Verification of alternative splicing variants based on domain integrity, truncation length and intrinsic protein disorder

H. Hegyi, L. Kalmár, Tamas Horvath, Peter Tompa

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

According to current estimations ∼95 of multi-exonic human protein-coding genes undergo alternative splicing (AS). However, for 4000 human proteins in PDB, only 14 human proteins have structures of at least two alternative isoforms. Surveying these structural isoforms revealed that the maximum insertion accommodated by an isoform of a fully ordered protein domain was 5 amino acids, other instances of domain changes involved intrinsic structural disorder. After collecting 505 minor isoforms of human proteins with evidence for their existence we analyzed their length, protein disorder and exposed hydrophobic surface. We found that strict rules govern the selection of alternative splice variants aimed to preserve the integrity of globular domains: alternative splice sites (i) tend to avoid globular domains or (ii) affect them only marginally or (iii) tend to coincide with a location where the exposed hydrophobic surface is minimal or (iv) the protein is disordered. We also observed an inverse correlation between the domain fraction lost and the full length of the minor isoform containing the domain, possibly indicating a buffering effect for the isoform protein counteracting the domain truncation effect. These observations provide the basis for a prediction method (currently under development) to predict the viability of splice variants. The Author(s) 2010. Published by Oxford University Press.2010This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Original languageEnglish
Pages (from-to)1208-1219
Number of pages12
JournalNucleic Acids Research
Volume39
Issue number4
DOIs
Publication statusPublished - Mar 2011

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Alternative Splicing
Protein Isoforms
Proteins
Licensure
RNA Splice Sites
Reproduction
Amino Acids

ASJC Scopus subject areas

  • Genetics

Cite this

Verification of alternative splicing variants based on domain integrity, truncation length and intrinsic protein disorder. / Hegyi, H.; Kalmár, L.; Horvath, Tamas; Tompa, Peter.

In: Nucleic Acids Research, Vol. 39, No. 4, 03.2011, p. 1208-1219.

Research output: Contribution to journalArticle

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