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Gene Review

ANB1  -  translation elongation factor eIF-5A

Saccharomyces cerevisiae S288c

Synonyms: Anaerobically induced protein 1, Eukaryotic translation initiation factor 5A-2, HYP1, Hypusine-containing protein HP1, J1651, ...
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High impact information on ANB1

  • A number of trans-acting mutations affecting a gene designated ROX1 caused constitutive expression of both the fused and wild-type genes, indicating that the ROX1 gene product operates through the ANB1 modulator sequence at the level of transcription [1].
  • The Mot3 protein was demonstrated to bind to the ANB1 OpA in vitro [2].
  • We demonstrate here that under repressed conditions a nucleosome is positioned over the TATA box in the wild-type ANB1 promoter [2].
  • The regulatory region of one well-studied hypoxic gene, ANB1, is comprised of two operators, OpA and OpB, each of which has two strong Rox1 binding sites, yet OpA represses transcription almost 10 times more effectively than OpB [2].
  • Northern (RNA) blot analysis shows two mRNA species, a larger mRNA (0.9 kb) transcribed from TIF51A and a smaller mRNA (0.8 kb) encoded by TIF51B [3].

Biological context of ANB1

  • TIF51B, also called ANB1, is located on chromosome X in a region called COR [4].
  • Expression of DAN1 was regulated in parallel with the hypoxic gene ANB1, showing identical kinetics of induction and dose response to heme [5].
  • We found that the rate of derepression was independent of the positioned nucleosome and that the TATA binding protein was excluded from ANB1 even in the absence of the positioned nucleosome [6].
  • To determine the DNA sequence requirements for repression, we carried out a mutational analysis of the consensus Rox1-binding site and an analysis of the arrangement of the Rox1 sites into operators in the hypoxic ANB1 gene [7].
  • We found that single base pair substitutions in the consensus sequence resulted in lower affinities for Rox1, and the decreased affinity of Rox1 for mutant sites correlated with the ability of these sites to repress expression of the hypoxic ANB1 gene [7].

Anatomical context of ANB1

  • Translation initiation factor eIF-5A (formerly called eIF-4D) is a small, highly conserved protein in eukaryotic cells that undergoes a unique modification at one of its lysine residues to form hypusine. eIF-5A stimulates in vitro the synthesis of methionyl-puromycin, a model reaction for formation of the first peptide bond [8].

Associations of ANB1 with chemical compounds

  • Mutations in the gene caused an eightfold increase in the expression of the heme-activated CYC1 gene in the absence of heme, a substantial increase in the expression of the heme-repressed ANB1 gene in the presence of heme, and a 13-fold increase in the expression of the catabolite-repressed GAL1 gene in the presence of glucose [9].
  • Factor eIF-4D is the only known mammalian protein that undergoes a unique post-translational modification of Lys-50 to the amino acid hypusine, and interestingly the same lysine is also present in the ANB1 gene product [10].

Regulatory relationships of ANB1

  • ROX1 encodes a heme-induced repression factor regulating ANB1 and CYC7 of Saccharomyces cerevisiae [11].
  • Under the aerobic growth conditions of this study, the 0.8-kb TIF51B transcript is not detected in the wild-type strain and is expressed only when TIF51A is disrupted [3].

Other interactions of ANB1

  • The aer2 null mutant was shown to have increased aerobic and anaerobic levels of RNA encoding the ROX1 repressor, normally expressed only aerobically and responsible for the aerobic repression of ANB1 expression [9].
  • Deletion of the mot3 gene also resulted in reduced repression of ANB1 [2].
  • Repression by heme cannot be attributed to the respiratory competence conferred by heme since both ANB1 and the aerobic genes tr-1 and CYC1 were regulated normally in [rho 0] mutants [12].
  • We addressed the requirements for Tup1-Ssn6 recruitment to two hypoxic genes, ANB1 and HEM13, by using chromatin immunoprecipitation assays [6].
  • The factor is encoded by two genes in Saccharomyces cerevisiae, called TIF51A and TIF51B, which are regulated reciprocally by oxygen and by heme [4].


  1. Oxygen regulation of anaerobic and aerobic genes mediated by a common factor in yeast. Lowry, C.V., Zitomer, R.S. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  2. Roles of transcription factor Mot3 and chromatin in repression of the hypoxic gene ANB1 in yeast. Kastaniotis, A.J., Mennella, T.A., Konrad, C., Torres, A.M., Zitomer, R.S. Mol. Cell. Biol. (2000) [Pubmed]
  3. Translation initiation factor 5A and its hypusine modification are essential for cell viability in the yeast Saccharomyces cerevisiae. Schnier, J., Schwelberger, H.G., Smit-McBride, Z., Kang, H.A., Hershey, J.W. Mol. Cell. Biol. (1991) [Pubmed]
  4. The two genes encoding protein synthesis initiation factor eIF-5A in Saccharomyces cerevisiae are members of a duplicated gene cluster. Kang, H.A., Schwelberger, H.G., Hershey, J.W. Mol. Gen. Genet. (1992) [Pubmed]
  5. The DAN1 gene of S. cerevisiae is regulated in parallel with the hypoxic genes, but by a different mechanism. Sertil, O., Cohen, B.D., Davies, K.J., Lowry, C.V. Gene (1997) [Pubmed]
  6. Recruitment of Tup1-Ssn6 by yeast hypoxic genes and chromatin-independent exclusion of TATA binding protein. Mennella, T.A., Klinkenberg, L.G., Zitomer, R.S. Eukaryotic Cell (2003) [Pubmed]
  7. The anatomy of a hypoxic operator in Saccharomyces cerevisiae. Deckert, J., Torres, A.M., Hwang, S.M., Kastaniotis, A.J., Zitomer, R.S. Genetics (1998) [Pubmed]
  8. Translation initiation factor eIF-5A, the hypusine-containing protein, is phosphorylated on serine in Saccharomyces cerevisiae. Kang, H.A., Schwelberger, H.G., Hershey, J.W. J. Biol. Chem. (1993) [Pubmed]
  9. A yeast protein with homology to the beta-subunit of G proteins is involved in control of heme-regulated and catabolite-repressed genes. Zhang, M., Rosenblum-Vos, L.S., Lowry, C.V., Boakye, K.A., Zitomer, R.S. Gene (1991) [Pubmed]
  10. The ANB1 locus of Saccharomyces cerevisiae encodes the protein synthesis initiation factor eIF-4D. Mehta, K.D., Leung, D., Lefebvre, L., Smith, M. J. Biol. Chem. (1990) [Pubmed]
  11. ROX1 encodes a heme-induced repression factor regulating ANB1 and CYC7 of Saccharomyces cerevisiae. Lowry, C.V., Zitomer, R.S. Mol. Cell. Biol. (1988) [Pubmed]
  12. Negative regulation of the Saccharomyces cerevisiae ANB1 gene by heme, as mediated by the ROX1 gene product. Lowry, C.V., Lieber, R.H. Mol. Cell. Biol. (1986) [Pubmed]
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