Characterization of the human UBE3B gene: Structure, expression, evolution, and alternative splicing

Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States
Genomics (Impact Factor: 2.28). 09/2003; 82(2):143-52. DOI: 10.1016/S0888-7543(03)00111-3
Source: PubMed


E3 ubiquitin ligases target proteins for degradation by adding ubiquitin residues. We characterized full-length cDNAs for human and mouse UBE3B, a novel HECT-domain E3 ligase, and analyzed the structure of human UBE3B on chromosome 12q24.1. Alternative splicing of exon 20 of UBE3B generated two major transcripts. The 5.7-kb mRNA lacked exon 20 and encoded a full-length protein ligase, variant 1 (UBE3B_v1). A second transcript contained a 97-bp insertion encoded by exon 20 that introduced an in-frame stop codon. The predicted protein (UBE3B_v2) would lack the HECT domain and would be nonfunctional, since the HECT domain constitutes the active site for ubiquitin transfer. No alternative splicing was observed in this region of mouse UBE3B. Elimination of the HECT domain by alternative splicing has not been reported in any genes encoding HECT domain ligases and may represent a novel mechanism in regulating intracellular levels of functional HECT-domain ligases.

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    • "Transcripts downregulated in blastomere- relative to the whole embryo-derived lines include UBE3B, that encodes a HECT-domain E3 ubiquitin ligase which targets proteins for degradation [33]; QK1 which product is RNA binding protein important for normal development in vertebrates and regulates protein translation, RNA splicing, export from the nucleus, and stability [34], [35]; PASK that encodes a PAS domain-containing protein kinase involved in regulation of many intracellular signaling pathways in response to both extrinsic and intrinsic stimuli [36] and RAB3B that encodes one of the Ras-associated GTP-binding protein 3 family members that regulates secretory vesicle transport between the Golgi apparatus and the plasma membrane [37]. "
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    • "Additionally, alternative splicing of exons 24 and 25 in HERC4 may result in altered binding to the ubiquitin conjugase, a further possibility for interfering with ubiquitin ligase activity. Alternative splicing was also recently reported for the HECT ubiquitin ligase UBE3B [27], but no functional consequences are known so far. It will be interesting to elucidate further the possible regulation of ubiquitin ligases by alternative splicing and find out its functional con- sequences. "
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