SH2D1B Human

SH2 domain containing 1B (SH2D1B), also known as EAT-2 (EWS/FLI1-Activated Transcript 2), is a protein encoded by the SH2D1B gene in humans. This protein is a member of the SH2 domain-containing family, which plays a crucial role in intracellular signal transduction.

The SH2D1B gene is located on chromosome 1 and encodes a protein that contains a single SH2 domain. This domain is responsible for binding to phosphorylated tyrosine residues on other proteins, thereby modulating their function or activity . The SH2 domain is a structurally conserved protein domain found in many intracellular signal-transducing proteins .

SH2D1B is predominantly expressed in lymphoid tissues and bone marrow, where it is involved in cell proliferation and the innate immune response . It is also expressed in other tissues such as the testis, skeletal muscle, and various immune cells including NK cells and T cells .

SH2D1B functions as a cytoplasmic adapter protein that regulates receptors of the signaling lymphocytic activation molecule (SLAM) family, such as CD84, SLAMF1, LY9, and CD244 . It plays a significant role in the regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4 without affecting its tyrosine phosphorylation . Additionally, SH2D1B negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors .

By binding phosphotyrosines through its SH2 domain, SH2D1B regulates signal transduction through receptors expressed on the surface of antigen-presenting cells . In the context of NK cell-mediated cytotoxicity, SH2D1B stimulates the polarization of the microtubule-organizing center and cytotoxic granules toward the NK cell synapse .

Mutations or dysregulation of the SH2D1B gene have been associated with various diseases, including sarcoma and episodic ataxia, type 2 . Understanding the function and regulation of SH2D1B is crucial for developing therapeutic strategies for these conditions.