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.[5]
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.[6]
Gene
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.[7]
Function
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.[8] Absence of the ζ chain results in a failure of exocytosis and direction of the other receptor components to lysosomes for degradation.[8]
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).[9] 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,[10] 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.
Interactions
CD247 has been shown to interact with Janus kinase 3[11] and Protein unc-119 homolog.[12]
See also
References
- GRCh38: Ensembl release 89: ENSG00000198821 – Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000005763 – Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- Weissman AM, Hou D, Orloff DG, Modi WS, Seuanez H, O'Brien SJ, et al. (December 1988). "Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex". Proceedings of the National Academy of Sciences of the United States of America. 85 (24): 9709–9713. Bibcode:1988PNAS...85.9709W. doi:10.1073/pnas.85.24.9709. PMC 282845. PMID 2974162.
- Clayton LK, D'Adamio L, Howard FD, Sieh M, Hussey RE, Koyasu S, et al. (June 1991). "CD3 eta and CD3 zeta are alternatively spliced products of a common genetic locus and are transcriptionally and/or post-transcriptionally regulated during T-cell development". Proceedings of the National Academy of Sciences of the United States of America. 88 (12): 5202–5206. Bibcode:1991PNAS...88.5202C. doi:10.1073/pnas.88.12.5202. PMC 51840. PMID 1828894.
- "Entrez Gene: CD247 CD247 molecule".
- Weissman AM, Frank SJ, Orloff DG, Merćep M, Ashwell JD, Klausner RD (December 1989). "Role of the zeta chain in the expression of the T cell antigen receptor: genetic reconstitution studies". The EMBO Journal. 8 (12): 3651–3656. doi:10.1002/j.1460-2075.1989.tb08539.x. PMC 402047. PMID 2583115.
- Dushek O, Goyette J, van der Merwe PA (November 2012). "Non-catalytic tyrosine-phosphorylated receptors". Immunological Reviews. 250 (1): 258–276. doi:10.1111/imr.12008. PMID 23046135.
- Hwang JR, Byeon Y, Kim D, Park SG (May 2020). "Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development". Experimental & Molecular Medicine. 52 (5): 750–761. doi:10.1038/s12276-020-0435-8. PMC 7272404. PMID 32439954.
- Tomita K, Saijo K, Yamasaki S, Iida T, Nakatsu F, Arase H, et al. (July 2001). "Cytokine-independent Jak3 activation upon T cell receptor (TCR) stimulation through direct association of Jak3 and the TCR complex". The Journal of Biological Chemistry. 276 (27): 25378–25385. doi:10.1074/jbc.M011363200. PMID 11349123.
- Gorska MM, Stafford SJ, Cen O, Sur S, Alam R (February 2004). "Unc119, a novel activator of Lck/Fyn, is essential for T cell activation". The Journal of Experimental Medicine. 199 (3): 369–379. doi:10.1084/jem.20030589. PMC 2211793. PMID 14757743.
Further reading
- Geyer M, Fackler OT, Peterlin BM (2001). "Structure--function relationships in HIV-1 Nef". EMBO Reports. 2 (7): 580–585. doi:10.1093/embo-reports/kve141. PMC 1083955. PMID 11463741.
- Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (2004). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". Journal of Biosciences. 28 (3): 323–335. doi:10.1007/BF02970151. PMID 12734410. S2CID 33749514.
- Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects". Current HIV Research. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID 16454711.
External links
- CD247+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human CD247 genome location and CD247 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P20963 (Human T-cell surface glycoprotein CD3 zeta chain (CD247)) at the PDBe-KB.