  In this paper we propose a straightforward operational definition of variants
of disordered proteins, taking the human proteome as a case study. The focus is
on a distinction between mostly unstructured proteins and proteins which
contain long unstructured regions accommodated in an overall folded structure.
In particular we distinguish: i) Not disordered proteins (NDPs), that either
have all their residues ordered or do not have disordered segments longer than
30 residues nor more than 30% of disordered residues; ii) Proteins with
intrinsically disordered regions (IDRPs), that have at least one disordered
domain longer than 30 residues, but disordered in less than 30% of their
residues; iii) Proteins that are intrinsically disordered (IDPs), that have
both at least one disordered segment longer than 30 residues and that are
disordered on more than 30% of their residues; iv) Proteins with fragmented
disorder (FRAG_IDPs), that do not have a disordered fragment longer than 30
residues but that, nevertheless, have at least 30% or more of their residues
predicted as disordered. The potential use of these variants is checked over
several groups of disease-related proteins. Our main conclusions point out that
IDRPs are more similar to NDPs than to IDPs. IDRPs and NDPs have a similar
functional repertoire and probably share a lock-and-key mechanism of
interaction with substrates. IDRPs and IDPs are differently present among human
disease-related proteins. IDRPs probably do not play a specific role in the
development of complex diseases, since their frequency is similar in
disease-related proteins and in the entire human proteome. IDPs can play a role
in the emergence of cancer, neurodegenerative, thyroid and liver disease.
