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Published online before print November 8, 2000, 10.1101/gr.GR-1405R
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Vol. 10, Issue 11, 1743-1756, November 2000

LETTER
Fusion of the Human Gene for the Polyubiquitination Coeffector UEV1 with Kua, a Newly Identified Gene

Timothy M. Thomson,1,2,7,8 Juan José Lozano,1,2,3,7 Noureddine Loukili,1,2,7 Roberto Carrió,4 Florenci Serras,5 Bru Cormand,2,6 Marta Valeri,2 Víctor M. Díaz,1,2 Josep Abril,3 Moisés Burset,3 Jesús Merino,4 Alfons Macaya,2,6 Montserrat Corominas,5 and Roderic Guigó3

1 Institut de Biologia Molecular, Consejo Superior de Investigaciones Cientificas, Barcelona, Spain; 2 Unitat de Recerca Biomèdica, Hospital Materno-Infantil, Hospitals Vall d'Hebrón, Barcelona, Spain; 3 Grup de Recerca en Informática Mèdica, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, Barcelona, Spain; 4 Departamento de Biología Molecular, Facultad de Medicina, Universidad de Cantabria, Santander, Spain; 5 Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain; 6 Unitat de Malaties Neurometabòliques, Hospital Materno-Infantil, Hospitals Vall d'Hebrón, Barcelona, Spain

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.

[Kua cDNAs isolated by RT-PCR and described in this paper have been deposited in the GenBank data library under accession nos. AF1155120 (H. sapiens) and AF152361 (D. melanogaster). Genomic clones containing UEV genes: S. cerevisiae, YGL087c (accession no. Z72609); S. pombe, c338 (accession no. AL023781); P. falciparum, MAL3P2 (accession no. AL034558); A. thaliana, F26F24 (accession no. AC005292); C. elegans, F39B2 (accession no. Z92834); D. melanogaster, AC014908; and H. sapiens, 1185N5 (accession no. AL034423). Accession numbers for Kua cDNAs in GenBank dbEST: M. musculus, AA7853; T. cruzi, AI612534. Other Kua-containing sequences: A. thaliana genomic clones F10M23 (accession no. AL035440), F19K23 (accession no. AC000375), and T20K9 (accession no. AC004786).]


7 These authors have contributed equally to this work.

8 Corresponding author.


10:1743-1756 ©2000 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/00 $5.00

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