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Protein

Erythropoietin receptor

Gene

EPOR

Organism
Sus scrofa (Pig)
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
Sitei427 – 4271Required for STAT5/PTPN11/SOCS3 binding

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Names & Taxonomyi

Protein namesi
Recommended name:
Erythropoietin receptor
Short name:
EPO-R
Gene namesi
Name:EPOR
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Chromosome 2

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini25 – 251227ExtracellularSequence analysisAdd
BLAST
Transmembranei252 – 27423HelicalSequence analysisAdd
BLAST
Topological domaini275 – 509235CytoplasmicSequence 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 – 509485Erythropoietin receptorPRO_0000010870Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi52 ↔ 62By similarity
Disulfide bondi91 ↔ 107By similarity
Glycosylationi184 – 1841N-linked (GlcNAc...)Sequence analysis
Cross-linki282 – 282Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei369 – 3691Phosphotyrosine; by JAK2By similarity
Modified residuei427 – 4271Phosphotyrosine; by JAK2By similarity
Cross-linki454 – 454Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei455 – 4551Phosphotyrosine; by JAK2By similarity
Modified residuei457 – 4571Phosphotyrosine; by JAK2By similarity
Modified residuei469 – 4691Phosphotyrosine; by JAK2By similarity
Modified residuei486 – 4861Phosphotyrosine; by JAK2By similarity
Modified residuei490 – 4901Phosphotyrosine; by JAK2By similarity
Modified residuei505 – 5051Phosphotyrosine; 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-455 is required for PTPN6 interaction, Tyr-427 for PTPN11. Tyr-427 is also required for SOCS3 binding, but Tyr-455/Tyr-457 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-282 mediates receptor internalization, whereas ubiquitination at Lys-454 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

PaxDbiQ9MYZ9.

Expressioni

Developmental stagei

Low expression at day 24 gestation in fetal liver. Expression increases dramatically thereafter to day 30. Levels then remain constant up to day 40.1 Publication

Gene expression databases

BgeeiENSSSCG00000013618.
GenevisibleiQ9MYZ9. SS.

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-455 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
Sitei369 – 3691Interaction with APS and STAT5, and activationBy similarity
Sitei455 – 4551Interaction with PTPN6

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000014472.

Structurei

3D structure databases

ProteinModelPortaliQ9MYZ9.
SMRiQ9MYZ9. Positions 32-248.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini148 – 248101Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi234 – 2385WSXWS motif
Motifi283 – 2919Box 1 motif
Motifi453 – 4586ITIM 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.
GeneTreeiENSGT00840000129885.
HOGENOMiHOG000059639.
HOVERGENiHBG005595.
InParanoidiQ9MYZ9.
KOiK05079.
OMAiFMVRARM.
OrthoDBiEOG091G0AK8.
TreeFamiTF336573.

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.

Q9MYZ9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MYHFGATLWP GVGSLCLLLA GATWAPSPNS PDAKFESKAA LLAARGPEEL
60 70 80 90 100
LCFTERLEDL VCFWEEAGSA GVGPEDYSFS YQLEGEPWKP CHLHQGPTAR
110 120 130 140 150
GSVRFWCSLP TADTSSFVPL ELRVTEVSSG APRYHRIIHI NEVVLLDPPA
160 170 180 190 200
GLLARRAEES GHVVLRWLPP PGAPMASLIR YEVNISTENA AGGVQRVEIL
210 220 230 240 250
DGRTECVLSN LRGGTRYTFM VRARMAEPSF GGFWSAWSEP ASLLTASDLD
260 270 280 290 300
PLILTLSLIL VLILLLLAVL ALLSHRRTLK QKIWPGIPSP EGEFEGLFTT
310 320 330 340 350
HKGNFQLWLY QTDGCLWWSP CTPFAEDPPA PLEVLSERCW GVTQAVEPAA
360 370 380 390 400
DDEGSLLEPV GSEHARDTYL VLDKWLLPRR PASEDLPQPG GDLDMAAMDE
410 420 430 440 450
ASEASFCSSA LALKPGPEGA SAASFEYTIL DPSSQLLRPR ALPAELPPTP
460 470 480 490 500
PHLKYLYLVV SDSGISTDYS SGGSQETQGG SSSGPYSNPY ENSLVPAPEP

SPPNYVTCS
Length:509
Mass (Da):55,184
Last modified:October 1, 2000 - v1
Checksum:i35B565D07C6BCD8A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF274305 mRNA. Translation: AAF77065.1.
RefSeqiNP_999457.1. NM_214292.1.
UniGeneiSsc.16355.

Genome annotation databases

EnsembliENSSSCT00000014873; ENSSSCP00000014472; ENSSSCG00000013618.
GeneIDi397554.
KEGGissc:397554.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF274305 mRNA. Translation: AAF77065.1.
RefSeqiNP_999457.1. NM_214292.1.
UniGeneiSsc.16355.

3D structure databases

ProteinModelPortaliQ9MYZ9.
SMRiQ9MYZ9. Positions 32-248.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000014472.

Proteomic databases

PaxDbiQ9MYZ9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSSSCT00000014873; ENSSSCP00000014472; ENSSSCG00000013618.
GeneIDi397554.
KEGGissc:397554.

Organism-specific databases

CTDi2057.

Phylogenomic databases

eggNOGiENOG410IFGH. Eukaryota.
ENOG4111PGS. LUCA.
GeneTreeiENSGT00840000129885.
HOGENOMiHOG000059639.
HOVERGENiHBG005595.
InParanoidiQ9MYZ9.
KOiK05079.
OMAiFMVRARM.
OrthoDBiEOG091G0AK8.
TreeFamiTF336573.

Gene expression databases

BgeeiENSSSCG00000013618.
GenevisibleiQ9MYZ9. SS.

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...

Entry informationi

Entry nameiEPOR_PIG
AccessioniPrimary (citable) accession number: Q9MYZ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: October 1, 2000
Last modified: September 7, 2016
This is version 100 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.