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Protein

Erythropoietin receptor

Gene

EPOR

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 4 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
Sitei117 – 1171Required for ligand bindingBy similarity
Sitei426 – 4261Required for STAT5/PTPN11/SOCS3 bindingBy similarity
Sitei456 – 4561Required for STAT1/STAT3 activation
Sitei485 – 4851Required for CrkL bindingBy similarity

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Receptor

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 250226ExtracellularSequence analysisAdd
BLAST
Transmembranei251 – 27323HelicalSequence analysisAdd
BLAST
Topological domaini274 – 508235CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2424Sequence analysisAdd
BLAST
Chaini25 – 508484Erythropoietin receptorPRO_0000231014Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi52 ↔ 62By similarity
Glycosylationi76 – 761N-linked (GlcNAc...)Sequence analysis
Disulfide bondi91 ↔ 107By similarity
Glycosylationi184 – 1841N-linked (GlcNAc...)Sequence analysis
Cross-linki281 – 281Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei368 – 3681Phosphotyrosine; by JAK2By similarity
Modified residuei426 – 4261Phosphotyrosine; by JAK2By similarity
Cross-linki453 – 453Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei454 – 4541Phosphotyrosine; by JAK2By similarity
Modified residuei456 – 4561Phosphotyrosine; by JAK2By similarity
Modified residuei468 – 4681Phosphotyrosine; by JAK2By similarity
Modified residuei489 – 4891Phosphotyrosine; by JAK2By similarity
Modified residuei504 – 5041Phosphotyrosine; 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-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)LengthDescriptionGraphical viewFeature identifierActions
Sitei368 – 3681Interaction with APS and STAT5, and activationBy similarity
Sitei454 – 4541Interaction with PTPN6By similarity

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000025668.

Structurei

3D structure databases

ProteinModelPortaliQ2KL21.
SMRiQ2KL21. Positions 32-247.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini148 – 247100Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni454 – 4563Required for high-affinity SOCS3 binding

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi233 – 2375WSXWS motif
Motifi282 – 2909Box 1 motif
Motifi452 – 4576ITIM 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

eggNOGiENOG410IFGH. Eukaryota.
ENOG4111PGS. LUCA.
HOGENOMiHOG000059639.
HOVERGENiHBG005595.
InParanoidiQ2KL21.
KOiK05079.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR009167. Erythropoietin_rcpt.
IPR003961. FN3_dom.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PANTHERiPTHR23037:SF28. PTHR23037:SF28. 1 hit.
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]

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.

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortaliQ2KL21.
SMRiQ2KL21. Positions 32-247.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000025668.

Proteomic databases

PaxDbiQ2KL21.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi484943.
KEGGicfa:484943.

Organism-specific databases

CTDi2057.

Phylogenomic databases

eggNOGiENOG410IFGH. Eukaryota.
ENOG4111PGS. LUCA.
HOGENOMiHOG000059639.
HOVERGENiHBG005595.
InParanoidiQ2KL21.
KOiK05079.

Miscellaneous databases

NextBioi20859009.

Family and domain databases

Gene3Di2.60.40.10. 2 hits.
InterProiIPR009167. Erythropoietin_rcpt.
IPR003961. FN3_dom.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PANTHERiPTHR23037:SF28. PTHR23037:SF28. 1 hit.
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]
ProtoNetiSearch...

Publicationsi

  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].

Entry informationi

Entry nameiEPOR_CANLF
AccessioniPrimary (citable) accession number: Q2KL21
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: March 7, 2006
Last modified: December 9, 2015
This is version 67 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.