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Q07303

- EPOR_RAT

UniProt

Q07303 - EPOR_RAT

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Protein

Erythropoietin receptor

Gene

Epor

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- 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)LengthDescriptionGraphical viewFeature identifierActions
Sitei116 – 1161Required for ligand bindingBy similarity
Sitei367 – 3671Interaction with APS and STAT5, and activation
Sitei425 – 4251Required for STAT5/PTPN11/SOCS3 binding
Sitei453 – 4531Interaction with PTPN6

GO - Molecular functioni

  1. erythropoietin receptor activity Source: UniProtKB

GO - Biological processi

  1. erythropoietin-mediated signaling pathway Source: GOC
  2. negative regulation of neuron apoptotic process Source: RGD
  3. positive regulation of cytosolic calcium ion concentration Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Names & Taxonomyi

Protein namesi
Recommended name:
Erythropoietin receptor
Short name:
EPO-R
Gene namesi
Name:Epor
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi2560. Epor.

Subcellular locationi

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424By similarityAdd
BLAST
Chaini25 – 507483Erythropoietin receptorPRO_0000010871Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi52 ↔ 62By similarity
Glycosylationi75 – 751N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi90 ↔ 106By similarity
Cross-linki280 – 280Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei367 – 3671Phosphotyrosine; by JAK2By similarity
Modified residuei425 – 4251Phosphotyrosine; by JAK2By similarity
Cross-linki452 – 452Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei453 – 4531Phosphotyrosine; by JAK2By similarity
Modified residuei455 – 4551Phosphotyrosine; by JAK2By similarity
Modified residuei467 – 4671Phosphotyrosine; by JAK2By similarity
Modified residuei484 – 4841Phosphotyrosine; by JAK2By similarity
Modified residuei488 – 4881Phosphotyrosine; by JAK2By similarity
Modified residuei503 – 5031Phosphotyrosine; by JAK2By similarity

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.

PTM databases

PhosphoSiteiQ07303.

Expressioni

Tissue specificityi

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

Gene expression databases

GenevestigatoriQ07303.

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000017369.

Structurei

3D structure databases

ProteinModelPortaliQ07303.
SMRiQ07303. Positions 32-246.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 249225ExtracellularSequence AnalysisAdd
BLAST
Topological domaini273 – 507235CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei250 – 27223HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini146 – 246101Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi232 – 2365WSXWS motif
Motifi281 – 2899Box 1 motif
Motifi451 – 4566ITIM motif

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

Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG46583.
HOGENOMiHOG000059639.
HOVERGENiHBG005595.
InParanoidiQ07303.
PhylomeDBiQ07303.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR009167. Erythropoietin_rcpt.
IPR003961. Fibronectin_type3.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamiPF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
[Graphical view]
PIRSFiPIRSF001959. EPO_receptor. 1 hit.
SMARTiSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 2 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]

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. Align

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei246 – 26520DLDPL…ISLLL → GEATVPRGGGGAGPNTSKPP in isoform EPOR-S. 1 PublicationVSP_009514Add
BLAST
Alternative sequencei266 – 507242Missing in isoform EPOR-S. 1 PublicationVSP_009515Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D13566 mRNA. Translation: BAA02761.1.
PIRiA46713.
UniGeneiRn.22394.

Genome annotation databases

UCSCiRGD:2560. rat. [Q07303-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D13566 mRNA. Translation: BAA02761.1 .
PIRi A46713.
UniGenei Rn.22394.

3D structure databases

ProteinModelPortali Q07303.
SMRi Q07303. Positions 32-246.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000017369.

PTM databases

PhosphoSitei Q07303.

Proteomic databases

PaxDbi Q07303.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

UCSCi RGD:2560. rat. [Q07303-1 ]

Organism-specific databases

RGDi 2560. Epor.

Phylogenomic databases

eggNOGi NOG46583.
HOGENOMi HOG000059639.
HOVERGENi HBG005595.
InParanoidi Q07303.
PhylomeDBi Q07303.

Miscellaneous databases

PROi Q07303.

Gene expression databases

Genevestigatori Q07303.

Family and domain databases

Gene3Di 2.60.40.10. 2 hits.
InterProi IPR009167. Erythropoietin_rcpt.
IPR003961. Fibronectin_type3.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view ]
Pfami PF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
[Graphical view ]
PIRSFi PIRSF001959. EPO_receptor. 1 hit.
SMARTi SM00060. FN3. 1 hit.
[Graphical view ]
SUPFAMi SSF49265. SSF49265. 2 hits.
PROSITEi PS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiEPOR_RAT
AccessioniPrimary (citable) accession number: Q07303
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: October 1, 2014
This is version 118 of the entry and version 1 of the sequence. [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

External Data

Dasty 3