Protein Sequence–Structure–Function–Network Links Discovered with the ANNOTATOR Software Suite: Application to ELYS/Mel-28

While very little genomic sequence is interpretable in terms of biological mechanism directly, the chances are much better for protein-coding genes that can be translated into protein sequences. This review considers the different concepts applicable to sequence analysis and function prediction of globular and non-globular protein segments. The publicly accessible ANNOTATOR software environment integrates most of the reliable protein sequence-based function prediction methods, protein domain databases and pathway, and protein–protein interaction collections developed in academia. As application example, the structural and functional domains of mel-28/ELYS, an important nuclear protein, are delineated and are proposed for experimental follow-up in structural biology and functional studies.