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P01588 (EPO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Erythropoietin
Alternative name(s):
INN=Epoetin
Gene names
Name:EPO
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length193 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (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.

Subcellular location

Secreted.

Tissue specificity

Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals.

Involvement in disease

Microvascular complications of diabetes 2 (MVCD2) [MIM:612623]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Pharmaceutical use

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.

Sequence similarities

Belongs to the EPO/TPO family.

Ontologies

Keywords
   Biological processErythrocyte maturation
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionHormone
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Pharmaceutical
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Inferred from electronic annotation. Source: Ensembl

blood circulation

Non-traceable author statement Ref.1. Source: ProtInc

cellular hyperosmotic response

Inferred from direct assay PubMed 14569084. Source: BHF-UCL

cellular response to hypoxia

Traceable author statement. Source: Reactome

embryo implantation

Inferred from electronic annotation. Source: Ensembl

erythrocyte maturation

Inferred from electronic annotation. Source: UniProtKB-KW

hemoglobin biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of calcium ion transport into cytosol

Inferred from direct assay PubMed 14569084. Source: BHF-UCL

negative regulation of cation channel activity

Inferred from direct assay PubMed 14569084. Source: BHF-UCL

negative regulation of erythrocyte apoptotic process

Inferred from direct assay PubMed 14569084. Source: BHF-UCL

negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress

Inferred from direct assay PubMed 14569084. Source: BHF-UCL

peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of DNA replication

Inferred from direct assay PubMed 9722506. Source: BHF-UCL

positive regulation of Ras protein signal transduction

Inferred from direct assay PubMed 9722506. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from direct assay PubMed 9722506. Source: BHF-UCL

positive regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 9722506. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of Stat5 protein

Inferred from direct assay PubMed 9722506. Source: BHF-UCL

regulation of transcription from RNA polymerase II promoter in response to hypoxia

Traceable author statement. Source: Reactome

response to axon injury

Inferred from electronic annotation. Source: Ensembl

response to electrical stimulus

Inferred from electronic annotation. Source: Ensembl

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to hyperoxia

Inferred from electronic annotation. Source: Ensembl

response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to salt stress

Inferred from electronic annotation. Source: Ensembl

response to testosterone

Inferred from electronic annotation. Source: Ensembl

response to vitamin A

Inferred from electronic annotation. Source: Ensembl

signal transduction

Non-traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcell surface

Inferred from direct assay PubMed 14569084. Source: BHF-UCL

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 14569084. Source: BHF-UCL

   Molecular_functionprotein kinase activator activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

EPORP192352EBI-1027362,EBI-617321

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Ref.8 Ref.9
Chain28 – 193166Erythropoietin
PRO_0000008401

Amino acid modifications

Glycosylation511N-linked (GlcNAc...) Ref.8
CAR_000052
Glycosylation651N-linked (GlcNAc...) Ref.8
CAR_000166
Glycosylation1101N-linked (GlcNAc...) Ref.8
CAR_000192
Glycosylation1531O-linked (GalNAc...) Ref.8
Disulfide bond34 ↔ 188 Ref.8
Disulfide bond56 ↔ 60 Ref.8

Natural variations

Natural variant131 – 1322SL → NF in a hepatocellular carcinoma.
VAR_009870
Natural variant1491P → Q in a hepatocellular carcinoma. Ref.7
VAR_009871

Experimental info

Sequence conflict401E → Q in CAA26095. Ref.1
Sequence conflict851Q → QQ AA sequence Ref.8
Sequence conflict1401G → R in CAA26095. Ref.1

Secondary structure

....................... 193
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01588 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: C91F0E4C26A52033

FASTA19321,307
        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 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterization of genomic and cDNA clones of human erythropoietin."
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.
Nature 313:806-810(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"Cloning and expression of the human erythropoietin gene."
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.
Proc. Natl. Acad. Sci. U.S.A. 82:7580-7584(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"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."
Gloeckner G., Scherer S., Schattevoy R., Boright A.P., Weber J., Tsui L.-C., Rosenthal A.
Genome Res. 8:1060-1073(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Erythropoietin gene sequence in the Quechua, a high altitude native population."
Rupert J.L., Hochachka P.W.
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"The DNA sequence of human chromosome 7."
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. expand/collapse author list , 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.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Gene expression of mutant erythropoietin in hepatocellular carcinoma."
Funakoshi A., Muta H., Baba T., Shimizu S.
Biochem. Biophys. Res. Commun. 195:717-722(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 58-193, VARIANTS HEPATOCELLULAR CARCINOMA 131-ASN-PHE-132 AND GLN-149.
[8]"Structural characterization of human erythropoietin."
Lai P.H., Everett R., Wang F.F., Arakawa T., Goldwasser E.
J. Biol. Chem. 261:3116-3121(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 28-193, DISULFIDE BONDS.
Tissue: Urine.
[9]"Isolation of human erythropoietin with monoclonal antibodies."
Yanagawa S., Hirade K., Ohnota H., Sasaki R., Chiba H., Ueda M., Goto M.
J. Biol. Chem. 259:2707-2710(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: PRELIMINARY PROTEIN SEQUENCE OF 28-57.
[10]"Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells."
Takeuchi M., Takasaki S., Miyazaki H., Kato T., Hoshi S., Kochibe N., Kobata A.
J. Biol. Chem. 263:3657-3663(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE OF CARBOHYDRATES.
[11]"Site-specific glycosylation of human recombinant erythropoietin: analysis of glycopeptides or peptides at each glycosylation site by fast atom bombardment mass spectrometry."
Sasaki H., Ochi N., Dell A., Fukuda M.
Biochemistry 27:8618-8626(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE OF CARBOHYDRATES.
[12]"Structures and functional roles of the sugar chains of human erythropoietins."
Takeuchi M., Kobata A.
Glycobiology 1:337-346(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE OF CARBOHYDRATES.
[13]"Sugar profiling proves that human serum erythropoietin differs from recombinant human erythropoietin."
Skibeli V., Nissen-Lie G., Torjesen P.
Blood 98:3626-3634(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE OF CARBOHYDRATES.
[14]"Efficiency of signalling through cytokine receptors depends critically on receptor orientation."
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.
Nature 395:511-516(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 28-193.
[15]"NMR structure of human erythropoietin and a comparison with its receptor bound conformation."
Cheetham J.C., Smith D.M., Aoki K.H., Stevenson J.L., Hoeffel T.J., Syed R.S., Egrie J., Harvey T.S.
Nat. Struct. Biol. 5:861-866(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 28-193.
[16]"Promoter polymorphism of the erythropoietin gene in severe diabetic eye and kidney complications."
Genetics of diabetes and diabetic complication study group
Tong Z., Yang Z., Patel S., Chen H., Gibbs D., Yang X., Hau V.S., Kaminoh Y., Harmon J., Pearson E., Buehler J., Chen Y., Yu B., Tinkham N.H., Zabriskie N.A., Zeng J., Luo L., Sun J.K. expand/collapse author list , Prakash M., Hamam R.N., Tonna S., Constantine R., Ronquillo C.C., Sadda S., Avery R.L., Brand J.M., London N., Anduze A.L., King G.L., Bernstein P.S., Watkins S., Jorde L.B., Li D.Y., Aiello L.P., Pollak M.R., Zhang K.
Proc. Natl. Acad. Sci. U.S.A. 105:6998-7003(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO MICROVASCULAR COMPLICATIONS OF DIABETES TYPE 2.
+Additional computationally mapped references.

Web resources

R&D Systems' cytokine source book: Erythropoietin
Wikipedia

Erythropoietin entry

Protein Spotlight

Journey into a tiny world - Issue 84 of July 2007

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X02158 Genomic DNA. Translation: CAA26095.1.
X02157 mRNA. Translation: CAA26094.1.
M11319 Genomic DNA. Translation: AAA52400.1.
AF053356 Genomic DNA. Translation: AAC78791.1.
AF202308, AF202306, AF202307 Genomic DNA. Translation: AAF23132.1.
AH009004 Genomic DNA. Translation: AAF23133.1.
AF202311 Genomic DNA. Translation: AAF17572.1.
AF202314, AF202312, AF202313 Genomic DNA. Translation: AAF23134.1.
AC009488 Genomic DNA. Translation: AAP22357.1.
BC093628 mRNA. Translation: AAH93628.1.
BC111937 mRNA. Translation: AAI11938.1.
S65458 mRNA. Translation: AAD13964.1.
PIRZUHU. A01855.
RefSeqNP_000790.2. NM_000799.2.
UniGeneHs.2303.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BUYNMR-A28-193[»]
1CN4X-ray2.80C28-193[»]
1EERX-ray1.90A28-193[»]
ProteinModelPortalP01588.
SMRP01588. Positions 28-193.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108370. 2 interactions.
DIPDIP-5731N.
IntActP01588. 2 interactions.
STRING9606.ENSP00000252723.

Chemistry

ChEMBLCHEMBL5837.
DrugBankDB00012. Darbepoetin alfa.
DB00016. Epoetin alfa.

PTM databases

PhosphoSiteP01588.
UniCarbKBP01588.

Polymorphism databases

DMDM119526.

Proteomic databases

PRIDEP01588.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252723; ENSP00000252723; ENSG00000130427.
GeneID2056.
KEGGhsa:2056.
UCSCuc003uwi.3. human.

Organism-specific databases

CTD2056.
GeneCardsGC07P100318.
HGNCHGNC:3415. EPO.
HPACAB010336.
HPA027572.
MIM133170. gene.
612623. phenotype.
neXtProtNX_P01588.
PharmGKBPA27833.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG43828.
HOGENOMHOG000052505.
HOVERGENHBG003978.
InParanoidP01588.
KOK05437.
OMANVTMGCA.
OrthoDBEOG7DVDCR.
PhylomeDBP01588.
TreeFamTF333413.

Enzyme and pathway databases

ReactomeREACT_120956. Cellular responses to stress.
SignaLinkP01588.

Gene expression databases

ArrayExpressP01588.
BgeeP01588.
CleanExHS_EPO.
GenevestigatorP01588.

Family and domain databases

Gene3D1.20.1250.10. 1 hit.
InterProIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR019767. EPO/TPO_CS.
IPR001323. EPO_TPO.
IPR003013. Erythroptn.
[Graphical view]
PANTHERPTHR10370. PTHR10370. 1 hit.
PfamPF00758. EPO_TPO. 1 hit.
[Graphical view]
PIRSFPIRSF001951. EPO. 1 hit.
PRINTSPR00272. ERYTHROPTN.
SUPFAMSSF47266. SSF47266. 1 hit.
PROSITEPS00817. EPO_TPO. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01588.
GeneWikiErythropoietin.
GenomeRNAi2056.
NextBio8361.
PROP01588.
SOURCESearch...

Entry information

Entry nameEPO_HUMAN
AccessionPrimary (citable) accession number: P01588
Secondary accession number(s): Q2M2L6 expand/collapse secondary AC list , Q549U2, Q9UDZ0, Q9UEZ5, Q9UHA0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 16, 2014
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM