Functional Sites in Proteins: analysis and annotation of five nuclear functional sites for the ELM resource

Abstract

Proteins are molecular tools which a cell expresses from specific genes, where the protein has one or several functions. An example of a protein function can be to detect a particular hormone, transporting itself to the nucleus and promoting transcription of other genes, as a response to the hormone signal. These three “actions” that the protein performs, can be narrowed down to regions inside the protein sequence. These regions are in this thesis termed functional units. In this example, one functional unit which recognizes the hormone, another unit which interacts with proteins that transport it to the nucleus and another unit which interacts with a DNA-bound protein, which results in transcription of target genes. Thus, several functional units defines the protein function. These functional units can be classified into different categories. One of these is functional sites.Functional sites are small linear subsequences in proteins which can be related to a biological function. Such a function may be modification sites like phosphorylation or protein-protein interactions sites like the LxCxE motif, which interacts with retinoblastoma proteins (Rbs). The problem with these sites is that they are so short, often not more then 3-5 amino acids in length. This implies an informatical problem when recognizing and predicting these short sites in protein sequences, which leads to a lot of hits and hence overprediction. The goal of the ELM project is to provide an Internet service for information retrieval and prediction of functional sites in proteins. The idea behind the ELM resource is to apply biological knowledge as context filters, and remove biological meaningless predictions, and thereby reducing the overprediction problem. For example, its meaningless to predict the LxCxE motif in extracellular proteins, since this functional site is only active inside the cell nucleus, where the Rbs are localized. During this thesis five functional site have been annotated into the ELM resource. These functional sites are: LxCxE, SID, RxL, PxDLS and PxVxL.