Moonlighting Proteins

The ability of a protein to have multiple functions and be involved in different multi‐protein complexes or pathways can complicate the prediction of the protein function from sequence or structure and the annotation of sequence and structure databases. We are studying moonlighting proteins, a class of multifunctional proteins in which a single polypeptide chain has multiple biochemical functions that are not due to gene fusions, multiple splice variants or multiple proteolytic fragments. Many of the known moonlighting proteins are cytosolic enzymes that are also transcription factors, crystallins, chaperones, extracellular growth factors, or cell surface adhesins. The variety of known moonlighting proteins, the multiple ways in which one protein can have multiple functions, the potential benefits to the organism of combining two functions in one protein, and the methods proposed for a protein to evolve a second function suggest that moonlighting proteins might be common. To date, most moonlighting functions have been found by serendipity. There is currently no straightforward method to identify which proteins have moonlighting functions, or for determining if a protein of interest is a moonlighting protein. In addition, sequence homologues of moonlighting proteins often do not perform both functions. We are currently organizing information about the sequences, structures, functions and functional sites of the over 200 known moonlighting proteins with the goal of preparing an online, searchable database of moonlighting proteins