title: Cloning and characterization of the gene encoding human NPL4, a protein interacting with the ubiquitin fusion-degradation protein (UFD1L).
abstract: The ubiquitin fusion-degradation gene (UFD1L) encodes the human homologue of the yeast ubiquitin fusion-degradation 1 protein, an essential component of the ubiquitin-dependent proteolytic turnover and mRNA processing. Although the UFD1L gene has been mapped in the region commonly deleted in patients with DiGeorge syndrome (DGS)/velocardiofacial syndrome (VCFS), correlation between its haploinsufficiency and the phenotype has not yet been established. The only functional data available about mammalian Ufd1p is the ability to form a complex with the rat Npl4 protein, a component of the nuclear pore complex. In this paper we report the cloning and molecular characterization of the human NPL4 gene. This gene encodes for a protein 96% homologous to the rat Npl4, and 44 and 34% homologous to the C. elegans and S. cerevisiae Npl4 gene products, respectively. Fluorescence in situ hybridization experiments on human metaphases localized the NPL4 gene on the most telomeric region of chromosome 17q. Northern blots analysis on foetal and adult human tissues revealed a major approximately 4.5 kb transcript most abundant in heart, brain, kidney and skeletal muscle. In order to test a potential relationship between nuclear transport defects and some aspect of the DGS/VCFS phenotype, we also exclude the presence of mutations in the NPL4 coding sequence in a subset of patients with DGS/VCFS and no detectable 22q11 deletion or mutations at the UFD1L locus.
authors.affiliation: Department of Biopathology, Tor Vergata University of Rome, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Botta
authors.forename: C
authors.initials: C
authors.lastname: Tandoi
authors.forename: G
authors.initials: G
authors.lastname: Fini
authors.forename: G
authors.initials: G
authors.lastname: Calabrese
authors.forename: B
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: G
authors.initials: G
authors.lastname: Novelli
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D018797:Cell Cycle Proteins; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002972:Cleft Palate / Q000473:pathology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics; D005145:Face / Q000002:abnormalities; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006330:Heart Defects, Congenital / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; C104361:NPL4 protein, S cerevisiae; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D011506:Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C491497:UFD1 protein, human; C491496:Ufd1 protein, rat