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P01588

- EPO_HUMAN

UniProt

P01588 - EPO_HUMAN

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Protein
Erythropoietin
Gene
EPO
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Erythropoietin is the principal hormone involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass.

GO - Molecular functioni

  1. protein binding Source: IntAct
  2. protein kinase activator activity Source: Ensembl

GO - Biological processi

  1. aging Source: Ensembl
  2. apoptotic process Source: Ensembl
  3. blood circulation Source: ProtInc
  4. cellular hyperosmotic response Source: BHF-UCL
  5. cellular response to hypoxia Source: Reactome
  6. embryo implantation Source: Ensembl
  7. erythrocyte maturation Source: UniProtKB-KW
  8. hemoglobin biosynthetic process Source: Ensembl
  9. negative regulation of calcium ion transport into cytosol Source: BHF-UCL
  10. negative regulation of cation channel activity Source: BHF-UCL
  11. negative regulation of erythrocyte apoptotic process Source: BHF-UCL
  12. negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress Source: BHF-UCL
  13. peptidyl-serine phosphorylation Source: Ensembl
  14. positive regulation of DNA replication Source: BHF-UCL
  15. positive regulation of Ras protein signal transduction Source: BHF-UCL
  16. positive regulation of cell proliferation Source: BHF-UCL
  17. positive regulation of neuron differentiation Source: Ensembl
  18. positive regulation of transcription, DNA-templated Source: BHF-UCL
  19. positive regulation of tyrosine phosphorylation of Stat5 protein Source: BHF-UCL
  20. regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Reactome
  21. response to axon injury Source: Ensembl
  22. response to electrical stimulus Source: Ensembl
  23. response to estrogen Source: Ensembl
  24. response to hyperoxia Source: Ensembl
  25. response to interleukin-1 Source: Ensembl
  26. response to lipopolysaccharide Source: Ensembl
  27. response to salt stress Source: Ensembl
  28. response to testosterone Source: Ensembl
  29. response to vitamin A Source: Ensembl
  30. signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hormone

Keywords - Biological processi

Erythrocyte maturation

Enzyme and pathway databases

ReactomeiREACT_121092. Regulation of gene expression by Hypoxia-inducible Factor.
SignaLinkiP01588.

Names & Taxonomyi

Protein namesi
Recommended name:
Erythropoietin
Alternative name(s):
INN: Epoetin
Gene namesi
Name:EPO
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:3415. EPO.

Subcellular locationi

GO - Cellular componenti

  1. cell surface Source: BHF-UCL
  2. extracellular region Source: Reactome
  3. extracellular space Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

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 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.

Organism-specific databases

MIMi612623. phenotype.
PharmGKBiPA27833.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 27272 Publications
Add
BLAST
Chaini28 – 193166Erythropoietin
PRO_0000008401Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi34 ↔ 1881 Publication
Glycosylationi51 – 511N-linked (GlcNAc...)1 Publication
CAR_000052
Disulfide bondi56 ↔ 601 Publication
Glycosylationi65 – 651N-linked (GlcNAc...)1 Publication
CAR_000166
Glycosylationi110 – 1101N-linked (GlcNAc...)1 Publication
CAR_000192
Glycosylationi153 – 1531O-linked (GalNAc...)1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP01588.

PTM databases

PhosphoSiteiP01588.
UniCarbKBiP01588.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiP01588.
BgeeiP01588.
CleanExiHS_EPO.
GenevestigatoriP01588.

Organism-specific databases

HPAiCAB010336.
HPA027572.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
EPORP192352EBI-1027362,EBI-617321

Protein-protein interaction databases

BioGridi108370. 2 interactions.
DIPiDIP-5731N.
IntActiP01588. 2 interactions.
STRINGi9606.ENSP00000252723.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi32 – 343
Helixi36 – 5217
Helixi53 – 553
Beta strandi57 – 604
Beta strandi61 – 688
Helixi75 – 784
Beta strandi79 – 813
Helixi83 – 10927
Helixi118 – 13821
Helixi141 – 1477
Beta strandi160 – 1645
Helixi165 – 17713
Helixi179 – 18810

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BUYNMR-A28-193[»]
1CN4X-ray2.80C28-193[»]
1EERX-ray1.90A28-193[»]
ProteinModelPortaliP01588.
SMRiP01588. Positions 28-193.

Miscellaneous databases

EvolutionaryTraceiP01588.

Family & Domainsi

Sequence similaritiesi

Belongs to the EPO/TPO family.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG43828.
HOGENOMiHOG000052505.
HOVERGENiHBG003978.
InParanoidiP01588.
KOiK05437.
OMAiNVTMGCA.
OrthoDBiEOG7DVDCR.
PhylomeDBiP01588.
TreeFamiTF333413.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR019767. EPO/TPO_CS.
IPR001323. EPO_TPO.
IPR003013. Erythroptn.
[Graphical view]
PANTHERiPTHR10370. PTHR10370. 1 hit.
PfamiPF00758. EPO_TPO. 1 hit.
[Graphical view]
PIRSFiPIRSF001951. EPO. 1 hit.
PRINTSiPR00272. ERYTHROPTN.
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00817. EPO_TPO. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01588-1 [UniParc]FASTAAdd to Basket

« Hide

MGVHECPAWL WLLLSLLSLP LGLPVLGAPP RLICDSRVLE RYLLEAKEAE    50
NITTGCAEHC SLNENITVPD TKVNFYAWKR MEVGQQAVEV WQGLALLSEA 100
VLRGQALLVN SSQPWEPLQL HVDKAVSGLR SLTTLLRALG AQKEAISPPD 150
AASAAPLRTI TADTFRKLFR VYSNFLRGKL KLYTGEACRT GDR 193
Length:193
Mass (Da):21,307
Last modified:July 21, 1986 - v1
Checksum:iC91F0E4C26A52033
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti131 – 1322SL → NF in a hepatocellular carcinoma.
VAR_009870
Natural varianti149 – 1491P → Q in a hepatocellular carcinoma. 1 Publication
VAR_009871

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti40 – 401E → Q in CAA26095. 1 Publication
Sequence conflicti85 – 851Q → QQ AA sequence 1 Publication
Sequence conflicti140 – 1401G → R in CAA26095. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
CCDSiCCDS5705.1.
PIRiA01855. ZUHU.
RefSeqiNP_000790.2. NM_000799.2.
UniGeneiHs.2303.

Genome annotation databases

EnsembliENST00000252723; ENSP00000252723; ENSG00000130427.
GeneIDi2056.
KEGGihsa:2056.
UCSCiuc003uwi.3. human.

Polymorphism databases

DMDMi119526.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

R&D Systems' cytokine source book: Erythropoietin
Wikipedia

Erythropoietin entry

Protein Spotlight

Journey into a tiny world - Issue 84 of July 2007

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGenei Hs.2303.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali P01588.
SMRi P01588. Positions 28-193.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108370. 2 interactions.
DIPi DIP-5731N.
IntActi P01588. 2 interactions.
STRINGi 9606.ENSP00000252723.

Chemistry

ChEMBLi CHEMBL5837.
DrugBanki DB00012. Darbepoetin alfa.
DB00016. Epoetin alfa.

PTM databases

PhosphoSitei P01588.
UniCarbKBi P01588.

Polymorphism databases

DMDMi 119526.

Proteomic databases

PRIDEi P01588.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000252723 ; ENSP00000252723 ; ENSG00000130427 .
GeneIDi 2056.
KEGGi hsa:2056.
UCSCi uc003uwi.3. human.

Organism-specific databases

CTDi 2056.
GeneCardsi GC07P100318.
HGNCi HGNC:3415. EPO.
HPAi CAB010336.
HPA027572.
MIMi 133170. gene.
612623. phenotype.
neXtProti NX_P01588.
PharmGKBi PA27833.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG43828.
HOGENOMi HOG000052505.
HOVERGENi HBG003978.
InParanoidi P01588.
KOi K05437.
OMAi NVTMGCA.
OrthoDBi EOG7DVDCR.
PhylomeDBi P01588.
TreeFami TF333413.

Enzyme and pathway databases

Reactomei REACT_121092. Regulation of gene expression by Hypoxia-inducible Factor.
SignaLinki P01588.

Miscellaneous databases

EvolutionaryTracei P01588.
GeneWikii Erythropoietin.
GenomeRNAii 2056.
NextBioi 8361.
PROi P01588.
SOURCEi Search...

Gene expression databases

ArrayExpressi P01588.
Bgeei P01588.
CleanExi HS_EPO.
Genevestigatori P01588.

Family and domain databases

Gene3Di 1.20.1250.10. 1 hit.
InterProi IPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR019767. EPO/TPO_CS.
IPR001323. EPO_TPO.
IPR003013. Erythroptn.
[Graphical view ]
PANTHERi PTHR10370. PTHR10370. 1 hit.
Pfami PF00758. EPO_TPO. 1 hit.
[Graphical view ]
PIRSFi PIRSF001951. EPO. 1 hit.
PRINTSi PR00272. ERYTHROPTN.
SUPFAMi SSF47266. SSF47266. 1 hit.
PROSITEi PS00817. EPO_TPO. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
  2. 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.
    , 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. 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. Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO MICROVASCULAR COMPLICATIONS OF DIABETES TYPE 2.

Entry informationi

Entry nameiEPO_HUMAN
AccessioniPrimary (citable) accession number: P01588
Secondary accession number(s): Q2M2L6
, Q549U2, Q9UDZ0, Q9UEZ5, Q9UHA0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: September 3, 2014
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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