Fusion of the human gene for the polyubiquitination coeffector UEV1 with Kua, a newly identified gene

UEV proteins are enzymatically inactive variants of the E2 ubiquitin-conjug ating enzymes that regulate noncanonical elongation of ubiquitin chains. In Saccharomyces cerevisiae, UEV is part of the RAD6-mediated error-free DNA repair pathway. In mammalian cells, UEV proteins can modulate c-FOS transcr iption and the G2-M transition of the cell cycle. Here we show that the UEV genes from phylogenetically distant organisms present a remarkable conserv ation in their exon-intron structure. We also show that the human UEV1 gene is fused with the previously unknown gene Kua. In Caenorhabditis elegans a nd Drosophila melanogaster, Kua and UEV are in separated Loci, and are expr essed as independent transcripts and proteins. In humans, Kua and UEV1 are adjacent genes, expressed either as separate transcripts encoding independe nt Kua and UEV1 proteins, or as a hybrid Kua-UEV transcript, encoding a two -domain protein. Kua proteins represent a novel class of conserved proteins with juxtamembrane histidine-rich motifs. Experiments with epitope-tagged proteins show that UEV1A is a nuclear protein, whereas both Kua and Kua-UEV localize to cytoplasmic structures, indicating that the Kua domain determi nes the cytoplasmic localization of Kua-UEV. Therefore, the addition of a K ua domain to UEV in the fused Kua-UEV protein confers new biological proper ties to this regulator of variant polyubiquitination.