Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098). In addition to this role of signal transduction in T-cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface (PubMed:8187769). Indeed, constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3G. The TCR-CD3 complex is composed of a CD3D/CD3E and a CD3G/CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha/CD3E/CD3G and TCRbeta/CD3G/CD3E trimers. In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta. A di-leucine motif and a tyrosine-based motif are individually sufficient to induce both endocytosis and delivery to lysosomes. Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8 (PubMed:2470098). Phosphorylated also by PKC; leading to the TCR complex down-regulation (PubMed:8187769). Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8. The disease is caused by variants affecting the gene represented in this entry. CD3G mutation db CD3 receptor entry