title: Sequence patterns mediating functions of disordered proteins.
abstract: Disordered proteins lack specific 3D structure in their native state and have been implicated with numerous cellular functions as well as with the induction of severe diseases, e.g., cardiovascular and neurodegenerative diseases as well as diabetes. Due to their conformational flexibility they are often found to interact with a multitude of protein molecules; this one-to-many interaction which is vital for their versatile functioning involves short consensus protein sequences, which are normally detected using slow and cumbersome experimental procedures. In this work we exploit information from disorder-oriented protein interaction networks focused specifically on humans, in order to assemble, by means of overrepresentation, a set of sequence patterns that mediate the functioning of disordered proteins; hence, we are able to identify how a single protein achieves such functional promiscuity. Next, we study the sequential characteristics of the extracted patterns, which exhibit a striking preference towards a very limited subset of amino acids; specifically, residues leucine, glutamic acid, and serine are particularly frequent among the extracted patterns, and we also observe a nontrivial propensity towards alanine and glycine. Furthermore, based on the extracted patterns we set off to infer potential functional implications in order to verify our findings and potentially further extrapolate our knowledge regarding the functioning of disordered proteins. We observe that the extracted patterns are primarily involved with regulation, binding and posttranslational modifications, which constitute the most prominent functions of disordered proteins.
authors.affiliation: Unit of Medical Technology and Intelligent Information Systems, Department of Materials Science and Engineering, University of Ioannina, Ioannina, Greece, kexarcho@gmail.com.
authors.forename: Konstantinos P
authors.initials: KP
authors.lastname: Exarchos
authors.forename: Konstantina
authors.initials: K
authors.lastname: Kourou
authors.forename: Themis P
authors.initials: TP
authors.lastname: Exarchos
authors.forename: Costas
authors.initials: C
authors.lastname: Papaloukas
authors.forename: Michalis V
authors.initials: MV
authors.lastname: Karamouzis
authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Fotiadis
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins