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Gene Review

EGLN2  -  egl-9 family hypoxia-inducible factor 2

Homo sapiens

Synonyms: EIT6, Egl nine homolog 2, Estrogen-induced tag 6, HIF-PH1, HIF-prolyl hydroxylase 1, ...
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Disease relevance of EGLN2


High impact information on EGLN2

  • Thus, the control of PHD1/3 by Siah1a/2 constitutes another level of complexity in the regulation of HIF1alpha during hypoxia [5].
  • An absolute requirement for dioxygen as a cosubstrate and iron as cofactor suggests that HIF-PH functions directly as a cellular oxygen sensor [6].
  • The significance of this finding was underscored by the fact that disease-causing missense mutations in the PHD1 (C311Y and P326Q) abolished its E3 ligase activity [7].
  • Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2) [8].
  • ING4 directly associates with the HIF prolyl hydroxylase, an Fe(II)-dependent oxygenase previously shown to mediate HIF stability as a function of oxygen availability [9].

Biological context of EGLN2


Anatomical context of EGLN2


Associations of EGLN2 with chemical compounds


Other interactions of EGLN2

  • Suppression of hypoxia-inducible factor 1alpha (HIF-1alpha) transcriptional activity by the HIF prolyl hydroxylase EGLN1 [21].
  • Recent biochemical and candidate gene approach studies have led to the discovery of three HIF-regulatory prolyl hydroxylases, PHD-1, -2 and -3 and an asparaginyl hydroxylase, also known as FIH (factor inhibiting HIF) [22].
  • Taken together, our findings suggest a hypoxia-induced regulatory loop of PHD1 expression, mediated by ARNT [23].
  • By contrast, BAPTA-am exerted its effects via inhibition of HIF-prolyl hydroxylase activity and von Hippel-Lindau tumor repressor protein (VHL) interaction [24].
  • PHI-1 treatment also increased PHD-2, but not PHD-1 or -3, protein [25].


  1. Expression of prolyl-hydroxylase-1 (PHD1/EGLN2) suppresses hypoxia inducible factor-1alpha activation and inhibits tumor growth. Erez, N., Milyavsky, M., Eilam, R., Shats, I., Goldfinger, N., Rotter, V. Cancer Res. (2003) [Pubmed]
  2. Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression). Seth, P., Krop, I., Porter, D., Polyak, K. Oncogene (2002) [Pubmed]
  3. Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness. Jokilehto, T., Rantanen, K., Luukkaa, M., Heikkinen, P., Grenman, R., Minn, H., Kronqvist, P., Jaakkola, P.M. Clin. Cancer Res. (2006) [Pubmed]
  4. HIF prolyl hydroxylases in the rat; organ distribution and changes in expression following hypoxia and coronary artery ligation. William, C., Maxwell, P.H., Nichols, L., Lygate, C., Tian, Y.M., Bernhardt, W., Wiesener, M., Ratcliffe, P.J., Eckardt, K.U., Pugh, C.W. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  5. Siah2 regulates stability of prolyl-hydroxylases, controls HIF1alpha abundance, and modulates physiological responses to hypoxia. Nakayama, K., Frew, I.J., Hagensen, M., Skals, M., Habelhah, H., Bhoumik, A., Kadoya, T., Erdjument-Bromage, H., Tempst, P., Frappell, P.B., Bowtell, D.D., Ronai, Z. Cell (2004) [Pubmed]
  6. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Jaakkola, P., Mole, D.R., Tian, Y.M., Wilson, M.I., Gielbert, J., Gaskell, S.J., Kriegsheim Av, n.u.l.l., Hebestreit, H.F., Mukherji, M., Schofield, C.J., Maxwell, P.H., Pugh, C.W., Ratcliffe, P.J. Science (2001) [Pubmed]
  7. AIRE functions as an E3 ubiquitin ligase. Uchida, D., Hatakeyama, S., Matsushima, A., Han, H., Ishido, S., Hotta, H., Kudoh, J., Shimizu, N., Doucas, V., Nakayama, K.I., Kuroda, N., Matsumoto, M. J. Exp. Med. (2004) [Pubmed]
  8. Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2). McDonough, M.A., Li, V., Flashman, E., Chowdhury, R., Mohr, C., Liénard, B.M., Zondlo, J., Oldham, N.J., Clifton, I.J., Lewis, J., McNeill, L.A., Kurzeja, R.J., Hewitson, K.S., Yang, E., Jordan, S., Syed, R.S., Schofield, C.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF). Ozer, A., Wu, L.C., Bruick, R.K. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  10. Characterization and comparative analysis of the EGLN gene family. Taylor, M.S. Gene (2001) [Pubmed]
  11. Dynamic HIF1A regulation during human placental development. Ietta, F., Wu, Y., Winter, J., Xu, J., Wang, J., Post, M., Caniggia, I. Biol. Reprod. (2006) [Pubmed]
  12. Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Pan, Y., Mansfield, K.D., Bertozzi, C.C., Rudenko, V., Chan, D.A., Giaccia, A.J., Simon, M.C. Mol. Cell. Biol. (2007) [Pubmed]
  13. Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3. Huang, J., Zhao, Q., Mooney, S.M., Lee, F.S. J. Biol. Chem. (2002) [Pubmed]
  14. The HIF prolyl hydroxylase PHD3 is a potential substrate of the TRiC chaperonin. Masson, N., Appelhoff, R.J., Tuckerman, J.R., Tian, Y.M., Demol, H., Puype, M., Vandekerckhove, J., Ratcliffe, P.J., Pugh, C.W. FEBS Lett. (2004) [Pubmed]
  15. Hypoxia-inducible Factors in the First Trimester Human Lung. Groenman, F., Rutter, M., Caniggia, I., Tibboel, D., Post, M. J. Histochem. Cytochem. (2007) [Pubmed]
  16. Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: Relationship between maturation and apoptotic sensitivity. Terkhorn, S.P., Bohensky, J., Shapiro, I.M., Koyama, E., Srinivas, V. J. Cell. Physiol. (2007) [Pubmed]
  17. Coordinate regulation of the oxygen-dependent degradation domains of hypoxia-inducible factor 1 alpha. Chan, D.A., Sutphin, P.D., Yen, S.E., Giaccia, A.J. Mol. Cell. Biol. (2005) [Pubmed]
  18. Regulation of HIF by the von Hippel-Lindau tumour suppressor: implications for cellular oxygen sensing. Mole, D.R., Maxwell, P.H., Pugh, C.W., Ratcliffe, P.J. IUBMB Life (2001) [Pubmed]
  19. The polybasic region that follows the plant homeodomain zinc finger 1 of pf1 is necessary and sufficient for specific phosphoinositide binding. Kaadige, M.R., Ayer, D.E. J. Biol. Chem. (2006) [Pubmed]
  20. Gallate, the component of HIF-inducing catechins, inhibits HIF prolyl hydroxylase. Tsukiyama, F., Nakai, Y., Yoshida, M., Tokuhara, T., Hirota, K., Sakai, A., Hayashi, H., Katsumata, T. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  21. Suppression of hypoxia-inducible factor 1alpha (HIF-1alpha) transcriptional activity by the HIF prolyl hydroxylase EGLN1. To, K.K., Huang, L.E. J. Biol. Chem. (2005) [Pubmed]
  22. Use of novel monoclonal antibodies to determine the expression and distribution of the hypoxia regulatory factors PHD-1, PHD-2, PHD-3 and FIH in normal and neoplastic human tissues. Soilleux, E.J., Turley, H., Tian, Y.M., Pugh, C.W., Gatter, K.C., Harris, A.L. Histopathology (2005) [Pubmed]
  23. Hypoxia-dependent regulation of PHD1: cloning and characterization of the human PHD1/EGLN2 gene promoter. Erez, N., Stambolsky, P., Shats, I., Milyavsky, M., Kachko, T., Rotter, V. FEBS Lett. (2004) [Pubmed]
  24. Induction of plasminogen activator inhibitor I gene expression by intracellular calcium via hypoxia-inducible factor-1. Liu, Q., Möller, U., Flügel, D., Kietzmann, T. Blood (2004) [Pubmed]
  25. Stimulation of HIF-1alpha, HIF-2alpha, and VEGF by prolyl 4-hydroxylase inhibition in human lung endothelial and epithelial cells. Asikainen, T.M., Ahmad, A., Schneider, B.K., Ho, W.B., Arend, M., Brenner, M., Günzler, V., White, C.W. Free Radic. Biol. Med. (2005) [Pubmed]
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