Recombinant Human Erythropoietin (EPO) (Active)
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Description
Molecular Structure and Production
rHuEPO comprises 165 amino acids (aa 28–193) with a molecular weight of ~30,400 Daltons. Key structural features include:
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Disulfide bonds: Cys7-Cys160 and Cys29-Cys33 critical for conformational stability .
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Glycosylation: N-linked and O-linked oligosaccharides ensure proper folding, secretion, and receptor binding .
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Expression system: Produced in HEK 293 cells or Chinese Hamster Ovary (CHO) cells, with endotoxin levels ≤0.005 EU/μg .
| Parameter | Value | Source |
|---|---|---|
| Amino Acid Sequence | 165 residues (28–193 aa) | |
| Molecular Weight | ~30,400 Daltons | |
| Expression System | HEK 293 or CHO cells | |
| Endotoxin Level | ≤0.005 EU/μg |
Mechanism of Action
rHuEPO binds to EPOR on erythroid progenitor cells, activating intracellular signaling cascades:
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EPOR dimerization → JAK2 phosphorylation → STAT5/STAT3 activation .
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PI3K/Akt and Ras MAPK pathways promote cell survival and proliferation .
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Negative regulation by SOCS1/SOCS3 proteins limits signaling duration .
Key Receptor Interactions:
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Tissue-protective receptor (TPR): EPOR/CD131 heterodimer mediates anti-inflammatory and anti-apoptotic effects in non-erythroid tissues .
Anemia Treatment
rHuEPO is FDA-approved for:
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Chronic kidney disease (CKD): Restores hemoglobin levels, reducing transfusion needs .
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Cancer-related anemia: Enhances erythropoiesis during chemotherapy .
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Perioperative settings: Mobilizes red blood cells (RBCs) pre- and post-surgery .
Immunomodulation
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Dendritic cells: Inhibits maturation via SOCS1 upregulation, reducing pro-inflammatory cytokines .
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T-cells: Suppresses conventional T-cell proliferation while enhancing Treg stability via SHP-1/STAT5 crosstalk .
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Th17/Th1 responses: Reduced in autoimmune models (e.g., EAN rats) with non-erythropoietic EPO derivatives .
Neutralizing Antibodies
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Pure red cell aplasia (PRCA): Linked to anti-EPO antibodies, particularly in HLA-DRB1*09 carriers .
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Incidence: ~22% of Thai populations express HLA-DRB1*09, increasing PRCA risk .
Engineered EPO Derivatives
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MHC-binding mutants: Designed to disrupt HLA-DRB1*09 interactions, reducing immunogenicity in ex vivo assays .
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Non-erythropoietic derivatives (e.g., ARA290): Retain TPR-binding capacity without hematopoietic effects, mitigating cardiovascular risks .
Tissue Protection
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Neuroprotection: EPO reduces apoptosis and inflammation in ischemic brain models .
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Wound healing: TPR-mediated angiogenesis and collagen synthesis .
Immune Regulation
Product Specs
Buffer
Lyophilized from a 0.2 µm filtered 1xPBS, pH 7.4.
Form
Lyophilized powder
Lead Time
Typically, we can ship the products within 5-10 business days after receiving your order. Delivery time may vary depending on the purchasing method or location. For specific delivery timeframes, please consult your local distributors.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Reconstitution
Prior to opening, we recommend briefly centrifuging the vial to ensure the contents settle to the bottom. Reconstitute the protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. We suggest adding 5-50% glycerol (final concentration) and aliquoting for long-term storage at -20°C/-80°C. Our standard final glycerol concentration is 50%, which can be used as a reference.
Shelf Life
Shelf life is influenced by various factors, including storage conditions, buffer composition, storage temperature, and the inherent stability of the protein. Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. Lyophilized form has a shelf life of 12 months at -20°C/-80°C.
Storage Condition
Store at -20°C/-80°C upon receipt. Aliquoting is necessary for multiple uses. Avoid repeated freeze-thaw cycles.
Tag Info
C-terminal 6xHis-tagged
Synonyms
EPOErythropoietin; Epoetin
Datasheet & Coa
Please contact us to get it.
Expression Region
28-193aa
Mol. Weight
19.2 kDa
Protein Length
Full Length of Mature Protein
Purity
Greater than 95% as determined by SDS-PAGE.
Research Area
Signal Transduction
Source
Mammalian cell
Species
Homo sapiens (Human)
Target Names
Uniprot No.
Target Background
Function
Erythropoietin is a hormone that plays a crucial role in regulating erythrocyte proliferation and differentiation, ensuring the maintenance of a physiologically normal level of circulating red blood cells. It binds to the erythropoietin receptor (EPOR), triggering EPOR dimerization and activation of JAK2, thereby activating downstream effectors such as STAT1 and STAT3.
Gene References Into Functions
- Elevated plasma erythropoietin and erythropoietin receptor activation are implicated as mechanisms contributing to increased plasma FGF23 levels in acute kidney injury. PMID: 29395333
- The alpha-7-nAChR-JAK-2/STAT-3-Nrf-2 signaling cascade is implicated in the radiomitigative potential of EPO against acute radiation syndrome. PMID: 29220591
- Pro-inflammatory proteins S100A9 and tumor necrosis factor-alpha suppress erythropoietin production in myelodysplastic syndromes. PMID: 28983059
- EPO levels in the coronary artery disease (CAD) group were significantly higher than those in the non-CAD group. A statistically significant correlation between red cell distribution width and EPO levels was observed among CAD patients. PMID: 28885393
- CD133(+) cells contribute to local erythropoietin production, as evidenced by the detection of circulating human erythropoietin. CD133(+) cells therefore appear to be an effective source for cell repair, capable of restoring renal functions, including erythropoietin release, and limiting long-term maldifferentiation and fibrosis. PMID: 27853265
- Circulating anti-EPO antibodies are detected in a significant proportion of treatment-naive HCV-infected patients and are independently associated with anemia, suggesting a further involvement of autoimmunity in the pathophysiology of HCV-related anemia. PMID: 28603097
- The T allele of SNP rs60684937 located at 67,419,130 bp on chromosome 17 was associated with increased plasma EPO and a relatively increased expression of a non-coding transcript of PRKAR1A in sickle cell disease patients. PMID: 28173069
- A study describes a gain-of-function variant in EPO in an extended kindred with familial erythrocytosis, encompassing 10 affected family members across four generations. This mutation, a single-nucleotide deletion (c.32delG), introduces a frameshift in exon 2. PMID: 29514032
- Using zebrafish, murine, and human models, the authors demonstrate that erythropoietin (EPO) signaling, in conjunction with the GATA1 transcriptional target, AKAP10, regulates heme biosynthesis during erythropoiesis at the outer mitochondrial membrane. PMID: 28553927
- A decrease in central venous blood pressure triggers an increase in plasma EPO concentration independent of hemoconcentration, suggesting that CVP itself serves as an acute regulator of EPO synthesis. PMID: 27169519
- EPO (7q22) and SEC-61(7p11) emerged as novel candidate genes susceptible to genetic losses, with 57.7% deletions identified in regions on chromosome 7. PMID: 27282568
- The current debate regarding EPO's skeletal effects may stem from a context-dependent mode of action, exhibiting opposing skeletal actions during bone regeneration and steady-state bone remodeling. PMID: 26822707
- High EPO expression is associated with monoclonal gammopathy of undetermined significance and multiple myeloma. PMID: 26919105
- Plasma levels of EPO at age 3 were found to be related to childhood asthma. PMID: 27434124
- EPO induces an epithelial-mesenchymal transition (EMT)-like process in mammary non-tumorigenic epithelial cells. PMID: 28247960
- These findings suggest that the cytoprotective effects of quercetin in HepG2 cells are mediated via EPO production. PMID: 29080630
- Serum Epo and VEGF may serve as markers of hypoxia-ischemia severity and brain injury due to their close association with hypoxic exposure. PMID: 27902983
- CIS interacts with phosphorylated EpoR at Y401, which is essential for the activation of STAT5 and ERK. PMID: 28038963
- EPO-dependent regulation pathway of FGF23 gene expression. PMID: 29073196
- Fetal plasma EPO concentrations are selectively elevated in monochorionic twin pregnancies with intrauterine growth restriction. PMID: 27161360
- This study indicates that EPO is involved in the pathogenesis of sepsis-induced acute kidney injury. PMID: 27266727
- Erythropoietin proves superior to standard prognostic scores in predicting 28-day mortality in patients with acute-on-chronic liver failure. PMID: 27981303
- EPO levels were found to be positively correlated with heme, TNF-alpha, IL-10, IP-10, and MCP-1 during cerebral malaria. PMID: 27441662
- Three single nucleotide polymorphisms are associated with an increased risk of diabetic retinopathy in a Chinese Han population. PMID: 27190272
- Pharmacokinetic animal studies revealed a substantial 15.6-fold extension in plasma half-life for the PASylated EPO (83.16 +/- 13.28 h) compared to epoetin alpha (8.5 +/- 2.4 h) and darbepoetin alpha (25.3 +/- 2.2h). PMID: 28168382
- Secreted MIR122 reaches the kidney and reduces erythropoietin expression, contributing to inflammation-induced anemia. PMID: 27477940
- This paper demonstrates that Epo can directly down-regulate pro-inflammatory T cell responses without impacting T cell activation status. PMID: 27208431
- Findings suggest that erythropoietin levels in anemia of unknown etiology, while elevated, remain inappropriately low compared to other forms of anemia. This indicates a relative erythropoietin deficiency or a blunted erythroid cell response. PMID: 26747131
- Plasma IGFBP-1 was significantly associated with plasma EPO concentration in acute kidney injury, suggesting an unknown mechanism related to systemic stress conditions for EPO regulation in AKI. PMID: 26479890
- Our results indicate that the EPO/EPOR pathway promotes gastric cancer formation, proliferation, migration, and decreases apoptosis. PMID: 27086036
- These results suggest that both EpoR-positive and EpoR-negative cancer cells can be regulated by exogenous Epo. However, an enhanced response to erythropoietin was observed in EpoR-positive cells. Therefore, erythropoietin increases the risk of tumor progression in colon cancer and should not be used to treat anemia in this type of cancer. PMID: 27543111
- Overexpression of EPO is associated with clear cell renal cell carcinoma. PMID: 27468719
- EPO may play a significant role in stem cell mobilization by upregulating HGF in mesenchymal stem cells and inducing migration of hematopoietic stem/progenitor cells. PMID: 27865586
- A review of contemporary aspects of EPO in relation to chronic liver disease. [review] PMID: 26919118
- Hepatic EPO synthesis is not enhanced in cirrhosis. PMID: 26924722
- Conclusion: Anemia in cancers is not due to inadequate Epo or Fe levels, but rather to an improper Epo response. PMID: 26838000
- In multivariate survival analysis, age, Epo, and EpoR emerged as independent prognostic factors related to overall survival in hepatocellular carcinoma. PMID: 26097591
- This suggests that hypoxia prevents EPO suppression and exacerbates the plasma volume reduction induced by bed rest. PMID: 27081163
- An inadequate erythropoietin response may partly explain anemia in anorexia nervosa. PMID: 26049959
- These findings suggest that TGF-beta suppression and EPO stimulation promote erythropoiesis of CD34(+)CD31(+) progenitor cells derived from human pluripotent stem cells. PMID: 26012423
- Our findings have important potential clinical implications, indicating that EPO supplementation in rhabdomyosarcoma patients may have the undesirable side effect of tumor progression. PMID: 26412593
- This suggests that rhEPO regulates apoptosis-related genes and affects apoptosis in the hippocampus of aging rats by upregulating SIRT. PMID: 26261574
- Higher levels of endogenous erythropoietin are associated with an increased incidence of heart failure in older adults. PMID: 26721912
- Erythropoietin protects the mouse renal tubular basement membrane by promoting bone marrow cells to generate and secrete miR-144, which, in turn, inhibits activation of the tPA/MMP9-mediated proteolytic network. PMID: 26469975
- This review outlines the induction of erythropoietin gene expression in the liver, reproductive, and hematopoietic systems during hypoxia or a state of proliferation. PMID: 26995951
- Our data indicate that rs507392 and rs551238 in the erythropoietin gene likely act to lessen the risk of diabetic retinopathy (DR) in a Chinese cohort with type 2 diabetes mellitus (T2DM). PMID: 25675872
- Data suggest that maternal circulating 25-hydroxyvitamin D during mid-pregnancy and at delivery is inversely related to serum EPO. An indirect relationship observed between circulating vitamin D and circulating hemoglobin is at least partly mediated by EPO. PMID: 26447159
- This review examines these diverse strategies and highlights the leading molecular recognition elements that potentially play roles in rHuEPO doping detection. PMID: 25058943
- The addition of salt, even low concentrations of the strong chaotropic salt guanidinium hydrochloride, exponentially decreased the initial rate of soluble erythropoietin non-native aggregation during storage at 37 degrees C. PMID: 25628168
- A study investigated whether elevated perinatal erythropoietin (EPO) concentrations in very preterm infants are associated with increased risks of indicators of brain damage. PMID: 25793991
Database Links
Involvement In Disease
Microvascular complications of diabetes 2 (MVCD2)
Protein Families
EPO/TPO family
Subcellular Location
Secreted.
Tissue Specificity
Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals.
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