CD154 CD40L, TNFSF5 (TNF superfamily, member 5 hyper-IgM sydrome), T-BAM, TRAP (TNF-related activation protein), gp 39
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 2 glycoprotein
Dendritic Cell
Lymphocyte
NK Cell
Mast Cell
Basophil
T Cell
Platelet
Monocyte
B Cell
Macrophage
33 / 33

Expression
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. 

Structure
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. 

 MOLECULAR MASS
Cell Type Unreduced Reduced
33 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD154 is not O-glycosylated.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD154

CD154 binds to CD40, a member of the TNFR superfamily.

Function
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. 

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD154: No information.

SUBSTRATE: No information.

ENZYMES WHICH MODIFY CD154: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 959P29965
MouseS21738P27548X65453
Antibodies
TRAP1   View Reactivity
YMF323.6.2   View Reactivity
YMF325.6A62   View Reactivity

Revised June 25, 2008


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