Conervation of OFD1 Protein Motifs Implications for Discovery of Novel Interactors

OFD1 is a protein involved in many cellular processes, including cilia biogenesis, mitotic spindle assembly, translation, autophagy and repair of double-strand DNA breaks. Despite many potential interactors identified in high-throughput studies, only few have been directly confirmed and their binding sites identified.We performed analysis of the evolutionary conservation of OFD1 sequence in 80 Tetrapoda, 144 Vertebrata or 26 Animalia species, and identified 59 protein-binding motifs localized in the OFD1 regions conserved in various clades. Our results indicate that OFD1 is tightly regulated by posttranslational modifications (PTM) and may also regulate other proteins: it contains 14 potential PTM sites targeted by at least eight protein kinases, 7 motifs bound by proteins recognizing phosphorylated aa residues, as well as a binding site for phosphatase 2A. Moreover, OFD1 harbors both, a motif that enables its phosphorylation by mitogen-activated protein kinases (MAPKs), and a docking site specific for these proteins. Generally, our results suggest that OFD1 forms a scaffold for interaction with many proteins and is tightly regulated by post-translational modifications and ligands. Future research on OFD1 should focus on regulation of OFD1 function and localization.