ID EPO_HUMAN Reviewed; 193 AA. AC P01588; Q2M2L6; Q549U2; Q9UDZ0; Q9UEZ5; Q9UHA0; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 02-SEP-2026, entry version 229. DE RecName: Full=Erythropoietin {ECO:0000303|PubMed:3838366}; DE AltName: INN=Epoetin; DE Flags: Precursor; GN Name=EPO; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=3838366; DOI=10.1038/313806a0; RA Jacobs K., Shoemaker C., Rudersdorf R., Neill S.D., Kaufman R.J., RA Mufson A., Seehra J., Jones S.S., Hewick R., Fritsch E.F., Kawakita M., RA Shimizu T., Miyake T.; RT "Isolation and characterization of genomic and cDNA clones of human RT erythropoietin."; RL Nature 313:806-810(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY. RX PubMed=3865178; DOI=10.1073/pnas.82.22.7580; RA Lin F.-K., Suggs S., Lin C.-H., Browne J.K., Smalling R., Egrie J.C., RA Chen K.K., Fox G.M., Martin F., Stabinsky Z., Badrawi S.M., Lai P.-H., RA Goldwasser E.; RT "Cloning and expression of the human erythropoietin gene."; RL Proc. Natl. Acad. Sci. U.S.A. 82:7580-7584(1985). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9799793; DOI=10.1101/gr.8.10.1060; RA Gloeckner G., Scherer S., Schattevoy R., Boright A.P., Weber J., RA Tsui L.-C., Rosenthal A.; RT "Large-scale sequencing of two regions in human chromosome 7q22: analysis RT of 650 kb of genomic sequence around the EPO and CUTL1 loci reveals 17 RT genes."; RL Genome Res. 8:1060-1073(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Rupert J.L., Hochachka P.W.; RT "Erythropoietin gene sequence in the Quechua, a high altitude native RT population."; RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 58-193, AND VARIANTS HEPATOCELLULAR CARCINOMA RP 131-SER-LEU-132 DELINS ASN-PHE AND GLN-149. RX PubMed=8396923; DOI=10.1006/bbrc.1993.2104; RA Funakoshi A., Muta H., Baba T., Shimizu S.; RT "Gene expression of mutant erythropoietin in hepatocellular carcinoma."; RL Biochem. Biophys. Res. Commun. 195:717-722(1993). RN [8] RP PROTEIN SEQUENCE OF 28-193, AND DISULFIDE BONDS. RC TISSUE=Urine; RX PubMed=3949763; DOI=10.1016/s0021-9258(17)35756-3; RA Lai P.H., Everett R., Wang F.F., Arakawa T., Goldwasser E.; RT "Structural characterization of human erythropoietin."; RL J. Biol. Chem. 261:3116-3121(1986). RN [9] RP PRELIMINARY PROTEIN SEQUENCE OF 28-57. RX PubMed=6698989; DOI=10.1016/s0021-9258(17)43202-9; RA Yanagawa S., Hirade K., Ohnota H., Sasaki R., Chiba H., Ueda M., Goto M.; RT "Isolation of human erythropoietin with monoclonal antibodies."; RL J. Biol. Chem. 259:2707-2710(1984). RN [10] RP STRUCTURE OF CARBOHYDRATES. RX PubMed=3346214; DOI=10.1016/s0021-9258(18)68975-6; RA Takeuchi M., Takasaki S., Miyazaki H., Kato T., Hoshi S., Kochibe N., RA Kobata A.; RT "Comparative study of the asparagine-linked sugar chains of human RT erythropoietins purified from urine and the culture medium of recombinant RT Chinese hamster ovary cells."; RL J. Biol. Chem. 263:3657-3663(1988). RN [11] RP STRUCTURE OF CARBOHYDRATES. RX PubMed=3219367; DOI=10.1021/bi00423a017; RA Sasaki H., Ochi N., Dell A., Fukuda M.; RT "Site-specific glycosylation of human recombinant erythropoietin: analysis RT of glycopeptides or peptides at each glycosylation site by fast atom RT bombardment mass spectrometry."; RL Biochemistry 27:8618-8626(1988). RN [12] RP STRUCTURE OF CARBOHYDRATES. RX PubMed=1820196; DOI=10.1093/glycob/1.4.337; RA Takeuchi M., Kobata A.; RT "Structures and functional roles of the sugar chains of human RT erythropoietins."; RL Glycobiology 1:337-346(1991). RN [13] RP STRUCTURE OF CARBOHYDRATES. RX PubMed=11739166; DOI=10.1182/blood.v98.13.3626; RA Skibeli V., Nissen-Lie G., Torjesen P.; RT "Sugar profiling proves that human serum erythropoietin differs from RT recombinant human erythropoietin."; RL Blood 98:3626-3634(2001). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=32989016; DOI=10.1128/mcb.00180-20; RA Lin Z., King R., Tang V., Myers G., Balbin-Cuesta G., Friedman A., RA McGee B., Desch K., Ozel A.B., Siemieniak D., Reddy P., Emmer B., RA Khoriaty R.; RT "The endoplasmic reticulum cargo receptor SURF4 facilitates efficient RT erythropoietin secretion."; RL Mol. Cell. Biol. 40:0-0(2020). RN [15] RP INVOLVEMENT IN ECYT5. RX PubMed=29514032; DOI=10.1056/nejmoa1709064; RA Zmajkovic J., Lundberg P., Nienhold R., Torgersen M.L., Sundan A., RA Waage A., Skoda R.C.; RT "A Gain-of-function mutation in EPO in familial erythrocytosis."; RL N. Engl. J. Med. 378:924-930(2018). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 28-193 IN COMPLEX WITH EPOR, AND RP FUNCTION. RX PubMed=9774108; DOI=10.1038/26773; RA Syed R.S., Reid S.W., Li C., Cheetham J.C., Aoki K.H., Liu B., Zhan H., RA Osslund T.D., Chirino A.J., Zhang J., Finer-Moore J., Elliott S., RA Sitney K., Katz B.A., Matthews D.J., Wendoloski J.J., Egrie J., RA Stroud R.M.; RT "Efficiency of signalling through cytokine receptors depends critically on RT receptor orientation."; RL Nature 395:511-516(1998). RN [17] RP STRUCTURE BY NMR OF 28-193. RX PubMed=9783743; DOI=10.1038/2302; RA Cheetham J.C., Smith D.M., Aoki K.H., Stevenson J.L., Hoeffel T.J., RA Syed R.S., Egrie J., Harvey T.S.; RT "NMR structure of human erythropoietin and a comparison with its receptor RT bound conformation."; RL Nat. Struct. Biol. 5:861-866(1998). RN [18] RP INVOLVEMENT IN SUSCEPTIBILITY TO MICROVASCULAR COMPLICATIONS OF DIABETES RP TYPE 2. RX PubMed=18458324; DOI=10.1073/pnas.0800454105; RG Genetics of diabetes and diabetic complication study group; RA Tong Z., Yang Z., Patel S., Chen H., Gibbs D., Yang X., Hau V.S., RA Kaminoh Y., Harmon J., Pearson E., Buehler J., Chen Y., Yu B., RA Tinkham N.H., Zabriskie N.A., Zeng J., Luo L., Sun J.K., Prakash M., RA Hamam R.N., Tonna S., Constantine R., Ronquillo C.C., Sadda S., Avery R.L., RA Brand J.M., London N., Anduze A.L., King G.L., Bernstein P.S., Watkins S., RA Jorde L.B., Li D.Y., Aiello L.P., Pollak M.R., Zhang K.; RT "Promoter polymorphism of the erythropoietin gene in severe diabetic eye RT and kidney complications."; RL Proc. Natl. Acad. Sci. U.S.A. 105:6998-7003(2008). RN [19] RP INVOLVEMENT IN ECYT5, VARIANTS ECYT5 ASN-70; ARG-84; LEU-114 AND CYS-147, RP AND VARIANT GLY-99. RX PubMed=27651169; DOI=10.3324/haematol.2016.144063; RA Camps C., Petousi N., Bento C., Cario H., Copley R.R., McMullin M.F., RA van Wijk R., Ratcliffe P.J., Robbins P.A., Taylor J.C.; RT "Gene panel sequencing improves the diagnostic work-up of patients with RT idiopathic erythrocytosis and identifies new mutations."; RL Haematologica 101:1306-1318(2016). RN [20] RP INVOLVEMENT IN DBAL, VARIANT DBAL GLN-177, CHARACTERIZATION OF VARIANT DBAL RP GLN-177, FUNCTION, AND MUTAGENESIS OF SER-127. RX PubMed=28283061; DOI=10.1016/j.cell.2017.02.026; RA Kim A.R., Ulirsch J.C., Wilmes S., Unal E., Moraga I., Karakukcu M., RA Yuan D., Kazerounian S., Abdulhay N.J., King D.S., Gupta N., Gabriel S.B., RA Lander E.S., Patiroglu T., Ozcan A., Ozdemir M.A., Garcia K.C., Piehler J., RA Gazda H.T., Klein D.E., Sankaran V.G.; RT "Functional selectivity in cytokine signaling revealed through a pathogenic RT EPO mutation."; RL Cell 168:1053-1064(2017). CC -!- FUNCTION: Hormone involved in the regulation of erythrocyte CC proliferation and differentiation and the maintenance of a CC physiological level of circulating erythrocyte mass (PubMed:28283061). CC Binds to EPOR leading to EPOR dimerization and JAK2 activation thereby CC activating specific downstream effectors, including STAT1 and STAT3 CC (PubMed:9774108). {ECO:0000269|PubMed:28283061, CC ECO:0000269|PubMed:9774108}. CC -!- INTERACTION: CC P01588; P54760: EPHB4; NbExp=6; IntAct=EBI-1027362, EBI-702121; CC P01588; P19235: EPOR; NbExp=3; IntAct=EBI-1027362, EBI-617321; CC P01588; P33908: MAN1A1; NbExp=2; IntAct=EBI-1027362, EBI-12586254; CC PRO_0000008401; P19235: EPOR; NbExp=2; IntAct=EBI-11508463, EBI-617321; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:32989016}. CC -!- TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by CC liver of fetal or neonatal mammals. {ECO:0000269|PubMed:3865178}. CC -!- DISEASE: Microvascular complications of diabetes 2 (MVCD2) CC [MIM:612623]: Pathological conditions that develop in numerous tissues CC and organs as a consequence of diabetes mellitus. They include diabetic CC retinopathy, diabetic nephropathy leading to end-stage renal disease, CC and diabetic neuropathy. Diabetic retinopathy remains the major cause CC of new-onset blindness among diabetic adults. It is characterized by CC vascular permeability and increased tissue ischemia and angiogenesis. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- DISEASE: Erythrocytosis, familial, 5 (ECYT5) [MIM:617907]: An autosomal CC dominant disorder characterized by elevated serum hemoglobin and CC hematocrit. Some patients have increased serum erythropoietin levels. CC {ECO:0000269|PubMed:27651169, ECO:0000269|PubMed:29514032}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Diamond-Blackfan anemia-like (DBAL) [MIM:617911]: An autosomal CC recessive hematologic disease characterized by severe red cell CC hypoplastic anemia, selective absence of red cell precursors and CC progenitors seen on bone marrow biopsy, and increased serum CC erythropoietin. {ECO:0000269|PubMed:28283061}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- PHARMACEUTICAL: Used for the treatment of anemia. Available under the CC names Epogen (Amgen), Epogin (Chugai), Epomax (Elanex), Eprex (Janssen- CC Cilag), NeoRecormon or Recormon (Roche), Dynepo (Shire Pharmaceuticals) CC and Procrit (Ortho Biotech). Variations in the glycosylation pattern of CC EPO distinguishes these products. Epogen, Epogin, Eprex and Procrit are CC generically known as epoetin alfa, NeoRecormon and Recormon as epoetin CC beta, Dynepo as epoetin delta and Epomax as epoetin omega. Epoetin zeta CC is the name used for some 'biosimilars' forms of epoetin alfa and is CC available under the names Silapo (Stada) and Retacrit (Hospira). CC Darbepoetin alfa is a form created by 5 substitutions (Asn-57, Thr-59, CC Val-114, Asn-115 and Thr-117) that create 2 new N-glycosylation sites. CC It has a longer circulating half-life in vivo. It is available under CC the name Aranesp (Amgen). EPO is being much misused as a performance- CC enhancing drug in endurance athletes. CC -!- SIMILARITY: Belongs to the EPO/TPO family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Erythropoietin entry; CC URL="https://en.wikipedia.org/wiki/Erythropoietin"; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Journey into a tiny world CC - Issue 84 of July 2007; CC URL="https://www.proteinspotlight.org/back_issues/084/"; 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; X02158; CAA26095.1; -; Genomic_DNA. DR EMBL; X02157; CAA26094.1; -; mRNA. DR EMBL; M11319; AAA52400.1; -; Genomic_DNA. DR EMBL; AF053356; AAC78791.1; -; Genomic_DNA. DR EMBL; AF202308; AAF23132.1; -; Genomic_DNA. DR EMBL; AF202306; AAF23132.1; JOINED; Genomic_DNA. DR EMBL; AF202307; AAF23132.1; JOINED; Genomic_DNA. DR EMBL; AH009004; AAF23133.1; -; Genomic_DNA. DR EMBL; AF202311; AAF17572.1; -; Genomic_DNA. DR EMBL; AF202314; AAF23134.1; -; Genomic_DNA. DR EMBL; AF202312; AAF23134.1; JOINED; Genomic_DNA. DR EMBL; AF202313; AAF23134.1; JOINED; Genomic_DNA. DR EMBL; AC009488; AAP22357.1; -; Genomic_DNA. DR EMBL; BC093628; AAH93628.1; -; mRNA. DR EMBL; BC111937; AAI11938.1; -; mRNA. DR EMBL; S65458; AAD13964.1; -; mRNA. DR CCDS; CCDS5705.1; -. DR PIR; A01855; ZUHU. DR RefSeq; NP_000790.2; NM_000799.4. DR PDB; 1BUY; NMR; -; A=28-193. DR PDB; 1CN4; X-ray; 2.80 A; C=28-193. DR PDB; 1EER; X-ray; 1.90 A; A=28-193. DR AlphaFoldDB; P01588; -. DR MDposit; P01588; -. DR SMR; P01588; -. DR BioGRID; 108370; 35. DR ComplexPortal; CPX-26531; Erythropoietin receptor-ligand complex. DR CORUM; P01588; -. DR DIP; DIP-5731N; -. DR FunCoup; P01588; 843. DR IntAct; P01588; 11. DR MINT; P01588; -. DR NDEx; IQUERY-CP-EPO; 18 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000252723; -. DR ChEMBL; CHEMBL5837; -. DR Allergome; 11697; Hom s EPO. DR GlyConnect; P01588; 201 N-Linked glycans (3 sites), 26 O-Linked glycans (1 site). DR GlyCosmos; P01588; 4 sites, 210 glycans. DR GlyGen; P01588; 5 sites, 190 N-linked glycans (4 sites), 18 O-linked glycans (2 sites). DR iPTMnet; P01588; -. DR MetOSite; P01588; -. DR PhosphoSitePlus; P01588; -. DR BioMuta; EPO; -. DR DMDM; 119526; -. DR MassIVE; P01588; -. DR PaxDb; 9606-ENSP00000252723; -. DR PeptideAtlas; P01588; -. DR Antibodypedia; 4151; 1324 antibodies from 42 providers. DR DNASU; 2056; -. DR Ensembl; ENST00000252723.3; ENSP00000252723.2; ENSG00000130427.3. DR GeneID; 2056; -. DR KEGG; hsa:2056; -. DR MANE-Select; ENST00000252723.3; ENSP00000252723.2; NM_000799.4; NP_000790.2. DR UCSC; uc003uwi.5; human. DR AGR; HGNC:3415; -. DR ClinPGx; PA27833; -. DR CTD; 2056; -. DR DisGeNET; 2056; -. DR GeneCards; EPO; -. DR HGNC; HGNC:3415; EPO. DR HPA; ENSG00000130427; Tissue enriched (liver). DR MalaCards; EPO; -. DR MIM; 133170; gene. DR MIM; 612623; phenotype. DR MIM; 617907; phenotype. DR MIM; 617911; phenotype. DR OpenTargets; ENSG00000130427; -. DR Orphanet; 247511; Autosomal dominant secondary polycythemia. DR VEuPathDB; HostDB:ENSG00000130427; -. DR eggNOG; ENOG502RXRC; Eukaryota. DR GeneTree; ENSGT00390000017226; -. DR HOGENOM; CLU_110946_0_0_1; -. DR InParanoid; P01588; -. DR OMA; AMEFPRL; -. DR OrthoDB; 9892121at2759; -. DR PAN-GO; P01588; 8 GO annotations based on evolutionary models. DR PhylomeDB; P01588; -. DR PathwayCommons; P01588; -. DR Reactome; R-HSA-1234158; Regulation of gene expression by Hypoxia-inducible Factor. DR Reactome; R-HSA-9006335; Signaling by Erythropoietin. DR Reactome; R-HSA-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K). DR Reactome; R-HSA-9027277; Erythropoietin activates Phospholipase C gamma (PLCG). DR Reactome; R-HSA-9027283; Erythropoietin activates STAT5. DR Reactome; R-HSA-9027284; Erythropoietin activates RAS. DR SignaLink; P01588; -. DR SIGNOR; P01588; -. DR Agora; ENSG00000130427; -. DR BioGRID-ORCS; 2056; 14 hits in 1149 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR EvolutionaryTrace; P01588; -. DR GeneWiki; Erythropoietin; -. DR GenomeRNAi; 2056; -. DR Pharos; P01588; Tbio. DR PRO; PR:P01588; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P01588; protein. DR Bgee; ENSG00000130427; Expressed in right lobe of liver and 65 other cell types or tissues. DR ExpressionAtlas; P01588; baseline and differential. DR GO; GO:0044297; C:cell body; IEA:Ensembl. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0043235; C:signaling receptor complex; IPI:ComplexPortal. DR GO; GO:0005125; F:cytokine activity; IDA:UniProtKB. DR GO; GO:0005128; F:erythropoietin receptor binding; IMP:UniProtKB. DR GO; GO:0005179; F:hormone activity; IDA:BHF-UCL. DR GO; GO:0030295; F:protein kinase activator activity; IBA:GO_Central. DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl. DR GO; GO:0008015; P:blood circulation; NAS:ProtInc. DR GO; GO:0097696; P:cell surface receptor signaling pathway via STAT; IDA:BHF-UCL. DR GO; GO:0071474; P:cellular hyperosmotic response; IDA:BHF-UCL. DR GO; GO:0030218; P:erythrocyte differentiation; IDA:BHF-UCL. DR GO; GO:0038162; P:erythropoietin-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0010523; P:negative regulation of calcium ion transport into cytosol; IDA:BHF-UCL. DR GO; GO:1902251; P:negative regulation of erythrocyte apoptotic process; IDA:BHF-UCL. DR GO; GO:1902219; P:negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress; IDA:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IDA:BHF-UCL. DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl. DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl. DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl. DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl. DR GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0009651; P:response to salt stress; IEA:Ensembl. DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl. DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; NAS:ProtInc. DR FunFam; 1.20.1250.10:FF:000013; Erythropoietin; 1. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR019767; EPO/TPO_CS. DR InterPro; IPR001323; EPO_TPO. DR InterPro; IPR003013; Erythroptn. DR PANTHER; PTHR10370; ERYTHROPOIETIN; 1. DR PANTHER; PTHR10370:SF0; ERYTHROPOIETIN; 1. DR Pfam; PF00758; EPO_TPO; 1. DR PIRSF; PIRSF001951; EPO; 1. DR PRINTS; PR00272; ERYTHROPTN. DR SUPFAM; SSF47266; 4-helical cytokines; 1. DR PROSITE; PS00817; EPO_TPO; 1. DR PDBsum; 1BUY; -. DR PDBsum; 1CN4; -. DR PDBsum; 1EER; -. PE 1: Evidence at protein level; KW 3D-structure; Congenital erythrocytosis; Direct protein sequencing; KW Disease variant; Disulfide bond; Erythrocyte maturation; Glycoprotein; KW Hormone; Pharmaceutical; Proteomics identification; Reference proteome; KW Secreted; Signal. FT SIGNAL 1..27 FT /evidence="ECO:0000269|PubMed:3949763" FT CHAIN 28..193 FT /note="Erythropoietin" FT /id="PRO_0000008401" FT CARBOHYD 51 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:3949763" FT /id="CAR_000052" FT CARBOHYD 65 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:3949763" FT /id="CAR_000166" FT CARBOHYD 110 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:3949763" FT /id="CAR_000192" FT CARBOHYD 153 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000269|PubMed:3949763" FT DISULFID 34..188 FT /evidence="ECO:0000269|PubMed:3949763" FT DISULFID 56..60 FT /evidence="ECO:0000269|PubMed:3949763" FT VARIANT 70 FT /note="D -> N (in ECYT5; uncertain significance; FT dbSNP:rs62483572)" FT /evidence="ECO:0000269|PubMed:27651169" FT /id="VAR_080573" FT VARIANT 84 FT /note="G -> R (in ECYT5; uncertain significance; FT dbSNP:rs137953994)" FT /evidence="ECO:0000269|PubMed:27651169" FT /id="VAR_080574" FT VARIANT 99 FT /note="E -> G (found in a patient thought to have FT erythrocytosis, but had normal red cell mass; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:27651169" FT /id="VAR_080575" FT VARIANT 114 FT /note="P -> L (in ECYT5; uncertain significance; FT dbSNP:rs11976235)" FT /evidence="ECO:0000269|PubMed:27651169" FT /id="VAR_080576" FT VARIANT 131..132 FT /note="SL -> NF (in a hepatocellular carcinoma)" FT /evidence="ECO:0000269|PubMed:8396923" FT /id="VAR_009870" FT VARIANT 147 FT /note="S -> C (in ECYT5; uncertain significance; FT dbSNP:rs149431976)" FT /evidence="ECO:0000269|PubMed:27651169" FT /id="VAR_080577" FT VARIANT 149 FT /note="P -> Q (in a hepatocellular carcinoma)" FT /evidence="ECO:0000269|PubMed:8396923" FT /id="VAR_009871" FT VARIANT 177 FT /note="R -> Q (in DBAL; loss of support of normal erythroid FT expansion or differentiation; reduced ability to promote FT EPOR dimer formation upon binding, resulting in reduced FT JAK2 activation and decreased STAT1 and STAT3 FT phosphorylation; mild decrease in affinity for EPOR; no FT effect on STAT5A phosphorylation; dbSNP:rs1358275550)" FT /evidence="ECO:0000269|PubMed:28283061" FT /id="VAR_078447" FT MUTAGEN 127 FT /note="S->E: Decreased erythrocyte proliferation; impaired FT EPOR dimerization following binding." FT /evidence="ECO:0000269|PubMed:28283061" FT CONFLICT 40 FT /note="E -> Q (in Ref. 1; CAA26095)" FT /evidence="ECO:0000305" FT CONFLICT 85 FT /note="Q -> QQ (in Ref. 8; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 140 FT /note="G -> R (in Ref. 1; CAA26095)" FT /evidence="ECO:0000305" FT HELIX 32..34 FT /evidence="ECO:0007829|PDB:1EER" FT HELIX 36..52 FT /evidence="ECO:0007829|PDB:1EER" FT HELIX 53..55 FT /evidence="ECO:0007829|PDB:1EER" FT STRAND 57..60 FT /evidence="ECO:0007829|PDB:1BUY" FT STRAND 61..68 FT /evidence="ECO:0007829|PDB:1EER" FT HELIX 75..78 FT /evidence="ECO:0007829|PDB:1EER" FT STRAND 79..81 FT /evidence="ECO:0007829|PDB:1BUY" FT HELIX 83..109 FT /evidence="ECO:0007829|PDB:1EER" FT HELIX 118..138 FT /evidence="ECO:0007829|PDB:1EER" FT HELIX 141..147 FT /evidence="ECO:0007829|PDB:1EER" FT STRAND 160..164 FT /evidence="ECO:0007829|PDB:1EER" FT HELIX 165..175 FT /evidence="ECO:0007829|PDB:1EER" FT HELIX 176..180 FT /evidence="ECO:0007829|PDB:1EER" FT HELIX 181..188 FT /evidence="ECO:0007829|PDB:1EER" SQ SEQUENCE 193 AA; 21307 MW; C91F0E4C26A52033 CRC64; MGVHECPAWL WLLLSLLSLP LGLPVLGAPP RLICDSRVLE RYLLEAKEAE NITTGCAEHC SLNENITVPD TKVNFYAWKR MEVGQQAVEV WQGLALLSEA VLRGQALLVN SSQPWEPLQL HVDKAVSGLR SLTTLLRALG AQKEAISPPD AASAAPLRTI TADTFRKLFR VYSNFLRGKL KLYTGEACRT GDR //