EXON DUPLICATION AND DIVERGENCE IN THE HUMAN PREPROGLUCAGON GENE
EXON DUPLICATION AND DIVERGENCE IN THE HUMAN PREPROGLUCAGON GENE
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DOI：
10.1038/304368a0
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发表时间：
1983-01-01
期刊：
影响因子：
64.8
通讯作者：
NAJARIAN, RC
中科院分区：
文献类型：
--
作者：
BELL, GI;SANCHEZPESCADOR, R;NAJARIAN, RC
胰高血糖素是一种含有29个氨基酸的胰腺激素，通过刺激肝糖原分解和糖原合成1抵消胰岛素的降血糖作用。仓鼠胰高血糖素前体的结构最近已从克隆的cDNA 2的序列中确定。胰高血糖素前原是一种180个氨基酸的蛋白质，含有5个功能区：信号或前肽、NH 2末端肽（也称为胰高血糖素相关胰肽，GRPP）、胰高血糖素和两个羧基末端胰高血糖素样肽（GLP-1和GLP-2）。两种非等位琵琶鱼胰高血糖素受体的序列也已确定3 - 5，它们的组织与仓鼠蛋白相似但不相同;它们缺乏对应于仓鼠GLP-2的多肽片段。具有内部同源性的三个区域，即胰高血糖素，GLP-1和GLP-2，内胰高血糖素原的存在下，和GLP-2的情况下，在琵琶鱼前体表明，前胰高血糖素原基因的结构可能提供深入了解这种多聚蛋白的进化。我们已经分离并测序了人前胰高血糖素原基因，并在此报告，从该序列推断的人前体的组织与仓鼠蛋白相同。该基因含有至少三个间插序列，其将基因的蛋白质编码部分分成四个区域，对应于信号肽和部分NH 2-末端肽、NH 2-末端肽的剩余部分和胰高血糖素、GLP-1和GLP-2。这些数据表明，编码胰高血糖素或胰高血糖素样肽的外显子的三重化和随后的序列趋异产生了这种多蛋白前体。
Glucagon is a 29-amino acid pancreatic hormone which counteracts the blood glucose-lowering action of insulin by stimulating hepatic glycogenolysis and gluconeogenesis1. The structure of the hamster pancreatic glucagon precursor has recently been determined from the sequence of a cloned cDNA2. Hamster preproglucagon is a 180-amino acid protein which contains five functional regions; a signal or pre-peptide, an NH2-terminal peptide (also called glicentin-related pancreatic peptide, GRPP), glucagon, and two carboxy-terminal glucagon-like peptides (GLP-1 and GLP-2). The sequences of two non-allelic anglerfish pancreatic glucagon precursors3–5have also been determined and their organization is similar but not identical to the hamster protein; they lack the polypeptide segment corresponding to hamster GLP-2. The presence of three regions possessing internal homology, that is, glucagon, GLP-1 and GLP-2, within proglucagon, and the absence of GLP-2 in the anglerfish precursors suggests that the structure of the preproglucagon gene might provide insight into the evolution of this polyprotein. We have isolated and sequenced the human preproglucagon gene and report here that the organization of the human precursor deduced from this sequence is identical to the hamster protein. The gene contains at least three intervening sequences which divide the protein-coding portion of the gene into four regions corresponding to the signal peptide and part of the NH2-terminal peptide, the remainder of the NH2-terminal peptide and glucagon, GLP-1, and GLP-2. The data suggest that triplication and subsequent sequence divergence of an exon encoding glucagon or a glucagon-like peptide produced this polyprotein precursor.