Eukaryotic innate immune systems use pattern recognition receptors (PRRs) to sense infection by detecting pathogen-associated molecular patterns, which then triggers an immune response. Bacteria have similarly evolved immunity proteins that sense certain components of their viral predators known as bacteriophages1–6. Although different immunity proteins can recognize distinct phage-encoded triggers, individual bacterial immunity proteins have only been found to sense a single trigger, suggesting a one-to-one relationship between bacterial PRRs and their ligands7–11. Here, we demonstrate that the anti-phage defense protein CapRelSJ46 in Escherichia coli can directly bind and sense two completely unrelated and structurally different proteins using the same sensory domain, with overlapping but distinct interfaces. Here we tried to find the epitope between capRel and gp54 with HDX-MS.