|CD154||CD40L, TNFSF5 (TNF superfamily, member 5 hyper-IgM sydrome), T-BAM, TRAP (TNF-related activation protein), gp 39|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Non-lineage Restricted Molecule|
Type 2 glycoprotein
|33 / 33|
|CD154 is expressed on B cells, macrophages, dendritic cells and on the surface of T cells. CD154 is not present on resting lymphocytes but is rapidly expressed on activation. It is present mostly on CD4+ cells and also on a small population of CD8+ T cells, gd T cells, mast cells, activated basophils, activated platelets, monocytes, NK cells and polymorphs. |
|MOLECULAR FAMILY NAME: Belongs to the tumor necrosis factor superfamily.|
CD154 is a multi-pass type-2 261 aa glycoprotein. It contains an extracellular domain which contains a C-terminal, a transmembrane domain and a cytoplasmic domain. The crystal structure of the extracellular region has confirmed the similarity to TNF with differences in loop regions predicted to be involved in binding 3 CD40 molecules. CD154 is biologically active as a membrane-bound molecule or as soluble multimers (probably homotrimers). The soluble forms of CD154 are produced as a result of intracellular cleavage by a matrix metalloproteinase in activated cells.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
CD154 is not O-glycosylated.
|LIGANDS AND MOLECULES ASSOCIATED WITH CD154|
CD154 binds to CD40, a member of the TNFR superfamily.
|CD154 is a co-stimulatory molecule and a regulator of the Th1 generation and function. CD154 regulates B cell function by engaging CD40 on the B cell surface. Ligation of CD154 and CD40 provides a survival signal to CD40+ B cells in germinal centers and is essential for immune responses and germinal center formation as well as Ig class switching. The CD40/CD154 complex mediates B cell proliferation in the absence of costimulus as well as IgE production in the presence of IL-4. Mutations in CD154 which abolish binding to CD40 cause the immunodeficiency disease, hyper-IgM syndrome which is characterized by lack of isotype switching in Ig production, lack of germinal centers and is associated with hyper-IgM syndrome. Activation of the CD40/CD154 pathway in nonimmune cells leads to the production of pro-inflammatory cytokines, matrix metalloproteases, prostaglandins and upregulation of adhesion molecules. There is evidence for a role for the CD154-CD40 interaction in negative selection and peripheral tolerance. Mice deficient in CD40 or CD154 have increased susceptibility to parasite infection pointing to a role in cell-mediated immunity as well as the humoral response.|
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD154 IN INTACT ANIMAL
Defects in CD154 are the cause of X-linked immunodeficiency with hyper-IgM type-1 (HIGM). Patients displaying elevated circulating levels of IgM and little or no IgG, IgA and IgE due to the inability of B cells to undergo class switiching in response to antigenic challenge. Additionally these patients display defective T and B cell memory responses to recall antigen and are susceptible to opportunistic infections. CD154 deficient mice display a similar phenotype to HIGM patients but additionally have depressed production of IFN-γ and IL-2. Elevated levels of CD154 are found in several autoimmune diseases including SLE, multiple sclerosis and inflammatory bowel diseases as well as athersosclerosis. The potential of CD154 as a therapeutic target in the treatment of these diseases has shown promise in animal models.
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD154: No information.
SUBSTRATE: No information.
ENZYMES WHICH MODIFY CD154: No information.
Database accession numbers
Revised June 25, 2008