An intracellular Drosophila protein, Yippee, was identified in a yeast interaction trap screen as physically interacting with Hyalophora cecropia Hemolin. The Yippee gene was isolated, structurally characterized, and mapped to the region 12A on the X-chromosome. Yippee contains a putative zinc-finger-like metal binding domain. It is the first characterized member of a conserved gene family of proteins present in diverse eukaryotic organisms, ranging from cellular slime mould to humans. A human cDNA clone was isolated and shown to be 76% identical to Drosophila Yippee. Yippee is ubiquitously expressed in different developmental stages of Drosophila and in different fetal tissues from human. Although the Hemolin-Yippee interaction remains to be further elucidated, the high degree of Yippee sequence conservation between a wide range of species suggests that this protein is of general importance in eukaryotes.