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 24-JAN-2024, entry version 218. 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}. 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; 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 GlyCosmos; P14753; 2 sites, No reported glycans. DR GlyGen; P14753; 2 sites. DR iPTMnet; P14753; -. DR PhosphoSitePlus; P14753; -. DR PaxDb; 10090-ENSMUSP00000006397; -. DR ProteomicsDB; 275461; -. [P14753-1] DR ProteomicsDB; 275462; -. [P14753-2] DR Antibodypedia; 13130; 1126 antibodies from 37 providers. DR DNASU; 13857; -. DR Ensembl; ENSMUST00000006397.7; ENSMUSP00000006397.6; ENSMUSG00000006235.7. [P14753-1] DR GeneID; 13857; -. DR KEGG; mmu:13857; -. DR UCSC; uc009ond.1; mouse. [P14753-1] DR UCSC; uc009one.1; mouse. [P14753-2] DR AGR; MGI:95408; -. 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; ERCWGTM; -. DR OrthoDB; 5360031at2759; -. DR PhylomeDB; P14753; -. DR TreeFam; TF336573; -. DR Reactome; R-MMU-9006335; Signaling by Erythropoietin. 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 82 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 122 other cell types or tissues. DR ExpressionAtlas; P14753; baseline and differential. DR GO; GO:0009986; C:cell surface; 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:0016607; C:nuclear speck; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. 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: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:1901033; P:positive regulation of response to reactive oxygen species; 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; 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. DR Genevisible; P14753; MM. 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 //