Prevalence and functional roles of intrinsic disorder in the [F-actin]-monooxygenase MICAL family members and their interactors

Members of the family of molecule interacting with CASL protein (MICAL) proteins play crucial roles in the cytoskeleton rearrangements by promoting depolymerization of F-actin via oxidation of the specific methionine residues to methionine-sulfoxides. These proteins also have multiple other functions and are related to the pathogenesis of various maladies. However, not much is known about the prevalence and functionality of intrinsically disordered regions in MICALs. To fill this gap, we conducted a comprehensive bioinformatics analysis of five human MICAL protein family members, MICAL1, MICAL2, MICAL3, MICAL-L1, and MICAL-L2, to assess their intrinsic disorder characteristics. We also focused on the top 10 most disordered interactors of these proteins. We utilized a set of bioinformatics tools, FuzDrop, RIDAO, InterPro, IuPred, STRING, AlphaFold, and UniProt, for the extensive analysis of these proteins. This analysis revealed that all five MICALs are highly disordered; they take part in myriad of cellular functions, and are also involved in pathogenesis of various diseases, such as neurodegeneration, cancer, and muscle dystrophy. Our study focused on the intrinsic disorder of these proteins to highlight important implications of disorder in protein functionality. These insights may help to find out potential therapeutic targets in biological processes controlled by MICAL proteins.