Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing

Xinping Yang, Jasmin Coulombe-Huntington, Shuli Kang, Gloria M. Sheynkman, Tong Hao, Aaron Richardson, Song Sun, Fan Yang, Yun A. Shen, Ryan R. Murray, Kerstin Spirohn, Bridget E. Begg, Miquel Duran-Frigola, Andrew MacWilliams, Samuel J. Pevzner, Quan Zhong, Shelly A. Wanamaker, Stanley Tam, Lila Ghamsari, Nidhi SahniSong Yi, Maria D. Rodriguez, Dawit Balcha, Guihong Tan, Michael Costanzo, Brenda Andrews, Charles Boone, Xianghong J. Zhou, Kourosh Salehi-Ashtiani, Benoit Charloteaux, Alyce A. Chen, Michael A. Calderwood, Patrick Aloy, Frederick P. Roth, David E. Hill, Lilia M. Iakoucheva, Yu Xia, Marc Vidal

Research output: Contribution to journalArticlepeer-review


While alternative splicing is known to diversify the functional characteristics of some genes, the extent to which protein isoforms globally contribute to functional complexity on a proteomic scale remains unknown. To address this systematically, we cloned full-length open reading frames of alternatively spliced transcripts for a large number of human genes and used protein-protein interaction profiling to functionally compare hundreds of protein isoform pairs. The majority of isoform pairs share less than 50% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other. Interaction partners specific to alternative isoforms tend to be expressed in a highly tissue-specific manner and belong to distinct functional modules. Our strategy, applicable to other functional characteristics, reveals a widespread expansion of protein interaction capabilities through alternative splicing and suggests that many alternative "isoforms" are functionally divergent (i.e., "functional alloforms").

Original languageEnglish (US)
Pages (from-to)805-817
Number of pages13
Issue number4
StatePublished - Feb 11 2016

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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