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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
Corresponding disease
HIGM1 immunodeficiency with hyper IgM, syndrome 1
Location Xq26.3      Physical location : 135.730.335 - 135.742.548
Synonym name
  • CD40 ligand on B cell
  • tumor necrosis factor (ligand) superfamily, member 5 (hyper-IgM syndrome)
  • T-B cell-activating molecule
  • CD40 ligand, membrane form
  • CD40 ligand, soluble form
  • TNF-related activation protein
  • Synonym symbol(s) CD40L, gp39, TNFSF5, RP3-527F8.3, CD154, HIGM1, IGM, IMD3, T-BAM, TRAP,
    DNA
    TYPE functioning gene
    STRUCTURE 12.21 kb     5 Exon(s)
    regulatory sequence Promoter
    Binding site   enhancer
    text structure
  • T-cell-specific transcriptional enhancer located just upstream of the promoter (
  • MAPPING cloned Y linked   status confirmed
    Map cen - HPRT1 - DXS10 - DXS177 - DXS144E - CD40LG - DXS1256 - DXS300 - DXS1041 - DXS1062 - DXS99 - DXS274 - qter
    Authors Pilia (94,97), Consensus (95)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - - - - - 2008 18849075
  • sCD40L production is blocked by Zn(2+)-dependent metalloproteinase inhibitors
  • role of sCD40L in numerous disease pathologies and having ability to activate proximal and distal immune responses
  • significantly higher expression in pre-eclampsia than in normal pregnant women
  • induces proliferation and migration of vascular smooth muscle cells (VSMCs) through activation of matrix metalloproteinases (MMPs)
  • 5 - 1840 - 261 - 2008 18849075
  • mCD40L
  • important immunoregulatory protein expressed by T cells, induced by the calcium
  • 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