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Protein

Erythropoietin receptor

Gene

Epor

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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 LYN tyrosine kinase (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei116Required for ligand bindingBy similarity1
Sitei425Required for STAT5/PTPN11/SOCS3 binding1

GO - Molecular functioni

  • erythropoietin receptor activity Source: RGD

GO - Biological processi

Keywordsi

Molecular functionReceptor

Names & Taxonomyi

Protein namesi
Recommended name:
Erythropoietin receptor
Short name:
EPO-R
Gene namesi
Name:Epor
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2560 Epor

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 249ExtracellularSequence analysisAdd BLAST225
Transmembranei250 – 272HelicalSequence analysisAdd BLAST23
Topological domaini273 – 507CytoplasmicSequence analysisAdd BLAST235

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24By similarityAdd BLAST24
ChainiPRO_000001087125 – 507Erythropoietin receptorAdd BLAST483

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi52 ↔ 62By similarity
Glycosylationi75N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi90 ↔ 106By similarity
Cross-linki280Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei367Phosphotyrosine; by JAK2By similarity1
Modified residuei425Phosphotyrosine; by JAK2By similarity1
Cross-linki452Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei453Phosphotyrosine; by JAK2By similarity1
Modified residuei455Phosphotyrosine; by JAK2By similarity1
Modified residuei467Phosphotyrosine; by JAK2By similarity1
Modified residuei484Phosphotyrosine; by JAK2By similarity1
Modified residuei488Phosphotyrosine; by JAK2By similarity1
Modified residuei503Phosphotyrosine; by JAK2By similarity1

Post-translational modificationi

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-453 is required for PTPN6 interaction, Tyr-425 for PTPN11. Tyr-425 is also required for SOCS3 binding, but Tyr-453/Tyr-455 motif is the preferred binding site (By similarity).By similarity
Ubiquitinated by NOSIP; appears to be either multi-monoubiquitinated or polyubiquitinated. Ubiquitination mediates proliferation and survival of EPO-dependent cells. Ubiquitination at Lys-280 mediates receptor internalization, whereas ubiquitination at Lys-452 promotes trafficking of activated receptors to the lysosomes for degradation (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ07303
PRIDEiQ07303

PTM databases

iPTMnetiQ07303
PhosphoSitePlusiQ07303

Expressioni

Tissue specificityi

Isoform EPOR-F and isoform EPOR-S are expressed in bone marrow, spleen and eythroleukemia cell lines.

Interactioni

Subunit structurei

Forms homodimers on EPO stimulation. The tyrosine-phosphorylated form interacts with several SH2 domain-containing proteins including LYN, the adapter protein APS, PTPN6, PTPN11, JAK2, PI3 kinases, STAT5A/B, SOCS3 and CRKL. The N-terminal SH2 domain of PTPN6 binds Tyr-453 and inhibits signaling through dephosphorylation of JAK2. APS binding also inhibits the JAK-STAT signaling. Binding to PTPN11, preferentially through the N-terminal SH2 domain, promotes mitogenesis and phosphorylation of PTPN11. Binding of JAK2 (through its N-terminal) promotes cell-surface expression. Interaction with the ubiquitin ligase NOSIP mediates EPO-induced cell proliferation. Interacts with ATXN2L and INPP5D/SHIP1 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei367Interaction with APS and STAT5, and activation1
Sitei453Interaction with PTPN61

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000017369

Structurei

3D structure databases

ProteinModelPortaliQ07303
SMRiQ07303
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini146 – 246Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST101

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi232 – 236WSXWS motif5
Motifi281 – 289Box 1 motif9
Motifi451 – 456ITIM motif6

Domaini

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFGH Eukaryota
ENOG4111PGS LUCA
HOGENOMiHOG000059639
HOVERGENiHBG005595
InParanoidiQ07303
PhylomeDBiQ07303

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR009167 Erythropoietin_rcpt
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR015152 Growth/epo_recpt_lig-bind
IPR013783 Ig-like_fold
IPR003528 Long_hematopoietin_rcpt_CS
PANTHERiPTHR23037:SF28 PTHR23037:SF28, 1 hit
PfamiView protein in Pfam
PF09067 EpoR_lig-bind, 1 hit
PF00041 fn3, 1 hit
PIRSFiPIRSF001959 EPO_receptor, 1 hit
SMARTiView protein in SMART
SM00060 FN3, 1 hit
SUPFAMiSSF49265 SSF49265, 2 hits
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
PS01352 HEMATOPO_REC_L_F1, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform EPOR-F (identifier: Q07303-1) [UniParc]FASTAAdd to basket
Also known as: Full-length form

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MDQLRVARWP RVSPLCLLLA GAAWASSPSL PDPKFESKAA LLASRGSEEL
60 70 80 90 100
LCFTQRLEDL VCFWEEAANS GMGFNYSFSY QLEGESRKSC RLHQAPTVRG
110 120 130 140 150
SMRFWCSLPT ADTSSFVPLE LQVTEASGSP RYHRIIHINE VVLLDAPAGL
160 170 180 190 200
LARRAEEGSH VVLRWLPPPG APMTTHIRYE VDVSAGNRAG GTQRVEVLEG
210 220 230 240 250
RTECVLSNLR GGTRYTFAVR ARMAEPSFSG FWSAWSEPAS LLTASDLDPL
260 270 280 290 300
ILTLSLILVL ISLLLTVLAL LSHRRALRQK IWPGIPSPEN EFEGLFTTHK
310 320 330 340 350
GNFQLWLLQR DGCLWWSPSS PFPEDPPAHL EVLSERRWGV TQAGDAGAED
360 370 380 390 400
KGPLLEPVGS ERAQDTYLVL DEWLLPRCPC SENLSGPGDS VDPATMDEGS
410 420 430 440 450
ETSSCPSDLA SKPRPEGTSP SSFEYTILDP SSKLLCPRAL PPELPPTPPH
460 470 480 490 500
LKYLYLVVSD SGISTDYSSG GSQGVHGDSS DGPYSHPYEN SLVPDTEPLR

PSYVACS
Length:507
Mass (Da):55,500
Last modified:February 1, 1995 - v1
Checksum:iAC79AF22D06A7312
GO
Isoform EPOR-S (identifier: Q07303-2) [UniParc]FASTAAdd to basket
Also known as: Soluble form

The sequence of this isoform differs from the canonical sequence as follows:
     246-265: DLDPLILTLSLILVLISLLL → GEATVPRGGGGAGPNTSKPP
     266-507: Missing.

Show »
Length:265
Mass (Da):28,806
Checksum:i78D59A1F936A9155
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5FVS4Q5FVS4_RAT
Erythropoietin receptor
Epor rCG_31781
507Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_009514246 – 265DLDPL…ISLLL → GEATVPRGGGGAGPNTSKPP in isoform EPOR-S. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_009515266 – 507Missing in isoform EPOR-S. 1 PublicationAdd BLAST242

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13566 mRNA Translation: BAA02761.1
PIRiA46713
UniGeneiRn.22394

Genome annotation databases

UCSCiRGD:2560 rat [Q07303-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D13566 mRNA Translation: BAA02761.1
PIRiA46713
UniGeneiRn.22394

3D structure databases

ProteinModelPortaliQ07303
SMRiQ07303
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000017369

PTM databases

iPTMnetiQ07303
PhosphoSitePlusiQ07303

Proteomic databases

PaxDbiQ07303
PRIDEiQ07303

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:2560 rat [Q07303-1]

Organism-specific databases

RGDi2560 Epor

Phylogenomic databases

eggNOGiENOG410IFGH Eukaryota
ENOG4111PGS LUCA
HOGENOMiHOG000059639
HOVERGENiHBG005595
InParanoidiQ07303
PhylomeDBiQ07303

Miscellaneous databases

PROiPR:Q07303

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR009167 Erythropoietin_rcpt
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR015152 Growth/epo_recpt_lig-bind
IPR013783 Ig-like_fold
IPR003528 Long_hematopoietin_rcpt_CS
PANTHERiPTHR23037:SF28 PTHR23037:SF28, 1 hit
PfamiView protein in Pfam
PF09067 EpoR_lig-bind, 1 hit
PF00041 fn3, 1 hit
PIRSFiPIRSF001959 EPO_receptor, 1 hit
SMARTiView protein in SMART
SM00060 FN3, 1 hit
SUPFAMiSSF49265 SSF49265, 2 hits
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
PS01352 HEMATOPO_REC_L_F1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiEPOR_RAT
AccessioniPrimary (citable) accession number: Q07303
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: May 23, 2018
This is version 139 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health

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