Recombinant Human HIF-1 alpha Protein (His Tag)

Beta LifeScience SKU/CAT #: BLPSN-2434

Recombinant Human HIF-1 alpha Protein (His Tag)

Beta LifeScience SKU/CAT #: BLPSN-2434
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Product Overview

Tag His
Host Species Human
Accession Q16665
Synonym bHLHe78, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1, PASD8
Background HIF-1 alpha, also known as HIF1A, contains 1 basic helix-loop-helix (bHLH) domain, 1 PAC (PAS-associated C-terminal) domain and 2 PAS (PER-ARNT-SIM) domains. It is one of the two subunits of Hypoxia-inducible factor-1 (HIF1). HIF1 is a transcription factor found in mammalian cells cultured under reduced oxygen tension that plays an essential role in cellular and systemic homeostatic responses to hypoxia. HIF1 is a heterodimer composed of an alpha subunit and a beta subunit. The beta subunit has been identified as the aryl hydrocarbon receptor nuclear translocator (ARNT). HIF-1 alpha is expressed in most tissues with highest levels in kidney and heart. It is overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. HIF-1 alpha functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, it activates the transcription of over 4 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF1A plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. HIF-1 alpha binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP3.
Description A DNA sequence encoding the human HIF1A isoform 1 (Q16665-1) N-terminal segment (Arg 575-Asn 826) was expressed, with a His tag at the N-terminus.
Source E.coli
Predicted N Terminal Met
AA Sequence Arg 575-Asn 826
Molecular Weight The recombinant human HIF1A consisting of 259 a.a. and has a calculated molecular mass of 28.4 kDa. It migrates as an approximately 34 kDa band in SDS-PAGE under reducing conditions.
Purity >95% as determined by SDS-PAGE
Endotoxin Please contact us for more information.
Bioactivity Please contact us for detailed information
Formulation Lyophilized from sterile PBS, pH 7.4.
Stability The recombinant proteins are stable for up to 1 year from date of receipt at -70°C.
Usage For Research Use Only
Storage Store the protein under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300. Activity is enhanced by interaction with NCOA1 and/or NCOA2. Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia.; (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent proinflammatory state. In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons. Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response.
Subcellular Location Cytoplasm. Nucleus. Nucleus speckle.
Database References
Tissue Specificity Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumo

Gene Functions References

  1. These findings demonstrated a valuable antitumor synergism in combining CRISPR/Cas9mediated HIF1alpha knockout with Transarterial embolization (TAE)in mice and highlighted the possibility that HIF1a may be an effective therapeutic knockout target in combination with TAE for hepatocellular carcinoma treatment PMID: 30226584
  2. Since the FIH-1 dependent hydroxylation of NAA10 occurs oxygen-dependently, NAA10 acetylates HIF-1alpha under normoxia but does not under hypoxia. PMID: 30237125
  3. HIF1A is upregulated in breast and bladder tumors with high NRF2 activity. NRF2 targets a functional antioxidant response element at the HIF1A locus, which reveals a direct regulatory connection between two important oxygen responsive transcription factors. PMID: 30241031
  4. CPT1A is repressed by HIF1 and HIF2, reducing fatty acid transport into the mitochondria, and forcing fatty acids to lipid droplets for storage. PMID: 29176561
  5. MiR-497 approximately 195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch1 and HIF1A activity. PMID: 28685750
  6. Study revealed that HIF1alpha was significantly upregulated in gallbladder cancer (GBC) tissues. HIF1alpha overexpression was closely associated with lymph node metastasis and TNM stage. HIF1alpha was able to promote cell migration in a hypoxic microenvironment by overexpressing VEGF in GBC cell line. PMID: 30272364
  7. HIF-1alpha "positive" had decreased overall survival compared to HIF-1alpha "negative" patients and this was an independent adverse prognostic factor for HCC patients with cirrhosis, but not for cirrhosis-free patients. PMID: 30274686
  8. genetic polymorphisms in HIF1A were not associated with persistent apical periodontitis PMID: 29898065
  9. Hypoxia-induced angiogenesis is a complex process that involves distinct but also overlapping functions of HIF-1alpha and HIF- 2alpha in regard to angiogenesis, bioenergetic adaption and the redundant transcriptional induction of MIF. PMID: 28993199
  10. High HIF1A expression is associated with high Collagen I Fibers in Triple Negative Breast Cancer. PMID: 29247885
  11. Cathepsin B (CTSB) is a novel target gene of hypoxia-inducible factor-1-alpha (HIF-1alpha). CTSB mRNA and protein levels can be up-regulated in a HIF-1alpha-dependent manner. PMID: 29935187
  12. this is the first case-control study uncovering that the HIF1A gene rs10873142 polymorphism increases the risk of COPD in a Chinese Han population. PMID: 29339421
  13. ST6Gal-I activity augmented HIF-1alpha accumulation in cells grown in a hypoxic environment or treated with two chemical hypoxia mimetics, deferoxamine and dimethyloxalylglycine. PMID: 29475939
  14. mRNA expression levels of both HIF1A and LACC1 were upregulated in the skin lesions of individuals with leprosy. PMID: 29706348
  15. data suggest an important role of miR-210 in sustaining HIF-1alpha activity via the suppression of HIF-3alpha, regulating cell growth and chemotherapeutic drug resistance in cholangiocarcinoma. PMID: 29953500
  16. HOXA9 inhibits HIF1A-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development. PMID: 29662084
  17. HIF-1alpha inhibits NCR1/NKp46 pathway through up-regulating miR-224, which affects the killing capability of NK cells on prostate cancer, thus inducing immune escape of tumor cells. PMID: 29885835
  18. The findings demonstrate that AGPAT2, which is mutated in patients with congenital generalized lipodystrophy and over-expressed in different types of cancer, is a direct transcriptional target of HIF-1, suggesting that upregulation of lipid storage by HIF-1 plays an important role in adaptation and survival of cancer cells under low oxygen conditions. PMID: 29908837
  19. Overexpression of HIF1A leads to radioresistance of cervical cancer. PMID: 30355300
  20. Knockdown of DEC2 resulted in a significant (26.7%) reduction of VEGF expression in MIO-M1 cells under hypoxia-mimicking conditions induced by DFO (P < .05). Levels of HIF1alpha protein were also reduced significantly, by 60.2%, in MIO-M1 cells treated with siRNA against the DEC2 gene (P < .05). Moreover, HIF1alpha levels showed a significant (2.5-fold) increase in MIO-M1 cells overexpressing DEC2 (P < .05). PMID: 30250985
  21. High HIF1A expression is associated with salivary adenoid cystic carcinoma. PMID: 30015895
  22. we found that Hif-1alpha directly promoted H19 expression through binding to the H19 promoter and indirectly through SP1-mediated H19 transcriptional activation under hypoxia in glioblastoma cells. PMID: 28327666
  23. The IRIS-driven metastatic mechanism results from IRIS-dependent suppression of phosphatase and tensin homolog (PTEN) transcription, which in turn perturbs the PI3K/AKT/GSK-3beta pathway leading to prolyl hydroxylase-independent HIF-1alpha stabilization and activation in a normoxic environment. PMID: 30254159
  24. Data show that von Hippel-Lindau-binding protein 1 (VBP1) enhances the stability of von Hippel-Lindau tumor suppressor protein (pVHL) and facilitates pVHL-mediated ubiquitination of hypoxia-inducible factor 1, alpha subunit (HIF-1alpha). PMID: 29121446
  25. Multifunctional proteins epigenetically modulating HIF1A stability and activity have been described. (Review) PMID: 29032501
  26. Studies have shown that both HIF1alpha and HIF2alpha may contribute to the regulation of cellular adaptation to hypoxia and resistance to cancer therapies with their potential to exert significant effects on the maintenance and evolution of cancer stem cells. Also, HIF1alpha and HIF2alpha seemed to have significant prognostic and predictive value. [review] PMID: 29845228
  27. HIF-1 was overexpressed in osteosarcoma tissues and cell lines, which promoted cell proliferation, clone formation, migration, invasion and inhibited cell apoptosis. PMID: 29807229
  28. hypoxiainduced expression of CXCR4 promoted trophoblast cell migration and invasion via the activation of HIF1alpha, which is crucial during placentation. PMID: 29786753
  29. Data suggest that NRF2/NFE2L2 promotes breast cancer progression by enhancing glycolysis through co-activation of HIF1A; NRF2 and HIF1A mRNA and protein levels are significantly up-regulated in breast cancer cells as compared to benign breast epithelial cells. (NRF2/NFE2L2 = nuclear factor erythroid 2-related factor 2; HIF1A = hypoxia inducible factor 1 subunit alpha) PMID: 29275212
  30. the expression of MMIF, HIF-1alpha, and VEGF in the serum and endometrial tissues may be used to assess the stage of endometriosis and the severity of dysmenorrhea. PMID: 30074218
  31. Findings revealed an HIF-1alpha/IL-1beta signaling loop between cancer cells and tumor-associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial-mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti-inflammatory strategy in hepatocellular carcinoma treatment PMID: 29171040
  32. Overexpression of HIF-1alpha and P4HB is associated with poor prognosis in patients with gastric cancer. PMID: 29904245
  33. hypoxic stress in the hepatocellular carcinoma (HCC)cells promoted YAP binding to HIF-1a in the nucleus and sustained HIF-1a protein stability to bind to PKM2 gene and directly activates PKM2 transcription to accelerate glycolysis PMID: 30180863
  34. Overexpression of VHL was more successful at inhibiting fibrosis compared with 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
  35. Results find that knockdown of HIF-1alpha reduced hypoxia-induced SENP1 expression, suggesting that induction of SENP1 expression is mediated by hypoxia-inducible factor HIF-1alpha. PMID: 28796315
  36. ADM was an upstream molecule of HIF-1alpha/VEGF and it promoted angiogenesis through upregulating HIF-1alpha/VEGF in epithelial ovarian cancer. PMID: 28091613
  37. HIF-1alpha expression correlates with the expression level of IL- 8, as evidenced by the down regulation of IL-8 in response to silencing of HIF-1alpha in HCC cell lines under hypoxic conditions. PMID: 29881400
  38. MOLP8/R cells display a very high overexpression of LCP1 gene (l-Plastin) controlled by HIF1&alpha. PMID: 29882856
  39. the role of FTH1 in the FIH control of HIF-1 activity, is reported. PMID: 29580991
  40. The findings of the current study demonstrate presence of the IDH1 R132H mutation in primary human glioblastoma cell lines with upregulated HIF-1alpha expression, downregulating c-MYC activity and resulting in a consequential decrease in miR-20a, which is responsible for cell proliferation and resistance to standard temozolomide treatment. PMID: 29625108
  41. The cross-talk between HIF1A, NRF2 and NF-kappaB is required to adapt to changes in oxygen availability. (Review) PMID: 29485192
  42. PKD1 not only regulates the hypoxic glycolytic metabolism of cancer cells via regulation of the expression of HIF-1alpha and glycolytic enzymes. PMID: 29901206
  43. Results provide evidence that HIF1alpha overexpression promotes the radioresistance of prostate cancer cells through enhanced betacatenin nuclear translocation. PMID: 29658569
  44. Collectively, the present study demonstrated mitochondrial fission as a tumor suppression process that is regulated by the HIF/miR125a/Mfn2 pathways, acting to restrict PANC1 cell survival, energy metabolism and migration, with potential implications for novel approaches for PC therapy. PMID: 29749475
  45. the results of the present study demonstrated that hypoxia-induced cytoprotective autophagy counteracted gemcitabine-induced apoptosis through increasing HIF1alpha expression PMID: 29693166
  46. CD40 is a key molecule for the upregulation of HIF-1alpha and PTEN underlying the severity of microangiopathy. PMID: 29549140
  47. Enhanced expression of HIF-1alpha may be related to autophagy activation in SH-SY5Y cells, thus contributing to ischemic/hypoxic brain damage. PMID: 29724989
  48. Data show that deletion of hypoxia inducible factor 1 subunit alpha (HIF-1alpha) in NK cells inhibited tumour growth despite impaired tumour cell killing. PMID: 29150606
  49. AEG-1 was found to be significantly associated with hypoxia in ovarian cancer by regulating the HIF-1alpha/NF-kappaB/VEGF pathway. PMID: 29770329
  50. no significant differences in the serum levels between early-onset pre-eclampsia, late-onset pre-eclampsia, and controls PMID: 28574293

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