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Characterization of the human UBE3B gene: structure, expression, evolution, and alternative splicing small star, filled.

机译:人类UBE3B基因的特征:结构,表达,进化和可替代的剪接小星星。

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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.
机译:E3泛素连接酶通过添加泛素残基来降解目标蛋白。我们表征了人类和小鼠UBE3B,一种新型的HECT域E3连接酶的全长cDNA,并分析了人类UBE3B在12q24.1染色体上的结构。 UBE3B外显子​​20的选择性剪接产生了两个主要转录本。 5.7-kb mRNA缺少外显子20,编码全长蛋白质连接酶,变体1(UBE3B_v1)。第二个转录本包含由外显子20编码的97 bp插入,该插入引入了读框内终止密码子。预测的蛋白质(UBE3B_v2)将缺少HECT结构域,并且将不起作用,因为HECT结构域构成了泛素转移的活性位点。在小鼠UBE3B的此区域未观察到其他剪接。在编码HECT域连接酶的任何基因中,尚未报道过通过选择性剪接消除HECT域的现象,这可能代表了调节功能性HECT域连接酶细胞内水平的新机制。

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