Human SH2 Domain Containing 1B (SH2D1B) Protein

Background

SH2D1B, also known as EAT-2 (EWS-FLI1-activated transcript 2), is an SH2 domain-containing adaptor protein that regulates signaling pathways downstream of SLAM family receptors, particularly in innate immune cells like NK cells, macrophages, and dendritic cells. It binds to SLAM receptors and modulates their signaling, influencing NK cell cytotoxicity, macrophage activation, and cytokine production. SH2D1B promotes immune responses by enhancing IFN-γ production, immune synapse formation, and innate immune cell activation. It functions as a positive regulator of SLAM signaling, in contrast to SH2D1A, which can have inhibitory roles depending on context. Dysregulation of SH2D1B is associated with impaired innate immune responses, susceptibility to infections, and inflammatory disorders. Knockout studies reveal reduced NK cell function, impaired macrophage activation, and defective cytokine responses, highlighting its role in fine-tuning innate immunity and SLAM receptor signaling.