title: Fusion of the human gene for the polyubiquitination coeffector UEV1 with Kua, a newly identified gene.
abstract: UEV proteins are enzymatically inactive variants of the E2 ubiquitin-conjugating 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 transcription and the G2-M transition of the cell cycle. Here we show that the UEV genes from phylogenetically distant organisms present a remarkable conservation in their exon-intron structure. We also show that the human UEV1 gene is fused with the previously unknown gene Kua. In Caenorhabditis elegans and Drosophila melanogaster, Kua and UEV are in separated loci, and are expressed as independent transcripts and proteins. In humans, Kua and UEV1 are adjacent genes, expressed either as separate transcripts encoding independent 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 determines the cytoplasmic localization of Kua-UEV. Therefore, the addition of a Kua domain to UEV in the fused Kua-UEV protein confers new biological properties to this regulator of variant polyubiquitination.
authors.affiliation: Institut de Biologia Molecular, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain. tthomson@hg.vhebron.es
authors.forename: T M
authors.initials: TM
authors.lastname: Thomson
authors.forename: J J
authors.initials: JJ
authors.lastname: Lozano
authors.forename: N
authors.initials: N
authors.lastname: Loukili
authors.forename: R
authors.initials: R
authors.lastname: Carrió
authors.forename: F
authors.initials: F
authors.lastname: Serras
authors.forename: B
authors.initials: B
authors.lastname: Cormand
authors.forename: M
authors.initials: M
authors.lastname: Valeri
authors.forename: V M
authors.initials: VM
authors.lastname: Díaz
authors.forename: J
authors.initials: J
authors.lastname: Abril
authors.forename: M
authors.initials: M
authors.lastname: Burset
authors.forename: J
authors.initials: J
authors.lastname: Merino
authors.forename: A
authors.initials: A
authors.lastname: Macaya
authors.forename: M
authors.initials: M
authors.lastname: Corominas
authors.forename: R
authors.initials: R
authors.lastname: Guigó
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001704:Biopolymers / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D019169:Jurkat Cells; D008025:Ligases / Q000235:genetics* / Q000302:isolation & purification; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D025821:Polyubiquitin; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D001704:Biopolymers; D008025:Ligases; D025821:Polyubiquitin; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins; C471606:RAD6 protein, S cerevisiae; C499239:PEDS1 protein, human; C471624:UBE2V1 protein, human