T-cell surface glycoprotein CD3 zeta chain

CD247
Identifiers
Aliases	CD247, CD3-ZETA, CD3H, CD3Q, CD3Z, IMD25, T3Z, TCRZ, CD247 molecule, CD3zeta
External IDs	OMIM: 186780; MGI: 88334; GeneCards: CD247
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1TCE, 1YGR, 2HAC, 2OQ1, 3IK5, 3IOZ, 4XZ1
Gene location (Human) Chr. Chromosome 1 (human) Band 1q24.2 Start 167,430,640 bp End 167,518,610 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1 H2.3|1 73.14 cM Start 165,616,250 bp End 165,704,846 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte thymus blood gonad lymph node spleen appendix testicle bone marrow bone marrow cell Top expressed in thymus mesenteric lymph nodes blood aortic valve ascending aorta tail of embryo spleen subcutaneous adipose tissue genital tubercle spermatid More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding transmembrane signaling receptor activity identical protein binding protein homodimerization activity protein tyrosine kinase binding Cellular component cytoplasm integral component of membrane alpha-beta T cell receptor complex plasma membrane T cell receptor complex membrane Biological process cell surface receptor signaling pathway mitigation of host defenses by virus T cell receptor signaling pathway Fc-gamma receptor signaling pathway involved in phagocytosis regulation of immune response viral process protein homotetramerization protein homotrimerization adaptive immune response immune system process interleukin-2 production positive regulation of protein localization to cell surface Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 919 12503 Ensembl ENSG00000198821 ENSMUSG00000005763 UniProt P20963 Q3UU54 P24161 RefSeq (mRNA) NM_000734 NM_198053 NM_001378515 NM_001378516 NM_001113391 NM_001113392 NM_001113393 NM_001113394 NM_031162 RefSeq (protein) NP_000725 NP_932170 NP_001365444 NP_001365445 NP_112439.1 NP_001106862.1 NP_001106862 NP_001106863 NP_001106864 NP_112439 Location (UCSC) Chr 1: 167.43 – 167.52 Mb Chr 1: 165.62 – 165.7 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

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.

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. 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.

Interactions

CD247 has been shown to interact with Janus kinase 3 and Protein unc-119 homolog.

See also

• Cluster of differentiation
• ZAP70

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.