Moonlighting proteins perform multiple independent cellular functions within one polypeptide chain. Moonlighting proteins switch functions depending on various factors including the cell-type in which they are expressed, cellular location, oligomerization status and the binding of different ligands at different sites. Although an increasing number of moonlighting proteins have been experimentally identified in recent years, the quantity of known moonlighting proteins is insufficient to elucidate their overall landscape. Moreover, most moonlighting proteins have been identified as a serendipitous discovery. Hence, characterization of moonlighting proteins using bioinformatics approaches can have a significant impact on the overall understanding of protein function. In this work, we provide a short review of existing computational approaches for illuminating the functional diversity of moonlighting proteins.

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