Large-scale analysis of human alternative protein isoforms: pattern classification and correlation with subcellular localization signals

Large-scale analysis of human alternative protein isoforms: pattern classification and correlation with subcellular localization signals
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DOI:
10.1093/nar/gki520
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发表时间:
2005-01-01
影响因子:
14.9
通讯作者:
Nakai, K
Nakai, K
中科院分区:
生物学2区
文献类型:
--
作者:
Nakao, M;Barrero, RA;Nakai, K

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我们基于全长cDNA克隆和SwissProt研究了>2600基因的人类替代蛋白同工型。我们对同种异构体进行了分类,并检查了每个基因的共现性。此外,我们研究了这些变化与不同亚细胞定位之间的潜在关系。两种最丰富的模式是具有不同c端区域的模式和具有内插入的模式,共占总数的43%。虽然n端区域的变化比c端区域的变化少,但c端区域的延伸比n端区域的延伸要少得多,这可能是因为在一个同工异构体中很难去除终止密码子。我们还发现在不同的同工异构体中有一些经常使用的共现组合。我们将此解释为存在某种结构关系的证据,这种关系产生了一系列同形模式。最后,许多终端变化被预测会导致亚细胞定位的差异,特别是针对过氧化物酶体或线粒体。我们的研究揭示了人类蛋白质组通过选择性剪接和相关事件的富集。我们的替代蛋白质异构体数据库可通过互联网获得。
We investigated human alternative protein isoforms of >2600 genes based on full-length cDNA clones and SwissProt. We classified the isoforms and examined their co-occurrence for each gene. Further, we investigated potential relationships between these changes and differential subcellular localization. The two most abundant patterns were the one with different C-terminal regions and the one with an internal insertion, which together account for 43% of the total. Although changes of the N-terminal region are less common than those of the C-terminal region, extension of the C-terminal region is much less common than that of the N-terminal region, probably because of the difficulty of removing stop codons in one isoform. We also found that there are some frequently used combinations of co-occurrence in alternative isoforms. We interpret this as evidence that there is some structural relationship which produces a repertoire of isoformal patterns. Finally, many terminal changes are predicted to cause differential subcellular localization, especially in targeting either peroxisomes or mitochondria. Our study sheds new light on the enrichment of the human proteome through alternative splicing and related events. Our database of alternative protein isoforms is available through the internet.