Aasland group

Functional annotation of proteins and protein domains

The majority of proteins have a modular architechture: they are composed of one or more globular domains and other more or less structured modules. Globular domains can often be associated with a particular molecular function. Therefore, functional annotation of individual proteins as well as whole proteomes relies, to a large extent, on prediction of globular domains and transfer of functional annotation by homology.

While there are several excellent tools and resources available for prediction of globular domains, there is a general lack of detail in the functional annotation of many of the domains. We are therefore developing a new computational resource for management and web-based dissemination of detailed functional annotation of proteins and protein domains.The resource, called CHRAB, is designed for use with chromatin associated proteins since this is the topic of research of our experimental group at the Department of Molecular Biology (MBI). CHRAB consists of a relational database for recording annotation as well as a globular domain prediction system based.

A second aerea of bioinformatics which is poorly developed is the prediction and annotation of functional sites in proteins: short linear motifs that are associated with molecular function. Functional sites are both biochemically hard to determine and bioinformatically hard to predict. The prediction problem stems from the fact that the functional sites are short (typically 5-10 residues) and many of them have evolved by mechanisms different from proteins and protein domains. Prediction of most functional sites therefore results in severe overprediction. To meet this challenge, we participate in the EU-funded ELM consortium which has developed a novel resource for improved prediction of functional sites. In ELM we combine traditional detection methods based on experimentally verified sites with contextual information that is used to evaluate the relevance of the predictions. The current version of ELM uses three aspects of context: the site must be in (i) a relevant cellular compartment; (ii) a relevant organism and (iii) it must be accessible and thus outside globular domains.

Please refer to my MBI home page for information on my molecular biological research interests and group at MBI.

Selected publications:

• Puntervoll P, Linding R, Gemund C, Chabanis-Davidson S, Mattingsdal M, et al., and Aasland R, Gibson TJ. (2003) ELM server: A new resource for investigating short functional sites in modular eukaryotic proteins. Nucleic Acids Res. 31:3625-3630.
• Brehm A, Tufteland KR, Aasland R, Becker PB. (2004) The many colours of chromodomains. BioEssays. 26:133-40.
• Conklin D, Jonassen I, Aasland R, Taylor WR. (2002) Association of nucleotide patterns with gene function classes: application to human 3' untranslated sequences. Bioinformatics. 18:182-189
• Gaullier JM, Simonsen A, D'Arrigo A, Bremnes B, Aasland R., Stenmark H, (1998) FYVE fingers bind PtdIns(3)P. Nature 394:432-433
• Aasland, R., Gibson, T. J., and Stewart, A. F. (1995). The PHD-finger: implications for chromatin-mediated transcriptional regulation. Trends Biochem. Sci. 20, 56-59.