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FLASH GENE
Symbol TNFRSF18 contributors: mct - updated : 11-05-2016
HGNC name tumor necrosis factor receptor superfamily, member 18
HGNC id 11914
Location 1p36.33      Physical location : 1.138.888 - 1.142.089
Synonym name
  • glucocorticoid induced tumor necrosis factor receptor family-related gene
  • TNF receptor superfamily activation-inducible protein
  • activation-inducible TNFR family receptor
  • Synonym symbol(s) AITR, GITR, GITR-D
    DNA
    TYPE functioning gene
    STRUCTURE 3.20 kb     5 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1214 - 241 - 2013 23892569
    Cell membrane; single-pass type I membrane protein
    4 - 1003 - 255 - 2013 23892569
    secreted protein
    5 - 1193 - 234 - 2013 23892569
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus    
     stomach    
    Lymphoid/Immunelymph node    
    Respiratoryrespiratory tracttrachea   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    Lymphoid/ImmuneT cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • extracellular N terminus
  • three extracytoplasmic cysteine-rich pseudorepeats typical for the TNFR superfamily (3 TNFR-Cys repeats)
  • with a preligand assembly domain (PLAD) in CRD1 mediating ligand-independent receptor assembly and signaling,
  • a small cytoplasmic tail
  • a DEATH domain
  • cytoplasmic C terminus, and it shares significant homology in the C-terminal domain with other members of the TNF receptor family
  • mono polymer homomer , trimer
    HOMOLOGY
    Homologene
    FAMILY tumor necrosis factor receptor superfamily
    CATEGORY receptor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text type 1 membrane protein
    basic FUNCTION
  • involved in regulation of T cell receptor-mediated cell death
  • may be involved in interactions between activated
  • T-lymphocytes and endothelial cells and in the regulation of T-cell receptor-mediated cell death
  • TNFRSF18, but also TNFSF18 is capable of transducing signals, and the consequences of TNFRSF18-TNFSF18 interaction may vary among different effector cell types, differ upon signal transduction via the receptor, the ligand, or both, depend on the level of an ongoing immune response
  • stimulation of TNFRSF18 on effector CD8 T cells results in high-avidity T cell responses to tumor-specific Ags, thereby inducing potent antitumor immunity in the absence of autoimmunity
  • dexamethasone-inducible molecule in T cells
  • ligation of TNFRSF18 had profound effects on kinase phosphorylation, surface receptor expression, suppressive activity, and cytokine production
  • TNFRSF18 is a coactivating receptor that is constitutively expressed on Treg cells and induced on activated T cells
  • contributes to TNFRSF9 expression on CD8 T cells upon their entry into the bone marrow (BM) or liver
  • TNFRSF4, TNFRSF18 play important roles in regulating activities of effector and regulatory T cells (Treg)
  • expressed on macrophages, drives cytokine release and T cell activation, resulting in neuropathic pain via TNFRSF18-dependent actions
  • is likely a crucial player in the differentiation of thymic Tregs (tTregs), and expansion of both tTregs and peripheral Tregs (pTregs)
  • TNFRSF18 co-stimulation mediates antitumor immunity by promoting TH9 cell differentiation and enhancing CTL responses
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • TNFRSF18 pathway activation abrogates tumor immune suppression through loss of regulatory T cell lineage stability
  • involvement of the TNFRSF18/TNFSF18 pathway in interactions with Epidermal keratinocytes (KCs) and Langerhans cells (LCs) and the migration of dendritic cells (DCs)
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds to TRAF1, TRAF2, and TRAF3, but not TRAF5 and TRAF6
  • receptor for TNFSF18
  • TRAF5 plays a crucial role in TNFRSF18-induced signaling pathways that augment T cell activation
  • TNFSF18 utilizes multiple oligomerization states to regulate TNFRSF18-mediated signaling during T cell costimulation
  • TNFRSF18/TNFSF18 system participates in the development of autoimmune/inflammatory responses and graft vs. host disease and potentiates response to infection and tumors
  • stimulation of nTregs through TNFRSF18 initiates a signaling cascade that involves MAP2K7, MAPK8 phosphorylation, JUN activation, and the activation of NFKB1
  • platelet-derived TNFSF18 mediates NK-inhibitory forward signaling via TNFRSF18
  • enhanced TNFRSF18/TNFSF18 interactions have a pleiotropic role on the regulation of T-cell responses, which includes promoting the differentiation of Tr-1-like cells, which contribute to the maintenance of peripheral T-cell tolerance
  • cell & other
    REGULATION
    Other expression in the TNFRSF18 locus is regulated by NFKB1 and FOXP3 through an enhancer
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in peripherical mononuclear cells after antigen stimulation/lymphocyteactivation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • should be considered as a marker for isolating Tregs
  • Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    TNFRSF18-TNFSF18 pathway might represent a novel target for the treatment of neuropathic pain
    ANIMAL & CELL MODELS
  • mice lacking the glucocorticoid-induced tumor necrosis factor receptor related protein (Gitr) exhibit defective CD8 T cell accumulation, increased T cell exhaustion and impaired viral control