ABSTRACT
Cancer proteins have an elevated level of predicted disorder, as demonstrated by comparing disorder in four protein datasets: human cancer-associated proteins (HCAP), signaling proteins collected by the Alliance for Cellular Signaling (AfCS), eukaryotic proteins from SwissProt, and non-homologous protein segments with well-defined 3-D structures (Iakoucheva et al. 2002). HCAP contain significantly more disorder than proteins in the other datasets, with 79 ± 5%, 66 ± 6%, 47 ± 4%, and 13 ± 4% of the proteins in HCAP, AfCS, SwissProt, and ordered datasets having at least one IDR ≥30 consecutive residues (see Figure 15.1). In addition, only 17.3% of the cancer-associated proteins have sequence alignments with structures in the Protein Data Bank (PDB) covering at least 75% of their lengths, which also points to the prevalence of disorder in the HCAP dataset. The correlation is underscored by some intrinsically disordered proteins (IDPs) involved in cancer, which are among the best characterized proteins for both structural disorder and pathophysiological function. These cases also demonstrate the complexity of the structure-function relationship of modular IDPs.
