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Gene Review

HIF1AN  -  hypoxia inducible factor 1, alpha subunit...

Homo sapiens

Synonyms: DKFZp762F1811, FIH-1, FIH1, FLJ20615, FLJ22027, ...
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Disease relevance of HIF1AN


High impact information on HIF1AN


Chemical compound and disease context of HIF1AN


Biological context of HIF1AN


Associations of HIF1AN with chemical compounds


Physical interactions of HIF1AN

  • The structural core of FIH-1 consists of a jellyroll-like beta-barrel containing the conserved ferrous-binding triad residues, confirming that FIH-1 is a member of the 2-oxoglutarate-dependent dioxygenase family [13].
  • Siah-1 was found both to interact with the JmjC domain of FIH through its substrate-binding domain and to specifically ubiquitinate FIH via its RING finger domain [14].

Enzymatic interactions of HIF1AN


Other interactions of HIF1AN

  • Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau [13].
  • Except for the core structure and triad residues, FIH-1 has many structural deviations from other family members including N- and C-terminal insertions and various deletions in the middle of the structure [13].
  • Sequence analyses involving FIH link the 2-OG oxygenases with members of the cupin superfamily, including Zn(II)-utilizing phosphomannose isomerase, revealing structural and evolutionary links between these metal-binding proteins that share common motifs [8].
  • 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) [16].
  • Furthermore, the asparagine hydroxylase FIH-1 (factor inhibiting HIF) has been found to hydroxylate Asp803 of the HIF-1 C-terminal transactivation domain, which results in the decreased ability of HIF-1 to bind to the transcriptional coactivator p300/CBP [17].

Analytical, diagnostic and therapeutic context of HIF1AN


  1. Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor. Linke, S., Stojkoski, C., Kewley, R.J., Booker, G.W., Whitelaw, M.L., Peet, D.J. J. Biol. Chem. (2004) [Pubmed]
  2. Molecular genetic analysis of FIH-1, FH, and SDHB candidate tumour suppressor genes in renal cell carcinoma. Morris, M.R., Maina, E., Morgan, N.V., Gentle, D., Astuti, D., Moch, H., Kishida, T., Yao, M., Schraml, P., Richards, F.M., Latif, F., Maher, E.R. J. Clin. Pathol. (2004) [Pubmed]
  3. Down-regulation of the expression of the FIH-1 and ARD-1 genes at the transcriptional level by nickel and cobalt in the human lung adenocarcinoma A549 cell line. Ke, Q., Kluz, T., Costa, M. International journal of environmental research and public health [electronic resource]. (2005) [Pubmed]
  4. Proline hydroxylation and gene expression. Kaelin, W.G. Annu. Rev. Biochem. (2005) [Pubmed]
  5. FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Mahon, P.C., Hirota, K., Semenza, G.L. Genes Dev. (2001) [Pubmed]
  6. Posttranslational hydroxylation of ankyrin repeats in I{kappa}B proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH). Cockman, M.E., Lancaster, D.E., Stolze, I.P., Hewitson, K.S., McDonough, M.A., Coleman, M.L., Coles, C.H., Yu, X., Hay, R.T., Ley, S.C., Pugh, C.W., Oldham, N.J., Masson, N., Schofield, C.J., Ratcliffe, P.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway. Dann, C.E., Bruick, R.K., Deisenhofer, J. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. Hewitson, K.S., McNeill, L.A., Riordan, M.V., Tian, Y.M., Bullock, A.N., Welford, R.W., Elkins, J.M., Oldham, N.J., Bhattacharya, S., Gleadle, J.M., Ratcliffe, P.J., Pugh, C.W., Schofield, C.J. J. Biol. Chem. (2002) [Pubmed]
  9. Amphotericin B blunts erythropoietin response to hypoxia by reinforcing FIH-mediated repression of HIF-1. Yeo, E.J., Ryu, J.H., Cho, Y.S., Chun, Y.S., Huang, L.E., Kim, M.S., Park, J.W. Blood (2006) [Pubmed]
  10. Regulation of HIF: asparaginyl hydroxylation. Peet, D., Linke, S. Novartis Found. Symp. (2006) [Pubmed]
  11. Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases. Koivunen, P., Hirsilä, M., Günzler, V., Kivirikko, K.I., Myllyharju, J. J. Biol. Chem. (2004) [Pubmed]
  12. Clioquinol, a Cu(II)/Zn(II) Chelator, Inhibits Both Ubiquitination and Asparagine Hydroxylation of Hypoxia-inducible Factor-1{alpha}, Leading to Expression of Vascular Endothelial Growth Factor and Erythropoietin in Normoxic Cells. Choi, S.M., Choi, K.O., Park, Y.K., Cho, H., Yang, E.G., Park, H. J. Biol. Chem. (2006) [Pubmed]
  13. Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau. Lee, C., Kim, S.J., Jeong, D.G., Lee, S.M., Ryu, S.E. J. Biol. Chem. (2003) [Pubmed]
  14. Siah-1 facilitates ubiquitination and degradation of factor inhibiting HIF-1alpha (FIH). Fukuba, H., Yamashita, H., Nagano, Y., Jin, H.G., Hiji, M., Ohtsuki, T., Takahashi, T., Kohriyama, T., Matsumoto, M. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  15. The zinc chelator, N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine, increases the level of nonfunctional HIF-1alpha protein in normoxic cells. Choi, S.M., Choi, K.O., Lee, N., Oh, M., Park, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  16. 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]
  17. Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing. Metzen, E., Berchner-Pfannschmidt, U., Stengel, P., Marxsen, J.H., Stolze, I., Klinger, M., Huang, W.Q., Wotzlaw, C., Hellwig-Bürgel, T., Jelkmann, W., Acker, H., Fandrey, J. J. Cell. Sci. (2003) [Pubmed]
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