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Nucleic Acids Research 2005 33(8):2355-2363; doi:10.1093/nar/gki520
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Published online 28 April 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

Article

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

Mitsuteru Nakao1,2, Roberto A. Barrero3, Yuri Mukai2, Chie Motono2, Makiko Suwa2 and Kenta Nakai1,*

1Human Genome Center, Institute of Medical Science, University of Tokyo Tokyo, Japan 2Computational Biology Research Center, National Institute of Advanced Industry Science and Technology Tokyo, Japan 3Center for Information Biology and DNA Data Bank Japan, National Institute of Genetics Shizuoka, Japan

*To whom correspondence should be addressed. Tel: +81 3 5449 5131; Fax: +81 3 5449 5133; Email: knakai{at}ims.u-tokyo.ac.jp

Received November 18, 2004. Revised December 28, 2004. Accepted March 29, 2005.

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.


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