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Q07303 (EPOR_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Erythropoietin receptor

Short name=EPO-R
Gene names
Name:Epor
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length507 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

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 LYN tyrosine kinase By similarity.

Subunit structure

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.

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

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

Domain

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.

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.

Post-translational modification

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.

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.

Sequence similarities

Belongs to the type I cytokine receptor family. Type 1 subfamily.

Contains 1 fibronectin type-III domain.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform EPOR-F (identifier: Q07303-1)

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.
Isoform EPOR-S (identifier: Q07303-2)

Also known as: Soluble form;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 By similarity
Chain25 – 507483Erythropoietin receptor
PRO_0000010871

Regions

Topological domain25 – 249225Extracellular Potential
Transmembrane250 – 27223Helical; Potential
Topological domain273 – 507235Cytoplasmic Potential
Domain146 – 246101Fibronectin type-III
Motif232 – 2365WSXWS motif
Motif281 – 2899Box 1 motif
Motif451 – 4566ITIM motif

Sites

Site1161Required for ligand binding By similarity
Site3671Interaction with APS and STAT5, and activation
Site4251Required for STAT5/PTPN11/SOCS3 binding
Site4531Interaction with PTPN6

Amino acid modifications

Modified residue3671Phosphotyrosine; by JAK2 By similarity
Modified residue4251Phosphotyrosine; by JAK2 By similarity
Modified residue4531Phosphotyrosine; by JAK2 By similarity
Modified residue4551Phosphotyrosine; by JAK2 By similarity
Modified residue4671Phosphotyrosine; by JAK2 By similarity
Modified residue4841Phosphotyrosine; by JAK2 By similarity
Modified residue4881Phosphotyrosine; by JAK2 By similarity
Modified residue5031Phosphotyrosine; by JAK2 By similarity
Glycosylation751N-linked (GlcNAc...) Potential
Disulfide bond52 ↔ 62 By similarity
Disulfide bond90 ↔ 106 By similarity
Cross-link280Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link452Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence246 – 26520DLDPL…ISLLL → GEATVPRGGGGAGPNTSKPP in isoform EPOR-S.
VSP_009514
Alternative sequence266 – 507242Missing in isoform EPOR-S.
VSP_009515

Sequences

Sequence LengthMass (Da)Tools
Isoform EPOR-F (Full-length form) [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: AC79AF22D06A7312

FASTA50755,500
        10         20         30         40         50         60 
MDQLRVARWP RVSPLCLLLA GAAWASSPSL PDPKFESKAA LLASRGSEEL LCFTQRLEDL 

        70         80         90        100        110        120 
VCFWEEAANS GMGFNYSFSY QLEGESRKSC RLHQAPTVRG SMRFWCSLPT ADTSSFVPLE 

       130        140        150        160        170        180 
LQVTEASGSP RYHRIIHINE VVLLDAPAGL LARRAEEGSH VVLRWLPPPG APMTTHIRYE 

       190        200        210        220        230        240 
VDVSAGNRAG GTQRVEVLEG RTECVLSNLR GGTRYTFAVR ARMAEPSFSG FWSAWSEPAS 

       250        260        270        280        290        300 
LLTASDLDPL ILTLSLILVL ISLLLTVLAL LSHRRALRQK IWPGIPSPEN EFEGLFTTHK 

       310        320        330        340        350        360 
GNFQLWLLQR DGCLWWSPSS PFPEDPPAHL EVLSERRWGV TQAGDAGAED KGPLLEPVGS 

       370        380        390        400        410        420 
ERAQDTYLVL DEWLLPRCPC SENLSGPGDS VDPATMDEGS ETSSCPSDLA SKPRPEGTSP 

       430        440        450        460        470        480 
SSFEYTILDP SSKLLCPRAL PPELPPTPPH LKYLYLVVSD SGISTDYSSG GSQGVHGDSS 

       490        500 
DGPYSHPYEN SLVPDTEPLR PSYVACS 

« Hide

Isoform EPOR-S (Soluble form) [UniParc].

Checksum: 78D59A1F936A9155
Show »

FASTA26528,806

References

[1]"Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells."
Masuda S., Nagao M., Takahata K., Konishi Y., Gallyas F., Tabira T., Sasaki R.
J. Biol. Chem. 268:11208-11216(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM EPOR-F).
Tissue: Pheochromocytoma.
[2]"Alternative splicing of the erythropoietin receptor gene correlates with erythroid differentiation in rat hematopoietic and leukemic cells."
Fujita M., Takahashi R., Kitada K., Watanabe R., Kitazawa S., Ashoori F., Liang P., Saya H., Serikawa T., Maeda S.
Cancer Lett. 112:47-55(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS EPOR-F AND EPOR-S).
Strain: Long Evans.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D13566 mRNA. Translation: BAA02761.1.
PIRA46713.
UniGeneRn.22394.

3D structure databases

ProteinModelPortalQ07303.
SMRQ07303. Positions 32-246.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000017369.

PTM databases

PhosphoSiteQ07303.

Proteomic databases

PaxDbQ07303.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:2560. rat. [Q07303-1]

Organism-specific databases

RGD2560. Epor.

Phylogenomic databases

eggNOGNOG46583.
HOGENOMHOG000059639.
HOVERGENHBG005595.
InParanoidQ07303.
PhylomeDBQ07303.

Gene expression databases

GenevestigatorQ07303.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR009167. Erythropoietin_rcpt.
IPR003961. Fibronectin_type3.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamPF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
[Graphical view]
PIRSFPIRSF001959. EPO_receptor. 1 hit.
SMARTSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 2 hits.
PROSITEPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROQ07303.

Entry information

Entry nameEPOR_RAT
AccessionPrimary (citable) accession number: Q07303
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: June 11, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families