Intrinsic protein disorder in human pathways

Abstract

We analyze human-specific KEGG pathways trying to understand the functional role of intrinsic disorder in proteins. Pathways provide a comprehensive picture of biological processes and allow better understanding of a protein's function within the specific context of its surroundings. Our study pinpoints a few specific pathways significantly enriched in disorder-containing proteins and identifies the role of these proteins within the framework of pathway relationships. Three major categories of relations are shown to be significantly enriched in disordered proteins: gene expression, protein binding and to a lesser degree, protein phosphorylation. Finally we find that relations involving protein activation and to some extent inhibition are characterized by low disorder content.

Fig 1

Distributions of disorder content among pathways (a) and proteins (b) for metabolic and non-metabolic pathways.

Fig 2

Bar plot showing an average disorder content in nodes and proteins for the top disorder containing metabolic (a) and non-metabolic pathways (b). Those pathways significantly enriched with disorder according to Fisher’s exact test with Holm–Bonferroni correction for multiple testing are shown by asterisks.

Fig 3

Diagram showing the disorder content of the nodes for the “Tight junction” (hsa04530) pathway, adapted from KEGG. Nodes are colored according to a gradient with 0% disorder colored green, 25% yellow, 50% orange, and 75% or higher red.