Rbx1/ROC1/Hrt1 (Rbx1) has been recently shown to be involved in the regulation of protein turn-over. Here, we report the organization of the human Rbx1 gene, established by both a cloning and a functional genomics approach. The human gene, composed of five exons, encompasses 22.3 kb on chromosome 22q 13. The expression of Rbx1 transcripts (0.5 kb) appears developmentally regulated during mouse embryonic development and is prevalent in the adult mouse genital tract. A Genbank database search for Rbx1 related sequences in various species, from plants to mammals, is indicative of a high degree of evolutionary conservation in mouse rat and zebra fish and also, for the main functional part of the molecule, in other living species, although their gene structures can be significantly altered.