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CD40LG

OverviewProducts

Function

Cytokine that acts as a ligand to CD40/TNFRSF5 (PubMed:1280226, PubMed:31331973). Costimulates T-cell proliferation and cytokine production (PubMed:8617933). Its cross-linking on T-cells generates a costimulatory signal which enhances the production of IL4 and IL10 in conjunction with the TCR/CD3 ligation and CD28 costimulation (PubMed:8617933). Induces the activation of NF-kappa-B (PubMed:15067037, PubMed:31331973). Induces the activation of kinases MAPK8 and PAK2 in T-cells (PubMed:15067037). Induces tyrosine phosphorylation of isoform 3 of CD28 (PubMed:15067037). Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL4 (By similarity). Involved in immunoglobulin class switching (By similarity).

CD40 ligand, soluble form

Acts as a ligand for integrins, specifically ITGA5:ITGB1 and ITGAV:ITGB3; both integrins and the CD40 receptor are required for activation of CD40-CD40LG signaling, which have cell-type dependent effects, such as B-cell activation, NF-kappa-B signaling and anti-apoptotic signaling.

Involvement in disease

Immunodeficiency with hyper-IgM, type 1

HIGM1

Immunoglobulin isotype switch defect characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including Pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

The soluble form derives from the membrane form by proteolytic processing.

N-linked glycan is a mixture of high mannose and complex type. Glycan structure does not influence binding affinity to CD40.

Not O-glycosylated.

Sequence similarities

Belongs to the tumor necrosis factor family.

Tissue specificity

Specifically expressed on activated CD4+ T-lymphocytes.

Cellular localization

  • Cell membrane
  • Single-pass type II membrane protein
  • Cell surface
  • CD40 ligand, soluble form
  • Secreted
  • Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and a matrix metalloproteinases (MMP) inhibitor-sensitive pathway.

Alternative names

  • CD40 ligand
  • CD40-L
  • T-cell antigen Gp39
  • TNF-related activation protein
  • Tumor necrosis factor ligand superfamily member 5
  • TRAP
  • TRAP
  • TNFSF5
  • CD40L
  • CD40LG

Database links

Target type

Proteins

Primary research area

Immuno-oncology

Other research areas

  • Immunology & Infectious Disease

Molecular weight

29274Da