The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Eif2ak1  -  eukaryotic translation initiation factor 2...

Mus musculus

Synonyms: Eukaryotic translation initiation factor 2-alpha kinase 1, HCR, Heme-controlled repressor, Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase, Heme-regulated inhibitor, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Eif2ak1

  • Results showed an inhibition of papilloma number in both restricted groups and the inhibition was greatest in the HCR mice [1].
  • HCR, previously identified as alpha-helix coiled-coil rod homologue, is one of the psoriasis vulgaris (PV) candidate genes [2].

High impact information on Eif2ak1

  • Expression of a kinase-defective Raf-1 mutant (craf301) or a regulatory domain fragment (HCR) inhibited serum-induced NIH/3T3-cell proliferation and raf transformation even more efficiently [3].
  • We propose that an equilibrium state exists between Gadd34/PP1c and the opposing heme-regulated inhibitor kinase during hemoglobin synthesis in the reticulocyte [4].
  • However, reactive oxygen species are involved only in HRI activation by arsenite [5].
  • While autophosphorylation is essential for the activation of HRI, the phosphorylation status of HRI activated by different stresses is different [5].
  • The contributions of HRI in various stress responses were assessed with the aid of HRI-null reticulocytes and fetal liver erythroid cells [5].

Biological context of Eif2ak1


Anatomical context of Eif2ak1


Associations of Eif2ak1 with chemical compounds

  • In vivo studies elucidated a fundamental requirement for HRI in murine survival upon acute arsenite exposure [6].
  • Finally, we found that HRI is inhibited by bilirubin at physiological/pathological levels (IC(50) = 20 microM) [7].
  • The function of HCR was analyzed in transgenic mice and turned out to be a position-specific regulatory element of human, setting the precise anterior boundary of expression in transgenic embryos; at day 12.5 post-coitum a distinct anterior limit of expression was noted at the level of C5 in neural tube and spinal ganglia in transgenic embryos [13].
  • CF1 mice and BN, HCR and HCS rats fed 0.1% BSA for 56 days also did not produce circulating antibodies during ingestion, and almost all were hyporesponsive after parenteral challenge [14].

Other interactions of Eif2ak1

  • Here, we found that the rate of dissociation for Fe(III)-protoporphyrin IX was much higher for full-length HRI (1.5 x 10(-)(3) s(-)(1)) than for myoglobin (8.4 x 10(-)(7) s(-)(1)) or the alpha-subunit of hemoglobin (7.1 x 10(-)(6) s(-)(1)), demonstrating the heme-sensing character of HRI [7].

Analytical, diagnostic and therapeutic context of Eif2ak1


  1. Inhibition of skin tumor promotion by restriction of fat and carbohydrate calories in SENCAR mice. Birt, D.F., Pinch, H.J., Barnett, T., Phan, A., Dimitroff, K. Cancer Res. (1993) [Pubmed]
  2. RNA polymerase II subunit 3 is retained in the cytoplasm by its interaction with HCR, the psoriasis vulgaris candidate gene product. Corbi, N., Bruno, T., De Angelis, R., Di Padova, M., Libri, V., Di Certo, M.G., Spinardi, L., Floridi, A., Fanciulli, M., Passananti, C. J. Cell. Sci. (2005) [Pubmed]
  3. Raf-1 protein kinase is required for growth of induced NIH/3T3 cells. Kolch, W., Heidecker, G., Lloyd, P., Rapp, U.R. Nature (1991) [Pubmed]
  4. Gadd34 requirement for normal hemoglobin synthesis. Patterson, A.D., Hollander, M.C., Miller, G.F., Fornace, A.J. Mol. Cell. Biol. (2006) [Pubmed]
  5. Translation initiation control by heme-regulated eukaryotic initiation factor 2alpha kinase in erythroid cells under cytoplasmic stresses. Lu, L., Han, A.P., Chen, J.J. Mol. Cell. Biol. (2001) [Pubmed]
  6. Heme-regulated inhibitor kinase-mediated phosphorylation of eukaryotic translation initiation factor 2 inhibits translation, induces stress granule formation, and mediates survival upon arsenite exposure. McEwen, E., Kedersha, N., Song, B., Scheuner, D., Gilks, N., Han, A., Chen, J.J., Anderson, P., Kaufman, R.J. J. Biol. Chem. (2005) [Pubmed]
  7. Characterization of heme-regulated eIF2alpha kinase: roles of the N-terminal domain in the oligomeric state, heme binding, catalysis, and inhibition. Miksanova, M., Igarashi, J., Minami, M., Sagami, I., Yamauchi, S., Kurokawa, H., Shimizu, T. Biochemistry (2006) [Pubmed]
  8. Structure of the hepatic control region of the human apolipoprotein E/C-I gene locus. Dang, Q., Walker, D., Taylor, S., Allan, C., Chin, P., Fan, J., Taylor, J. J. Biol. Chem. (1995) [Pubmed]
  9. Two hepatic enhancers, HCR.1 and HCR.2, coordinate the liver expression of the entire human apolipoprotein E/C-I/C-IV/C-II gene cluster. Allan, C.M., Taylor, S., Taylor, J.M. J. Biol. Chem. (1997) [Pubmed]
  10. Characterization of the hemin-sensitive eukaryotic initiation factor 2alpha kinase from mouse nonerythroid cells. Berlanga, J.J., Herrero, S., de Haro, C. J. Biol. Chem. (1998) [Pubmed]
  11. Cloning of hHRI, human heme-regulated eukaryotic initiation factor 2alpha kinase: down-regulated in epithelial ovarian cancers. Hwang, S.Y., Kim, M.K., Kim, J.C. Mol. Cells (2000) [Pubmed]
  12. Tissue distribution and immunoreactivity of heme-regulated eIF-2 alpha kinase determined by monoclonal antibodies. Pal, J.K., Chen, J.J., London, I.M. Biochemistry (1991) [Pubmed]
  13. Sequence and functional analysis of an upstream regulatory region of human HOXA7 gene. Min, W., Cho, M., Jang, S.I., Chang, H.H., Lee, C.S., Jun, M.H., Kim, M.H. Gene (1996) [Pubmed]
  14. Systemic antibody responses of different species following ingestion of soluble protein antigens. Silverman, G.A., Peri, B.A., Rothberg, R.M. Dev. Comp. Immunol. (1982) [Pubmed]
  15. Purification and characterisation of an initiation-factor-2 kinase from uninduced mouse erythroleukaemia cells. Mellor, H., Price, N.T., Oldfield, S., Sarre, T.F., Proud, C.G. Eur. J. Biochem. (1993) [Pubmed]
  16. A far-downstream hepatocyte-specific control region directs expression of the linked human apolipoprotein E and C-I genes in transgenic mice. Simonet, W.S., Bucay, N., Lauer, S.J., Taylor, J.M. J. Biol. Chem. (1993) [Pubmed]
WikiGenes - Universities