CD247 TCRζ (T cell receptor ζ-chain), CD3-ζ (Part of CD3 family)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
T Cell
NK Cell
16 / 16

Expression
CD247 is expressed on CD3-CD56+CD16+ NKcells during thymopoiesis and on all T cells in the periphery.

Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin gene superfamily.

CD247 is a single-pass type-1 143 aa glycoprotein.  It contains a 21 aa signal sequence, a 9 aa extracellular domain which contains no glycosylation sites, a 21 aa transmembrane domain and a cytoplasmic domain containing 3 immunoreceptor tyrosine-based activation motifs (ITAMs).  CD247 dimers form part of the T-cell receptor (TCR)-CD3 complex in T cells.  This complex consists of T cell receptor α/β or γ/δ heterodimers associated with three distinct dimers: CD3γ/ε, CD3δ/ε and CD3ζ/ζ (CD247).  Each of these dimers associates with a specific basic residue in the TCR transmembrane region.  Assembly of CD247 dimer into the complex requires the interaction of aspartic acid residues in the CD247 TM with arginine in the TM of TCRα or TCRδ.


MOLECULAR MASS 
Cell Type Unreduced Reduced
16 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.

POST-TRANSLATIONAL MODIFICATION

CD247 is phosphorylated on Tyr residues after T cell receptor triggering.  The ζ chain is nonglycosylated and exists in the T-cell receptor as a disulfide-linked homodimer.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD247

CD247 is a component of the CD3/TCR complex.  Phosphorylated ITAM motifs of the CD3 and z chains bind to SH2 domains of intracellular signaling molecules. 
Phosphorylated z chains bind to ZAP-70.


Function
CD247 forms a dimeric transmembrane signaling molecule that is associated with the TCR-CD3 complex and is essential for the activation of T cells.  CD247, the T-cell receptor z, together with T-cell receptor a/b and g/d heterodimers and CD3-g, -d, and -e, forms the complex.  TCR ligation results in phosphorylation of the ITAM motifs of by tyrosine kinases Lck and Fyn.  After phosphorylation, Sky family kinases ZAP-70 and Sky are recruited and activated, ultimately leading to NK-κB activation and translocation to the nucleus and T cell  activation.  The T cell activation is self-limiting and downregulation of TCR triggering involves loss of CD247 probably via internalization and degradation of TCR chains including CD247.  The z chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways.  Low expression of the antigen results in the impaired immune responses.  CD3ζ forms either homodimers or heterodimers with CD3-η.  Interaction is with SLA and SLA2, with DOCK2 and TRAT1, and with HIV-1 nef protein.  Recognition of the antigen leads to recognition and signal transduction mediated by the invariant chains and subsequently T cell activation.  Ligation of CD43 in T cells and NK cells can lead to CD247 phosphorylation and recruitment to the CD43 signaling pathway.  CD2 and CD16 (FcγRIII) can associate with CD247 in NK cells. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD247 IN INTACT ANIMAL

Reduced expression of CD247 in tumor-infiltrating lymphocytes is strongly correlated with progressive disease in gastric carcinoma and a defective expression is found in a large proportion of patients with autoimmune diseases.  Chronic antigenic stimulation via TCRs can result in prolonged or permanent downregulation of CD247 expression.  This has been observed in patients with AIDS, cancer, leprosy and SLE in which there are circulating immune complexes.  Expression of CD247 is decreased in CD4+ and CD8+ cells of some patients with cancer and correlates with poor prognosis and survival.


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD247: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD247: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntezgene 919P20963
Antibodies
G3   View Reactivity

Revised June 25, 2008


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