title: Alternative splicing determines the domain structure of WWP1, a Nedd4 family protein.
abstract: Nedd-4-like proteins are E3 ubiquitin-ligase molecules which regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Here we show that a human Nedd4 family gene, WWP1, is localized on 8q21 and generates at least six isoforms through alternative splicing. We show that alternative splicing affects the domain structure of WWP1, with forms that contain or lack an N-terminal C2 domain. Interestingly, the relative ratio of these forms varies in a tissue-specific manner. Other splice forms were also identified which may disrupt the structure of the C2 domain by removing its predicted C-terminal beta-strands. One splice form generates, through the introduction of a reading frame shift, a C2 domain-only form of WWP1. We discuss the hypothesis that regulation of splice site usage may modulate the activity of WWP1 and possibly other Nedd4 family proteins.
authors.affiliation: School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom.
authors.forename: Marzena
authors.initials: M
authors.lastname: Flasza
authors.forename: Patricia
authors.initials: P
authors.lastname: Gorman
authors.forename: Rebecca
authors.initials: R
authors.lastname: Roylance
authors.forename: Ann E
authors.initials: AE
authors.lastname: Canfield
authors.forename: Martin
authors.initials: M
authors.lastname: Baron
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D005091:Exons; D020224:Expressed Sequence Tags; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008025:Ligases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D000075702:Nedd4 Ubiquitin Protein Ligases; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D044767:Ubiquitin-Protein Ligases
chemical_list: D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D056827:Endosomal Sorting Complexes Required for Transport; D012333:RNA, Messenger; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C471642:WWP1 protein, human; D044767:Ubiquitin-Protein Ligases; D008025:Ligases