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 13-FEB-2019, entry version 193. DE RecName: Full=Erythropoietin; DE AltName: INN=Epoetin; DE Flags: Precursor; GN Name=EPO; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Kawakita M., 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]. 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; 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: RT analysis of 650 kb of genomic sequence around the EPO and CUTL1 loci RT reveals 17 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., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA 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., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 58-193, AND VARIANTS HEPATOCELLULAR RP CARCINOMA 131-ASN-PHE-132 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 RT 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; 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; RA Yanagawa S., Hirade K., Ohnota H., Sasaki R., Chiba H., Ueda M., RA 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; 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 RT recombinant 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: RT analysis of glycopeptides or peptides at each glycosylation site by RT fast atom 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 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 [15] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 28-193. RX PubMed=9774108; DOI=10.1038/26773; RA Syed R.S., Reid S.W., Li C., Cheetham J.C., Aoki K.H., Liu B., RA Zhan H., Osslund T.D., Chirino A.J., Zhang J., Finer-Moore J., RA Elliott S., Sitney K., Katz B.A., Matthews D.J., Wendoloski J.J., RA Egrie J., Stroud R.M.; RT "Efficiency of signalling through cytokine receptors depends RT critically on receptor orientation."; RL Nature 395:511-516(1998). RN [16] 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 RT receptor bound conformation."; RL Nat. Struct. Biol. 5:861-866(1998). RN [17] RP INVOLVEMENT IN SUSCEPTIBILITY TO MICROVASCULAR COMPLICATIONS OF RP DIABETES 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., RA Avery R.L., Brand J.M., London N., Anduze A.L., King G.L., RA Bernstein P.S., Watkins S., Jorde L.B., Li D.Y., Aiello L.P., RA Pollak M.R., Zhang K.; RT "Promoter polymorphism of the erythropoietin gene in severe diabetic RT eye and kidney complications."; RL Proc. Natl. Acad. Sci. U.S.A. 105:6998-7003(2008). RN [18] RP INVOLVEMENT IN ECYT5, VARIANTS ECYT5 ASN-70; ARG-84; LEU-114 AND RP CYS-147, 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 RT with idiopathic erythrocytosis and identifies new mutations."; RL Haematologica 101:1306-1318(2016). RN [19] RP INVOLVEMENT IN DBAL, VARIANT DBAL GLN-177, CHARACTERIZATION OF VARIANT RP DBAL 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., RA Gabriel S.B., Lander E.S., Patiroglu T., Ozcan A., Ozdemir M.A., RA Garcia K.C., Piehler J., Gazda H.T., Klein D.E., Sankaran V.G.; RT "Functional selectivity in cytokine signaling revealed through a RT pathogenic 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. Binds to EPOR CC leading to EPOR dimerization and JAK2 activation thereby CC activating specific downstream effectors, including STAT1 and CC STAT3. {ECO:0000269|PubMed:28283061}. CC -!- INTERACTION: CC P54760:EPHB4; NbExp=6; IntAct=EBI-1027362, EBI-702121; CC P19235:EPOR; NbExp=3; IntAct=EBI-1027362, EBI-617321; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals CC and by liver of fetal or neonatal mammals. CC -!- DISEASE: Microvascular complications of diabetes 2 (MVCD2) CC [MIM:612623]: Pathological conditions that develop in numerous CC tissues and organs as a consequence of diabetes mellitus. They CC include diabetic retinopathy, diabetic nephropathy leading to end- CC stage renal disease, and diabetic neuropathy. Diabetic retinopathy CC remains the major cause of new-onset blindness among diabetic CC adults. It is characterized by vascular permeability and increased CC tissue ischemia and angiogenesis. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. CC -!- DISEASE: Erythrocytosis, familial, 5 (ECYT5) [MIM:617907]: An CC autosomal dominant disorder characterized by increased serum red CC blood cell mass, and elevated serum hemoglobin and hematocrit. CC Some patients have increased serum erythropoietin levels. CC {ECO:0000269|PubMed:27651169, ECO:0000269|PubMed:29514032}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Diamond-Blackfan anemia-like (DBAL) [MIM:617911]: An CC autosomal recessive hematologic disease characterized by severe CC red cell hypoplastic anemia, selective absence of red cell CC precursors and progenitors seen on bone marrow biopsy, and CC increased serum erythropoietin. {ECO:0000269|PubMed:28283061}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- PHARMACEUTICAL: Used for the treatment of anemia. Available under CC the names Epogen (Amgen), Epogin (Chugai), Epomax (Elanex), Eprex CC (Janssen-Cilag), NeoRecormon or Recormon (Roche), Dynepo (Shire CC Pharmaceuticals) and Procrit (Ortho Biotech). Variations in the CC glycosylation pattern of EPO distinguishes these products. Epogen, CC Epogin, Eprex and Procrit are generically known as epoetin alfa, CC NeoRecormon and Recormon as epoetin beta, Dynepo as epoetin delta CC and Epomax as epoetin omega. Epoetin zeta is the name used for CC some 'biosimilars' forms of epoetin alfa and is available under CC the names Silapo (Stada) and Retacrit (Hospira). Darbepoetin alfa CC is a form created by 5 substitutions (Asn-57, Thr-59, Val-114, CC Asn-115 and Thr-117) that create 2 new N-glycosylation sites. It CC has a longer circulating half-life in vivo. It is available under CC the name Aranesp (Amgen). EPO is being much misused as a CC performance-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 CC world - Issue 84 of July 2007; CC URL="https://web.expasy.org/spotlight/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_000799.2. DR UniGene; Hs.2303; -. 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 PDBsum; 1BUY; -. DR PDBsum; 1CN4; -. DR PDBsum; 1EER; -. DR ProteinModelPortal; P01588; -. DR SMR; P01588; -. DR BioGrid; 108370; 6. DR CORUM; P01588; -. DR DIP; DIP-5731N; -. DR IntAct; P01588; 4. DR STRING; 9606.ENSP00000252723; -. DR ChEMBL; CHEMBL5837; -. DR Allergome; 11697; Hom s EPO. DR GlyConnect; 140; -. DR GlyConnect; 141; -. DR GlyConnect; 142; -. DR iPTMnet; P01588; -. DR PhosphoSitePlus; P01588; -. DR UniCarbKB; P01588; -. DR BioMuta; EPO; -. DR DMDM; 119526; -. DR EPD; P01588; -. DR PaxDb; P01588; -. DR PRIDE; P01588; -. DR ProteomicsDB; 51392; -. DR Ensembl; ENST00000252723; ENSP00000252723; ENSG00000130427. DR GeneID; 2056; -. DR KEGG; hsa:2056; -. DR UCSC; uc003uwi.5; human. DR CTD; 2056; -. DR DisGeNET; 2056; -. DR EuPathDB; HostDB:ENSG00000130427.2; -. DR GeneCards; EPO; -. DR HGNC; HGNC:3415; EPO. DR HPA; CAB010336; -. DR MalaCards; EPO; -. DR MIM; 133170; gene. DR MIM; 612623; phenotype. DR MIM; 617907; phenotype. DR MIM; 617911; phenotype. DR neXtProt; NX_P01588; -. DR OpenTargets; ENSG00000130427; -. DR Orphanet; 247511; Autosomal dominant secondary polycythemia. DR PharmGKB; PA27833; -. DR eggNOG; ENOG410IHW5; Eukaryota. DR eggNOG; ENOG410XTRF; LUCA. DR GeneTree; ENSGT00390000017226; -. DR HOGENOM; HOG000052505; -. DR HOVERGEN; HBG003978; -. DR InParanoid; P01588; -. DR KO; K05437; -. DR OMA; MGCAEGC; -. DR OrthoDB; 1112828at2759; -. DR PhylomeDB; P01588; -. DR TreeFam; TF333413; -. 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 EvolutionaryTrace; P01588; -. DR GeneWiki; Erythropoietin; -. DR GenomeRNAi; 2056; -. DR PRO; PR:P01588; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; ENSG00000130427; Expressed in 66 organ(s), highest expression level in right lobe of liver. DR ExpressionAtlas; P01588; baseline and differential. DR Genevisible; P01588; HS. 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; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL. DR GO; GO:0005128; F:erythropoietin receptor binding; IMP:UniProtKB. DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW. 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:0007568; P:aging; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl. DR GO; GO:0008015; P:blood circulation; NAS:ProtInc. DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB. DR GO; GO:0071474; P:cellular hyperosmotic response; IDA:BHF-UCL. DR GO; GO:0007566; P:embryo implantation; IEA:Ensembl. DR GO; GO:0030218; P:erythrocyte differentiation; IDA:BHF-UCL. DR GO; GO:0043249; P:erythrocyte maturation; IEA:UniProtKB-KW. DR GO; GO:0038162; P:erythropoietin-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0042541; P:hemoglobin biosynthetic process; IBA:GO_Central. DR GO; GO:0010523; P:negative regulation of calcium ion transport into cytosol; IDA:BHF-UCL. DR GO; GO:2001258; P:negative regulation of cation channel activity; 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:1901215; P:negative regulation of neuron death; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl. 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:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; TAS:Reactome. DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL. DR GO; GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome. 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; IBA:GO_Central. 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 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; PTHR10370; 1. DR Pfam; PF00758; EPO_TPO; 1. DR PIRSF; PIRSF001951; EPO; 1. DR PRINTS; PR00272; ERYTHROPTN. DR SUPFAM; SSF47266; SSF47266; 1. DR PROSITE; PS00817; EPO_TPO; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Congenital erythrocytosis; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW Erythrocyte maturation; Glycoprotein; Hormone; Pharmaceutical; KW Polymorphism; Reference proteome; Secreted; Signal. FT SIGNAL 1 27 {ECO:0000269|PubMed:3949763}. FT CHAIN 28 193 Erythropoietin. FT /FTId=PRO_0000008401. FT CARBOHYD 51 51 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:3949763}. FT /FTId=CAR_000052. FT CARBOHYD 65 65 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:3949763}. FT /FTId=CAR_000166. FT CARBOHYD 110 110 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:3949763}. FT /FTId=CAR_000192. FT CARBOHYD 153 153 O-linked (GalNAc...) serine. FT {ECO:0000269|PubMed:3949763}. FT DISULFID 34 188 {ECO:0000269|PubMed:3949763}. FT DISULFID 56 60 {ECO:0000269|PubMed:3949763}. FT VARIANT 70 70 D -> N (in ECYT5; unknown pathological FT significance; dbSNP:rs62483572). FT {ECO:0000269|PubMed:27651169}. FT /FTId=VAR_080573. FT VARIANT 84 84 G -> R (in ECYT5; unknown pathological FT significance; dbSNP:rs137953994). FT {ECO:0000269|PubMed:27651169}. FT /FTId=VAR_080574. FT VARIANT 99 99 E -> G (found in a patient thought to FT have erythrocytosis, but had normal red FT cell mass; unknown pathological FT significance). FT {ECO:0000269|PubMed:27651169}. FT /FTId=VAR_080575. FT VARIANT 114 114 P -> L (in ECYT5; unknown pathological FT significance; dbSNP:rs11976235). FT {ECO:0000269|PubMed:27651169}. FT /FTId=VAR_080576. FT VARIANT 131 132 SL -> NF (in a hepatocellular carcinoma). FT /FTId=VAR_009870. FT VARIANT 147 147 S -> C (in ECYT5; unknown pathological FT significance; dbSNP:rs149431976). FT {ECO:0000269|PubMed:27651169}. FT /FTId=VAR_080577. FT VARIANT 149 149 P -> Q (in a hepatocellular carcinoma). FT {ECO:0000269|PubMed:8396923}. FT /FTId=VAR_009871. FT VARIANT 177 177 R -> Q (in DBAL; loss of support of FT normal erythroid expansion or FT differentiation; reduced ability to FT promote EPOR dimer formation upon FT binding, resulting in reduced JAK2 FT activation and decreased STAT1 and STAT3 FT phosphorylation; mild decrease in FT affinity for EPOR; no effect on STAT5A FT phosphorylation; dbSNP:rs1358275550). FT {ECO:0000269|PubMed:28283061}. FT /FTId=VAR_078447. FT MUTAGEN 127 127 S->E: Decreased erythrocyte FT proliferation; impaired EPOR dimerization FT following binding. FT {ECO:0000269|PubMed:28283061}. FT CONFLICT 40 40 E -> Q (in Ref. 1; CAA26095). FT {ECO:0000305}. FT CONFLICT 85 85 Q -> QQ (in Ref. 8; AA sequence). FT {ECO:0000305}. FT CONFLICT 140 140 G -> R (in Ref. 1; CAA26095). FT {ECO:0000305}. FT HELIX 32 34 {ECO:0000244|PDB:1EER}. FT HELIX 36 52 {ECO:0000244|PDB:1EER}. FT HELIX 53 55 {ECO:0000244|PDB:1EER}. FT STRAND 57 60 {ECO:0000244|PDB:1BUY}. FT STRAND 61 68 {ECO:0000244|PDB:1EER}. FT HELIX 75 78 {ECO:0000244|PDB:1EER}. FT STRAND 79 81 {ECO:0000244|PDB:1BUY}. FT HELIX 83 109 {ECO:0000244|PDB:1EER}. FT HELIX 118 138 {ECO:0000244|PDB:1EER}. FT HELIX 141 147 {ECO:0000244|PDB:1EER}. FT STRAND 160 164 {ECO:0000244|PDB:1EER}. FT HELIX 165 177 {ECO:0000244|PDB:1EER}. FT HELIX 179 188 {ECO:0000244|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 //