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Protein

Erythropoietin receptor

Gene

EPOR

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
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
Sitei117Required for ligand bindingBy similarity1
Sitei426Required for STAT5/PTPN11/SOCS3 bindingBy similarity1
Sitei456Required for STAT1/STAT3 activation1
Sitei485Required for CrkL bindingBy similarity1

GO - Molecular functioni

Keywordsi

Molecular functionReceptor

Names & Taxonomyi

Protein namesi
Recommended name:
Erythropoietin receptor
Short name:
EPO-R
Gene namesi
Name:EPOR
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 250ExtracellularSequence analysisAdd BLAST226
Transmembranei251 – 273HelicalSequence analysisAdd BLAST23
Topological domaini274 – 508CytoplasmicSequence analysisAdd BLAST235

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000023101425 – 508Erythropoietin receptorAdd BLAST484

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi52 ↔ 62By similarity
Glycosylationi76N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi91 ↔ 107By similarity
Glycosylationi184N-linked (GlcNAc...) asparagineSequence analysis1
Cross-linki281Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei368Phosphotyrosine; by JAK2By similarity1
Modified residuei426Phosphotyrosine; by JAK2By similarity1
Cross-linki453Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei454Phosphotyrosine; by JAK2By similarity1
Modified residuei456Phosphotyrosine; by JAK2By similarity1
Modified residuei468Phosphotyrosine; by JAK2By similarity1
Modified residuei489Phosphotyrosine; by JAK2By similarity1
Modified residuei504Phosphotyrosine; 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-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).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-281 mediates receptor internalization, whereas ubiquitination at Lys-453 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

PaxDbiQ2KL21

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-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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei368Interaction with APS and STAT5, and activationBy similarity1
Sitei454Interaction with PTPN6By similarity1

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000025668

Structurei

3D structure databases

ProteinModelPortaliQ2KL21
SMRiQ2KL21
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini148 – 247Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST100

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni454 – 456Required for high-affinity SOCS3 binding3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi233 – 237WSXWS motif5
Motifi282 – 290Box 1 motif9
Motifi452 – 457ITIM 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
InParanoidiQ2KL21
KOiK05079

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

Sequencei

Sequence statusi: Complete.

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

Q2KL21-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNHLWTHLWP GVGSLCLLLA GAAWASLPKP LDPKFESKAA LLAARAPEEL
60 70 80 90 100
LCFTERLEDL VCFWEEAASA GVGPDNYSFF YQLEGEPWKT CSLHQAPTTR
110 120 130 140 150
GAVRFWCSLP TADTSSFVPL ELRATAVSSG ALLYRRIIHI NEVVLLDPPA
160 170 180 190 200
GLLARRADEG GHVVLRWLPP PGAPVASLIR YEVNISGSVA GGSQKVEILD
210 220 230 240 250
GRTECVLSNL RGGTRYTFMV RARMAEPSFG GFWSAWSEPA SLLTASDLDP
260 270 280 290 300
LILTLSLILV LILLLLAVLA LLSHRRTLKQ KIWPGIPSPE SEFEGLFTTH
310 320 330 340 350
KGNFQLWLYQ NEGCLWWSPC TPLAEDPPAP LEVLSERCWG APQAVEPGAD
360 370 380 390 400
DEGPLLEPVG SEHSQDTYLV LDKWLLPRNP SSEDVSQSGG SLDIVAMDKG
410 420 430 440 450
SEASSCSSGL SLKPGPEGAL GASFEYTILD PSSQLLCPRA LPPELPPTPP
460 470 480 490 500
HIKYLYLMVS DSGISTDYSS GGSQGAQGDS LNSPFLNPYE NSLIPAPEPS

PPGYVACS
Length:508
Mass (Da):54,838
Last modified:March 7, 2006 - v1
Checksum:iB740559861DCD1A9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY908987 mRNA Translation: AAX89035.1
RefSeqiNP_001041576.1, NM_001048111.1
UniGeneiCfa.24663

Genome annotation databases

GeneIDi484943
KEGGicfa:484943

Similar proteinsi

Entry informationi

Entry nameiEPOR_CANLF
AccessioniPrimary (citable) accession number: Q2KL21
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: March 7, 2006
Last modified: February 28, 2018
This is version 77 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

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