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Description

T-cell surface glycoprotein CD3 zeta chain (UniProt: P20963, also known as T-cell receptor T3 zeta chain, CD247) is encoded by the CD247 (also known as CD3Z, T3Z, TCRZ) gene (Gene ID: 919) in human. CD3 zeta is a single-pass type I membrane protein that is synthesized with a signal peptide (aa 1-21), which is subsequently cleaved off to generate the mature form that contains a short extracellular domain (aa 22-30), a transmembrane domain (aa 31-51), and a cytoplasmic domain (aa 52-164). CD3 zeta is expressed in normal lymphoid tissues and in peripheral blood mononuclear cells (PBMC). It is a part of the TCR-CD3 complex that is present of the surface of T-cells and 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 various CD3 chains (CD3D, CD3E, CD3G and CD3Z). These chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. The ITAM motifs CD3 zeta are localized to amino acids 61-89, 100-128, and 131-159. These motifs are reported to be phosphorylated by Src family protein tyrosine kinases Lck and Fyn, resulting in the activation of downstream signaling pathways. In CD3 zeta, phosphorylation of ITAMs by Lck is reported to be an initial step in the transduction of signaling cascades. It creates multiple docking sites for protein kinase ZAP70, which is also phosphorylated by Lck. Phosphorylation of ZAP70 converts it into a catalytically active form. It is reported that CD3 zeta phosphorylation can also be promoted by ZAP70 and TCR-induced zeta phosphorylation is shown to be defective in ZAP70-deficient T-cells.