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UniProtKB - P01588 (EPO_HUMAN)
Protein
Erythropoietin
Gene
EPO
Organism
Homo sapiens (Human)
Status
Functioni
Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation thereby activating specific downstream effectors, including STAT1 and STAT3.
1 PublicationGO - Molecular functioni
- cytokine activity Source: BHF-UCL
- erythropoietin receptor binding Source: UniProtKB
- hormone activity Source: UniProtKB-KW
- protein kinase activator activity Source: GO_Central
GO - Biological processi
- acute-phase response Source: Ensembl
- aging Source: Ensembl
- apoptotic process Source: Ensembl
- blood circulation Source: ProtInc
- cellular hyperosmotic response Source: BHF-UCL
- embryo implantation Source: Ensembl
- erythrocyte differentiation Source: BHF-UCL
- erythrocyte maturation Source: UniProtKB-KW
- erythropoietin-mediated signaling pathway Source: UniProtKB
- hemoglobin biosynthetic process Source: Ensembl
- negative regulation of calcium ion transport into cytosol Source: BHF-UCL
- negative regulation of cation channel activity Source: BHF-UCL
- negative regulation of erythrocyte apoptotic process Source: BHF-UCL
- negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress Source: BHF-UCL
- negative regulation of neuron death Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: BHF-UCL
- peptidyl-serine phosphorylation Source: Ensembl
- positive regulation of activated T cell proliferation Source: Ensembl
- positive regulation of cell population proliferation Source: BHF-UCL
- positive regulation of ERK1 and ERK2 cascade Source: Ensembl
- positive regulation of neuron differentiation Source: Ensembl
- positive regulation of neuron projection development Source: Ensembl
- positive regulation of Ras protein signal transduction Source: BHF-UCL
- positive regulation of transcription, DNA-templated Source: BHF-UCL
- positive regulation of tyrosine phosphorylation of STAT protein Source: BHF-UCL
- response to axon injury Source: Ensembl
- response to dexamethasone Source: Ensembl
- response to electrical stimulus Source: Ensembl
- response to estrogen Source: Ensembl
- response to hyperoxia Source: Ensembl
- response to hypoxia Source: Ensembl
- response to interleukin-1 Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- response to salt stress Source: Ensembl
- response to testosterone Source: Ensembl
- response to vitamin A Source: Ensembl
- signal transduction Source: ProtInc
Keywordsi
Molecular function | Hormone |
Biological process | Erythrocyte maturation |
Enzyme and pathway databases
PathwayCommonsi | P01588 |
Reactomei | R-HSA-1234158, Regulation of gene expression by Hypoxia-inducible Factor R-HSA-9006335, Signaling by Erythropoietin R-HSA-9027276, Erythropoietin activates Phosphoinositide-3-kinase (PI3K) R-HSA-9027277, Erythropoietin activates Phospholipase C gamma (PLCG) R-HSA-9027283, Erythropoietin activates STAT5 R-HSA-9027284, Erythropoietin activates RAS |
SignaLinki | P01588 |
SIGNORi | P01588 |
Names & Taxonomyi
Protein namesi | Recommended name: ErythropoietinAlternative name(s): INN: Epoetin |
Gene namesi | Name:EPO |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3415, EPO |
MIMi | 133170, gene |
neXtProti | NX_P01588 |
VEuPathDBi | HostDB:ENSG00000130427 |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: BHF-UCL
Other locations
- cell body Source: Ensembl
- cell surface Source: BHF-UCL
Keywords - Cellular componenti
SecretedPathology & Biotechi
Involvement in diseasei
Microvascular complications of diabetes 2 (MVCD2)
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionPathological 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.
Related information in OMIMErythrocytosis, familial, 5 (ECYT5)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit. Some patients have increased serum erythropoietin levels.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_080573 | 70 | D → N in ECYT5; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs62483572EnsemblClinVar. | 1 | |
Natural variantiVAR_080574 | 84 | G → R in ECYT5; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs137953994EnsemblClinVar. | 1 | |
Natural variantiVAR_080576 | 114 | P → L in ECYT5; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs11976235EnsemblClinVar. | 1 | |
Natural variantiVAR_080577 | 147 | S → C in ECYT5; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs149431976Ensembl. | 1 |
Diamond-Blackfan anemia-like (DBAL)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive hematologic disease characterized by severe red cell hypoplastic anemia, selective absence of red cell precursors and progenitors seen on bone marrow biopsy, and increased serum erythropoietin.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078447 | 177 | R → Q in DBAL; loss of support of normal erythroid expansion or differentiation; reduced ability to promote EPOR dimer formation upon binding, resulting in reduced JAK2 activation and decreased STAT1 and STAT3 phosphorylation; mild decrease in affinity for EPOR; no effect on STAT5A phosphorylation. 1 PublicationCorresponds to variant dbSNP:rs1358275550EnsemblClinVar. | 1 |
Pharmaceutical usei
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.
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 127 | S → E: Decreased erythrocyte proliferation; impaired EPOR dimerization following binding. 1 Publication | 1 |
Keywords - Diseasei
Congenital erythrocytosis, Disease variantOrganism-specific databases
DisGeNETi | 2056 |
MalaCardsi | EPO |
MIMi | 612623, phenotype 617907, phenotype 617911, phenotype |
OpenTargetsi | ENSG00000130427 |
Orphaneti | 247511, Autosomal dominant secondary polycythemia |
PharmGKBi | PA27833 |
Miscellaneous databases
Pharosi | P01588, Tbio |
Protein family/group databases
Allergomei | 11697, Hom s EPO |
Chemistry databases
ChEMBLi | CHEMBL5837 |
Genetic variation databases
BioMutai | EPO |
DMDMi | 119526 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 27 | 1 PublicationAdd BLAST | 27 | |
ChainiPRO_0000008401 | 28 – 193 | ErythropoietinAdd BLAST | 166 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 34 ↔ 188 | 1 Publication | ||
GlycosylationiCAR_000052 | 51 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 56 ↔ 60 | 1 Publication | ||
GlycosylationiCAR_000166 | 65 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
GlycosylationiCAR_000192 | 110 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 153 | O-linked (GalNAc...) serine1 Publication | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | P01588 |
MassIVEi | P01588 |
PaxDbi | P01588 |
PeptideAtlasi | P01588 |
PRIDEi | P01588 |
PTM databases
GlyConnecti | 140, 212 N-Linked glycans (3 sites), 27 O-Linked glycans (1 site) |
GlyGeni | P01588, 5 sites, 179 N-linked glycans (4 sites), 17 O-linked glycans (2 sites) |
iPTMneti | P01588 |
MetOSitei | P01588 |
PhosphoSitePlusi | P01588 |
Expressioni
Tissue specificityi
Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals.
Gene expression databases
Bgeei | ENSG00000130427, Expressed in right lobe of liver and 84 other tissues |
ExpressionAtlasi | P01588, baseline and differential |
Genevisiblei | P01588, HS |
Organism-specific databases
HPAi | ENSG00000130427, Tissue enriched (liver) |
Interactioni
Binary interactionsi
P01588
With | #Exp. | IntAct |
---|---|---|
EPHB4 [P54760] | 6 | EBI-1027362,EBI-702121 |
EPOR [P19235] | 3 | EBI-1027362,EBI-617321 |
Erythropoietin (PRO_0000008401)
With | #Exp. | IntAct |
---|---|---|
EPOR [P19235] | 2 | EBI-11508463,EBI-617321 |
GO - Molecular functioni
- cytokine activity Source: BHF-UCL
- erythropoietin receptor binding Source: UniProtKB
- hormone activity Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 108370, 31 interactors |
CORUMi | P01588 |
DIPi | DIP-5731N |
IntActi | P01588, 5 interactors |
STRINGi | 9606.ENSP00000252723 |
Miscellaneous databases
RNActi | P01588, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
AlphaFoldDBi | P01588 |
SMRi | P01588 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P01588 |
Family & Domainsi
Sequence similaritiesi
Belongs to the EPO/TPO family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502RXRC, Eukaryota |
GeneTreei | ENSGT00390000017226 |
HOGENOMi | CLU_110946_0_0_1 |
InParanoidi | P01588 |
OMAi | GVRECPA |
OrthoDBi | 1175751at2759 |
PhylomeDBi | P01588 |
TreeFami | TF333413 |
Family and domain databases
Gene3Di | 1.20.1250.10, 1 hit |
InterProi | View protein in InterPro IPR009079, 4_helix_cytokine-like_core IPR019767, EPO/TPO_CS IPR001323, EPO_TPO IPR003013, Erythroptn |
PANTHERi | PTHR10370, PTHR10370, 1 hit |
Pfami | View protein in Pfam PF00758, EPO_TPO, 1 hit |
PIRSFi | PIRSF001951, EPO, 1 hit |
PRINTSi | PR00272, ERYTHROPTN |
SUPFAMi | SSF47266, SSF47266, 1 hit |
PROSITEi | View protein in PROSITE PS00817, EPO_TPO, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P01588-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGVHECPAWL WLLLSLLSLP LGLPVLGAPP RLICDSRVLE RYLLEAKEAE
60 70 80 90 100
NITTGCAEHC SLNENITVPD TKVNFYAWKR MEVGQQAVEV WQGLALLSEA
110 120 130 140 150
VLRGQALLVN SSQPWEPLQL HVDKAVSGLR SLTTLLRALG AQKEAISPPD
160 170 180 190
AASAAPLRTI TADTFRKLFR VYSNFLRGKL KLYTGEACRT GDR
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 40 | E → Q in CAA26095 (PubMed:3838366).Curated | 1 | |
Sequence conflicti | 85 | Q → QQ AA sequence (PubMed:3949763).Curated | 1 | |
Sequence conflicti | 140 | G → R in CAA26095 (PubMed:3838366).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_080573 | 70 | D → N in ECYT5; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs62483572EnsemblClinVar. | 1 | |
Natural variantiVAR_080574 | 84 | G → R in ECYT5; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs137953994EnsemblClinVar. | 1 | |
Natural variantiVAR_080575 | 99 | E → G Found in a patient thought to have erythrocytosis, but had normal red cell mass; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_080576 | 114 | P → L in ECYT5; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs11976235EnsemblClinVar. | 1 | |
Natural variantiVAR_009870 | 131 – 132 | SL → NF in a hepatocellular carcinoma. | 2 | |
Natural variantiVAR_080577 | 147 | S → C in ECYT5; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs149431976Ensembl. | 1 | |
Natural variantiVAR_009871 | 149 | P → Q in a hepatocellular carcinoma. 1 Publication | 1 | |
Natural variantiVAR_078447 | 177 | R → Q in DBAL; loss of support of normal erythroid expansion or differentiation; reduced ability to promote EPOR dimer formation upon binding, resulting in reduced JAK2 activation and decreased STAT1 and STAT3 phosphorylation; mild decrease in affinity for EPOR; no effect on STAT5A phosphorylation. 1 PublicationCorresponds to variant dbSNP:rs1358275550EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS5705.1 |
PIRi | A01855, ZUHU |
RefSeqi | NP_000790.2, NM_000799.2 |
Genome annotation databases
Ensembli | ENST00000252723.3; ENSP00000252723.2; ENSG00000130427.3 |
GeneIDi | 2056 |
KEGGi | hsa:2056 |
MANE-Selecti | ENST00000252723.3; ENSP00000252723.2; NM_000799.4; NP_000790.2 |
UCSCi | uc003uwi.5, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Erythropoietin entry |
Protein Spotlight Journey into a tiny world - Issue 84 of July 2007 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 |
CCDSi | CCDS5705.1 |
PIRi | A01855, ZUHU |
RefSeqi | NP_000790.2, NM_000799.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1BUY | NMR | - | A | 28-193 | [»] | |
1CN4 | X-ray | 2.80 | C | 28-193 | [»] | |
1EER | X-ray | 1.90 | A | 28-193 | [»] | |
AlphaFoldDBi | P01588 | |||||
SMRi | P01588 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108370, 31 interactors |
CORUMi | P01588 |
DIPi | DIP-5731N |
IntActi | P01588, 5 interactors |
STRINGi | 9606.ENSP00000252723 |
Chemistry databases
ChEMBLi | CHEMBL5837 |
Protein family/group databases
Allergomei | 11697, Hom s EPO |
PTM databases
GlyConnecti | 140, 212 N-Linked glycans (3 sites), 27 O-Linked glycans (1 site) |
GlyGeni | P01588, 5 sites, 179 N-linked glycans (4 sites), 17 O-linked glycans (2 sites) |
iPTMneti | P01588 |
MetOSitei | P01588 |
PhosphoSitePlusi | P01588 |
Genetic variation databases
BioMutai | EPO |
DMDMi | 119526 |
Proteomic databases
EPDi | P01588 |
MassIVEi | P01588 |
PaxDbi | P01588 |
PeptideAtlasi | P01588 |
PRIDEi | P01588 |
Protocols and materials databases
Antibodypediai | 4151, 1310 antibodies from 40 providers |
DNASUi | 2056 |
Genome annotation databases
Ensembli | ENST00000252723.3; ENSP00000252723.2; ENSG00000130427.3 |
GeneIDi | 2056 |
KEGGi | hsa:2056 |
MANE-Selecti | ENST00000252723.3; ENSP00000252723.2; NM_000799.4; NP_000790.2 |
UCSCi | uc003uwi.5, human |
Organism-specific databases
CTDi | 2056 |
DisGeNETi | 2056 |
GeneCardsi | EPO |
HGNCi | HGNC:3415, EPO |
HPAi | ENSG00000130427, Tissue enriched (liver) |
MalaCardsi | EPO |
MIMi | 133170, gene 612623, phenotype 617907, phenotype 617911, phenotype |
neXtProti | NX_P01588 |
OpenTargetsi | ENSG00000130427 |
Orphaneti | 247511, Autosomal dominant secondary polycythemia |
PharmGKBi | PA27833 |
VEuPathDBi | HostDB:ENSG00000130427 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RXRC, Eukaryota |
GeneTreei | ENSGT00390000017226 |
HOGENOMi | CLU_110946_0_0_1 |
InParanoidi | P01588 |
OMAi | GVRECPA |
OrthoDBi | 1175751at2759 |
PhylomeDBi | P01588 |
TreeFami | TF333413 |
Enzyme and pathway databases
PathwayCommonsi | P01588 |
Reactomei | R-HSA-1234158, Regulation of gene expression by Hypoxia-inducible Factor R-HSA-9006335, Signaling by Erythropoietin R-HSA-9027276, Erythropoietin activates Phosphoinositide-3-kinase (PI3K) R-HSA-9027277, Erythropoietin activates Phospholipase C gamma (PLCG) R-HSA-9027283, Erythropoietin activates STAT5 R-HSA-9027284, Erythropoietin activates RAS |
SignaLinki | P01588 |
SIGNORi | P01588 |
Miscellaneous databases
BioGRID-ORCSi | 2056, 13 hits in 1071 CRISPR screens |
EvolutionaryTracei | P01588 |
GeneWikii | Erythropoietin |
GenomeRNAii | 2056 |
Pharosi | P01588, Tbio |
PROi | PR:P01588 |
RNActi | P01588, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000130427, Expressed in right lobe of liver and 84 other tissues |
ExpressionAtlasi | P01588, baseline and differential |
Genevisiblei | P01588, HS |
Family and domain databases
Gene3Di | 1.20.1250.10, 1 hit |
InterProi | View protein in InterPro IPR009079, 4_helix_cytokine-like_core IPR019767, EPO/TPO_CS IPR001323, EPO_TPO IPR003013, Erythroptn |
PANTHERi | PTHR10370, PTHR10370, 1 hit |
Pfami | View protein in Pfam PF00758, EPO_TPO, 1 hit |
PIRSFi | PIRSF001951, EPO, 1 hit |
PRINTSi | PR00272, ERYTHROPTN |
SUPFAMi | SSF47266, SSF47266, 1 hit |
PROSITEi | View protein in PROSITE PS00817, EPO_TPO, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | EPO_HUMAN | |
Accessioni | P01588Primary (citable) accession number: P01588 Secondary accession number(s): Q2M2L6 Q9UHA0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | July 21, 1986 | |
Last modified: | May 25, 2022 | |
This is version 209 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Pharmaceutical, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries