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Reviewed, UniProtKB/Swiss-Prot Q2KL21 (EPOR_CANFA)

Last modified June 16, 2009. Version 24. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Erythropoietin receptor
      Short name=EPO-R
Gene names
Name: EPOR
OrganismCanis familiaris (Dog)
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis

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Protein attributes

Sequence length508 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level.

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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-454 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 By similarity.

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-454 is required for PTPN6 interaction, Tyr-426 for PTPN11. Tyr-426 is also required for SOCS3 binding, but Tyr-454/Tyr-456 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 By similarity.

Sequence similarities

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

Contains 1 fibronectin type-III domain.

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Ontologies

Keywords
   Cellular componentMembrane
   DomainSignal
Transmembrane
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
Gene Ontology (GO)
   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functioncytokine receptor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 508484Erythropoietin receptor
PRO_0000231014

Regions

Topological domain25 – 250226Extracellular Potential
Transmembrane251 – 27323 Potential
Topological domain274 – 508235Cytoplasmic Potential
Domain144 – 24097Fibronectin type-III
Region454 – 4563Required for high-affinity SOCS3 binding
Motif233 – 2375WSXWS motif
Motif282 – 2909Box 1 motif
Motif452 – 4576ITIM motif

Sites

Site1171Required for ligand binding By similarity
Site3681Interaction with APS and STAT5, and activation By similarity
Site4261Required for STAT5/PTPN11/SOCS3 binding By similarity
Site4541Interaction with PTPN6 By similarity
Site4561Required for STAT1/STAT3 activation
Site4851Required for CrkL binding By similarity

Amino acid modifications

Modified residue3681Phosphotyrosine; by JAK2 By similarity
Modified residue4261Phosphotyrosine; by JAK2 By similarity
Modified residue4541Phosphotyrosine; by JAK2 By similarity
Modified residue4561Phosphotyrosine; by JAK2 By similarity
Modified residue4681Phosphotyrosine; by JAK2 By similarity
Modified residue4891Phosphotyrosine; by JAK2 By similarity
Modified residue5041Phosphotyrosine; by JAK2 By similarity
Glycosylation761N-linked (GlcNAc...) Potential
Glycosylation1841N-linked (GlcNAc...) Potential
Disulfide bond52 ↔ 62 By similarity
Disulfide bond91 ↔ 107 By similarity

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Sequences

Sequence LengthMass (Da)Tools
Q2KL21-1 [UniParc].

Last modified March 7, 2006. Version 1.
Checksum: B740559861DCD1A9

FASTA50854,838
        10         20         30         40         50         60 
MNHLWTHLWP GVGSLCLLLA GAAWASLPKP LDPKFESKAA LLAARAPEEL LCFTERLEDL 

        70         80         90        100        110        120 
VCFWEEAASA GVGPDNYSFF YQLEGEPWKT CSLHQAPTTR GAVRFWCSLP TADTSSFVPL 

       130        140        150        160        170        180 
ELRATAVSSG ALLYRRIIHI NEVVLLDPPA GLLARRADEG GHVVLRWLPP PGAPVASLIR 

       190        200        210        220        230        240 
YEVNISGSVA GGSQKVEILD GRTECVLSNL RGGTRYTFMV RARMAEPSFG GFWSAWSEPA 

       250        260        270        280        290        300 
SLLTASDLDP LILTLSLILV LILLLLAVLA LLSHRRTLKQ KIWPGIPSPE SEFEGLFTTH 

       310        320        330        340        350        360 
KGNFQLWLYQ NEGCLWWSPC TPLAEDPPAP LEVLSERCWG APQAVEPGAD DEGPLLEPVG 

       370        380        390        400        410        420 
SEHSQDTYLV LDKWLLPRNP SSEDVSQSGG SLDIVAMDKG SEASSCSSGL SLKPGPEGAL 

       430        440        450        460        470        480 
GASFEYTILD PSSQLLCPRA LPPELPPTPP HIKYLYLMVS DSGISTDYSS GGSQGAQGDS 

       490        500 
LNSPFLNPYE NSLIPAPEPS PPGYVACS

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References

[1]"Transcriptional regulation of EPO-R during lung growth."
Zhang Q., Moe O.W., Hsia C.C.W.
Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].

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Cross-references

Sequence databases

AY908987 mRNA. Translation: AAX89035.1.
RefSeqNP_001041576.1.
UniGeneCfa.24663

3D structure databases

SMRQ2KL21. Positions 32-249.
ModBaseSearch...

Genome annotation databases

EnsemblENSCAFG00000017411. Canis familiaris. [Contig view]
GeneID484943.
KEGGcfa:484943.

Phylogenomic databases

HOVERGENQ2KL21.

Family and domain databases

InterProIPR015152. EpoR_lig-bind.
IPR009167. Erythropoietin_rcpt.
IPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
Gene3DG3DSA:2.60.40.30. FN_III-like. 2 hits.
PfamPF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
[Graphical view]
PIRSFPIRSF001959. EPO_receptor. 1 hit.
SMARTSM00060. FN3. 1 hit.
[Graphical view]
PROSITEPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]
ProtoNetSearch...

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Entry information

Entry nameEPOR_CANFA
AccessionPrimary (citable) accession number: Q2KL21
Entry history
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: March 7, 2006
Last modified: June 16, 2009
This is version 24 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents