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Gene Review

EPAS1  -  endothelial PAS domain protein 1

Homo sapiens

Synonyms: BHLHE73, Basic-helix-loop-helix-PAS protein MOP2, Class E basic helix-loop-helix protein 73, ECYT4, EPAS-1, ...
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Disease relevance of EPAS1


High impact information on EPAS1


Chemical compound and disease context of EPAS1


Biological context of EPAS1

  • Together, these data demonstrate Src family kinases mediate the hypoxia-mediated EPAS1 gene expression, which in turn positively autoregulates its own expression [1].
  • Transient transfection assays revealed that EPAS1 increased PAI-1 gene transcription through a sequence containing 5'-CACGTACA-3' located at -194 (we refer to it as site HREPAI-1) and GT-box located at -78 [10].
  • Electrophoretic gel mobility shift assays revealed that HREPAI-1 serves as a binding site for EPAS1, and Sp1 constitutively binds to GT-box [10].
  • Transient transfection assays revealed that forced expression of EPAS1 increased the reporter gene activity driven by EPAS1 promoter as well as by VEGF promoter [1].
  • These observations are consistent with transactivation by EPAS1 of the expression of its putative target genes during embryogenesis, suggesting that this transcription factor is involved in human angiogenesis [11].

Anatomical context of EPAS1


Associations of EPAS1 with chemical compounds


Regulatory relationships of EPAS1

  • CONCLUSIONS: These results suggest that endogenous VEGF can be up-regulated transcriptionally by EPAS1, and EPAS1 may be involved in the angiogenesis of RCC [12].
  • In conclusion, PAI-1 expression is induced by EPAS1 through HREPAI-1 and through an Sp1-binding site [10].
  • The results indicate that the direct interaction of Int6 induces proteasome inhibitor-sensitive HIF-2 alpha degradation [17].

Other interactions of EPAS1


Analytical, diagnostic and therapeutic context of EPAS1


  1. Inducible expression of endothelial PAS domain protein-1 by hypoxia in human lung adenocarcinoma A549 cells. Role of Src family kinases-dependent pathway. Sato, M., Tanaka, T., Maeno, T., Sando, Y., Suga, T., Maeno, Y., Sato, H., Nagai, R., Kurabayashi, M. Am. J. Respir. Cell Mol. Biol. (2002) [Pubmed]
  2. Expression of HIF-2alpha/EPAS1 in hepatocellular carcinoma. Bangoura, G., Yang, L.Y., Huang, G.W., Wang, W. World J. Gastroenterol. (2004) [Pubmed]
  3. Expression of HIF-1{alpha}, HIF-2{alpha} (EPAS1), and Their Target Genes in Paraganglioma and Pheochromocytoma with VHL and SDH Mutations. Pollard, P.J., El-Bahrawy, M., Poulsom, R., Elia, G., Killick, P., Kelly, G., Hunt, T., Jeffery, R., Seedhar, P., Barwell, J., Latif, F., Gleeson, M.J., Hodgson, S.V., Stamp, G.W., Tomlinson, I.P., Maher, E.R. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  4. Nox4 is critical for hypoxia-inducible factor 2-alpha transcriptional activity in von Hippel-Lindau-deficient renal cell carcinoma. Maranchie, J.K., Zhan, Y. Cancer Res. (2005) [Pubmed]
  5. Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. Ema, M., Hirota, K., Mimura, J., Abe, H., Yodoi, J., Sogawa, K., Poellinger, L., Fujii-Kuriyama, Y. EMBO J. (1999) [Pubmed]
  6. Von Hippel-Lindau disease: clinical and molecular perspectives. Clifford, S.C., Maher, E.R. Adv. Cancer Res. (2001) [Pubmed]
  7. The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway. Gimenez-Roqueplo, A.P., Favier, J., Rustin, P., Mourad, J.J., Plouin, P.F., Corvol, P., Rötig, A., Jeunemaitre, X. Am. J. Hum. Genet. (2001) [Pubmed]
  8. Relation of hypoxia-inducible factor-2 alpha (HIF-2 alpha) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in Human breast cancer. Leek, R.D., Talks, K.L., Pezzella, F., Turley, H., Campo, L., Brown, N.S., Bicknell, R., Taylor, M., Gatter, K.C., Harris, A.L. Cancer Res. (2002) [Pubmed]
  9. A repertoire of differentially expressed transcription factors that offers insight into mechanisms of human cytotrophoblast differentiation. Janatpour, M.J., Utset, M.F., Cross, J.C., Rossant, J., Dong, J., Israel, M.A., Fisher, S.J. Dev. Genet. (1999) [Pubmed]
  10. The PAI-1 gene as a direct target of endothelial PAS domain protein-1 in adenocarcinoma A549 cells. Sato, M., Tanaka, T., Maemura, K., Uchiyama, T., Sato, H., Maeno, T., Suga, T., Iso, T., Ohyama, Y., Arai, M., Tamura, J., Sakamoto, H., Nagai, R., Kurabayashi, M. Am. J. Respir. Cell Mol. Biol. (2004) [Pubmed]
  11. Coexpression of endothelial PAS protein 1 with essential angiogenic factors suggests its involvement in human vascular development. Favier, J., Kempf, H., Corvol, P., Gasc, J.M. Dev. Dyn. (2001) [Pubmed]
  12. Regulation of vascular endothelial growth factor transcription by endothelial PAS domain protein 1 (EPAS1) and possible involvement of EPAS1 in the angiogenesis of renal cell carcinoma. Xia, G., Kageyama, Y., Hayashi, T., Kawakami, S., Yoshida, M., Kihara, K. Cancer (2001) [Pubmed]
  13. Prognostic significance of endothelial Per-Arnt-sim domain protein 1/hypoxia-inducible factor-2alpha expression in a subset of tumor associated macrophages in invasive bladder cancer. Koga, F., Kageyama, Y., Kawakami, S., Fujii, Y., Hyochi, N., Ando, N., Takizawa, T., Saito, K., Iwai, A., Masuda, H., Kihara, K. J. Urol. (2004) [Pubmed]
  14. Transcription Factor EPAS1 Regulates Insulin Signaling Pathway. Wada, T. Yakugaku Zasshi (2007) [Pubmed]
  15. A redox mechanism controls differential DNA binding activities of hypoxia-inducible factor (HIF) 1alpha and the HIF-like factor. Lando, D., Pongratz, I., Poellinger, L., Whitelaw, M.L. J. Biol. Chem. (2000) [Pubmed]
  16. Phenotypic persistence after reoxygenation of hypoxic neuroblastoma cells. Holmquist, L., Jögi, A., Påhlman, S. Int. J. Cancer (2005) [Pubmed]
  17. Mammalian tumor suppressor Int6 specifically targets hypoxia inducible factor 2 alpha for degradation by hypoxia- and pVHL-independent regulation. Chen, L., Uchida, K., Endler, A., Shibasaki, F. J. Biol. Chem. (2007) [Pubmed]
  18. Relation of vascular endothelial growth factor production to expression and regulation of hypoxia-inducible factor-1 alpha and hypoxia-inducible factor-2 alpha in human bladder tumors and cell lines. Jones, A., Fujiyama, C., Blanche, C., Moore, J.W., Fuggle, S., Cranston, D., Bicknell, R., Harris, A.L. Clin. Cancer Res. (2001) [Pubmed]
  19. Differentiating the functional role of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha (EPAS-1) by the use of RNA interference: erythropoietin is a HIF-2alpha target gene in Hep3B and Kelly cells. Warnecke, C., Zaborowska, Z., Kurreck, J., Erdmann, V.A., Frei, U., Wiesener, M., Eckardt, K.U. FASEB J. (2004) [Pubmed]
  20. Hypoxia inducible factor 1 alpha and 2 alpha expression is independent of anemia in patients with stage I endometrial cancer. Koukourakis, M.I., Giatromanolaki, A., Liberis, V., Sivridis, E. Anticancer Res. (2002) [Pubmed]
  21. Positive expression of HIF-2alpha/EPAS1 in invasive bladder cancer. Xia, G., Kageyama, Y., Hayashi, T., Hyochi, N., Kawakami, S., Kihara, K. Urology (2002) [Pubmed]
  22. Ribozyme mediated suppression of vascular endothelial growth factor gene expression enhances matrix metalloproteinase 1 expression in a human hepatocellular carcinoma cell line. Kamochi, J., Tokunaga, T., Morino, F., Nagata, J., Tomii, Y., Abe, Y., Hatanaka, H., Kijima, H., Yamazaki, H., Watanabe, N., Matsuzaki, S., Ueyama, Y., Nakamura, M. Int. J. Oncol. (2002) [Pubmed]
  23. E2A/HLF fusion cDNAs and the use of RT-PCR for the detection of minimal residual disease in t(17;19)(q22;p13) acute lymphoblastic leukemia. Devaraj, P.E., Foroni, L., Sekhar, M., Butler, T., Wright, F., Mehta, A., Samson, D., Prentice, H.G., Hoffbrand, A.V., Secker-Walker, L.M. Leukemia (1994) [Pubmed]
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