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UniProtKB/Swiss-Prot entry P01588


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name EPO_HUMAN
Primary accession number P01588
Secondary accession numbers Q2M2L6 Q549U2 Q9UDZ0 Q9UEZ5 Q9UHA0
Integrated into Swiss-Prot on July 21, 1986
Sequence was last modified on July 21, 1986 (Sequence version 1)
Annotations were last modified on    April 29, 2008 (Entry version 96)
Name and origin of the protein
Protein name Erythropoietin [Precursor]
Synonym Epoetin
Gene name
Name: EPO
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
DOI=10.1038/313806a0; PubMed=3838366 [NCBI, ExPASy, EBI, Israel, Japan]
Jacobs K., Shoemaker C., Rudersdorf R., Neill S.D., Kaufman R.J., Mufson A., Seehra J., Jones S.S., Hewick R., Fritsch E.F., Kawakita M., Shimizu T., Miyake T.;
"Isolation and characterization of genomic and cDNA clones of human erythropoietin.";
Nature 313:806-810(1985).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=3865178 [NCBI, ExPASy, EBI, Israel, Japan]
Lin F.-K., Suggs S., Lin C.-H., Browne J.K., Smalling R., Egrie J.C., Chen K.K., Fox G.M., Martin F., Stabinsky Z., Badrawi S.M., Lai P.-H., Goldwasser E.;
"Cloning and expression of the human erythropoietin gene.";
Proc. Natl. Acad. Sci. U.S.A. 82:7580-7584(1985).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=9799793 [NCBI, ExPASy, EBI, Israel, Japan]
Gloeckner G., Scherer S., Schattevoy R., Boright A.P., Weber J., Tsui L.-C., Rosenthal A.;
"Large-scale sequencing of two regions in human chromosome 7q22: analysis of 650 kb of genomic sequence around the EPO and CUTL1 loci reveals 17 genes.";
Genome Res. 8:1060-1073(1998).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Rupert J.L., Hochachka P.W.;
"Erythropoietin gene sequence in the Quechua, a high altitude native population.";
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature01782; PubMed=12853948 [NCBI, ExPASy, EBI, Israel, Japan]
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.;
"The DNA sequence of human chromosome 7.";
Nature 424:157-164(2003).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 58-193, AND VARIANTS HEPATOCELLULAR CARCINOMA 131-ASN-PHE-132 AND GLN-149.
DOI=10.1006/bbrc.1993.2104; PubMed=8396923 [NCBI, ExPASy, EBI, Israel, Japan]
Funakoshi A., Muta H., Baba T., Shimizu S.;
"Gene expression of mutant erythropoietin in hepatocellular carcinoma.";
Biochem. Biophys. Res. Commun. 195:717-722(1993).
[8]
PROTEIN SEQUENCE OF 28-193, AND DISULFIDE BONDS.
TISSUE=Urine;
PubMed=3949763 [NCBI, ExPASy, EBI, Israel, Japan]
Lai P.H., Everett R., Wang F.F., Arakawa T., Goldwasser E.;
"Structural characterization of human erythropoietin.";
J. Biol. Chem. 261:3116-3121(1986).
[9]
PRELIMINARY PROTEIN SEQUENCE OF 28-57.
PubMed=6698989 [NCBI, ExPASy, EBI, Israel, Japan]
Yanagawa S., Hirade K., Ohnota H., Sasaki R., Chiba H., Ueda M., Goto M.;
"Isolation of human erythropoietin with monoclonal antibodies.";
J. Biol. Chem. 259:2707-2710(1984).
[10]
STRUCTURE OF CARBOHYDRATES.
PubMed=3346214 [NCBI, ExPASy, EBI, Israel, Japan]
Takeuchi M., Takasaki S., Miyazaki H., Kato T., Hoshi S., Kochibe N., Kobata A.;
"Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells.";
J. Biol. Chem. 263:3657-3663(1988).
[11]
STRUCTURE OF CARBOHYDRATES.
DOI=10.1021/bi00423a017; PubMed=3219367 [NCBI, ExPASy, EBI, Israel, Japan]
Sasaki H., Ochi N., Dell A., Fukuda M.;
"Site-specific glycosylation of human recombinant erythropoietin: analysis of glycopeptides or peptides at each glycosylation site by fast atom bombardment mass spectrometry.";
Biochemistry 27:8618-8626(1988).
[12]
STRUCTURE OF CARBOHYDRATES.
DOI=10.1093/glycob/1.4.337; PubMed=1820196 [NCBI, ExPASy, EBI, Israel, Japan]
Takeuchi M., Kobata A.;
"Structures and functional roles of the sugar chains of human erythropoietins.";
Glycobiology 1:337-346(1991).
[13]
STRUCTURE OF CARBOHYDRATES.
DOI=10.1182/blood.V98.13.3626; PubMed=11739166 [NCBI, ExPASy, EBI, Israel, Japan]
Skibeli V., Nissen-Lie G., Torjesen P.;
"Sugar profiling proves that human serum erythropoietin differs from recombinant human erythropoietin.";
Blood 98:3626-3634(2001).
[14]
X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
DOI=10.1038/26773; PubMed=9774108 [NCBI, ExPASy, EBI, Israel, Japan]
Syed R.S., Reid S.W., Li C., Cheetham J.C., Aoki K.H., Liu B., Zhan H., Osslund T.D., Chirino A.J., Zhang J., Finer-Moore J., Elliott S., Sitney K., Katz B.A., Matthews D.J., Wendoloski J.J., Egrie J., Stroud R.M.;
"Efficiency of signalling through cytokine receptors depends critically on receptor orientation.";
Nature 395:511-516(1998).
[15]
STRUCTURE BY NMR OF 28-193.
DOI=10.1038/2302; PubMed=9783743 [NCBI, ExPASy, EBI, Israel, Japan]
Cheetham J.C., Smith D.M., Aoki K.H., Stevenson J.L., Hoeffel T.J., Syed R.S., Egrie J., Harvey T.S.;
"NMR structure of human erythropoietin and a comparison with its receptor bound conformation.";
Nat. Struct. Biol. 5:861-866(1998).
Comments
  • FUNCTION: Erythropoietin is the principal hormone involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass.
  • INTERACTION:
    O60496:DOK2; NbExp=1; IntAct=EBI-1027362, EBI-1046024;
  • SUBCELLULAR LOCATION: Secreted.
  • TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals.
  • PHARMACEUTICAL: Used for the treatment of anemia. Available under the names Epogen (Amgen), Epogin (Chugai), Epomax (Elanex), Eprex (Janssen-Cilag), NeoRecormon or Recormon (Roche), Dynepo (Shire Pharmaceuticals) and Procrit (Ortho Biotech). Variations in the glycosylation pattern of EPO distinguishes these products. Epogen, Epogin, Eprex and Procrit are generically known as epoetin alfa, NeoRecormon and Recormon as epoetin beta, Dynepo as epoetin delta and Epomax as epoetin omega. Epoetin zeta is the name used for some 'biosimilars' forms of epoetin alfa and is available under the names Silapo (Stada) and Retacrit (Hospira). Darbepoetin alfa is a form created by 5 substitutions (Asn-57, Thr-59, Val-114, Asn-115 and Thr-117) that create 2 new N-glycosylation sites. It has a longer circulating half-life in vivo. It is available under the name Aranesp (Amgen). EPO is being much misused as a performance-enhancing drug in endurance athletes.
  • SIMILARITY: Belongs to the EPO/TPO family.
  • WEB RESOURCE: Name=R&D Systems' cytokine source book: Erythropoietin; URL="http://www.rndsystems.com/molecule_detail.aspx?m=1405";.
  • WEB RESOURCE: Name=Wikipedia; Note=Erythropoietin entry; URL="http://en.wikipedia.org/wiki/Erythropoietin";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X02158; CAA26095.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X02157; CAA26094.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M11319; AAA52400.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF053356; AAC78791.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF202308; AAF23132.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF202306; AAF23132.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF202307; AAF23132.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF202310; AAF23133.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF202309; AAF23133.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF202311; AAF17572.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF202314; AAF23134.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF202312; AAF23134.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF202313; AAF23134.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AC009488; AAP22357.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC093628; AAH93628.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC111937; AAI11938.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S65458; AAD13964.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A01855; ZUHU.
RefSeq NP_000790.2; -.
UniGene Hs.2303
3D structure databases
PDB
1BUY; NMR; -; A=28-193.[ExPASy / RCSB / EBI]
1CN4; X-ray; 2.80 A; C=28-193.[ExPASy / RCSB / EBI]
1EER; X-ray; 1.90 A; A=28-193.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1BUY; -.
1CN4; -.
1EER; -.
ModBase P01588.
Protein-protein interaction databases
DIP DIP:5731N; -.
IntAct P01588; -.
PTM databases
GlycoSuiteDB P01588; -.
Organism-specific databases
H-InvDB HIX0033695; -.
HGNC HGNC:3415; EPO.
GeneLynx EPO; Homo sapiens.
GenAtlas EPO.
HPA CAB010336; -.
MIM 133170; gene. [NCBI / EBI]
PharmGKB PA27833; -.
GeneCards P01588.
Gene expression databases
ArrayExpress P01588; -.
CleanEx HS_EPO; -.
GermOnline ENSG00000130427; Homo sapiens.
Ontologies
GO
GO:0005615; Cellular component: extracellular space (traceable author statement from ProtInc).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0008015; Biological process: blood circulation (non-traceable author statement from ProtInc).
GO:0006950; Biological process: response to stress (traceable author statement from ProtInc).
GO:0007165; Biological process: signal transduction (non-traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR012351; 4_helix_cytokine_core.
IPR001323; EPO_TPO.
IPR003013; Erythroptn.
Graphical view of domain structure.
Gene3D G3DSA:1.20.1250.10; 4_helix_cytokine_core; 1.
PANTHER PTHR10370; Erythroptn; 1.
Pfam PF00758; EPO_TPO; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF001951; EPO; 1.
PRINTS PR00272; ERYTHROPTN.
PROSITE PS00817; EPO_TPO; 1.
BLOCKS P01588.
Genome annotation databases
Ensembl ENSG00000130427; Homo sapiens. [Contig view]
GeneID 2056; -.
KEGG hsa:2056; -.
Other
DrugBank DB00012; Darbepoetin alfa.
DB00016; Epoetin alfa.
LinkHub P01588; -.
SOURCE EPO; Homo sapiens.
ProtoNet P01588.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Direct protein sequencing; Erythrocyte maturation; Glycoprotein; Hormone; Pharmaceutical; Polymorphism; Secreted; Signal.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    27  27      
CHAIN   28   193  166     Erythropoietin. PRO_0000008401
PROPEP   190   193  4     Removed in mature form (Partial). PRO_0000008402
PROPEP   193   193  1     Removed in mature form (Partial). PRO_0000313669
CARBOHYD   51    51        N-linked (GlcNAc...) [GlycoSuiteDB]. CAR_000052
CARBOHYD   65    65        N-linked (GlcNAc...) [GlycoSuiteDB]. CAR_000166
CARBOHYD   110   110        N-linked (GlcNAc...) [GlycoSuiteDB]. CAR_000192
CARBOHYD   153   153        O-linked (GalNAc...). 
DISULFID   34   188         
DISULFID   56    60         
VARIANT   131   132  2     SL -> NF (in an hepatocellular carcinoma). VAR_009870
VARIANT   149   149  1     P -> Q (in an hepatocellular carcinoma). VAR_009871 
CONFLICT   40    40        E -> Q (in Ref. 1; CAA26095). 
CONFLICT   85    85        Q -> QQ (in Ref. 8; AA sequence). 
CONFLICT   140   140        G -> R (in Ref. 1; CAA26095). 
HELIX   32    34  3      
HELIX   36    52  17      
HELIX   53    55  3      
STRAND   61    68  8      
HELIX   75    78  4      
HELIX   83   109  27      
HELIX   118   138  21      
HELIX   141   147  7      
STRAND   160   164  5      
HELIX   165   177  13      
HELIX   179   188  10      
Sequence information
Length: 193 AA [This is the length of the unprocessed precursor] Molecular weight: 21307 Da [This is the MW of the unprocessed precursor] CRC64: C91F0E4C26A52033 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MGVHECPAWL WLLLSLLSLP LGLPVLGAPP RLICDSRVLE RYLLEAKEAE NITTGCAEHC 

        70         80         90        100        110        120 
SLNENITVPD TKVNFYAWKR MEVGQQAVEV WQGLALLSEA VLRGQALLVN SSQPWEPLQL 

       130        140        150        160        170        180 
HVDKAVSGLR SLTTLLRALG AQKEAISPPD AASAAPLRTI TADTFRKLFR VYSNFLRGKL 

       190 
KLYTGEACRT GDR 

P01588 in FASTA format

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