The mouse Ubr1 protein is a 1,757-residue, 200-kD protein that contains regions with sequence similarity to the 225-kD UBR1 protein of S. cerevisiae. There are apparent UBR1 homologs in other eukaryotes, thus defining a distinct family of proteins, the UBR family. The residues essential for substrate recognition by the yeast UBR1 protein are conserved in the mouse Ubr1 protein. Regions of similarity among the UBR family members include a putative zinc finger and RING-H2 finger, another zinc-binding domain. Northern blot analysis detected ubiquitous expression in human and adult mouse tissues, with highest levels in skeletal muscle and heart. In mouse embryos, in situ hybridization showed that Ubr1 expression is highest in the branchial arches and in the tail and limb buds.