ProSAS: a database for analyzing alternative splicing in the context of protein structures

Abstract

Alternative splicing is known to be one of the major sources for functional diversity in higher eukaryotes. Several splicing isoforms have been characterized in the literature that play important roles in cellular processes like apoptosis or signal transduction pathways. Splicing events can often be detected on the mRNA level by large-scale cDNA or EST experiments and such data is collected and annotated in several databases. Nevertheless, the effects of splicing on the structure of a protein are largely unknown. The ProSAS (Protein Structure and Alternative Splicing) database fills this gap and provides a unified resource for analyzing effects of alternative splicing events in the context of protein structures. ProSAS comprehensively annotates and models protein structures for several Ensembl genomes as well as SwissProt entries harbouring splicing events. Alternative isoforms annotated in Ensembl or SwissProt can be analyzed on the protein structure and protein function level using an intuitive user interface that provides several features and tools for a structure-based analysis of alternative splicing events. The ProSAS database is freely accessible at http://www.bio.ifi.lmu.de/ProSAS.

Figure 1.

Database content and annotation pipeline. Gene and alternative transcript information is obtained from the Ensembl database as well as from SwissProt. Additional information comes from InterPro patterns and orthologs are mapped by Ensembl database using BioMart. Protein structures from the PDB are annotated to transcripts using SIMAP and several structural features are computed using SCOP, PDP and DSSP annotations. Other data like the (structural) variance in the corresponding protein family will be added in the future (Other methods). Affymetrix probesets are mapped onto transcripts and genes.

Figure 2.

Details for gene ENSMUSG00000006611_13 from mouse showing all exons of the gene as well as different transcripts annotated for the gene in Ensembl. Matches of InterPro patterns and Affymetrix probesets onto exons are also shown.

Figure 3.

Transcript details view for transcript ENSMUST00000091706_13 from gene ENSMUSG00000006611_13. The structure of the transcript is visualized with Jmol (Jmol: an open-source Java viewer for chemical structures in 3D. http://www.jmol.org/) and the difference with respect to transcript ENSMUST00000091707_13, namely the deletion of a larger N-terminal part is visualized on the structure. The alternatively spliced region is characterized with respect to different features such as solvent accessibility or secondary structure content.