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Q07303

- EPOR_RAT

UniProt

Q07303 - EPOR_RAT

Protein

Erythropoietin receptor

Gene

Epor

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 1 (01 Feb 1995)
      Previous versions | rss
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    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

    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

    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

    MDQLRVARWP RVSPLCLLLA GAAWASSPSL PDPKFESKAA LLASRGSEEL    50
    LCFTQRLEDL VCFWEEAANS GMGFNYSFSY QLEGESRKSC RLHQAPTVRG 100
    SMRFWCSLPT ADTSSFVPLE LQVTEASGSP RYHRIIHINE VVLLDAPAGL 150
    LARRAEEGSH VVLRWLPPPG APMTTHIRYE VDVSAGNRAG GTQRVEVLEG 200
    RTECVLSNLR GGTRYTFAVR ARMAEPSFSG FWSAWSEPAS LLTASDLDPL 250
    ILTLSLILVL ISLLLTVLAL LSHRRALRQK IWPGIPSPEN EFEGLFTTHK 300
    GNFQLWLLQR DGCLWWSPSS PFPEDPPAHL EVLSERRWGV TQAGDAGAED 350
    KGPLLEPVGS ERAQDTYLVL DEWLLPRCPC SENLSGPGDS VDPATMDEGS 400
    ETSSCPSDLA SKPRPEGTSP SSFEYTILDP SSKLLCPRAL PPELPPTPPH 450
    LKYLYLVVSD SGISTDYSSG GSQGVHGDSS DGPYSHPYEN SLVPDTEPLR 500
    PSYVACS 507
    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