What is Protein Moonlighting and Why is it Important

Moonlighting proteins exhibit more than one physiologically relevant biochemical or biophysical function within one polypeptide chain (Jeffery 1999). In this class of multifunctional proteins, the multiple functions are not due to gene fusions, multiple RNA splice variants or multiple proteolytic fragments. The moonlighting proteins do not include pleiotropic proteins, where a protein has multiple downstream cellular roles in different pathways or physiological processes that result from a single biochemical or biophysical function of a protein. Moonlighting proteins also do not include families of homologous proteins if the different functions are performed by different members of the protein family. Some of the first moonlighting proteins to be identified were taxon‐specific crystallins in the lens of the eye. These proteins, including the delta 2 crystallin/ arginosuccinate lyase in the duck (Wistow and Piatigorsky 1987), upsilon crystallin/lactate dehydrogenase A in the duckbill platypus (van Rheede et al. 2003), eta‐crystallin/cytosolic aldehyde dehydrogenase (ALDH class 1) in the elephant shrew (Bateman et al. 2003), and several others, are ubiquitous soluble enzymes that were adopted as structural proteins in the lens. Other well‐known moonlighting proteins include soluble enzymes in biochemical pathways that also bind to DNA or RNA to regulate transcription or translation. Human thymidylate synthase (TS), a cytosolic enzyme in the de novo synthesis of the DNA precursor thymidylate, also binds to mRNA encoding TS to inhibit translation (Chu et al. 1991). The Salmonella typhimurium PutA protein is an enzyme with proline dehydrogenase and proline oxidase pyrroline‐5‐carboxylic acid dehydrogenase activity when it is bound to the inner side of the plasma membrane (Menzel and Roth 1981a, b), but it also binds to DNA and moonlights as a transcriptional repressor of the put operon (Ostrovsky de Spicer et al. 1991; Ostrovsky de Spicer and Maloy 1993). The E. coli BirA biotin synthase is an enzyme in the biotin biosynthetic pathway that is also a bio operon suppressor What is Protein Moonlighting and Why is it Important?

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