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Gene Review

HAP4  -  Hap4p

Saccharomyces cerevisiae S288c

Synonyms: Transcriptional activator HAP4, YKL109W, YKL465
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Disease relevance of HAP4

  • This domain consists of a central cluster rich in serine, threonine and proline (STP cluster) flanked by two negatively charged regions containing bulky hydrophobic residues similar to acidic activation domains of Vp1, the herpes simplex virus virion protein VP16 and transcription factors GCN4 and HAP4 from yeast [1].

High impact information on HAP4

  • Strikingly, the mutant extract responded like wild type to GAL4-HAP4 [2].
  • Previous studies have demonstrated that the HAP2, HAP3, and HAP4 subunits of the yeast CCAAT-binding factor are required for the transcriptional activation of genes containing a CCAAT box [3].
  • The acidic activation domains of VP16, Gcn4, Swi5, and Hap4 interacted directly with the purified SWI/SNF complex and with the SWI/SNF complex in whole-cell extracts [4].
  • A second domain that is essential for the recruitment of Hap4p into the CCAAT-binding complex was identified in Hap5p and Php5p [5].
  • Furthermore, both TFIID and HAP4 5' noncoding regions mediated translation of a second cistron when placed into the intercistronic spacer region of a dicistronic mRNA, indicating that these leader sequences can initiate translation by an internal ribosome binding mechanism in this in vitro translation system [6].

Biological context of HAP4


Associations of HAP4 with chemical compounds

  • In hap2, hap3 and hap4 null mutants, the specific activities of LPDH in cultures grown on galactose and raffinose showed only slight induction above the basal level on glucose medium [12].
  • Here the physiology of a HAP4-deleted S. cerevisiae strain was investigated, and we found that the hap4Delta S. cerevisiae exhibited poor growth on ethanol, although the growth rate on glucose was indifferent from the wild type in aerobic as well as anaerobic cultures [13].
  • Contrary to previous reports, a Hap4 fragment comprising amino acids 1 to 330 can support the growth of yeast on lactate medium, and when tethered to lexA, can activate a reporter gene with upstream lexA binding sites, demonstrating the presence of a second transcriptional activation domain [14].
  • The Region in a Subunit of the Aspergillus CCAAT-Binding Protein Similar to the HAP4p-Recruiting Domain of Saccharomyces cerevisiae Hap5p Is Not Essential for Transcriptional Enhancement [15].

Other interactions of HAP4

  • We have used a fission yeast library to clone a homolog of S. cerevisiae HAP2, which along with HAP3 and HAP4 forms a transcriptional activation complex that binds to the CCAAT box [16].
  • Consistent with the weak effect of Hap4p, the carbon source does not significantly affect expression of ASN1 [17].
  • Although the activation domain of the yeast activator HAP4 is also highly negatively charged, its function is independent of at least one component of the adaptor complex, ADA2 [18].
  • The HAP4 gene was overexpressed in a Delta mig1 deletion background, generating a mutant in which respiratory function is stimulated and glucose repression is diminished [19].
  • Previous reports suggested the presence of a transcriptional activation domain within the carboxyl-terminal half of Hap4 that can function in the absence of Gcn5, a transcriptional coactivator protein and histone acetyltransferase [14].

Analytical, diagnostic and therapeutic context of HAP4

  • Dissection of the promoter of the HAP4 gene in S. cerevisiae unveils a complex regulatory framework of transcriptional regulation [8].
  • In a Northern blot analysis, the transcriptional level of the HAP4 gene was higher in strain 20G-R39 than in strain K-701 [9].


  1. PvAlf, an embryo-specific acidic transcriptional activator enhances gene expression from phaseolin and phytohemagglutinin promoters. Bobb, A.J., Eiben, H.G., Bustos, M.M. Plant J. (1995) [Pubmed]
  2. Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. Berger, S.L., Piña, B., Silverman, N., Marcus, G.A., Agapite, J., Regier, J.L., Triezenberg, S.J., Guarente, L. Cell (1992) [Pubmed]
  3. Cloning of yeast HAP5: a novel subunit of a heterotrimeric complex required for CCAAT binding. McNabb, D.S., Xing, Y., Guarente, L. Genes Dev. (1995) [Pubmed]
  4. Activation domain-mediated targeting of the SWI/SNF complex to promoters stimulates transcription from nucleosome arrays. Neely, K.E., Hassan, A.H., Wallberg, A.E., Steger, D.J., Cairns, B.R., Wright, A.P., Workman, J.L. Mol. Cell (1999) [Pubmed]
  5. The Saccharomyces cerevisiae Hap5p homolog from fission yeast reveals two conserved domains that are essential for assembly of heterotetrameric CCAAT-binding factor. McNabb, D.S., Tseng, K.A., Guarente, L. Mol. Cell. Biol. (1997) [Pubmed]
  6. Cap-dependent and cap-independent translation by internal initiation of mRNAs in cell extracts prepared from Saccharomyces cerevisiae. Iizuka, N., Najita, L., Franzusoff, A., Sarnow, P. Mol. Cell. Biol. (1994) [Pubmed]
  7. Transcriptional regulation of the yeast vacuolar aminopeptidase yscI encoding gene (APE1) by carbon sources. Bordallo, J., Cueva, R., Suárez-Rendueles, P. FEBS Lett. (1995) [Pubmed]
  8. Dissection of the promoter of the HAP4 gene in S. cerevisiae unveils a complex regulatory framework of transcriptional regulation. Brons, J.F., De Jong, M., Valens, M., Grivell, L.A., Bolotin-Fukuhara, M., Blom, J. Yeast (2002) [Pubmed]
  9. Characterization of an alpha-ketoglutarate-resistant sake yeast mutant with high organic acid productivity. Yano, S., Asano, T., Kurose, N., Hiramatsu, J., Shimoi, H., Ito, K. J. Biosci. Bioeng. (2003) [Pubmed]
  10. Isolation of genes encoding novel transcription factors which interact with the Hap complex from Aspergillus species. Tanaka, A., Kato, M., Nagase, T., Kobayashi, T., Tsukagoshi, N. Biochim. Biophys. Acta (2002) [Pubmed]
  11. The DNA sequence analysis of the HAP4-LAP4 region on chromosome XI of Saccharomyces cerevisiae suggests the presence of a second aspartate aminotransferase gene in yeast. Chéret, G., Pallier, C., Valens, M., Diagnan-Fornier, B., Fukuhara, H., Bolotin-Fukuhara, M., Sor, F. Yeast (1993) [Pubmed]
  12. Positive regulation of the LPD1 gene of Saccharomyces cerevisiae by the HAP2/HAP3/HAP4 activation system. Bowman, S.B., Zaman, Z., Collinson, L.P., Brown, A.J., Dawes, I.W. Mol. Gen. Genet. (1992) [Pubmed]
  13. Hap4 Is Not Essential for Activation of Respiration at Low Specific Growth Rates in Saccharomyces cerevisiae. Raghevendran, V., Patil, K.R., Olsson, L., Nielsen, J. J. Biol. Chem. (2006) [Pubmed]
  14. Identification, mutational analysis, and coactivator requirements of two distinct transcriptional activation domains of the Saccharomyces cerevisiae Hap4 protein. Stebbins, J.L., Triezenberg, S.J. Eukaryotic Cell (2004) [Pubmed]
  15. The Region in a Subunit of the Aspergillus CCAAT-Binding Protein Similar to the HAP4p-Recruiting Domain of Saccharomyces cerevisiae Hap5p Is Not Essential for Transcriptional Enhancement. Tanoue, S., Kamei, K., Goda, H., Tanaka, A., Kobayashi, T., Tsukagoshi, N., Kato, M. Biosci. Biotechnol. Biochem. (2006) [Pubmed]
  16. The Schizosaccharomyces pombe homolog of Saccharomyces cerevisiae HAP2 reveals selective and stringent conservation of the small essential core protein domain. Olesen, J.T., Fikes, J.D., Guarente, L. Mol. Cell. Biol. (1991) [Pubmed]
  17. Cloning of the ASN1 and ASN2 genes encoding asparagine synthetases in Saccharomyces cerevisiae: differential regulation by the CCAAT-box-binding factor. Dang, V.D., Valens, M., Bolotin-Fukuhara, M., Daignan-Fornier, B. Mol. Microbiol. (1996) [Pubmed]
  18. The acidic transcriptional activation domains of herpes virus VP16 and yeast HAP4 have different co-factor requirements. Wang, L., Turcotte, B., Guarente, L., Berger, S.L. Gene (1995) [Pubmed]
  19. Overexpression of HAP4 in glucose-derepressed yeast cells reveals respiratory control of glucose-regulated genes. Lascaris, R., Piwowarski, J., van der Spek, H., Teixeira de Mattos, J., Grivell, L., Blom, J. Microbiology (Reading, Engl.) (2004) [Pubmed]
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