ID EPOR_CANLF Reviewed; 508 AA.
AC Q2KL21;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 27-MAR-2024, entry version 95.
DE RecName: Full=Erythropoietin receptor;
DE Short=EPO-R;
DE Flags: Precursor;
GN Name=EPOR;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang Q., Moe O.W., Hsia C.C.W.;
RT "Transcriptional regulation of EPO-R during lung growth.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
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-454 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 {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
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-454 is required for PTPN6
CC interaction, Tyr-426 for PTPN11. Tyr-426 is also required for SOCS3
CC binding, but Tyr-454/Tyr-456 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-281 mediates receptor internalization, whereas ubiquitination at
CC Lys-453 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY908987; AAX89035.1; -; mRNA.
DR RefSeq; NP_001041576.1; NM_001048111.1.
DR AlphaFoldDB; Q2KL21; -.
DR SMR; Q2KL21; -.
DR STRING; 9615.ENSCAFP00000025668; -.
DR GlyCosmos; Q2KL21; 2 sites, No reported glycans.
DR PaxDb; 9612-ENSCAFP00000025668; -.
DR GeneID; 484943; -.
DR KEGG; cfa:484943; -.
DR CTD; 2057; -.
DR eggNOG; ENOG502RYHW; Eukaryota.
DR InParanoid; Q2KL21; -.
DR OrthoDB; 5360031at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR Proteomes; UP000694429; Unplaced.
DR Proteomes; UP000694542; Unplaced.
DR Proteomes; UP000805418; Unplaced.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0004900; F:erythropoietin receptor activity; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
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..508
FT /note="Erythropoietin receptor"
FT /id="PRO_0000231014"
FT TOPO_DOM 25..250
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 251..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 274..508
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 148..247
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 454..456
FT /note="Required for high-affinity SOCS3 binding"
FT REGION 467..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 233..237
FT /note="WSXWS motif"
FT MOTIF 282..290
FT /note="Box 1 motif"
FT MOTIF 452..457
FT /note="ITIM motif"
FT COMPBIAS 467..489
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 368
FT /note="Interaction with APS and STAT5, and activation"
FT /evidence="ECO:0000250"
FT SITE 426
FT /note="Required for STAT5/PTPN11/SOCS3 binding"
FT /evidence="ECO:0000250"
FT SITE 454
FT /note="Interaction with PTPN6"
FT /evidence="ECO:0000250"
FT SITE 456
FT /note="Required for STAT1/STAT3 activation"
FT SITE 485
FT /note="Required for CrkL binding"
FT /evidence="ECO:0000250"
FT MOD_RES 368
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 426
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 454
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 456
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 468
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 489
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT MOD_RES 504
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT CARBOHYD 76
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 281
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P14753"
FT CROSSLNK 453
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P14753"
SQ SEQUENCE 508 AA; 54838 MW; B740559861DCD1A9 CRC64;
MNHLWTHLWP GVGSLCLLLA GAAWASLPKP LDPKFESKAA LLAARAPEEL LCFTERLEDL
VCFWEEAASA GVGPDNYSFF YQLEGEPWKT CSLHQAPTTR GAVRFWCSLP TADTSSFVPL
ELRATAVSSG ALLYRRIIHI NEVVLLDPPA GLLARRADEG GHVVLRWLPP PGAPVASLIR
YEVNISGSVA GGSQKVEILD GRTECVLSNL RGGTRYTFMV RARMAEPSFG GFWSAWSEPA
SLLTASDLDP LILTLSLILV LILLLLAVLA LLSHRRTLKQ KIWPGIPSPE SEFEGLFTTH
KGNFQLWLYQ NEGCLWWSPC TPLAEDPPAP LEVLSERCWG APQAVEPGAD DEGPLLEPVG
SEHSQDTYLV LDKWLLPRNP SSEDVSQSGG SLDIVAMDKG SEASSCSSGL SLKPGPEGAL
GASFEYTILD PSSQLLCPRA LPPELPPTPP HIKYLYLMVS DSGISTDYSS GGSQGAQGDS
LNSPFLNPYE NSLIPAPEPS PPGYVACS
//
