Reactome | UniProt:P19235 EPOR

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UniProt:P19235 EPOR Show undefined attributes

chain	signal peptide:1-24 chain:25-508
checksum	F9F326E162E9512A
comment	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).FUNCTION Acts as a dominant-negative receptor of EPOR-mediated signaling.SUBUNIT Forms homodimers on EPO stimulation (PubMed:10388848, PubMed:9774108, PubMed:9974392). The tyrosine-phosphorylated form interacts with several SH2 domain-containing proteins including LYN, the adapter protein SH2B2, PTPN6, PTPN11, JAK2, PI3 kinases, STAT5A/B, SOCS3, CRKL (PubMed:12027890, PubMed:7534299). Interacts with INPP5D/SHIP1 (By similarity). SH2B2 binding inhibits the JAK-STAT signaling (PubMed:10374881). Interacts with RHEX; this interaction occurs in a erythropoietin (EPO)-dependent manner (PubMed:25092874). Interacts with ATXN2L (PubMed:11784712).INTERACTION Secreted and located to the cell surface.ALTERNATIVE PRODUCTS Erythroid cells and erythroid progenitor cells.TISSUE SPECIFICITY Isoform EPOR-F is the most abundant form in EPO-dependent erythroleukemia cells and in late-stage erythroid progenitors.TISSUE SPECIFICITY Isoform EPOR-S and isoform EPOR-T are the predominant forms in bone marrow.TISSUE SPECIFICITY Isoform EPOR-S and isoform EPOR-T are the predominant forms in bone marrow (PubMed:1324524). Isoform EPOR-T is the most abundant from in early-stage erythroid progenitor cells (PubMed:1324524).DOMAIN The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.DOMAIN The box 1 motif is required for JAK interaction and/or activation.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.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).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).DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the type I cytokine receptor family. Type 1 subfamily.
crossReference	[DatabaseIdentifier:12208338] PDB:6MOH [DatabaseIdentifier:12816782] ZINC target:P19235 [DatabaseIdentifier:12813371] ZINC - Substances:EPOR_HUMAN [DatabaseIdentifier:12809362] ZINC - Predictions - Purchasable:EPOR_HUMAN [DatabaseIdentifier:12334835] RefSeq:NP_000112.1 [DatabaseIdentifier:12289324] Pharos - Targets:P19235 [DatabaseIdentifier:12250975] PRO:P19235 [DatabaseIdentifier:12208347] PDB:6MOE [DatabaseIdentifier:12208341] PDB:2MV6 [DatabaseIdentifier:12171196] PDB:1CN4 [DatabaseIdentifier:12208336] PDB:6MOI [DatabaseIdentifier:12208349] PDB:6E2Q [DatabaseIdentifier:12208348] PDB:1EBP [DatabaseIdentifier:12208343] PDB:8VVO [DatabaseIdentifier:12208342] PDB:6MOL [DatabaseIdentifier:12171195] PDB:1EER [DatabaseIdentifier:11457354] ENSEMBL:ENSG00000187266 [DatabaseIdentifier:11548851] ENSEMBL:ENSP00000467809 [DatabaseIdentifier:11548850] ENSEMBL:ENSP00000222139 [DatabaseIdentifier:11671549] ENSEMBL:ENST00000222139 [DatabaseIdentifier:11671550] ENSEMBL:ENST00000592375 [DatabaseIdentifier:11779827] Guide to Pharmacology - Targets:1718 [DatabaseIdentifier:11791483] GeneCards:EPOR [DatabaseIdentifier:11807497] GlyGen:P19235 [DatabaseIdentifier:11844484] HPA:ENSG00000187266-EPOR [DatabaseIdentifier:12129112] OpenTargets:ENSG00000187266 [DatabaseIdentifier:12137306] Orphanet:EPOR [DatabaseIdentifier:12208351] PDB:4Y5V [DatabaseIdentifier:12208346] PDB:4Y5Y [DatabaseIdentifier:12174134] PDB:4Y5X [DatabaseIdentifier:12208334] PDB:1EBA [DatabaseIdentifier:12208335] PDB:1ERN [DatabaseIdentifier:12208337] PDB:8VUI [DatabaseIdentifier:12208350] PDB:6MOF [DatabaseIdentifier:12208340] PDB:6MOJ [DatabaseIdentifier:12208345] PDB:2JIX [DatabaseIdentifier:12189458] PDB:6I4X [DatabaseIdentifier:12208339] PDB:6MOK [DatabaseIdentifier:12208344] PDB:8VVM
databaseName	UniProt
dbId	54394
description	recommendedName: fullName evidence="28"Erythropoietin receptor shortName evidence="28"EPO-R
displayName	UniProt:P19235 EPOR
geneName	EPOR
identifier	P19235
isSequenceChanged	false
keyword	3D-structure Alternative splicing Cell membrane Congenital erythrocytosis Disease variant Disulfide bond Glycoprotein Isopeptide bond Membrane Phosphoprotein Proteomics identification Receptor Reference proteome Secreted Signal Transmembrane Transmembrane helix Ubl conjugation
modified	[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	EPOR
otherIdentifier	1087_at 11740081_a_at 16868928 2057 209962_PM_at 209962_at 209963_PM_s_at 209963_s_at 215054_3p_at 215054_PM_at 215054_at 31681_at 37986_PM_at 37986_at 3850860 3850861 3850862 3850863 3850864 3850869 3850870 3850871 3850872 3850873 3850874 3850875 3850876 3850877 3850878 3850879 3850881 3850882 3850883 396_3p_f_at 396_PM_f_at 396_f_at 4876922C_3p_at 8034217 A_23_P367899 A_23_P381954 A_24_P914376 GE58209 GO:0004888 GO:0004896 GO:0004900 GO:0005515 GO:0005576 GO:0005886 GO:0007165 GO:0007420 GO:0007507 GO:0009897 GO:0016020 GO:0016607 GO:0019221 GO:0030163 GO:0038162 GO:0042802 GO:0043161 GO:0046697 GO:0048856 HMNXSV003015443 Hs.89548.1.S1_3p_s_at ILMN_2168347 M60459_at PH_hs_0007355 TC19002335.hg TC19002676.hg X97671cds_3p_s_at g182200_3p_at g182200_3p_x_at p26738
physicalEntity	[EntityWithAccessionedSequence:R-HSA-9006274] p-8Y-EPOR [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-1168347] EPOR [plasma membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000187266] ENSEMBL:ENSG00000187266 EPOR [ReferenceDNASequence:12676849] UCSC:P19235 EPOR [ReferenceDNASequence:11322111] BioGPS Gene:2057 EPOR [ReferenceDNASequence:11391657] COSMIC - genes:EPOR EPOR [ReferenceDNASequence:11419243] CTD Gene:2057 EPOR [ReferenceDNASequence:11427328] dbSNP Gene:2057 EPOR [ReferenceDNASequence:11823154] HGNC:3416 EPOR [ReferenceDNASequence:11864804] KEGG:hsa:2057 EPOR [ReferenceDNASequence:11951900] Monarch:2057 EPOR [ReferenceDNASequence:12035993] NCBI Gene:2057 EPOR [ReferenceDNASequence:12113800] OMIM:133171 EPOR
referenceTranscript	[ReferenceRNASequence:12516719] RefSeq:NM_000121.4 EPOR
schemaClass	ReferenceGeneProduct
secondaryIdentifier	EPOR_HUMAN B2RCG4 Q15443 Q2M205
sequenceLength	508
species	[Species:48887] Homo sapiens
stId	uniprot:P19235
url	http://purl.uniprot.org/uniprot/P19235

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-9006274] p-8Y-EPOR [plasma membrane] [EntityWithAccessionedSequence:R-HSA-1168347] EPOR [plasma membrane]
(referenceSequence)	[ModifiedResidue:9006280] O4'-phospho-L-tyrosine at 456 [ModifiedResidue:9006264] O4'-phospho-L-tyrosine at 504 [ModifiedResidue:9006267] O4'-phospho-L-tyrosine at 489 [ModifiedResidue:9006269] O4'-phospho-L-tyrosine at 368 [ModifiedResidue:9006271] O4'-phospho-L-tyrosine at 454 [ModifiedResidue:9006277] O4'-phospho-L-tyrosine at 468 [ModifiedResidue:9006263] O4'-phospho-L-tyrosine at 426 [ModifiedResidue:9006262] O4'-phospho-L-tyrosine at 485
(interactor)	[UndirectedInteraction:11207879] UniProt:P18031 <-> UniProt:P19235 (IntAct) [UndirectedInteraction:11222601] UniProt:P01588 <-> UniProt:P19235 (IntAct) [UndirectedInteraction:11232725] UniProt:P29350 <-> UniProt:P19235 (IntAct) [UndirectedInteraction:11276341] UniProt:Q92835 <-> UniProt:P19235 (IntAct)