Behavioral Medicine

The phenomenon of protein moonlighting was discovered in the 1980s and 1990s, and the current definition of what constitutes a moonlighting protein was provided at the end of the 1990s. Since this time, several hundred moonlighting proteins have been identified in all three domains of life, and the rate of discovery is accelerating as the importance of protein moonlighting in biology and medicine becomes apparent. The recent re-evaluation of the number of protein-coding genes in the human genome (approximately 19000) is one reason for believing that protein moonlighting may be a more general phenomenon than the current number of moonlighting proteins would suggest, and preliminary studies of the proportion of proteins that moonlight would concur with this hypothesis. Protein moonlighting could be one way of explaining the seemingly small number of proteins that are encoded in the human genome. It is emerging that moonlighting proteins can exhibit novel biological functions, thus extending the range of the human functional proteome. The several hundred moonlighting proteins so far discovered play important roles in many aspects of biology. For example, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), heat-shock protein 60 (Hsp60) and tRNA synthetases play a wide range of biological roles in eukaryotic cells, and a growing number of eukaryotic moonlighting proteins are recognized to play important roles in physiologica