The transcriptional regulator HAP4, whose expression is induced on respiratory substrates, has been shown to be involved in the balance between fermentation and respiration in Saccharomyces cerevisiae. We have previously identified a HAP4 orthologue in the yeast Hansenula polymorpha, called HpHAP4-A, which, despite its very limited sequence conservation (a 16 amino acid N-terminal motif), is fully functional in S. cerevisiae. Based on the same N-terminal motif, a second gene has now been identified in the same organism. It was shown to contain an additional cisbinding motif of the bZip type. We report on the cloning, heterologous expression and analysis in S. cerevisiae of this novel ScHAP4 orthologue. From these experiments we could conclude that, as with HpHAP4-A, the novel orthologue, designated HpHAP4-B, could functionally replace the S. cerevisiae gene but to a lesser extent. The relationship between the presence of the additional cis-binding motif and the weaker potential as a HAP4 functional homologue is discussed.

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