The Ub80 gene in eukaryotes produces a ubiquitin fusion protein in which ubiquitin is fused in frame to a tail protein (Redman and Rechsteiner, 1988; Finley et al., 1989; Barrio et al., 1994). The tail protein is incorporated into the ribosome, and ubiquitin is thought to act as a chaperone. The DUb80 gene of Drosophila melanogaster was cloned by Barrio et al. (1994) and contains a 5'-untranslated exon, followed by a large intron and then the first coding exon. We report that the large intron of DUb80 contains an open reading frame, which produces a 259-aa protein (IP259) that is conserved in eukaryotes from yeast to mammals. Transcription of the DUb80 and IP259 mRNAs begins at the same start sites. However, alternate splicing of the primary transcript produces two structurally unrelated proteins. This is the second reported instance of two structurally unrelated proteins being produced via alternate splicing, suggesting that this form of genomic organization may be more common than previously thought.