Erythropoietin precursor - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P01588 (EPO_HUMAN)

Last modified July 22, 2008. Version 98. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
Erythropoietin
Alternative name(s):
INN=Epoetin

Gene names

Name:

EPO

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	193 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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.
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.

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Ontologies

Keywords
Biological process	Erythrocyte maturation
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Hormone
PTM	Glycoprotein
Technical term	3D-structure Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological process	blood circulation Ref.1 Non-traceable author statement. Source: ProtInc positive regulation of DNA replication Inferred from direct assay. Source: UniProtKB positive regulation of Ras protein signal transduction Inferred from direct assay. Source: UniProtKB positive regulation of cell proliferation Inferred from direct assay. Source: UniProtKB positive regulation of gene-specific transcription Inferred from direct assay. Source: UniProtKB positive regulation of tyrosine phosphorylation of Stat5 protein Inferred from direct assay. Source: UniProtKB response to stress Traceable author statement. Source: ProtInc
Cellular component	extracellular space Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
DOK2	O60496	1	EBI-1027362,EBI-1046024

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 27

Chain

28 – 193

166

Erythropoietin

Propeptide

190 – 193

Removed in mature form (Partial)

Propeptide

193

Removed in mature form (Partial)

Amino acid modifications

Glycosylation

N-linked (GlcNAc...)

Glycosylation

N-linked (GlcNAc...)

Glycosylation

110

N-linked (GlcNAc...)

Glycosylation

153

O-linked (GalNAc...)

Disulfide bond

34 ↔ 188

Disulfide bond

56 ↔ 60

Natural variations

Natural variant

131 – 132

SL → NF in an hepatocellular carcinoma.

Natural variant

149

P → Q in an hepatocellular carcinoma.

Experimental info

Sequence conflict

E → Q in CAA26095. Ref.1

Sequence conflict

Q → QQ AA sequence Ref.8

Sequence conflict

140

G → R in CAA26095. Ref.1

Secondary structure

193

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P01588-1 [UniParc].

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

193

21,307

        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

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References

	« Hide 'large scale' referencesShow '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: 3838366] [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: 3865178] [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: 9799793] [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. Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [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: 15489334] [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: 8396923] [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: 3949763] [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: 6698989] [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: 3346214] [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: 3219367] [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: 1820196] [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: 11739166] [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: 9774108] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
[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: 9783743] [Abstract] Cited for: STRUCTURE BY NMR OF 28-193.
+	Additional computationally mapped references.

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Web resources

R&D Systems' cytokine source book: Erythropoietin

Wikipedia

Erythropoietin entry

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Cross-references

Sequence databases

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.
AF202310, AF202309 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.

PIR

ZUHU. A01855.

RefSeq

NP_000790.2.

UniGene

Hs.2303

3D structure databases

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	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:5731N.

IntAct

P01588.

PTM databases

GlycoSuiteDB

P01588.

Genome annotation databases

Ensembl

ENSG00000130427. Homo sapiens. [Contig view]

GeneID

2056.

KEGG

hsa:2056.

Organism-specific databases

H-InvDB

HIX0033695.

HGNC

HGNC:3415. EPO.

HPA

CAB010336.

MIM

133170. gene.

PharmGKB

PA27833.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P01588.

HOVERGEN

P01588.

Gene expression databases

ArrayExpress

P01588.

CleanEx

HS_EPO.

GermOnline

ENSG00000130427. Homo sapiens.

Family and domain databases

InterPro

IPR012351. 4_helix_cytokine_core.
IPR001323. EPO_TPO.
IPR003013. Erythroptn.
[Graphical view]

Gene3D

G3DSA:1.20.1250.10. 4_helix_cytokine_core. 1 hit.

PANTHER

PTHR10370. Erythroptn. 1 hit.

Pfam

PF00758. EPO_TPO. 1 hit.
[Graphical view]

PIRSF

PIRSF001951. EPO. 1 hit.

PRINTS

PR00272. ERYTHROPTN.

PROSITE

PS00817. EPO_TPO. 1 hit.
[Graphical view]

ProDom

P01588.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

Search...

Other Resources

DrugBank

DB00012. Darbepoetin alfa.
DB00016. Epoetin alfa.

LinkHub

P01588.

SOURCE

Search...

ProtoNet

Search...

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Entry information

Entry name

EPO_HUMAN

Accession

Primary (citable) accession number: P01588
Secondary accession number(s): Q2M2L6

Q9UHA0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	July 22, 2008
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 7

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

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

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents