SH2 domain containing 1A Protein

Background

SH2D1A, also known as SAP (SLAM-associated protein), is an SH2 domain-containing adaptor protein that regulates signaling pathways downstream of SLAM (Signaling Lymphocyte Activation Molecule) family receptors. It is predominantly expressed in T cells, NK cells, and other immune cells, where it plays a crucial role in immune cell activation, cytotoxicity, and cytokine production. SH2D1A binds to the cytoplasmic tails of SLAM receptors, modulating T-cell receptor (TCR) signaling, NK cell activation, and germinal center formation. Mutations or deletions in SH2D1A cause X-linked lymphoproliferative syndrome (XLP), a severe immunodeficiency characterized by uncontrolled lymphocyte proliferation, impaired antibody responses, and susceptibility to Epstein-Barr virus (EBV) infections. SH2D1A also regulates immune synapse formation and T-cell-B-cell interactions, ensuring proper immune homeostasis. Knockout studies reveal defects in immune cell activation, abnormal germinal center development, and impaired antiviral responses, underscoring its essential role in immune regulation.