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CD154; CD40 ligand; CD40-L; T-cell antigen Gp39; TNF-related activation protein; TRAP; tumor necrosis factor ligand superfamily member 5 (CD40LG, CD40L TNFSF5, TRAP)
Function:
- delivers a contact-dependent signal that stimulates B-cell survival, growth & differentiation
- activation of CD40 by CD40L results in activation of bcl-x in B-cells inhibiting apoptosis [3]
- mediates B-cell proliferation without co-stimulus & IgE production in the presence of IL-4
- role in immunoglobulin class switching
- release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, & matrixmetalloproteinases (MMP) inhibitor-sensitive pathway
- soluble form derives from proteolytic processing
Structure:
- N-linked glycan is a mixture of high mannose & complex type
- glycan structure does not influence binding affinity to CD40
- not O-glycosylated
- homotrimer
- belongs to the tumor necrosis factor family
Compartment:
- cell membrane; single-pass type 2 membrane protein
- CD40 ligand, soluble form: secreted
Expression:
- specifically expressed on activated CD4+ T-cells
- CD40L is found on lymphoid follicle CD4+ T-cells
Pathology:
- defects in CD40L in humans is manifested in X-linked hyper IgM syndrome
General
cluster-of-differentiation antigen; cluster designation antigen; CD antigen
phosphoprotein
tumor necrosis factor (TNF) family protein
Properties
SIZE: entity length = 261 aa
MW = 29 kD
COMPARTMENT: cellular membrane
MOTIF: Thr phosphorylation site {T4}
transmembrane domain {23-46}
proteolytic site {112-113}
cysteine residue {C178}
MODIFICATION: cysteine residue {C218}
cysteine residue {C218}
MODIFICATION: cysteine residue {C178}
N-glycosylation site {N240}
References
- UniProt :accession P29965
- Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S,
Baltimore D.
Involvement of CRAF1, a relative of TRAF, in CD40 signaling.
Science. 1995 Mar 10;267(5203):1494-8.
PMID: 7533327
- Wang Z, Karras JG, Howard RG, Rothstein TL.
Induction of bcl-x by CD40 engagement rescues sIg-induced
apoptosis in murine B cells.
J Immunol. 1995 Oct 15;155(8):3722-5.
PMID: 7561075
- Entrez Gene :accession 959
- CD40Lbase; Note: CD40L defect database
http://bioinf.uta.fi/CD40Lbase/
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/CD40LG
Databases & Figures
OMIM correlations
MORBIDMAP 300386
UniProt P29965
Pfam PF00229
Entrez Gene 959
Kegg hsa:959
Physiologic Inhibitors of Apoptosis