EPAS1 Antibody

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Description

Definition and Target Specificity

EPAS1 antibodies are monoclonal or polyclonal reagents that selectively bind to the EPAS1 protein. These antibodies enable researchers to:

  • Quantify EPAS1 expression levels in cells and tissues

  • Study its subcellular localization (e.g., nuclear vs. cytoplasmic)

  • Investigate post-translational modifications under varying oxygen conditions

Key epitopes targeted include the PAS domain and hydroxylation sites critical for HIF-2α stability .

Development and Validation

EPAS1 antibodies are generated using hybridoma or recombinant technologies:

MethodDescriptionExample
HybridomaB cells fused with myeloma cells to produce monoclonal antibodies Cusabio’s recombinant antibody
RecombinantcDNA sequences cloned into expression systems for consistent production Proteintech’s 66731-1-Ig

Validation Metrics:

  • Western Blot (WB): Detects EPAS1 at ~96–120 kDa in HeLa, HepG2, and 786-O cells .

  • Immunohistochemistry (IHC): Validated in human colon cancer tissues with antigen retrieval .

  • Species Reactivity: Confirmed in humans, bovines, and murine models .

Applications in Research

EPAS1 antibodies are pivotal in studying hypoxia-related pathways and diseases:

Key Applications

ApplicationProtocol DetailsFindings
AtherosclerosisEn face staining of murine aorta under low oscillatory shear stress (LOSS) EPAS1 enrichment at atheroprone sites reduces plaque formation
Cancer ResearchIHC in renal cell adenocarcinoma (786-O) and cervical carcinoma (HeLa) Elevated EPAS1 in clear cell carcinomas
Developmental BiologySingle-cell RNAseq in Epas1-KO mice EPAS1 maintains endothelial cell proliferation via fatty acid metabolism

Dilution Guidelines

ApplicationRecommended Dilution
WB1:1,000–1:5,000
IHC1:250–1:1,000

Clinical and Functional Insights

EPAS1 antibodies have revealed critical roles in:

  • Tumorigenesis: Somatic EPAS1 mutations stabilize HIF-2α, driving neuroendocrine tumors (e.g., pheochromocytomas) .

  • High-Altitude Adaptation: Alleles inherited from Denisovans enhance hypoxia tolerance but increase stroke risk at low altitudes .

  • Cardiovascular Disease: EPAS1 deficiency exacerbates atherosclerosis by impairing endothelial repair under disturbed flow .

Research Limitations and Future Directions

  • Cross-Reactivity: Some antibodies show nonspecific binding to HIF-1α, necessitating rigorous validation .

  • Therapeutic Potential: Targeting EPAS1 with inhibitory antibodies could mitigate polycythemia or tumor growth .

Product Specs

Form
Supplied at 1.0mg/mL in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Lead Time
Typically, we can ship the products within 1-3 business days after receiving your order. Delivery time may vary depending on the purchase method or location. Please consult your local distributors for specific delivery timelines.
Synonyms
Basic helix loop helix PAS protein MOP2 antibody; Basic-helix-loop-helix-PAS protein MOP2 antibody; bHLHe73 antibody; Class E basic helix-loop-helix protein 73 antibody; ECYT4 antibody; Endothelial PAS domain containing protein 1 antibody; Endothelial pas domain protein 1 antibody; Endothelial PAS domain-containing protein 1 antibody; EPAS 1 antibody; EPAS-1 antibody; EPAS1 antibody; EPAS1_HUMAN antibody; HIF 1 alpha like factor antibody; HIF 2 alpha antibody; HIF-1-alpha-like factor antibody; HIF-2-alpha antibody; HIF2-alpha antibody; HIF2A antibody; HLF antibody; Hypoxia inducible factor 2 alpha antibody; Hypoxia inducible factor 2 alpha subunit antibody; Hypoxia-inducible factor 2-alpha antibody; Member of PAS protein 2 antibody; Member of pas superfamily 2 antibody; MOP 2 antibody; MOP2 antibody; PAS domain-containing protein 2 antibody; PASD2 antibody
Target Names
Uniprot No.

Target Background

Function
EPAS1 antibody targets EPAS1, a transcription factor that plays a crucial role in inducing oxygen-regulated genes. It forms a heterodimer with ARNT, and this complex binds to the core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. EPAS1 regulates the expression of vascular endothelial growth factor (VEGF) and is implicated in the development of blood vessels and the tubular system of the lung. It may also be involved in the formation of the endothelium that constitutes the blood-brain barrier. EPAS1 is a potent activator of the Tie-2 tyrosine kinase expression, and its activation requires the recruitment of transcriptional coactivators such as CREBBP and potentially EP300. Interaction with the redox regulatory protein APEX1 appears to activate CTAD.
Gene References Into Functions
  • CPT1A is repressed by HIF1 and HIF2, leading to a reduction in fatty acid transport into the mitochondria, and forcing fatty acids to lipid droplets for storage. PMID: 29176561
  • PD-L1 tumor cell expression is strongly associated with increased HIF-2alpha expression and the presence of dense lymphocytic infiltration in clear cell renal cell carcinoma. PMID: 30144808
  • Hypoxia-induced angiogenesis is a complex process involving distinct but overlapping functions of HIF-1alpha and HIF- 2alpha in angiogenesis, bioenergetic adaptation, and the redundant transcriptional induction of MIF. PMID: 28993199
  • High HIF2A expression is associated with high Collagen I Fibers in Triple Negative Breast Cancer. PMID: 29247885
  • Studies indicate that HIF2-alpha induces myocardial AREG expression in cardiac myocytes, which increases myocardial ischemia tolerance. PMID: 29483579
  • High HIF2A expression is associated with Cervical Cancer. PMID: 29321085
  • Data reveal that overexpression of HIF-2alpha up-regulates the level of NEAT1 and promotes EMT and metastasis in hepatoma cells under hypoxia, while inhibition of HIF-2alpha reverses these effects. This suggests that HIF-2alpha can promote EMT and metastasis in hepatocellular carcinoma under hypoxic conditions. PMID: 29091312
  • Studies have shown that both HIF1alpha and HIF2alpha contribute to the regulation of cellular adaptation to hypoxia and resistance to cancer therapies, with the potential to significantly impact the maintenance and evolution of cancer stem cells. Additionally, HIF1alpha and HIF2alpha appear to have significant prognostic and predictive value. [review] PMID: 29845228
  • HIF-2alpha expression may be associated with the carcinogenesis of colorectal cancer (CRC), with higher expression in males than in females. It is negatively linked to tumor differentiation and correlated with worse disease-free survival of CRC - Systematic Analysis PMID: 30021192
  • Overexpression of VHL was more successful in inhibiting fibrosis compared to silencing HIF-1a plus HIF-2a. Normoxia-active HIF-1a or HIF-2a prevented the inhibitory effect of VHL on liver fibrosis, indicating that attenuating fibrosis via VHL is HIF-1a- and HIF-2a-dependent to some extent. PMID: 28112200
  • HDX negatively regulates EPAS1 expression through a release-of-inhibition mechanism. PMID: 29577908
  • Using imputed data, we found that this SNP remained significant in the entire TRICL-ILCCO consortium (p=.03). Further functional studies are warranted to better understand interrelationships among genetic polymorphisms, DNA methylation status, and EPAS1 expression. PMID: 29859855
  • Results suggest an interplay of the production and action of hydrogen sulfide during hypoxia with subsequent erythropoietin production regulated by HIF-1alpha and HIF-2alpha. PMID: 26880412
  • This suggests that higher aerobic capacities are caused by the presence of at least one minor A-Allele of the EPAS1 gene in the genome of an athlete PMID: 29446909
  • We report a rare case of renal-cell carcinoma and hereditary polycythemia. Genotyping revealed that the patient carried both a germline HIF2A mutation and a somatic VHL mutation. Both mutations result in overactivation of HIF2A and its downstream target genes PMID: 29172931
  • Identification of gain-of-function somatic mutations of EPAS1, which encodes for HIF-2alpha, in pheochromocytomas and paragangliomas in patients who presented with cyanotic congenital heart disease. PMID: 29601261
  • HIF-2a regulates non-canonical glutamine metabolism via activation of the PI3K/mTORC2 pathway and GOT1 expression in human pancreatic ductal adenocarcinoma. PMID: 28544376
  • We studied the hypoxic activation of the transcription factors HIF-1alpha and HIF-2alpha in endothelial cells within a spatial linear gradient of oxygen. Quantification of the nuclear to cytosolic ratio of HIF immunofluorescent staining demonstrated that the threshold for HIF-1alpha activation was below 2.5% O2 while HIF-2alpha was activated throughout the entire linear gradient. PMID: 28840922
  • miRNA-101 level is decreased in RCC tissues/cells, which could be responsible for DNA-PKcs overexpression and DNA-PKcs mediated oncogenic actions; DNA-PKcs over-expression regulates mTORC2-AKT activation, HIF-2alpha expression and RCC cell proliferation PMID: 27412013
  • This report shows that somatic gain-of-function HIF2A mutations are present in 20% of gangliocytic paragangliomas (GPGLs) in the present series. The mutations appear to be located in the hot spot of the oxygen-sensing domain of HIF-2alpha, resulting in increased HIF-2alpha stabilization and impaired ubiquitination and degradation PMID: 27130043
  • These findings establish a new link between HIF-2alpha and MAPK-signaling that mediates the adaptive regulation of mitochondrial gene expression under low oxygen tension. PMID: 28709643
  • HIF-2alpha and VM were overexpressed in pancreatic cancer tissues and were associated with poor pathological characteristics. HIF-2alpha contributes to VM formation by regulating the expression of VE-cadherin through the binding of the transcription factor Twist1 to the promoter of VE-cadherin in pancreatic cancer both in vitro and in vivo. PMID: 28599281
  • HIF-2alpha facilitated the preservation of Human placenta-derived mesenchymal stem cell stemness and promoted their proliferation by regulating CCND1 and MYC through the MAPK/ERK signaling pathway. PMID: 27765951
  • Results showed that HIF-1alpha and HIF-2alpha were highly expressed in vascular malformation (GIVM) and suggest that they induced angiogenesis in GIVM. PMID: 27249651
  • The present study demonstrates that hypoxia-induced downregulation of Dicer serves as a key mechanism in the maintenance of the hypoxic response in HCC and that prevention of hypoxic suppression of Dicer not only alleviates hypoxia-induced upregulation of HIF1alpha and HIF2alpha and other key hypoxia-responsive/HIF target genes but also inhibits hypoxia-induced metastatic phenotypes such as EMT and increased cell motility. PMID: 28167508
  • HIF-2alpha dictates the resistance of human pancreatic cancer cells to TRAIL under normoxic and hypoxic conditions and transcriptionally regulates survivin expression. PMID: 28476028
  • SOD3 reduced HIF prolyl hydroxylase domain protein activity, which increased hypoxia-inducible factor-2alpha (HIF-2alpha) stability and enhanced its binding to a specific vascular endothelial cadherin promoter region. PMID: 29422508
  • Functionally active PHD2 SNP rs516651 [18], located in the key pathway for the hypoxic-inflammatory response, is associated with increased 30-day mortality in Acute Respiratory Distress Syndrome (ARDS) patients. In contrast, the PHD2 SNP rs480902 is not. Furthermore, the HIF-2alpha SNP [ch2: 46441523(hg18)] GG-genotype was neither present in our ARDS patients of Caucasian heritage nor in healthy Caucasian blood donors. PMID: 28613249
  • We genotyped 347 Tibetan individuals from varying altitudes for both the Tibetan-specific EGLN1 haplotype and 10 candidate SNPs in the EPAS1 haplotype and correlated their association with hemoglobin levels. PMID: 28233034
  • HIF-2alpha plays a significant role in regulating the expression of c-Myc in chronic hypoxia, and consequently controls the sensitivity of colon cancer cells to 5-FU treatment in this environment. PMID: 27793037
  • The present study identifies novel HIF-2alpha-target genes that may regulate endothelial sprouting during prolonged hypoxia. PMID: 27699500
  • Exogenous acetate augments Acss2/HIF-2 dependent cancer growth and metastasis in cell culture and mouse models PMID: 29281714
  • The structural model of the HIF2a-pVHL complex presented in this study enhances understanding of how HIF2a is captured by pVHL. Moreover, the important contact amino acids that we identified may be useful in the development of drugs to treat HIF2a-related diseases. PMID: 27902963
  • Thus, we provide evidence here that HIF-2a is a critical regulator of PD-L1 at both mRNA and protein levels and that HIF-2a regulates the expression of PD-L1 by binding directly to the HRE-4 in the PD-L1 proximal promoter. PMID: 26707870
  • HIF2alpha has a role and is an independent marker of the metastatic potential of bone metastatic clear cell renal cell cancer. However, unlike HIF1alpha, increased HIF2alpha expression is a favorable prognostic factor PMID: 27244898
  • Knockdown of either HIF-1 or CREB or both in hypoxia reduced the expression of hypoxia-response elements- and CRE-mediated gene expression, diminished cell proliferation and increased caspase-3 activity. We did not detect any significant effect of the efficiently knocked down HIF-2 on any of the functions tested in vitro. PMID: 27934882
  • miR-558 facilitates the expression of HIF-2alpha through binding to its 5'-UTR, thus promoting the tumorigenesis and aggressiveness of neuroblastoma PMID: 27276678
  • Over-expression of HIF-2alpha induced apoptosis in HCC cells and increased the levels of pro-apoptotic proteins, Bak, ZBP-89 and PDCD4, whereas the inhibition of HIF-2alpha expression achieved opposite results. HIF-2alpha was decreased and played an anti-tumorigenic role in hepatocellular carcinoma. PMID: 27119229
  • Probiotic Bifidobacterium bifidum MIMBb75 may help attenuating EPAS1 overexpression associated with intestinal inflammation. PMID: 27883285
  • Data suggest that HIF2alpha mediates hypoxia-induced cancer growth/metastasis and that EFEMP1 is a downstream effector of hypoxia-induced HIF2alpha during breast tumorigenesis. PMID: 27270657
  • Intestinal HIF-2alpha regulates ceramide metabolism mainly from the salvage pathway, by positively regulating the expression of Neu3, the gene encoding neuraminidase 3. These results suggest that intestinal HIF-2alpha could be a viable target for hepatic steatosis therapy PMID: 29035368
  • Demonstrated that MM cells are resistant to hypoxia-mediated apoptosis in vivo and in vitro, and that constitutive expression of HIF2alpha contributed to this resistance PMID: 29206844
  • HIF1A and EPAS1 potentiate hypoxia-induced upregulation of INHA expression in human term cytotrophoblasts in vitro. PMID: 28115494
  • Data show there was a significant negative correlation between PHGDH copy-number alteration and EPAS1 (HIF2A) expression. PMID: 28951458
  • NAP peptide prevents outer blood retinal barrier breakdown by reducing HIF1alpha/HIF2alpha, VEGF/VEGFRs, and increasing HIF3alpha expression. Moreover, it is able to reduce the percentage of apoptotic cells by modulating the expression of two death related genes, BAX and Bcl2. PMID: 28436035
  • Data identify a previously unrecognized cellular process associated with hypoxia and suggests that in vivo tumor hypoxia determines copper isotope fractionation in hepatocellular carcinoma. They demonstrate that this effect of hypoxia is pH, HIF-1 and -2 independent. PMID: 27500357
  • Findings suggest the HIF-2alpha pathway predominates over HIF-1alpha signaling in neuronal-like cells following acute hypoxia PMID: 28968430
  • These findings demonstrated that HIF-2alpha in vselMSCs cooperated with Oct4 in survival and function. The identification of this interaction between HIF-2alpha and Oct4 will lead to a deeper characterization of the downstream targets and will have novel pathophysiological implications for the repair of infarcted myocardium. PMID: 28079892
  • Findings indicate that HIF-2alpha increases cancer cell growth by up-regulating YAP1 activity PMID: 28848049
  • Findings show that hypoxia inducible factor 1 alpha subunit (HIF-1alpha) is phylogenetically conserved among most metazoans, whereas HIF-2alpha protein appeared later. PMID: 28614393

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Database Links

HGNC: 3374

OMIM: 603349

KEGG: hsa:2034

STRING: 9606.ENSP00000263734

UniGene: Hs.468410

Involvement In Disease
Erythrocytosis, familial, 4 (ECYT4)
Subcellular Location
Nucleus. Nucleus speckle.
Tissue Specificity
Expressed in most tissues, with highest levels in placenta, lung and heart. Selectively expressed in endothelial cells.

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