Physiocrines are a recently elucidated class of endogenous human proteins that function as extracellular signaling molecules in a variety of physiologic settings.
Physiocrine proteins are derived from tRNA synthetases, an ancient and well understood family of enzymes, which function inside cells to produce proteins during RNA translation. In a surprising discovery, aTyr Pharma’s founders from the Schimmel-Yang laboratory at The Scripps Research Institute determined that in certain regulated settings specific fragments of tRNA synthetases were found functioning extracellularly as signaling molecules. These Physiocrines are produced by several mechanisms, including alternative splicing and site-specific proteolytic cleavage.
aTyr Pharma has determined that Physiocrines are a very large family of proteins, with few similarities across the class. Individual Physiocrine proteins vary across many dimensions, including:
- Physiological Source: Physiocrines are not ubiquitously expressed, but rather individual Physiocrine family members are found in specific cell or tissue types; or are only found in certain physiological states (e.g. after acute tissue injury)
- Receptor Interaction: Physiocrines bind and signal specifically via a wide range of receptor type. Individual Physiocrine proteins have been found to bind and signal through GPCRs and TM1 receptors, for example. In some instances these Physiocrine ligands are the first endogenous ligands for previously identified receptors of pharmaceutical interest.