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Gene Review

HIF3A  -  hypoxia inducible factor 3, alpha subunit

Homo sapiens

Synonyms: BHLHE17, Basic-helix-loop-helix-PAS protein MOP7, Class E basic helix-loop-helix protein 17, HIF-3-alpha, HIF-3A, ...
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Disease relevance of HIF3A

  • Ectopic expression of IPAS in hepatoma cells selectively impairs induction of genes involved in adaptation to a hypoxic environment, notably the vascular endothelial growth factor (VEGF) gene, and results in retarded tumour growth and tumour vascular density in vivo [1].
  • Virulent bacteria of the genera Yersinia, Shigella and Salmonella secrete a number of virulence determinants, Yops, Ipas and Sips respectively, by a type III secretion pathway [2].
  • This is illustrated in a study in which we have applied a three-dimensional intact protein analysis system (IPAS) to elucidate detectable protein changes in serum from immunodeficient mice with lung xenografts from orthotopically implanted human A549 lung adenocarcinoma cells [3].

High impact information on HIF3A

  • Expression of IPAS in the cornea correlates with low levels of expression of the VEGF gene under hypoxic conditions [1].
  • IPAS contains no endogenous transactivation function but demonstrates dominant negative regulation of HIF-mediated control of gene expression [1].
  • In mice, IPAS was predominantly expressed in Purkinje cells of the cerebellum and in corneal epithelium of the eye [1].
  • We have previously observed that IPAS is predominantly expressed in mice in Purkinje cells of the cerebellum and in corneal epithelium of the eye where it appears to play a role in negative regulation of angiogenesis and maintenance of an avascular phenotype [4].
  • Thus, in addition to three unique exons (1a, 4a, and 16) IPAS shares three exons (2, 4, and 5) with HIF-3alpha as well as alternatively spliced variants of exons 3 and 6 [4].

Biological context of HIF3A


Anatomical context of HIF3A

  • However, unlike the wild-type strain, the spa32 mutant could neither be induced to secrete the Ipas and IpgD instantaneously upon addition of Congo red nor penetrate HeLa cells in vitro [8].

Physical interactions of HIF3A

  • Interestingly, both HIF-1alpha and HIF-1beta interacted with the IPAS proteins [5].

Other interactions of HIF3A

  • Collectively, these results suggest that human IPAS proteins inhibit angiogenesis by binding to and inhibiting HIF-1alpha and HIF-1beta [5].
  • In this report, we cloned the human orthologs of the mouse IPAS gene, IPASH1 and IPASH2, to further study the regulatory mechanism of HIF-1 by the IPAS proteins [5].

Analytical, diagnostic and therapeutic context of HIF3A

  • Which cannulae fit the Ipas manual vacuum aspiration syringe [9]?
  • CONCLUSION: Several US manufacturers produce cannulae that fit on the Ipas MVA syringe without a leak, including Ipas flexible cannula; Berkeley flexible, rigid-straight and rigid-curve cannulae and MedGyn flexible cannula, but not their rigid cannulae [9].
  • This paper describes a collaborative project between Ipas Mexico and the Mexico City Department of Health to provide legal abortions in cases of rape and to ensure that comprehensive health services for survivors of sexual violence are available and accessible [10].


  1. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Makino, Y., Cao, R., Svensson, K., Bertilsson, G., Asman, M., Tanaka, H., Cao, Y., Berkenstam, A., Poellinger, L. Nature (2001) [Pubmed]
  2. Functional conservation of the secretion and translocation machinery for virulence proteins of yersiniae, salmonellae and shigellae. Rosqvist, R., Håkansson, S., Forsberg, A., Wolf-Watz, H. EMBO J. (1995) [Pubmed]
  3. Discovery of cancer biomarkers through the use of mouse models. Kuick, R., Misek, D.E., Monsma, D.J., Webb, C.P., Wang, H., Peterson, K.J., Pisano, M., Omenn, G.S., Hanash, S.M. Cancer Lett. (2007) [Pubmed]
  4. Inhibitory PAS domain protein (IPAS) is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus. Makino, Y., Kanopka, A., Wilson, W.J., Tanaka, H., Poellinger, L. J. Biol. Chem. (2002) [Pubmed]
  5. Binding and regulation of hypoxia-inducible factor-1 by the inhibitory PAS proteins. Jang, M.S., Park, J.E., Lee, J.A., Park, S.G., Myung, P.K., Lee, d.o. .H., Park, B.C., Cho, S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  6. Serum IgG antibody responses to Shigella invasion plasmid-coded antigens detected by immunoblot. Li, A., Zhao, C.R., Ekwall, E., Lindberg, A.A. Scand. J. Infect. Dis. (1994) [Pubmed]
  7. From research to reality: the challenges of introducing medical abortion into service delivery in Vietnam. Ganatra, B., Bygdeman, M., Phan, B.T., Nguyen, D.V., Vu, M.L. Reproductive health matters. (2004) [Pubmed]
  8. Spa32 regulates a switch in substrate specificity of the type III secreton of Shigella flexneri from needle components to Ipa proteins. Magdalena, J., Hachani, A., Chamekh, M., Jouihri, N., Gounon, P., Blocker, A., Allaoui, A. J. Bacteriol. (2002) [Pubmed]
  9. Which cannulae fit the Ipas manual vacuum aspiration syringe? Orbach, D., Schaff, E. Contraception. (2004) [Pubmed]
  10. Constructing access to legal abortion services in Mexico City. Billings, D.L., Moreno, C., Ramos, C., González de León, D., Ramírez, R., Villaseñor Martínez, L., Rivera Díaz, M. Reproductive health matters. (2002) [Pubmed]
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