ID EPOR_PIG Reviewed; 509 AA.
AC Q9MYZ9;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 24-JAN-2024, entry version 134.
DE RecName: Full=Erythropoietin receptor;
DE Short=EPO-R;
DE Flags: Precursor;
GN Name=EPOR;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC TISSUE=Liver;
RX PubMed=10962196; DOI=10.1016/s0739-7240(00)00062-x;
RA Pearson P.L., Smith T.P.L., Sonstegard T.S., Klemcke H.G.,
RA Christenson R.K., Vallet J.L.;
RT "Porcine erythropoietin receptor: molecular cloning and expression in
RT embryonic and fetal liver.";
RL Domest. Anim. Endocrinol. 19:25-38(2000).
CC -!- FUNCTION: Receptor for erythropoietin. Mediates erythropoietin-induced
CC erythroblast proliferation and differentiation. Upon EPO stimulation,
CC EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In some
CC cell types, can also activate STAT1 and STAT3. May also activate LYN
CC tyrosine kinase (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Forms homodimers on EPO stimulation. The tyrosine-
CC phosphorylated form interacts with several SH2 domain-containing
CC proteins including LYN, the adapter protein APS, PTPN6, PTPN11, JAK2,
CC PI3 kinases, STAT5A/B, SOCS3 and CRKL. The N-terminal SH2 domain of
CC PTPN6 binds Tyr-455 and inhibits signaling through dephosphorylation of
CC JAK2. APS binding also inhibits the JAK-STAT signaling. Binding to
CC PTPN11, preferentially through the N-terminal SH2 domain, promotes
CC mitogenesis and phosphorylation of PTPN11. Binding of JAK2 (through its
CC N-terminal) promotes cell-surface expression. Interaction with the
CC ubiquitin ligase NOSIP mediates EPO-induced cell proliferation.
CC Interacts with ATXN2L and INPP5D/SHIP1 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- DEVELOPMENTAL STAGE: Low expression at day 24 gestation in fetal liver.
CC Expression increases dramatically thereafter to day 30. Levels then
CC remain constant up to day 40. {ECO:0000269|PubMed:10962196}.
CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC folding and thereby efficient intracellular transport and cell-surface
CC receptor binding.
CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC activation.
CC -!- DOMAIN: Contains 1 copy of a cytoplasmic motif that is referred to as
CC the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is
CC involved in modulation of cellular responses. The phosphorylated ITIM
CC motif can bind the SH2 domain of several SH2-containing phosphatases.
CC -!- PTM: On EPO stimulation, phosphorylated on C-terminal tyrosine residues
CC by JAK2. The phosphotyrosine motifs are also recruitment sites for
CC several SH2-containing proteins and adapter proteins which mediate cell
CC proliferation. Phosphorylation on Tyr-455 is required for PTPN6
CC interaction, Tyr-427 for PTPN11. Tyr-427 is also required for SOCS3
CC binding, but Tyr-455/Tyr-457 motif is the preferred binding site (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by NOSIP; appears to be either multi-
CC monoubiquitinated or polyubiquitinated. Ubiquitination mediates
CC proliferation and survival of EPO-dependent cells. Ubiquitination at
CC Lys-282 mediates receptor internalization, whereas ubiquitination at
CC Lys-454 promotes trafficking of activated receptors to the lysosomes
CC for degradation (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; AF274305; AAF77065.1; -; mRNA.
DR RefSeq; NP_999457.1; NM_214292.1.
DR AlphaFoldDB; Q9MYZ9; -.
DR SMR; Q9MYZ9; -.
DR STRING; 9823.ENSSSCP00000014472; -.
DR GlyCosmos; Q9MYZ9; 1 site, No reported glycans.
DR PaxDb; 9823-ENSSSCP00000014472; -.
DR Ensembl; ENSSSCT00000014873.5; ENSSSCP00000014472.2; ENSSSCG00000013618.5.
DR Ensembl; ENSSSCT00015108584.1; ENSSSCP00015046071.1; ENSSSCG00015079906.1.
DR Ensembl; ENSSSCT00025028183.1; ENSSSCP00025011922.1; ENSSSCG00025020746.1.
DR Ensembl; ENSSSCT00065073601.1; ENSSSCP00065032041.1; ENSSSCG00065053747.1.
DR Ensembl; ENSSSCT00070049940.1; ENSSSCP00070042181.1; ENSSSCG00070024992.1.
DR GeneID; 397554; -.
DR KEGG; ssc:397554; -.
DR CTD; 2057; -.
DR VGNC; VGNC:87746; EPOR.
DR eggNOG; ENOG502RYHW; Eukaryota.
DR GeneTree; ENSGT00940000160315; -.
DR HOGENOM; CLU_041434_0_0_1; -.
DR InParanoid; Q9MYZ9; -.
DR OMA; ERCWGTM; -.
DR OrthoDB; 5360031at2759; -.
DR TreeFam; TF336573; -.
DR Reactome; R-SSC-9006335; Signaling by Erythropoietin.
DR Reactome; R-SSC-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-SSC-9027284; Erythropoietin activates RAS.
DR Proteomes; UP000008227; Chromosome 2.
DR Proteomes; UP000314985; Chromosome 2.
DR Proteomes; UP000694570; Unplaced.
DR Proteomes; UP000694571; Unplaced.
DR Proteomes; UP000694720; Unplaced.
DR Proteomes; UP000694722; Unplaced.
DR Proteomes; UP000694723; Unplaced.
DR Proteomes; UP000694724; Unplaced.
DR Proteomes; UP000694725; Unplaced.
DR Proteomes; UP000694726; Unplaced.
DR Proteomes; UP000694727; Unplaced.
DR Proteomes; UP000694728; Unplaced.
DR Bgee; ENSSSCG00000013618; Expressed in endocardial endothelium and 24 other cell types or tissues.
DR ExpressionAtlas; Q9MYZ9; baseline and differential.
DR Genevisible; Q9MYZ9; SS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
DR GO; GO:0004900; F:erythropoietin receptor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR InterPro; IPR009167; Erythropoietin_rcpt.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR015152; Growth/epo_recpt_lig-bind.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003528; Long_hematopoietin_rcpt_CS.
DR PANTHER; PTHR23037; CYTOKINE RECEPTOR; 1.
DR PANTHER; PTHR23037:SF28; ERYTHROPOIETIN RECEPTOR; 1.
DR Pfam; PF09067; EpoR_lig-bind; 1.
DR Pfam; PF00041; fn3; 1.
DR PIRSF; PIRSF001959; EPO_receptor; 1.
DR SMART; SM00060; FN3; 1.
DR SUPFAM; SSF49265; Fibronectin type III; 2.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Isopeptide bond; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..509
FT /note="Erythropoietin receptor"
FT /id="PRO_0000010870"
FT TOPO_DOM 25..251
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..274
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 275..509
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 148..248
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 467..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 234..238
FT /note="WSXWS motif"
FT MOTIF 283..291
FT /note="Box 1 motif"
FT MOTIF 453..458
FT /note="ITIM motif"
FT COMPBIAS 467..490
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 117
FT /note="Required for ligand binding"
FT /evidence="ECO:0000250"
FT SITE 369
FT /note="Interaction with APS and STAT5, and activation"
FT /evidence="ECO:0000250"
FT SITE 427
FT /note="Required for STAT5/PTPN11/SOCS3 binding"
FT SITE 455
FT /note="Interaction with PTPN6"
FT MOD_RES 369
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 427
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 455
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 457
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 469
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 486
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 490
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 505
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52..62
FT /evidence="ECO:0000250"
FT DISULFID 91..107
FT /evidence="ECO:0000250"
FT CROSSLNK 282
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT CROSSLNK 454
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P14753"
SQ SEQUENCE 509 AA; 55184 MW; 35B565D07C6BCD8A CRC64;
MYHFGATLWP GVGSLCLLLA GATWAPSPNS PDAKFESKAA LLAARGPEEL LCFTERLEDL
VCFWEEAGSA GVGPEDYSFS YQLEGEPWKP CHLHQGPTAR GSVRFWCSLP TADTSSFVPL
ELRVTEVSSG APRYHRIIHI NEVVLLDPPA GLLARRAEES GHVVLRWLPP PGAPMASLIR
YEVNISTENA AGGVQRVEIL DGRTECVLSN LRGGTRYTFM VRARMAEPSF GGFWSAWSEP
ASLLTASDLD PLILTLSLIL VLILLLLAVL ALLSHRRTLK QKIWPGIPSP EGEFEGLFTT
HKGNFQLWLY QTDGCLWWSP CTPFAEDPPA PLEVLSERCW GVTQAVEPAA DDEGSLLEPV
GSEHARDTYL VLDKWLLPRR PASEDLPQPG GDLDMAAMDE ASEASFCSSA LALKPGPEGA
SAASFEYTIL DPSSQLLRPR ALPAELPPTP PHLKYLYLVV SDSGISTDYS SGGSQETQGG
SSSGPYSNPY ENSLVPAPEP SPPNYVTCS
//
