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Alternative splice variants encoding unstable protein domains exist in the human brain
Keiichi Homma1, Reiko F Kikuno, Takahiro Nagase
1Laboratory of Gene-Product Informatics, Center for Information Biology-DNA Data Bank of Japan, National Institute of Genetics, Research Organization of Information and Systems, Shizuoka 411-8540, Japan.
Journal of Molecular Biology
|October 20, 2004
Summary
Alternative splicing can alter protein structures, sometimes disrupting protein domains. Many unstable splice variants are less abundant and may represent evolutionary dead-ends.
Area of Science:
- Molecular Biology
- Genomics
- Protein Structure
Background:
- Alternative splicing increases protein diversity without expanding genome size.
- Understanding structural changes from alternative splicing is crucial for medical implications.
- Many alternative splice variants are linked to disease.
Purpose of the Study:
- To systematically examine protein structures encoded by alternative splice variants.
- To analyze structural changes in proteins derived from long human brain cDNAs.
- To investigate the relationship between alternative splicing and protein structural domains.
Main Methods:
- Analysis of the HUGE protein database.
- Focus on reliable alternative splice junctions from long human brain cDNAs (>4 kb).
- Comparison of splice junction locations with SCOP domain boundaries.
Main Results:
- Alternative splice junctions tend to align with SCOP domain boundaries.
- Some alternative splicing events use protein structural units as cassettes.
- 50 cases showed SCOP domains disrupted by alternative splicing.
- Six cases involved insertions at the molecular surface, potentially affecting protein function.
- Eleven cases produced pairs of stable and unstable proteins.
Conclusions:
- Alternative splicing can disrupt protein domains, with some variants encoding unstable proteins.
- Unstable protein variants are less abundant and may lack normal function.
- These unstable proteins might be evolutionary dead-ends, especially those not conserved in non-primate species.