The murine TIS11 primary response gene is rapidly and transiently induced in response to many extracellular signals. A CX8CX5CX3H sequence is present twice in the TIS11 protein, in two additional murine proteins, TIS11B and TIS11D, that share regions of strong sequence conservation with TIS11, and in a Drosophila homologue (DTIS11). Although immunolocalization of TIS11 protein to the nucleus and zinc binding have lead to the speculation that the TIS11 family proteins are transcription factors, no function for these proteins has yet been clearly determined. We have now identified a TIS11 homologue, YTIS11, from Saccharomyces cerevisiae. The Ytis11p protein conserves both the two putative zinc finger CX8CX5CX3H sequences and the spacing between them, as well as additional amino acids in this region. The amino terminal 169 amino acid portion of Ytis11p protein, which contains a large number of acidic amino acids, can serve as a transactivator when fused to the Gal4 DNA-binding domain. Expression of the YTIS11 gene is not induced in response to DNA damaging agents, heat shock, sporulation conditions, or mating factor. However, YTIS11 expression is subjected to rapid glucose repression. Disruption of the YTIS11 gene in the M12B strain of Saccharomyces cerevisiae does not effect viability, growth in rich or synthetic medium, mating, or spore formation. However, YTIS11 gene disruption causes an alteration in metabolism that is reflected by a pH color change when cells are grown on YP plates supplemented with 2% glucose. Overexpression of murine TIS11 or TIS11B proteins dramatically attenuates the growth of both ytis11 and wild-type yeast.