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FLASH GENE
Symbol CD40LG contributors: npt/mct - updated : 04-11-2015
HGNC name CD40 ligand (TNF superfamily, member 5, hyper-IgM syndrome)
HGNC id 11935
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessels     Homo sapiens
Lymphoid/Immunethymus    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier/lining   
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticplatelet Homo sapiens
Cardiovascularendothelial cell Homo sapiens
Lymphoid/Immunemacrophage
Lymphoid/ImmuneT cell
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES fibrous ,globular
STRUCTURE
motifs/domains
  • four cysteine rich domains (CRDs)
  • a transmembrane domain
  • a signaling intracellular C-terminus
  • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY
  • tumor necrosis factor family
  • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text
  • type II transmembrane protein
  • expressed on the surface of activated CD4+ T cells
  • basic FUNCTION
  • involved in Ig class switching
  • potentially involved in pathogenic cytokine production in inflammatory bone disease
  • IgE production in presence of IL-4
  • playing a regulatory role in bone mineralization, in (regulating bone mass and in osteoclastogenesis
  • its expression on B cells prematurely terminated their ongoing germinal center response and produced plasma cells
  • costimulatory molecule expressed on T cells, and is also expressed and functional on platelets
  • platelet CD40LG plays a pivotal role in atherosclerosis, not only by affecting platelet-platelet interactions but especially by activating leukocytes, thereby increasing platelet-leukocyte and leukocyte-endothelium interactions
  • activation of CD40 by CD40LG plays a crucial role for the development and progression of a variety of inflammatory processes including atherosclerosis
  • is a thrombo-inflammatory molecule that predicts cardiovascular events
  • sCD40LG/CD40 axis triggers NFKB1 activation in platelets
  • soluble CD40LG is an important inducer of the NFKB1 signaling pathway activation in platelets independently of the MAPK14 pathway
  • IL21 and CD40LG collaborate through at least two distinct mechanisms to synergistically promote PRDM1 activation and plasma cells (PCs) differentiation
  • activation of CD40 on B cells, macrophages, and dendritic cells by its ligand CD40LG is essential for the development of humoral and cellular immune responses
  • may contribute directly to atherogenesis by activating endothelial cells and recruiting monocytes to them
  • soluble form of CD40LG(sCD40LG), which results from the shedding of membrane-bound CD40LG, plays a key role in the production of proinflammatory cytokines and has been linked to various autoimmune and vascular disorders
  • CD40-induced signalling through ligation with its natural ligand (CD40LG) is dependent on recruitment of TRAF molecules to the cytoplasmic domain of the receptor
  • role of sCD40LG in foam cell formation during atherosclerosis, which further confirms the importance of sCD40LG in atherosclerosis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • inducing tissue factor F3 in endothelial cells, under the mediation of AP1, NF-kappa B, EGR1
  • can influence RANKL signaling through T cell priming
  • CD40/CD40LG interaction induces E-selectin dependent adhesion of leukocytes to human endothelial cells and reduces endothelial cell migration by inhibiting the Akt/eNOS signaling pathway
  • in platelets, soluble CD40LG induces association of CD40 with its adaptor protein the TNFR associated factor 2 and triggers phosphorylation of CHUK
  • NFKB1 signaling pathway, which involves both NFKBIA and CHUK, plays an important role in platelet CD40 signaling, activation and aggregation in response to sCD40LG
  • is released from T-cells by ADAM10 and ADAM17 upon CD40 ligation
  • RAC1 controls surface mobilization of CD40LG on activated platelets and MMP9 secretion from neutrophils
  • may bind concomitantly to two receptors of the same or different family, and biologically activate cells expressing both receptors
  • novel role of SPAG9 scaffold protein in the bridging of CD40LG-triggered CD40 internalization and CD40-dependent signaling in splenic B lymphocytes
  • cell & other
    REGULATION
    Other cleaved by ADAM-10 protease to generate sCD40L
    ASSOCIATED DISORDERS
    corresponding disease(s) HIGM1
    related resource CD40Ldefectdatabase
    Susceptibility to Kawasaki disease with coronary artey lesions
    Variant & Polymorphism SNP in intron 4 associated with Kawasaki dsease with coronary artey lesions
    Candidate gene
    Marker
  • biomarker for the diagnosis of prostatic inflammation in benign prostatic hyperplasia
  • Therapy target
    ANIMAL & CELL MODELS