A Census of Human Methionine-Rich Prion-like Domain-Containing Proteins

Methionine-rich prion-like proteins can regulate liquid–liquid phase separation processes in response to stresses. To date, however, very few proteins have been identified as methionine-rich prion-like. Herein, we have performed a computational survey of the human proteome to search for methionine-rich prion-like domains. We present a census of 51 manually curated methionine-rich prion-like proteins. Our results show that these proteins tend to be modular in nature, with molecular sizes significantly greater than those we would expect due to random sampling effects. These proteins also exhibit a remarkably high degree of spatial compaction when compared to average human proteins, even when protein size is accounted for. Computational evidence suggests that such a high degree of compactness might be due to the aggregation of methionine residues, pointing to a potential redox regulation of compactness. Gene ontology and network analyses, performed to shed light on the biological processes in which these proteins might participate, indicate that methionine-rich and non-methionine-rich prion-like proteins share gene ontology terms related to the regulation of transcription and translation but, more interestingly, these analyses also reveal that proteins from the methionine-rich group tend to share more gene ontology terms among them than they do with their non-methionine-rich prion-like counterparts.