EPOR_MOUSE
ID EPOR_MOUSE Reviewed; 507 AA.
AC P14753; Q63852;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Erythropoietin receptor;
DE Short=EPO-R;
DE Flags: Precursor;
GN Name=Epor;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM EPOR-F).
RC TISSUE=Erythroleukemia;
RX PubMed=2539263; DOI=10.1016/0092-8674(89)90965-3;
RA D'Andrea A.D., Lodish H.F., Wong G.G.;
RT "Expression cloning of the murine erythropoietin receptor.";
RL Cell 57:277-285(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS
RP EPOR-F AND EPOR-S).
RC STRAIN=BALB/cJ; TISSUE=Erythroleukemia, and Liver;
RX PubMed=2175360; DOI=10.1016/0022-2836(90)90384-x;
RA Kuramochi S., Ikawa Y., Todokoro K.;
RT "Characterization of murine erythropoietin receptor genes.";
RL J. Mol. Biol. 216:567-575(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM EPOR-F), AND ALTERNATIVE SPLICING DUE
RP TO FRIEND SPLEEN FOCUS-FORMING VIRUS.
RC TISSUE=Erythroleukemia;
RX PubMed=1656233; DOI=10.1128/mcb.11.11.5527-5533.1991;
RA Hino M., Tojo A., Misawa Y., Morii H., Takaku F., Shibuya M.;
RT "Unregulated expression of the erythropoietin receptor gene caused by
RT insertion of spleen focus-forming virus long terminal repeat in a murine
RT erythroleukemia cell line.";
RL Mol. Cell. Biol. 11:5527-5533(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM EPOR-F).
RC STRAIN=C57BL/6J, and FVB/N-3; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-27.
RX PubMed=2162479; DOI=10.1128/mcb.10.7.3675-3682.1990;
RA Youssoufian H., Zon L.I., Orkin S.H., D'Andrea A.D., Lodish H.F.;
RT "Structure and transcription of the mouse erythropoietin receptor gene.";
RL Mol. Cell. Biol. 10:3675-3682(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
RX PubMed=1849897; DOI=10.1016/s0021-9258(20)89595-7;
RA Lacombe C., Chretien S., Lemarchandel V., Mayeux P., Romeo P.-H.,
RA Gisselbrecht S., Cartron J.-P.;
RT "Spleen focus-forming virus long terminal repeat insertional activation of
RT the murine erythropoietin receptor gene in the T3Cl-2 friend leukemia cell
RT line.";
RL J. Biol. Chem. 266:6952-6956(1991).
RN [7]
RP FUNCTION IN ERYTHROPOIETIN-INDUCED MITOGENESIS, AND MUTAGENESIS OF GLN-304;
RP TRP-306; SER-317; GLU-324; LEU-330 AND GLU-331.
RX PubMed=8382775; DOI=10.1128/mcb.13.3.1788-1795.1993;
RA Miura O., Cleveland J.L., Ihle J.N.;
RT "Inactivation of erythropoietin receptor function by point mutations in a
RT region having homology with other cytokine receptors.";
RL Mol. Cell. Biol. 13:1788-1795(1993).
RN [8]
RP INTERACTION WITH JAK2, PHOSPHORYLATION, AND MUTAGENESIS OF TRP-306.
RX PubMed=8068943;
RA Miura O., Nakamura N., Quelle F.W., Witthuhn B.A., Ihle J.N., Aoki N.;
RT "Erythropoietin induces association of the JAK2 protein tyrosine kinase
RT with the erythropoietin receptor in vivo.";
RL Blood 84:1501-1507(1994).
RN [9]
RP INTERACTION WITH PTPN6, PHOSPHORYLATION AT TYR-453, AND MUTAGENESIS OF
RP TYR-453; 453-TYR--TYR-455 AND TYR-455.
RX PubMed=7889566; DOI=10.1016/0092-8674(95)90351-8;
RA Klingmueller U., Lorenz U., Cantley L.C., Neel B.G., Lodish H.F.;
RT "Specific recruitment of SH-PTP1 to the erythropoietin receptor causes
RT inactivation of JAK2 and termination of proliferative signals.";
RL Cell 80:729-738(1995).
RN [10]
RP INTERACTION WITH PTPN11, PHOSPHORYLATION AT TYR-367; TYR-425; TYR-453;
RP TYR-455; TYR-467; TYR-484; TYR-488 AND TYR-503, AND MUTAGENESIS OF TYR-367;
RP TYR-425; TYR-453; TYR-455; TYR-467; TYR-484; TYR-488 AND TYR-503.
RX PubMed=8639815;
RA Tauchi T., Damen J.E., Toyama K., Feng G.-S., Broxmeyer H.E., Krystal G.;
RT "Tyrosine 425 within the activated erythropoietin receptor binds Syp,
RT reduces the erythropoietin required for Syp tyrosine phosphorylation, and
RT promotes mitogenesis.";
RL Blood 87:4495-4501(1996).
RN [11]
RP INTERACTION WITH STAT5, AND PHOSPHORYLATION AT TYR-367 AND TYR-425.
RX PubMed=8665851; DOI=10.1002/j.1460-2075.1996.tb00601.x;
RA Gobert S., Chretien S., Gouilleux F., Muller O., Pallard C.,
RA Dusanter-Fourt I., Groner B., Lacombe C., Gisselbrecht S., Mayeux P.;
RT "Identification of tyrosine residues within the intracellular domain of the
RT erythropoietin receptor crucial for STAT5 activation.";
RL EMBO J. 15:2434-2441(1996).
RN [12]
RP FUNCTION OF THE WSXWS MOTIF, AND MUTAGENESIS OF TRP-232; SER-233; ALA-234;
RP TRP-235 AND SER-236.
RX PubMed=8617735; DOI=10.1074/jbc.271.9.4699;
RA Hilton D.J., Watowich S.S., Katz L., Lodish H.F.;
RT "Saturation mutagenesis of the WSXWS motif of the erythropoietin
RT receptor.";
RL J. Biol. Chem. 271:4699-4708(1996).
RN [13]
RP INTERACTION WITH STAT5, PHOSPHORYLATION AT TYR-367, AND MUTAGENESIS OF
RP ARG-153; GLN-304; TRP-306; SER-317; GLU-324; LEU-330; GLU-331 AND TYR-367.
RX PubMed=8657137; DOI=10.1128/mcb.16.4.1622;
RA Quelle F.W., Wang D., Nosaka T., Thierfelder W.E., Stravopodis D.,
RA Weinstein Y., Ihle J.N.;
RT "Erythropoietin induces activation of Stat5 through association with
RT specific tyrosines on the receptor that are not required for a mitogenic
RT response.";
RL Mol. Cell. Biol. 16:1622-1631(1996).
RN [14]
RP INTERACTION WITH LYN.
RX PubMed=9573010;
RA Chin H., Arai A., Wakao H., Kamiyama R., Miyasaka N., Miura O.;
RT "Lyn physically associates with the erythropoietin receptor and may play a
RT role in activation of the Stat5 pathway.";
RL Blood 91:3734-3745(1998).
RN [15]
RP INTERACTION WITH INPP5D, AND PHOSPHORYLATION AT TYR-455.
RX PubMed=10660611; DOI=10.1074/jbc.275.6.4398;
RA Mason J.M., Beattie B.K., Liu Q., Dumont D.J., Barber D.L.;
RT "The SH2 inositol 5-phosphatase Ship1 is recruited in an SH2-dependent
RT manner to the erythropoietin receptor.";
RL J. Biol. Chem. 275:4398-4406(2000).
RN [16]
RP PHOSPHORYLATION, AND STAT5 ACTIVATION.
RX PubMed=11290583; DOI=10.1182/blood.v97.8.2230;
RA Barber D.L., Beattie B.K., Mason J.M., Nguyen M.H.-H., Yoakim M.,
RA Neel B.G., D'Andrea A.D., Frank D.A.;
RT "A common epitope is shared by activated signal transducer and activator of
RT transcription-5 (STAT5) and the phosphorylated erythropoietin receptor:
RT implications for the docking model of STAT activation.";
RL Blood 97:2230-2237(2001).
RN [17]
RP INTERACTION WITH CRKL AND LYN.
RX PubMed=11443118; DOI=10.1074/jbc.m102924200;
RA Arai A., Kanda E., Nosaka Y., Miyasaka N., Miura O.;
RT "CrkL is recruited through its SH2 domain to the erythropoietin receptor
RT and plays a role in Lyn-mediated receptor signaling.";
RL J. Biol. Chem. 276:33282-33290(2001).
RN [18]
RP INTERACTION WITH APS.
RX PubMed=12444928; DOI=10.1042/bj20020716;
RA Wollberg P., Lennartsson J., Gottfridsson E., Yoshimura A., Ronnstrand L.;
RT "The adapter protein APS associates with the multifunctional docking sites
RT Tyr-568 and Tyr-936 in c-Kit.";
RL Biochem. J. 370:1033-1038(2003).
RN [19]
RP MUTAGENESIS OF SER-233 AND ALA-234, AND GLYCOSYLATION AT TRP-232 (ISOFORM
RP EPOR-S).
RX PubMed=12859190; DOI=10.1021/bi034112p;
RA Furmanek A., Hess D., Rogniaux H., Hofsteenge J.;
RT "The WSAWS motif is C-hexosylated in a soluble form of the erythropoietin
RT receptor.";
RL Biochemistry 42:8452-8458(2003).
RN [20]
RP INTERACTION WITH FRIEND SPLEEN FOCUS-FORMING VIRUS GP55.
RX PubMed=12930840; DOI=10.1074/jbc.m302974200;
RA Constantinescu S.N., Keren T., Russ W.P., Ubarretxena-Belandia I.,
RA Malka Y., Kubatzky K.F., Engelman D.M., Lodish H.F., Henis Y.I.;
RT "The erythropoietin receptor transmembrane domain mediates complex
RT formation with viral anemic and polycythemic gp55 proteins.";
RL J. Biol. Chem. 278:43755-43763(2003).
RN [21]
RP UBIQUITINATION AT LYS-280 AND LYS-452.
RX PubMed=21183685; DOI=10.1074/jbc.m110.186890;
RA Bulut G.B., Sulahian R., Ma Y., Chi N.W., Huang L.J.;
RT "Ubiquitination regulates the internalization, endolysosomal sorting, and
RT signaling of the erythropoietin receptor.";
RL J. Biol. Chem. 286:6449-6457(2011).
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 the
CC LYN tyrosine kinase. {ECO:0000269|PubMed:8382775,
CC ECO:0000269|PubMed:8617735}.
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-453 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 (By similarity). Forms heterooligomers with
CC friend spleen focus-forming virus (FSFFV) gp55, probably via their
CC respective transmembrane domains. Interacts with INPP5D/SHIP1.
CC {ECO:0000250, ECO:0000269|PubMed:10660611, ECO:0000269|PubMed:11443118,
CC ECO:0000269|PubMed:12444928, ECO:0000269|PubMed:12930840,
CC ECO:0000269|PubMed:7889566, ECO:0000269|PubMed:8068943,
CC ECO:0000269|PubMed:8639815, ECO:0000269|PubMed:8657137,
CC ECO:0000269|PubMed:8665851, ECO:0000269|PubMed:9573010}.
CC -!- INTERACTION:
CC P14753; Q62120: Jak2; NbExp=4; IntAct=EBI-617901, EBI-646604;
CC P14753; Q62077: Plcg1; NbExp=4; IntAct=EBI-617901, EBI-300133;
CC P14753; Q8CIH5: Plcg2; NbExp=2; IntAct=EBI-617901, EBI-617954;
CC -!- SUBCELLULAR LOCATION: [Isoform EPOR-F]: Cell membrane; Single-pass type
CC I membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform EPOR-S]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=EPOR-F; Synonyms=Membrane-bound form;
CC IsoId=P14753-1; Sequence=Displayed;
CC Name=EPOR-S; Synonyms=Soluble form;
CC IsoId=P14753-2; Sequence=VSP_009512, VSP_009513;
CC -!- TISSUE SPECIFICITY: Expressed in relatively mature erythroid progenitor
CC cells and in EPO-responsive erythroleukemia cells.
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: The identity of the C-linked hexose on the WXXW motif has not been
CC determined. It is probably mannose.
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-453 is required for PTPN6
CC interaction, Tyr-425 for PTPN11. Tyr-425 is also required for SOCS3
CC binding, but Tyr-453/Tyr-455 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 (By similarity).
CC Ubiquitination at Lys-280 mediates receptor internalization, whereas
CC ubiquitination at Lys-452 promotes trafficking of activated receptors
CC to the lysosomes for degradation. {ECO:0000250,
CC ECO:0000269|PubMed:21183685}.
CC -!- MISCELLANEOUS: Interaction with FSFFV envelope-like membrane
CC glycoprotein gp55 leads to ligand-independent activation of EPOR and to
CC the abnormally rapid proliferation of erythroid precursor cells.
CC -!- MISCELLANEOUS: Viral promoter integration by Friend spleen focus-
CC forming virus (F-SFFVP) in the murine erythroleukemia cell line F5-5,
CC results in aberrant EPOR sequences and EPOR overexpression in erythroid
CC progenitor cells.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; J04843; AAA37571.1; -; mRNA.
DR EMBL; X53081; CAA37248.1; -; Genomic_DNA.
DR EMBL; S59388; AAB20029.2; -; mRNA.
DR EMBL; BC003953; AAH03953.1; -; mRNA.
DR EMBL; BC046282; AAH46282.1; -; mRNA.
DR EMBL; M38133; AAA37572.1; -; Genomic_DNA.
DR EMBL; M62360; AAA37582.1; -; Genomic_DNA.
DR CCDS; CCDS22915.1; -. [P14753-1]
DR PIR; A41686; A32385.
DR PIR; S14081; S14081.
DR RefSeq; NP_034279.3; NM_010149.3. [P14753-1]
DR PDB; 2MXB; NMR; -; A=236-283.
DR PDBsum; 2MXB; -.
DR AlphaFoldDB; P14753; -.
DR BMRB; P14753; -.
DR SMR; P14753; -.
DR BioGRID; 199488; 5.
DR CORUM; P14753; -.
DR DIP; DIP-657N; -.
DR IntAct; P14753; 10.
DR MINT; P14753; -.
DR STRING; 10090.ENSMUSP00000006397; -.
DR GlyGen; P14753; 2 sites.
DR iPTMnet; P14753; -.
DR PhosphoSitePlus; P14753; -.
DR PaxDb; P14753; -.
DR PRIDE; P14753; -.
DR ProteomicsDB; 275461; -. [P14753-1]
DR ProteomicsDB; 275462; -. [P14753-2]
DR Antibodypedia; 13130; 975 antibodies from 37 providers.
DR DNASU; 13857; -.
DR Ensembl; ENSMUST00000006397; ENSMUSP00000006397; ENSMUSG00000006235. [P14753-1]
DR GeneID; 13857; -.
DR KEGG; mmu:13857; -.
DR UCSC; uc009ond.1; mouse. [P14753-1]
DR UCSC; uc009one.1; mouse. [P14753-2]
DR CTD; 2057; -.
DR MGI; MGI:95408; Epor.
DR VEuPathDB; HostDB:ENSMUSG00000006235; -.
DR eggNOG; ENOG502RYHW; Eukaryota.
DR GeneTree; ENSGT00940000160315; -.
DR HOGENOM; CLU_041434_0_0_1; -.
DR InParanoid; P14753; -.
DR OMA; APRYHRI; -.
DR OrthoDB; 1442632at2759; -.
DR PhylomeDB; P14753; -.
DR TreeFam; TF336573; -.
DR Reactome; R-MMU-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-MMU-9027284; Erythropoietin activates RAS.
DR SABIO-RK; P14753; -.
DR BioGRID-ORCS; 13857; 1 hit in 77 CRISPR screens.
DR PRO; PR:P14753; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P14753; protein.
DR Bgee; ENSMUSG00000006235; Expressed in fetal liver hematopoietic progenitor cell and 120 other tissues.
DR ExpressionAtlas; P14753; baseline and differential.
DR Genevisible; P14753; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0004900; F:erythropoietin receptor activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; TAS:DFLAT.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0046697; P:decidualization; IDA:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0003007; P:heart morphogenesis; TAS:DFLAT.
DR GO; GO:0030097; P:hemopoiesis; IBA:GO_Central.
DR GO; GO:1903206; P:negative regulation of hydrogen peroxide-induced cell death; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; IDA:MGI.
DR GO; GO:0060979; P:vasculogenesis involved in coronary vascular morphogenesis; TAS:DFLAT.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; TAS:DFLAT.
DR GO; GO:0061032; P:visceral serous pericardium development; TAS:DFLAT.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 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:SF28; PTHR23037:SF28; 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; SSF49265; 2.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Host-virus interaction; Isopeptide bond; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..24
FT CHAIN 25..507
FT /note="Erythropoietin receptor"
FT /id="PRO_0000010869"
FT TOPO_DOM 25..249
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..272
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..507
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 146..246
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 381..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 466..507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 232..236
FT /note="WSXWS motif"
FT MOTIF 281..289
FT /note="Box 1 motif"
FT MOTIF 451..456
FT /note="ITIM motif"
FT COMPBIAS 396..423
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 116
FT /note="Required for ligand binding"
FT /evidence="ECO:0000250"
FT SITE 367
FT /note="Interaction with APS and STAT5, and activation"
FT SITE 425
FT /note="Required for STAT5/PTPN11/SOCS3 binding"
FT SITE 453
FT /note="Interaction with PTPN6"
FT MOD_RES 367
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000269|PubMed:8657137,
FT ECO:0000269|PubMed:8665851, ECO:0000305|PubMed:8639815"
FT MOD_RES 425
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000269|PubMed:8639815,
FT ECO:0000269|PubMed:8665851"
FT MOD_RES 453
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000269|PubMed:7889566,
FT ECO:0000305|PubMed:8639815"
FT MOD_RES 455
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000305|PubMed:10660611,
FT ECO:0000305|PubMed:8639815"
FT MOD_RES 467
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000305|PubMed:8639815"
FT MOD_RES 484
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000305|PubMed:8639815"
FT MOD_RES 488
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000305|PubMed:8639815"
FT MOD_RES 503
FT /note="Phosphotyrosine; by JAK2"
FT /evidence="ECO:0000305|PubMed:8639815"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 52..62
FT /evidence="ECO:0000250"
FT DISULFID 90..106
FT /evidence="ECO:0000250"
FT CROSSLNK 280
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21183685"
FT CROSSLNK 452
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:21183685"
FT VAR_SEQ 246..265
FT /note="DLDPLILTLSLILVLISLLL -> GEALVPRGAGGAGPNTRQTP (in
FT isoform EPOR-S)"
FT /evidence="ECO:0000305"
FT /id="VSP_009512"
FT VAR_SEQ 266..507
FT /note="Missing (in isoform EPOR-S)"
FT /evidence="ECO:0000305"
FT /id="VSP_009513"
FT MUTAGEN 153
FT /note="R->C: Reduced JAK2/STAT5 activation."
FT /evidence="ECO:0000269|PubMed:8657137"
FT MUTAGEN 232
FT /note="W->A,C,D,E,G,H,I,K,L,M,N,P,Q,R,S,T,V,Y: Loss of EPO
FT binding."
FT /evidence="ECO:0000269|PubMed:8617735"
FT MUTAGEN 232
FT /note="W->F: Greatly reduced EPO binding."
FT /evidence="ECO:0000269|PubMed:8617735"
FT MUTAGEN 233
FT /note="S->A: Not secreted and loss of EPO binding."
FT /evidence="ECO:0000269|PubMed:12859190,
FT ECO:0000269|PubMed:8617735"
FT MUTAGEN 233
FT /note="S->C,D,E,F,H,I,K,L,M,N,P,Q,R,V,W,Y: Loss of EPO
FT binding."
FT /evidence="ECO:0000269|PubMed:12859190,
FT ECO:0000269|PubMed:8617735"
FT MUTAGEN 233
FT /note="S->G: 50-fold less EPO binding."
FT /evidence="ECO:0000269|PubMed:12859190,
FT ECO:0000269|PubMed:8617735"
FT MUTAGEN 233
FT /note="S->T: 2-fold less EPO binding."
FT /evidence="ECO:0000269|PubMed:12859190,
FT ECO:0000269|PubMed:8617735"
FT MUTAGEN 234
FT /note="A->C,D,G,H,K,N,Q,R,S,T: No change in EPO binding."
FT /evidence="ECO:0000269|PubMed:12859190,
FT ECO:0000269|PubMed:8617735"
FT MUTAGEN 234
FT /note="A->E: Enhanced secretion and increased EPO binding."
FT /evidence="ECO:0000269|PubMed:12859190,
FT ECO:0000269|PubMed:8617735"
FT MUTAGEN 234
FT /note="A->F,I,M,W,Y: Little EPO binding."
FT /evidence="ECO:0000269|PubMed:12859190,
FT ECO:0000269|PubMed:8617735"
FT MUTAGEN 234
FT /note="A->L,P,V: Reduced EPO binding."
FT /evidence="ECO:0000269|PubMed:12859190,
FT ECO:0000269|PubMed:8617735"
FT MUTAGEN 235
FT /note="W->A,C,D,E,G,H,I,K,L,M,N,P,Q,R,S,T,V: Loss of EPO
FT binding."
FT /evidence="ECO:0000269|PubMed:8617735"
FT MUTAGEN 235
FT /note="W->F: 14-fold less EPO binding."
FT /evidence="ECO:0000269|PubMed:8617735"
FT MUTAGEN 235
FT /note="W->Y: 100-fold less EPO binding."
FT /evidence="ECO:0000269|PubMed:8617735"
FT MUTAGEN 236
FT /note="S->A,C,G: Reduced EPO binding."
FT /evidence="ECO:0000269|PubMed:8617735"
FT MUTAGEN 236
FT /note="S->D,E,F,H,I,K,L,M,N,P,Q,R,V,W: Loss of EPO
FT binding."
FT /evidence="ECO:0000269|PubMed:8617735"
FT MUTAGEN 236
FT /note="S->T: No loss of EPO binding."
FT /evidence="ECO:0000269|PubMed:8617735"
FT MUTAGEN 236
FT /note="S->Y: Greatly reduced EPO binding."
FT /evidence="ECO:0000269|PubMed:8617735"
FT MUTAGEN 304
FT /note="Q->L: Greatly reduced JAK2/STAT5 activation and some
FT loss of mitogenic response."
FT /evidence="ECO:0000269|PubMed:8382775,
FT ECO:0000269|PubMed:8657137"
FT MUTAGEN 306
FT /note="W->R: No JAK2 binding nor JAK2/STAT5 activation. No
FT EPO-induced phosphorylation. Complete loss of mitogenic
FT response."
FT /evidence="ECO:0000269|PubMed:8068943,
FT ECO:0000269|PubMed:8382775, ECO:0000269|PubMed:8657137"
FT MUTAGEN 317
FT /note="S->R: Slightly reduced JAK2/STAT5 activation and
FT mitogenic response."
FT /evidence="ECO:0000269|PubMed:8382775,
FT ECO:0000269|PubMed:8657137"
FT MUTAGEN 324
FT /note="E->V: No change in JAK2/STAT5 activation nor
FT mitogenic response."
FT /evidence="ECO:0000269|PubMed:8382775,
FT ECO:0000269|PubMed:8657137"
FT MUTAGEN 330
FT /note="L->R: Reduced JAK2/STAT5 activation."
FT /evidence="ECO:0000269|PubMed:8382775,
FT ECO:0000269|PubMed:8657137"
FT MUTAGEN 331
FT /note="E->A: No change in JAK2/STAT5 activation nor
FT mitogenic response."
FT /evidence="ECO:0000269|PubMed:8382775,
FT ECO:0000269|PubMed:8657137"
FT MUTAGEN 331
FT /note="E->K: Reduced JAK2/STAT5 activation and mitogenic
FT response."
FT /evidence="ECO:0000269|PubMed:8382775,
FT ECO:0000269|PubMed:8657137"
FT MUTAGEN 367
FT /note="Y->F: No STAT5 activation."
FT /evidence="ECO:0000269|PubMed:8639815,
FT ECO:0000269|PubMed:8657137"
FT MUTAGEN 425
FT /note="Y->F: No PTPN11 binding, reduced PTPN11 tyrosine
FT phosphorylation and reduced cell proliferation."
FT /evidence="ECO:0000269|PubMed:8639815"
FT MUTAGEN 453..455
FT /note="YLY->FLF: No binding to PTPN6 SH2 domains. Enhanced
FT JAK2 activation and cell proliferation."
FT /evidence="ECO:0000269|PubMed:7889566"
FT MUTAGEN 453
FT /note="Y->F: No PTPN6 binding, binds PTPN11."
FT /evidence="ECO:0000269|PubMed:7889566,
FT ECO:0000269|PubMed:8639815"
FT MUTAGEN 455
FT /note="Y->F: Binds to PTPN6 and PTPN11 SH2 domains."
FT /evidence="ECO:0000269|PubMed:7889566,
FT ECO:0000269|PubMed:8639815"
FT MUTAGEN 467
FT /note="Y->F: No loss of PTPN11 binding."
FT /evidence="ECO:0000269|PubMed:8639815"
FT MUTAGEN 484
FT /note="Y->F: No loss of PTPN11 binding."
FT /evidence="ECO:0000269|PubMed:8639815"
FT MUTAGEN 488
FT /note="Y->F: No loss of PTPN11 binding."
FT /evidence="ECO:0000269|PubMed:8639815"
FT MUTAGEN 503
FT /note="Y->F: No loss of PTPN11 binding."
FT /evidence="ECO:0000269|PubMed:8639815"
FT CONFLICT 291
FT /note="E -> D (in Ref. 3; AAB20029)"
FT /evidence="ECO:0000305"
FT HELIX 239..243
FT /evidence="ECO:0007829|PDB:2MXB"
FT TURN 244..246
FT /evidence="ECO:0007829|PDB:2MXB"
FT HELIX 249..281
FT /evidence="ECO:0007829|PDB:2MXB"
FT CARBOHYD P14753-2:232
FT /note="C-linked (Man) tryptophan"
FT /evidence="ECO:0000269|PubMed:12859190"
SQ SEQUENCE 507 AA; 55194 MW; 067657A2E26451CA CRC64;
MDKLRVPLWP RVGPLCLLLA GAAWAPSPSL PDPKFESKAA LLASRGSEEL LCFTQRLEDL
VCFWEEAASS GMDFNYSFSY QLEGESRKSC SLHQAPTVRG SVRFWCSLPT ADTSSFVPLE
LQVTEASGSP RYHRIIHINE VVLLDAPAGL LARRAEEGSH VVLRWLPPPG APMTTHIRYE
VDVSAGNRAG GTQRVEVLEG RTECVLSNLR GGTRYTFAVR ARMAEPSFSG FWSAWSEPAS
LLTASDLDPL ILTLSLILVL ISLLLTVLAL LSHRRTLQQK IWPGIPSPES EFEGLFTTHK
GNFQLWLLQR DGCLWWSPGS SFPEDPPAHL EVLSEPRWAV TQAGDPGADD EGPLLEPVGS
EHAQDTYLVL DKWLLPRTPC SENLSGPGGS VDPVTMDEAS ETSSCPSDLA SKPRPEGTSP
SSFEYTILDP SSQLLCPRAL PPELPPTPPH LKYLYLVVSD SGISTDYSSG GSQGVHGDSS
DGPYSHPYEN SLVPDSEPLH PGYVACS
