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Gene Review

HAP2  -  Hap2p

Saccharomyces cerevisiae S288c

Synonyms: Transcriptional activator HAP2, YGL237C
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High impact information on HAP2

  • Most surprisingly, the subunits of CP1 and HAP2/HAP3 are functionally interchangeable [1].
  • DNA binding was assessed both in vitro and in vivo whereas subunit association and transcriptional activation were analyzed in vivo by using a bifunctional lexA-HAP2 fusion [2].
  • Functional homologs of HAP2 and HAP3 have been conserved in HeLa cells where HAP2 activity corresponds to a chromatographic fraction designated CP1B [2].
  • Here, we describe deletion and codon insertion mutagenesis of the Saccharomyces cerevisiae HAP2 subunit [2].
  • The CYC1 gene of Saccharomyces cerevisiae is positively regulated by the HAP2 and HAP3 proteins, which form a heteromeric complex that binds to a CCAAT box in the upstream activation site, UAS2, and which activate transcription in a nonfermentable carbon source [3].

Biological context of HAP2


Associations of HAP2 with chemical compounds

  • Domain 1 is essential for transcription per se in cells grown on repressing carbon sources, is required for optimal transcription in cells grown on a derepressing carbon source, is sufficient for glucose repression-derepression, and is the element of UAS6 at which HAP2 affects COX6 transcription [9].
  • We show here that both HAP2 and HAP3 in yeast extracts bind to UAS2UP1 and give rise to a single protein-DNA complex, termed C, in nondenaturing polyacrylamide gels [10].
  • PUT1 is inducible by proline, responds only slightly to carbon catabolite repression, and is not regulated by the cytochrome activator proteins HAP1 and HAP2 [11].
  • The generality of the Sp1A results is supported by our finding that yeast glutamine-rich domains from HAP2 and MCM1 are also transcriptionally active in S. cerevisiae [12].
  • The first peptide is based on the native sequence of a protein-binding domain within a heteromeric transcriptional activator, HAP2, identified from yeast Saccharomyces cerevisiae, with tyrosine (Y) present at the 1st, 8th and 15th amino acid positions, hence we denote this YYY15 [13].

Physical interactions of HAP2

  • Within this region the binding sites for both the Hap2/3/4/5 complex and Hap1p were defined by gel retardation experiments and site-directed mutagenesis [14].
  • Mutagenesis of the perfect consensus for HAP2/3/4 complex binding at position -542 resulted in considerable reduction of UBI4 promoter derepression with respiratory adaptation in HAP wild-type cells and abolished the reduced UBI4-LacZ derepression normally seen when aerobic cultures of the hap1 mutant are transferred from glucose to lactate [15].
  • We describe a detailed genetic analysis of the DNA-binding regions in the HAP2/HAP3 CCAAT-binding heteromeric complex [16].
  • We demonstrated that mutations of the HAP2/3/4 binding site and of the two STress-Responsive cis-Elements (STRE) did not abolish the early induction of GSY2, although the latter mutation led to a 20-fold drop in the transcriptional activity of the promoter, as determined from lacZ gene fusions [17].
  • In this report we demonstrate that, in addition to these regulators, the Hap2/3/4/5 complex interacts specifically with a CAAT-box element in the JEN1 promoter, and acts to derepress JEN1 expression [18].

Regulatory relationships of HAP2

  • These findings identify COX6 as the fourth respiratory protein gene that is known to be regulated positively by heme and HAP2 [4].
  • This HAP3 mutation also suppresses mutations in a different region of HAP2 which promotes subunit assembly of the complex [16].
  • KlAAC was not subject to control by KlHap2, in contrast to AAC2 which is regulated by the Hap2 complex in S. cerevisiae [19].

Other interactions of HAP2

  • Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer [3].
  • It has consensus binding sequences for ABF1 and HAP2 [9].
  • However, we have found that HAP2 and HAP3 gene products are involved in the expression of HEM3 [20].
  • Results are consistent with generalized control of mitochondrial replication directed by the HAP1-HAP2 system and heme-directed control of formation of all apocytochromes mediated by HAP1 [21].
  • Replacement of this region with the activation domain of GAL4 restored activity, suggesting that it provides the principal activation domain to the bound HAP2/3/4 complex [3].


  1. A yeast and a human CCAAT-binding protein have heterologous subunits that are functionally interchangeable. Chodosh, L.A., Olesen, J., Hahn, S., Baldwin, A.S., Guarente, L., Sharp, P.A. Cell (1988) [Pubmed]
  2. The HAP2 subunit of yeast CCAAT transcriptional activator contains adjacent domains for subunit association and DNA recognition: model for the HAP2/3/4 complex. Olesen, J.T., Guarente, L. Genes Dev. (1990) [Pubmed]
  3. Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer. Forsburg, S.L., Guarente, L. Genes Dev. (1989) [Pubmed]
  4. Transcription of yeast COX6, the gene for cytochrome c oxidase subunit VI, is dependent on heme and on the HAP2 gene. Trawick, J.D., Wright, R.M., Poyton, R.O. J. Biol. Chem. (1989) [Pubmed]
  5. 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]
  6. Glucose derepression of gluconeogenic enzymes in Saccharomyces cerevisiae correlates with phosphorylation of the gene activator Cat8p. Randez-Gil, F., Bojunga, N., Proft, M., Entian, K.D. Mol. Cell. Biol. (1997) [Pubmed]
  7. 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]
  8. The HAP2,3,4 transcriptional activator is required for derepression of the yeast citrate synthase gene, CIT1. Rosenkrantz, M., Kell, C.S., Pennell, E.A., Devenish, L.J. Mol. Microbiol. (1994) [Pubmed]
  9. Regulation of yeast COX6 by the general transcription factor ABF1 and separate HAP2- and heme-responsive elements. Trawick, J.D., Kraut, N., Simon, F.R., Poyton, R.O. Mol. Cell. Biol. (1992) [Pubmed]
  10. Yeast HAP2 and HAP3 activators both bind to the CYC1 upstream activation site, UAS2, in an interdependent manner. Olesen, J., Hahn, S., Guarente, L. Cell (1987) [Pubmed]
  11. Proline utilization in Saccharomyces cerevisiae: sequence, regulation, and mitochondrial localization of the PUT1 gene product. Wang, S.S., Brandriss, M.C. Mol. Cell. Biol. (1987) [Pubmed]
  12. Glutamine-rich domains activate transcription in yeast Saccharomyces cerevisiae. Xiao, H., Jeang, K.T. J. Biol. Chem. (1998) [Pubmed]
  13. Interfacial nano-structuring of designed peptides regulated by solution pH. Lu, J.R., Perumal, S., Hopkinson, I., Webster, J.R., Penfold, J., Hwang, W., Zhang, S. J. Am. Chem. Soc. (2004) [Pubmed]
  14. Regulation of the Saccharomyces cerevisiae DLD1 gene encoding the mitochondrial protein D-lactate ferricytochrome c oxidoreductase by HAP1 and HAP2/3/4/5. Lodi, T., Alberti, A., Guiard, B., Ferrero, I. Mol. Gen. Genet. (1999) [Pubmed]
  15. UBI4, the polyubiquitin gene of Saccharomyces cerevisiae, is a heat shock gene that is also subject to catabolite derepression control. Watt, R., Piper, P.W. Mol. Gen. Genet. (1997) [Pubmed]
  16. Mutations in yeast HAP2/HAP3 define a hybrid CCAAT box binding domain. Xing, Y., Fikes, J.D., Guarente, L. EMBO J. (1993) [Pubmed]
  17. STRE- and cAMP-independent transcriptional induction of Saccharomyces cerevisiae GSY2 encoding glycogen synthase during diauxic growth on glucose. Parrou, J.L., Enjalbert, B., François, J. Yeast (1999) [Pubmed]
  18. Co-ordinate regulation of lactate metabolism genes in yeast: the role of the lactate permease gene JEN1. Lodi, T., Fontanesi, F., Guiard, B. Mol. Genet. Genomics (2002) [Pubmed]
  19. A Klaac null mutant of Kluyveromyces lactis is complemented by a single copy of the Saccharomyces cerevisiae AAC1 gene. Viola, A.M., Lodi, T., Ferrero, I. Curr. Genet. (1999) [Pubmed]
  20. Structure and regulation of yeast HEM3, the gene for porphobilinogen deaminase. Keng, T., Richard, C., Larocque, R. Mol. Gen. Genet. (1992) [Pubmed]
  21. Effects of hap mutations on heme and cytochrome formation in yeast. Mattoon, J.R., Caravajal, E., Guthrie, D. Curr. Genet. (1990) [Pubmed]
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