BACKGROUND: Analyzing the amino acid sequence of an intrinsically disordered 
protein (IDP) in an evolutionary context can yield novel insights on the 
functional role of disordered regions and sequence element(s). However, in the 
case of many IDPs, the lack of evolutionary conservation of the primary sequence 
can hamper the study of functionality, because the conservation of their 
disorder profile and ensuing function(s) may not appear in a traditional 
analysis of the evolutionary history of the protein.
RESULTS: Here we present DisCons (Disorder Conservation), a novel pipelined tool 
that combines the quantification of sequence- and disorder conservation to 
classify disordered residue positions. According to this scheme, the most 
interesting categories (for functional purposes) are constrained disordered 
residues and flexible disordered residues. The former residues show conservation 
of both the sequence and the property of disorder and are associated mainly with 
specific binding functionalities (e.g., short, linear motifs, SLiMs), whereas 
the latter class correspond to segments where disorder as a feature is important 
for function as opposed to the identity of the underlying sequence (e.g., 
entropic chains and linkers). DisCons therefore helps with elucidating the 
function(s) arising from the disordered state by analyzing individual proteins 
as well as large-scale proteomics datasets.
CONCLUSIONS: DisCons is an openly accessible sequence analysis tool that 
identifies and highlights structurally disordered segments of proteins where the 
conformational flexibility is conserved across homologs, and therefore 
potentially functional. The tool is freely available both as a web application 
and as stand-alone source code hosted at http://pedb.vib.be/discons .