T-cell surface glycoprotein CD3 zeta chain also known as T-cell receptor T3 zeta chain or CD247 (Cluster of Differentiation 247) is a protein that in humans is encoded by the CD247 gene.
Some older literature mention a similar protein called "CD3 eta" in mice. It is now understood to be an isoform differing in the last exon.
The gene is located on the long arm of chromosome 1 at location 1q22-q25 on the Crick (negative) strand. The encoded protein is 164 amino acids long with a predicted weight of 18.696 kiloDaltons.
Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.
T-cell receptor zeta (ζ), together with T-cell receptor αβ or γδ heterodimers and CD3 γ, δ, and ε units, forms the T-cell receptor-CD3 complex. The ζ chain appears in this complex as a disulfide-linked homodimer and appears to be necessary for the assembly of T-cell receptor components in the endoplasmic reticulum and trafficking to the plasma membrane in an adaptor protein-like manner. Absence of the ζ chain results in a failure of exocytosis and direction of the other receptor components to lysosomes for degradation.
The ζ chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. Propagation of the T-cell receptor intracellular signaling cascade relies on cytosolic phosphorylation of tyrosine residues within conserved Immunoreceptor Tyrosine-based Activation Motif (ITAM) domains by Src family kinases to produce binding sites for other, downstream proteins (e.g., SH2 proteins, including ZAP-70). The cytoplasmic tails of each CD3 γ, δ, and ε chain contain one such domain, while those of each ζ chain contain three. Thus, a total of six out of ten ITAMs on each T-cell receptor are found on the ζ chains. Given that the quantity of signaling through the T cell receptor conveys important information that determines such cellular responses as survival during selection, anergy, and functional avidity maturation, the signaling function of the ζ chain cannot be considered redundant despite the presence of ITAMs on the other chains. Low expression results in an impaired immune response.
CD247 has been shown to interact with Janus kinase 3 and Protein unc-119 homolog.
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