Human Gene EPO (ENST00000252723.3) Description and Page Index
  Description: Homo sapiens erythropoietin (EPO), mRNA. (from RefSeq NM_000799)
RefSeq Summary (NM_000799): This gene encodes a secreted, glycosylated cytokine composed of four alpha helical bundles. The encoded protein is mainly synthesized in the kidney, secreted into the blood plasma, and binds to the erythropoietin receptor to promote red blood cell production, or erythropoiesis, in the bone marrow. Expression of this gene is upregulated under hypoxic conditions, in turn leading to increased erythropoiesis and enhanced oxygen-carrying capacity of the blood. Expression of this gene has also been observed in brain and in the eye, and elevated expression levels have been observed in diabetic retinopathy and ocular hypertension. Recombinant forms of the encoded protein exhibit neuroprotective activity against a variety of potential brain injuries, as well as antiapoptotic functions in several tissue types, and have been used in the treatment of anemia and to enhance the efficacy of cancer therapies. [provided by RefSeq, Aug 2017].
Gencode Transcript: ENST00000252723.3
Gencode Gene: ENSG00000130427.3
Transcript (Including UTRs)
   Position: hg38 chr7:100,720,468-100,723,700 Size: 3,233 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg38 chr7:100,720,981-100,723,133 Size: 2,153 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:100,720,468-100,723,700)mRNA (may differ from genome)Protein (193 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: EPO_HUMAN
DESCRIPTION: RecName: Full=Erythropoietin; AltName: INN=Epoetin; Flags: Precursor;
FUNCTION: Erythropoietin is the principal hormone involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass.
INTERACTION: P19235:EPOR; NbExp=2; IntAct=EBI-1027362, EBI-617321;
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals.
DISEASE: Genetic variation in EPO is associated with susceptbility to microvascular complications of diabetes type 2 (MVCD2) [MIM:612623]. These are 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.
PHARMACEUTICAL: 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.
SIMILARITY: Belongs to the EPO/TPO family.
WEB RESOURCE: Name=R&D Systems' cytokine source book: Erythropoietin; URL="http://www.rndsystems.com/molecule_detail.aspx?m=1405";
WEB RESOURCE: Name=Wikipedia; Note=Erythropoietin entry; URL="http://en.wikipedia.org/wiki/Erythropoietin";

-  MalaCards Disease Associations
  MalaCards Gene Search: EPO
Diseases sorted by gene-association score: microvascular complications of diabetes 2* (594), pure red-cell aplasia (37), uremia (34), deficiency anemia (33), acquired polycythemia (27), anemia of prematurity (26), neonatal anemia (25), arteriovenous fistula (23), rh isoimmunization (20), hypertensive encephalopathy (20), myelofibrosis with myeloid metaplasia, somatic (20), ocular hypertension (20), polycythemia (19), chronic kidney failure (19), vibrio vulnificus infection (18), iron deficiency anemia (17), pancytopenia (17), congenital hypoplastic anemia (16), refractory anemia (16), primary polycythemia (16), end stage renal failure (15), thrombocytosis (15), stress polycythemia (15), ischemia (13), chronic mountain sickness (13), autoimmune autonomic ganglionopathy (13), hemosiderosis (13), diabetic autonomic neuropathy (13), miliary tuberculosis (13), iritis (13), hemangioblastoma (12), polycythemia vera, somatic (12), thalassemia intermedia (12), kidney disease (12), diabetic neuropathy (12), mirage syndrome (12), splenomegaly (12), brain injury (11), hypersplenism (11), bone marrow cancer (11), aplastic anemia (11), iron-refractory iron deficiency anemia (11), essential thrombocythemia (10), thalassemia (10), retinitis pigmentosa and erythrocytic microcytosis (10), thalassemia, hispanic gamma-delta-beta (10), erythrocytosis, familial, 2 (10), iron metabolism disease (9), renal hypertension (9), hyperparathyroidism (9), immune system disease (9), periventricular leukomalacia (9), autonomic neuropathy (9), diamond-blackfan anemia (8), folic acid deficiency anemia (8), erythrocytosis, somatic (8), transient erythroblastopenia of childhood (8), sickle cell anemia (8), myoma (8), congenital hemolytic anemia (8), renal artery disease (8), vitamin b12 deficiency (8), sickle cell disease (7), sheehan syndrome (7), microcytic anemia (7), natural killer cell leukemia (7), secondary hyperparathyroidism of renal origin (7), macrocytic anemia, refractory, due to 5q deletion, somatic (7), congestive heart failure (7), kidney fibrosarcoma (7), ureteral obstruction (7), acute monoblastic leukemia (7), poems syndrome (7), hemoglobinopathy (6), toxic optic neuropathy (6), analbuminemia (6), pure autonomic failure (6), thalassemia minor (6), uremic neuropathy (6), acute erythroid leukemia (6), ewing's family of tumors (6), diabetic macular edema (5), nephrogenic systemic fibrosis (5), pyruvate kinase deficiency (5), myelodysplastic syndrome (5), urinary system disease (5), exudative vitreoretinopathy 1 (5), nutritional deficiency disease (5), fetal erythroblastosis (5), leukomalacia (4), splenic disease (4), neutropenia (4), hepatocellular carcinoma (3), acquired immunodeficiency syndrome (3), malaria (2), leukemia, chronic myeloid, somatic (2), dyskeratosis congenita (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 5.47 RPKM in Liver
Total median expression: 16.54 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -206.30513-0.402 Picture PostScript Text
3' UTR -204.10567-0.360 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009079 - 4_helix_cytokine-like_core
IPR012351 - 4_helix_cytokine_core
IPR019767 - EPO/TPO_CS
IPR001323 - EPO_TPO
IPR003013 - Erythroptn

Pfam Domains:
PF00758 - Erythropoietin/thrombopoietin

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1BUY
- NMR MuPIT

1CN4
- X-ray MuPIT

1EER
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P01588
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005125 cytokine activity
GO:0005128 erythropoietin receptor binding
GO:0005179 hormone activity
GO:0005515 protein binding
GO:0030295 protein kinase activator activity

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001666 response to hypoxia
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006915 apoptotic process
GO:0006953 acute-phase response
GO:0007165 signal transduction
GO:0007566 embryo implantation
GO:0007568 aging
GO:0007584 response to nutrient
GO:0008015 blood circulation
GO:0008283 cell proliferation
GO:0008284 positive regulation of cell proliferation
GO:0009651 response to salt stress
GO:0010469 regulation of receptor activity
GO:0010523 negative regulation of calcium ion transport into cytosol
GO:0010976 positive regulation of neuron projection development
GO:0018105 peptidyl-serine phosphorylation
GO:0030218 erythrocyte differentiation
GO:0032147 activation of protein kinase activity
GO:0032496 response to lipopolysaccharide
GO:0033033 negative regulation of myeloid cell apoptotic process
GO:0033189 response to vitamin A
GO:0033574 response to testosterone
GO:0038162 erythropoietin-mediated signaling pathway
GO:0042104 positive regulation of activated T cell proliferation
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0042541 hemoglobin biosynthetic process
GO:0043066 negative regulation of apoptotic process
GO:0043249 erythrocyte maturation
GO:0043627 response to estrogen
GO:0045666 positive regulation of neuron differentiation
GO:0045860 positive regulation of protein kinase activity
GO:0045893 positive regulation of transcription, DNA-templated
GO:0046579 positive regulation of Ras protein signal transduction
GO:0048678 response to axon injury
GO:0051602 response to electrical stimulus
GO:0055093 response to hyperoxia
GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070555 response to interleukin-1
GO:0071474 cellular hyperosmotic response
GO:0071548 response to dexamethasone
GO:1901215 negative regulation of neuron death
GO:1902219 negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress
GO:1902251 negative regulation of erythrocyte apoptotic process
GO:2001258 negative regulation of cation channel activity

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0009986 cell surface
GO:0044297 cell body


-  Descriptions from all associated GenBank mRNAs
  MA347443 - JP 2018506542-A/17: NUCLEIC ACID PRODUCTS AND METHODS OF ADMINISTRATION THEREOF.
E00630 - DNA encoding human erythropoietin.
X02157 - Human mRNA for fetal erythropoietin.
JD395927 - Sequence 376951 from Patent EP1572962.
JD116112 - Sequence 97136 from Patent EP1572962.
JD392109 - Sequence 373133 from Patent EP1572962.
BC093628 - Homo sapiens erythropoietin, mRNA (cDNA clone MGC:120663 IMAGE:7939473), complete cds.
BC111937 - Homo sapiens erythropoietin, mRNA (cDNA clone MGC:138142 IMAGE:8327405), complete cds.
BC143225 - Homo sapiens erythropoietin, mRNA (cDNA clone MGC:176743 IMAGE:9051726), complete cds.
JD461839 - Sequence 442863 from Patent EP1572962.
AB463610 - Synthetic construct DNA, clone: pF1KB6846, Homo sapiens EPO gene for erythropoietin, without stop codon, in Flexi system.
KF178447 - Homo sapiens isolate NS.13 erythropoietin mRNA, complete cds.
KJ891118 - Synthetic construct Homo sapiens clone ccsbBroadEn_00512 EPO gene, encodes complete protein.
HW649485 - JP 2014523870-A/4: CLEAVABLE LIPIDS.
HW649495 - JP 2014523411-A/3: LIPID NANOPARTICLE COMPOSITIONS AND METHODS FOR MRNA DELIVERY.
HZ189936 - JP 2015519301-A/1: Ionizable Cationic Lipids.
JB074620 - Sequence 3 from Patent WO2012170930.
JB074632 - Sequence 4 from Patent WO2012170889.
JC570529 - Sequence 3 from Patent WO2014089486.
JN849371 - Homo sapiens erythropoietin mRNA, complete cds.
LP056567 - Sequence 1 from Patent EP2830595.
LQ790605 - Sequence 4 from Patent EP3336082.
LQ850111 - Sequence 4 from Patent EP3354644.
MA155777 - JP 2017014278-A/3: LIPID NANOPARTICLE COMPOSITIONS AND METHODS FOR MRNA DELIVERY.
MA156906 - JP 2017019857-A/4: CLEAVABLE LIPIDS.
S65458 - Homo sapiens mutant erythropoietin mRNA, partial cds.
JD546966 - Sequence 527990 from Patent EP1572962.
JD425553 - Sequence 406577 from Patent EP1572962.
JD414580 - Sequence 395604 from Patent EP1572962.
JD414420 - Sequence 395444 from Patent EP1572962.
JD194990 - Sequence 176014 from Patent EP1572962.
JD352172 - Sequence 333196 from Patent EP1572962.
JD380415 - Sequence 361439 from Patent EP1572962.
JD064168 - Sequence 45192 from Patent EP1572962.
JD177089 - Sequence 158113 from Patent EP1572962.
JD515304 - Sequence 496328 from Patent EP1572962.
JD316942 - Sequence 297966 from Patent EP1572962.
JD564790 - Sequence 545814 from Patent EP1572962.
JD093427 - Sequence 74451 from Patent EP1572962.
JD522802 - Sequence 503826 from Patent EP1572962.
JD411491 - Sequence 392515 from Patent EP1572962.
JD385820 - Sequence 366844 from Patent EP1572962.
JD473248 - Sequence 454272 from Patent EP1572962.
MA890446 - JP 2017203045-A/3: LIPID NANOPARTICLE COMPOSITIONS AND METHODS FOR MRNA DELIVERY.
MB437423 - JP 2018095653-A/1: Ionizable Cationic Lipids.
MB447295 - JP 2018141006-A/4: CLEAVABLE LIPIDS.
MP440716 - Sequence 3 from Patent EP3586861.
MP559897 - Sequence 3 from Patent EP3628335.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04060 - Cytokine-cytokine receptor interaction
hsa04630 - Jak-STAT signaling pathway
hsa04640 - Hematopoietic cell lineage

BioCarta from NCI Cancer Genome Anatomy Project
h_eponfkbPathway - Erythropoietin mediated neuroprotection through NF-kB
h_erythPathway - Erythrocyte Differentiation Pathway
h_epoPathway - EPO Signaling Pathway
h_hifPathway - Hypoxia-Inducible Factor in the Cardiovascular System
h_stemPathway - Regulation of hematopoiesis by cytokines

Reactome (by CSHL, EBI, and GO)

Protein P01588 (Reactome details) participates in the following event(s):

R-HSA-1234158 Regulation of gene expression by Hypoxia-inducible Factor
R-HSA-1234174 Regulation of Hypoxia-inducible Factor (HIF) by oxygen
R-HSA-2262749 Cellular response to hypoxia
R-HSA-2262752 Cellular responses to stress
R-HSA-8953897 Cellular responses to external stimuli

-  Other Names for This Gene
  Alternate Gene Symbols: EPO_HUMAN, NM_000799, P01588, Q2M2L6, Q549U2, Q9UDZ0, Q9UEZ5, Q9UHA0, uc003uwi.1, uc003uwi.2, uc003uwi.3, uc003uwi.4, uc003uwi.5, uc003uwi.6
UCSC ID: uc003uwi.6
RefSeq Accession: NM_000799
Protein: P01588 (aka EPO_HUMAN)
CCDS: CCDS5705.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.