent cells (By similarity). {ECO:0000250|UniProtKB:P14753, ECO:0000269|PubMed:11781573, ECO:0000269|PubMed:12746455, ECO:0000269|PubMed:31182716}.
uniprot
proteins
protein_family
Type 1 subfamily
uniprot
proteins
protein_family
Type I cytokine receptor family
uniprot
proteins
pubmed
10374881
uniprot
proteins
pubmed
10388848
uniprot
proteins
pubmed
11722595
uniprot
proteins
pubmed
11756159
uniprot
proteins
pubmed
11781573
uniprot
proteins
pubmed
11784712
uniprot
proteins
pubmed
12027890
uniprot
proteins
pubmed
12746455
uniprot
proteins
pubmed
1324524
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1654273
uniprot
proteins
pubmed
1657727
uniprot
proteins
pubmed
1664413
uniprot
proteins
pubmed
1668606
uniprot
proteins
pubmed
1668607
uniprot
proteins
pubmed
2163695
uniprot
proteins
pubmed
2163696
uniprot
proteins
pubmed
25092874
uniprot
proteins
pubmed
27535533
uniprot
proteins
pubmed
31182716
uniprot
proteins
pubmed
7534299
uniprot
proteins
pubmed
8174675
uniprot
proteins
pubmed
8506290
uniprot
proteins
pubmed
8608241
uniprot
proteins
pubmed
8662530
uniprot
proteins
pubmed
8662939
uniprot
proteins
pubmed
9774108
uniprot
proteins
pubmed
9808045
uniprot
proteins
pubmed
9974392
uniprot
proteins
sequence_length
508
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P14753}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform EPOR-S]: Secreted {ECO:0000269|PubMed:11722595}. Note=Secreted and located to the cell surface. {ECO:0000269|PubMed:11722595}.
uniprot
proteins
transmembrane_region
TRANSMEM 251..273; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins