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Protein

Erythropoietin

Gene

EPO

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

GO - Biological processi

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 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:3415. EPO.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: BHF-UCL
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Microvascular complications of diabetes 2 (MVCD2)

Disease susceptibility is associated with variations 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.

See also OMIM:612623

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.

Protein family/group databases

Allergomei11697. Hom s EPO.

Polymorphism and mutation databases

BioMutaiEPO.
DMDMi119526.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 27271 PublicationAdd
BLAST
Chaini28 – 193166ErythropoietinPRO_0000008401Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi34 ↔ 1881 Publication
Glycosylationi51 – 511N-linked (GlcNAc...)1 PublicationCAR_000052
Disulfide bondi56 ↔ 601 Publication
Glycosylationi65 – 651N-linked (GlcNAc...)1 PublicationCAR_000166
Glycosylationi110 – 1101N-linked (GlcNAc...)1 PublicationCAR_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

BgeeiP01588.
CleanExiHS_EPO.
ExpressionAtlasiP01588. baseline and differential.
GenevisibleiP01588. HS.

Organism-specific databases

HPAiCAB010336.
HPA027572.

Interactioni

Binary interactionsi

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

Protein-protein interaction databases

BioGridi108370. 4 interactions.
DIPiDIP-5731N.
IntActiP01588. 2 interactions.
STRINGi9606.ENSP00000252723.

Structurei

Secondary structure

1
193
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi32 – 343Combined sources
Helixi36 – 5217Combined sources
Helixi53 – 553Combined sources
Beta strandi57 – 604Combined sources
Beta strandi61 – 688Combined sources
Helixi75 – 784Combined sources
Beta strandi79 – 813Combined sources
Helixi83 – 10927Combined sources
Helixi118 – 13821Combined sources
Helixi141 – 1477Combined sources
Beta strandi160 – 1645Combined sources
Helixi165 – 17713Combined sources
Helixi179 – 18810Combined sources

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP01588.

Family & Domainsi

Sequence similaritiesi

Belongs to the EPO/TPO family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG43828.
GeneTreeiENSGT00390000017226.
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

        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
Length:193
Mass (Da):21,307
Last modified:July 21, 1986 - v1
Checksum:iC91F0E4C26A52033
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti40 – 401E → Q in CAA26095 (PubMed:3838366).Curated
Sequence conflicti85 – 851Q → QQ AA sequence (PubMed:3949763).Curated
Sequence conflicti140 – 1401G → R in CAA26095 (PubMed:3838366).Curated

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 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.
CCDSiCCDS5705.1.
PIRiA01855. ZUHU.
RefSeqiNP_000790.2. NM_000799.2.
UniGeneiHs.2303.

Genome annotation databases

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

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:
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.
CCDSiCCDS5705.1.
PIRiA01855. ZUHU.
RefSeqiNP_000790.2. NM_000799.2.
UniGeneiHs.2303.

3D structure databases

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

Protein-protein interaction databases

BioGridi108370. 4 interactions.
DIPiDIP-5731N.
IntActiP01588. 2 interactions.
STRINGi9606.ENSP00000252723.

Chemistry

ChEMBLiCHEMBL5837.

Protein family/group databases

Allergomei11697. Hom s EPO.

PTM databases

PhosphoSiteiP01588.
UniCarbKBiP01588.

Polymorphism and mutation databases

BioMutaiEPO.
DMDMi119526.

Proteomic databases

PRIDEiP01588.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2056.
GeneCardsiGC07P100318.
HGNCiHGNC:3415. EPO.
HPAiCAB010336.
HPA027572.
MIMi133170. gene.
612623. phenotype.
neXtProtiNX_P01588.
PharmGKBiPA27833.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG43828.
GeneTreeiENSGT00390000017226.
HOGENOMiHOG000052505.
HOVERGENiHBG003978.
InParanoidiP01588.
KOiK05437.
OMAiNVTMGCA.
OrthoDBiEOG7DVDCR.
PhylomeDBiP01588.
TreeFamiTF333413.

Enzyme and pathway databases

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

Miscellaneous databases

EvolutionaryTraceiP01588.
GeneWikiiErythropoietin.
GenomeRNAii2056.
NextBioi8361.
PROiP01588.
SOURCEiSearch...

Gene expression databases

BgeeiP01588.
CleanExiHS_EPO.
ExpressionAtlasiP01588. baseline and differential.
GenevisibleiP01588. HS.

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]
ProtoNetiSearch...

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: June 24, 2015
This is version 162 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.