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FLASH GENE
Symbol TRADD contributors: mct/npt - updated : 10-07-2019
HGNC name TNFRSF1A-associated via death domain
HGNC id 12030
Location 16q22.1      Physical location : 67.188.088 - 67.193.812
Synonym name
  • tumor necrosis factor receptor type 1 associated death domain protein
  • tumor necrosis factor receptor-1-associated protein
  • Synonym symbol(s) MGC11078, Hs.89862
    DNA
    TYPE functioning gene
    STRUCTURE 5.72 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    DNCLI2 16q22.1 dynein, cytoplasmic, light intermediate polypeptide 2 FLJ35894 16q22.1 hypothetical protein FLJ35894 APPBP1 16q22 amyloid beta precursor protein binding protein 1, 59kDa CA7 16q22.1 carbonic anhydrase VII KIAA1348 CDH16 16q22.1 cadherin 16, KSP-cadherin RRAD 16q22 Ras-related associated with diabetes CGI-128 16q22.1-q22.3 CGI-128 protein CES2 16q22.1 carboxylesterase 2 (intestine, liver) FLJ21736 16q22.1 esterase 31 FLJ37464 16q22.1 hypothetical protein FLJ37464 CBFB 16q22.1 core-binding factor, beta subunit Lin10 16q22.1 lin-10 protein homolog MGC4655 16q22.1 hypothetical protein MGC4655 TRADD 16q22 TNFRSF1A-associated via death domain FBXL8 16q23.1 F-box and leucine-rich repeat protein 8 HSF4 16q21 heat shock transcription factor 4 NOL3 16qp21-q23 nucleolar protein 3 (apoptosis repressor with CARD domain) LOC283849 16q22.1 hypothetical protein LOC283849 E2F4 16q22.1 E2F transcription factor 4, p107/p130-binding ELMO3 16q23.1 engulfment and cell motility 3 (ced-12 homolog, C. elegans) FBXL9 16q23-q31 F-box and leucine-rich repeat protein 9 HSPC171 16q22.1 HSPC171 protein FHOD1 16q22 formin homology 2 domain containing 1 SLC9A5 16q22.1 solute carrier family 9 (sodium/hydrogen exchanger), isoform 5 DKFZP434I216 16q22.1 DKFZP434I216 protein FLJ40162 16q22.1 FLJ40162 protein FLJ11004 16q22.1 hypothetical protein FLJ11004 CGI-38 16q22.1 brain specific protein ZDHHC1 16q23.1 zinc finger, DHHC domain containing 1 HSD11B2 16q22 hydroxysteroid (11-beta) dehydrogenase 2 ATP6V0D1 16q22 ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d isoform 1 AGRP 16q22.1 agouti related protein homolog (mouse)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1496 34.1 312 - 2017 28765645
    5 - 1496 - 312 - 2017 28765645
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   highly
    Lymphoid/Immunelymph node   highly
     spleen   highly
    Nervousbrain   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an N-terminal TRAF binding domain and
  • a leucine zipper domains,
  • a conserved TRAF-C domain, required for self association (dimerization) and receptor binding, export sequences that cause shuttling between the cytoplasm and nucleus
  • a SXXE/D motifs found in the cytoplasmic domains of many TNFR family members and their adaptor proteins, that may serve to function as a specific interaction module for the alpha-helical death domain signal
  • a C terminal DEATH domain, comprising a coiled coil region, responsible for binding other DD-containing proteins including the p75 neurotrophin receptor (p75NTR)
  • mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY adaptor , signaling , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus,nucleoplasm,nuclear bodies,PML
    text
  • translocated to nucleus in the absence of export
  • TRADD shuttles dynamically from the cytoplasm into the nucleus to modulate the interaction between CDKN2A and its E3 ubiquitin ligase TRIP12, thereby promoting CDKN2A stability and tumour suppression
  • cytoplasmic TRADD translocates to DNA double-strand break sites (DSBs) during the DNA damage response (DDR)
  • basic FUNCTION
  • recruiting signaling molecules to the TNFRSF1A (TNFR1) complex
  • mediating programmed cell death apoptosis and activating NF-Kappa B distinctly
  • activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm (can regulate cell death independently of FADD and caspase-8 that occurs from the nucleus rather than the cytoplasm)
  • may be a critical player in the host antiviral and antibacterial response
  • plays an important role in TLR signaling via participation in TICAM1-dependent NFKB activation
  • biological function of TRADD in TNF signaling (
  • plays a survival role in TNFSF10 signaling
  • key effector protein of TNFR1 signaling
  • essential role of TRADD in DR3 (death receptor) signaling
  • has a survival role in TNFSF10 signaling and may be one potential target for overcoming TNFSF10 resistance in cancer therapy
  • oncogenic role for TRADD in glioblastoma multiforme (GBM)
  • FADD and TRADD proteins are important regulators of cell fate in mammalian cells
  • translocation of TRADD to DSBs into the nucleus contributes to cell survival in response to DNA damage through an activation of DNA damage repair
  • is an intracellular adaptor protein involved in various signaling pathways, such as antiapoptosis
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • heterodimerizing with TNFRSF1A
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • mediating ubiquination and degradation of TRADD
  • TRAF2, crucial for the suppression of apoptosis
  • TNFR1SA1
  • critical signaling mediator of TRAF3 that is required for TRAF3 to recruit and activate I-kappaB kinase beta (IKKbeta)
  • RPS3 appears to be recruited to the death-inducing signaling complex (DISC) to induce apoptosis by interacting TRADD in response to extracellular stresses
  • TRADD is an adapter molecule that bridges the interaction between TNFRSF1A and receptor-interacting serine/threonine-protein kinase 1 (RIPK1)
  • mediating, in connection with TRAF2, the entry of TRAF6 into the TRAF3 (oncogenic latent membrane protein 1 of the Epstein-Barr virus) complex
  • essential role for the adaptor protein TRADD in CASP8 activation and necrosome formation triggered by MAP3K7 inhibition
  • CFTR binds to and colocalizes with TRADD
  • by reducing the levels of TRADD, CFTR suppresses downstream proinflammatory NFKB1 signaling
  • is an adaptor for TNFRSF1A-induced apoptosis and NFKB1 activation
  • TRADD plays a more dominating role in NFKB1-signaling than RIPK1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    in Alzheimer disease
    constitutional     --over  
    in glomerulus and tubule of class III and IV lupus nephritis
    Susceptibility to ankylosing spondylitis
    Variant & Polymorphism SNP
  • rs9939768 and rs6979, associated with ankylosing spondylitis
  • Candidate gene
    Marker
  • increased expression of cytoplasmic TRADD is both an important biomarker and a key driver of NFKB1 activation in glioblastoma multiforme (GBM)
  • Therapy target
    SystemTypeDisorderPubmed
    immunologyinfectious 
    may contribute to the development of new therapeutic strategies against viral diseases
    ANIMAL & CELL MODELS
    morphologically normal, TRADD-deficient mice were resistant to toxicity induced by TNF, lipopolysaccharide and polyinosinic-polycytidylic acid