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Gene Review

HAP3  -  Hap3p

Saccharomyces cerevisiae S288c

Synonyms: Transcriptional activator HAP3, UAS2 regulatory protein A, YBL021C, YBL0441
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High impact information on HAP3

  • Most surprisingly, the subunits of CP1 and HAP2/HAP3 are functionally interchangeable [1].
  • Yeast HAP2 and HAP3 activators both bind to the CYC1 upstream activation site, UAS2, in an interdependent manner [2].
  • 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 [2].
  • Furthermore, we demonstrate that purified recombinant HAP2, HAP3, and HAP5 are able to reconstitute CCAAT-binding activity in mobility shift analysis [3].
  • 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].

Biological context of HAP3

  • The promoter of this gene contains a number of motifs for DNA-binding transcriptional activators, including three which show strong sequence homology to the core HAP2/HAP3/HAP4 binding motif [4].
  • Mutations in HAP2, HAP3 or HAP4 block derepression of a CIT1-lacZ gene fusion [5].
  • Consensus sequences for the binding of yAP1 and the HAP2/HAP3/HAP4 complex are contained in those regions [6].
  • Analysis of the HAP3 DNA sequence showed that the 570-base transcript could encode a protein of 144 amino acids [7].
  • The predicted amino acid sequence of HapC shows extensive identity to HAP3 in the central conserved domain, but shows little conservation in the flanking sequences [8].

Anatomical context of HAP3

  • Functional homologs of HAP2 and HAP3 have been conserved in HeLa cells where HAP2 activity corresponds to a chromatographic fraction designated CP1B [9].

Associations of HAP3 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 [4].
  • The hap1 mutant grew at near-normal rates on glycerol, whereas hap2 and hap3 mutants grew very slowly [10].
  • We show that HEM1 (encoding 5-aminolevulinate synthase) expression, while constitutive under all steady-state growth conditions tested, is activated by the HAP2-HAP3 global activation system that controls expression of apocytochromes [11].
  • The protein contains a novel 4-cysteine zinc-finger motif and we propose by analogy that all other homologous HAP3 proteins contain the same motif, with the position containing the third cysteine being occupied by a serine residue [12].

Physical interactions of HAP3

  • We describe a detailed genetic analysis of the DNA-binding regions in the HAP2/HAP3 CCAAT-binding heteromeric complex [13].

Regulatory relationships of HAP3

  • This HAP3 mutation also suppresses mutations in a different region of HAP2 which promotes subunit assembly of the complex [13].

Other interactions of HAP3

  • Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer [14].
  • Simultaneous effects of mutations in the transcriptional regulatory genes, HAP1, HAP2 and HAP3, on all respiratory cytochromes of Saccharomyces cerevisiae were determined [10].
  • Transcriptional activation by the yeast CYC1 upstream activation site UAS2UP1 requires the products of both the HAP2 and HAP3 regulatory genes [2].

Analytical, diagnostic and therapeutic context of HAP3

  • Purification and molecular cloning of the "A" chain of a rat heteromeric CCAAT-binding protein. Sequence identity with the yeast HAP3 transcription factor [15].


  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. 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]
  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. 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]
  5. 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]
  6. 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]
  7. The HAP3 regulatory locus of Saccharomyces cerevisiae encodes divergent overlapping transcripts. Hahn, S., Pinkham, J., Wei, R., Miller, R., Guarente, L. Mol. Cell. Biol. (1988) [Pubmed]
  8. The hapC gene of Aspergillus nidulans is involved in the expression of CCAAT-containing promoters. Papagiannopoulos, P., Andrianopoulos, A., Sharp, J.A., Davis, M.A., Hynes, M.J. Mol. Gen. Genet. (1996) [Pubmed]
  9. 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]
  10. Effects of hap mutations on heme and cytochrome formation in yeast. Mattoon, J.R., Caravajal, E., Guthrie, D. Curr. Genet. (1990) [Pubmed]
  11. Constitutive expression of the yeast HEM1 gene is actually a composite of activation and repression. Keng, T., Guarente, L. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  12. Sequence of the HAP3 transcription factor of Kluyveromyces lactis predicts the presence of a novel 4-cysteine zinc-finger motif. Mulder, W., Scholten, I.H., de Boer, R.W., Grivell, L.A. Mol. Gen. Genet. (1994) [Pubmed]
  13. Mutations in yeast HAP2/HAP3 define a hybrid CCAAT box binding domain. Xing, Y., Fikes, J.D., Guarente, L. EMBO J. (1993) [Pubmed]
  14. Identification and characterization of HAP4: a third component of the CCAAT-bound HAP2/HAP3 heteromer. Forsburg, S.L., Guarente, L. Genes Dev. (1989) [Pubmed]
  15. Purification and molecular cloning of the "A" chain of a rat heteromeric CCAAT-binding protein. Sequence identity with the yeast HAP3 transcription factor. Vuorio, T., Maity, S.N., de Crombrugghe, B. J. Biol. Chem. (1990) [Pubmed]
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