EPO_HUMAN
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 03-AUG-2022, entry version 210.
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; 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].
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-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 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.
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. Binds to EPOR
CC leading to EPOR dimerization and JAK2 activation thereby activating
CC specific downstream effectors, including STAT1 and STAT3.
CC {ECO:0000269|PubMed:28283061}.
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 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.
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://web.expasy.org/spotlight/back_issues/084/";
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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 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 AlphaFoldDB; P01588; -.
DR SMR; P01588; -.
DR BioGRID; 108370; 31.
DR CORUM; P01588; -.
DR DIP; DIP-5731N; -.
DR IntAct; P01588; 5.
DR STRING; 9606.ENSP00000252723; -.
DR ChEMBL; CHEMBL5837; -.
DR Allergome; 11697; Hom s EPO.
DR GlyConnect; 140; 212 N-Linked glycans (3 sites), 27 O-Linked glycans (1 site).
DR GlyGen; P01588; 5 sites, 179 N-linked glycans (4 sites), 17 O-linked glycans (2 sites).
DR iPTMnet; P01588; -.
DR MetOSite; P01588; -.
DR PhosphoSitePlus; P01588; -.
DR BioMuta; EPO; -.
DR DMDM; 119526; -.
DR EPD; P01588; -.
DR MassIVE; P01588; -.
DR PaxDb; P01588; -.
DR PeptideAtlas; P01588; -.
DR PRIDE; P01588; -.
DR Antibodypedia; 4151; 1289 antibodies from 40 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 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 neXtProt; NX_P01588; -.
DR OpenTargets; ENSG00000130427; -.
DR Orphanet; 247511; Autosomal dominant secondary polycythemia.
DR PharmGKB; PA27833; -.
DR VEuPathDB; HostDB:ENSG00000130427; -.
DR eggNOG; ENOG502RXRC; Eukaryota.
DR GeneTree; ENSGT00390000017226; -.
DR HOGENOM; CLU_110946_0_0_1; -.
DR InParanoid; P01588; -.
DR OMA; GVRECPA; -.
DR OrthoDB; 1175751at2759; -.
DR PhylomeDB; P01588; -.
DR TreeFam; TF333413; -.
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 BioGRID-ORCS; 2056; 13 hits in 1071 CRISPR screens.
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 64 other tissues.
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:0008015; P:blood circulation; NAS:ProtInc.
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; IEA:Ensembl.
DR GO; GO:0033028; P:myeloid cell apoptotic process; IEA:Ensembl.
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: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: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: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 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; 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; Congenital erythrocytosis; Direct protein sequencing;
KW Disease variant; Disulfide bond; Erythrocyte maturation; Glycoprotein;
KW Hormone; Pharmaceutical; Reference proteome; 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; unknown pathological significance;
FT dbSNP:rs62483572)"
FT /evidence="ECO:0000269|PubMed:27651169"
FT /id="VAR_080573"
FT VARIANT 84
FT /note="G -> R (in ECYT5; unknown pathological 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; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:27651169"
FT /id="VAR_080575"
FT VARIANT 114
FT /note="P -> L (in ECYT5; unknown pathological 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 /id="VAR_009870"
FT VARIANT 147
FT /note="S -> C (in ECYT5; unknown pathological 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..177
FT /evidence="ECO:0007829|PDB:1EER"
FT HELIX 179..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
