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FLASH GENE
Symbol TRAF2 contributors: mct/ - updated : 09-07-2016
HGNC name TNF receptor-associated factor 2
HGNC id 12032
Location 9q34.3      Physical location : 139.780.964 - 139.821.066
Synonym name
  • tumor necrosis factor (TNF)- receptor-associated factor 2
  • tumor necrosis factor type 2 receptor associated protein 3
  • E3 ubiquitin-protein ligase TRAF2
  • Synonym symbol(s) TRAP3, TRAP, MGC:45012, KIAA0551, TNIK
    DNA
    TYPE functioning gene
    STRUCTURE 40.10 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D9S159 - ABCA2 - TRAF2 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 2298 55 501 - 2009 18827186
    - - 2107 - 447 - 2009 18827186
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveintestinesmall intestine  highly
    Lymphoid/Immunespleen   highly
     thymus   highly
    Nervousbrain    
    Reproductivefemale systemuteruscervix highly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta weakly
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal RING zinc finger
  • a stretch of zinc fingers
  • a (coiled coil) leucine zipper domain
  • C-terminal tumor necrosis factor receptor-associated factor (TRAF) domain TRAF-C domain, required for self association (dimerization) and receptor binding
  • conjugated ubiquitinated
    mono polymer homomer , heteromer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • TRAF family
  • CATEGORY adaptor , signaling cytokine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • involved in both IL1B and TNF/alpha signaling cascades, implicated in TNFR-mediated NF-kappa B activation in association with JNK (MAPK8)
  • regulate diverse physiological roles, ranging from T and B cell signaling and inflammatory responses to organogenesis and cell survival
  • potential mediator of CD40 (TNFRSF5) and TNFR2 (TNFRSF1B), CD30 (TNFRSF7) signaling
  • adaptor protein that regulates the activation of the c-Jun N-terminal kinase (JNK) and IKB kinase (IKK) signaling cascades in response to tumor necrosis factor alpha
  • TRAF2 expression and subsequent degradation are required for the differentiation of monocytes into fully functional macrophages
  • necessary for the polyubiquitination of receptor interacting protein 1 (RIPK1) that then serves as a platform for recruitment and stimulation of IKBKE, leading to activation of the transcription factor NFKB
  • expression of MINK1 and TRAF2 in neurons is required for normal dendritic arborization and surface expression of AMPA receptors
  • inhibits TNF-induced cell death but promotes oxidative stress-induced apoptosis
  • TRAF2 phosphorylation is essential for cell survival under conditions of oxidative stress
  • TRAF2 and CARD11 serve as keystones for formation of the full TNFRSF4 signalosome and for allowing NFkB activation by TNFRSF4 in T cells
  • adaptor protein which involves in the activation of the transcription factor, nuclear factor kappaB (NFKB1), in the tumor necrosis factor (TNF) receptor pathway
  • APPL1 synergized with TRAF2 to induce NFKB activation, and both proteins were necessary for this process and function upstream of the IKK complex
  • TRAF2 operates directly as an E3 ligase to tag DISC1-activated CASP8 with a K48-ubiquitin-based proteasomal shutoff timer
  • role for TRAF2-dependent CASP8 ubiquitination as a gatekeeper for extrinsic apoptosis activation in mammalian cells
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • NF-kappa N, JNK pathways
  • RNF13 is likely a critical mediator for facilitating ER stress-induced apoptosis through the activation of the ERN1-TRAF2-JNK signaling pathway
  • a component
  • homodomerizing or heterodimerizing with TRAF1 or BIRC2
  • TRAF2/MAP3K14/NFKB2 pathway regulates pancreatic ductal adenocarcinoma (PDAC) cell tumorigenicity
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • mediating in connection with TRADD, the entry of TRAF6 into the LMP1 (oncogenic latent membrane protein 1 of the Epstein-Barr virus)-complex
  • implicated in TNF mediated activation of (NF kappaB) in association with MAPK8
  • recruiting BIRC2, BIRC3 to TNFR2 (TNFRSF1B)
  • TRAF3
  • interacting with TNFSF14 and LTBR (plays a critical, nonredundant role in TNFSF14-LTBR signaling)
  • E3 ubiquitin ligase SMURF2 is a TRAF2 binding protein
  • interacting with SMURF2 and TNFRSF1B (SMURF2-induced TNFRSF1B ubiquitination and subcellular relocalization of TNFRSF1B and TRAF2 enables the specific activation of the JNK pathway)
  • rapidly binds to the IFNAR1 subunit of the IFN receptor upon IFN binding (role of TRAF2 binding to the type I interferon receptor in alternative NF kappaB activation and antiviral response)
  • MAPKBP1 interacted with not only NR2C2, but also with its upstream regulators, TNF-receptor associated factors 2 and 6 (TRAF2 and TRAF6)
  • binds to sphingosine kinase 1 (SPHK1), one of the isoenzymes that generates the pro-survival lipid mediator sphingosine-1-phosphate (SGPP1) inside cells
  • intracellular target of SGPP1
  • interacting wiuth TRPC4AP (region between AAs 249 and 440 is also important for the interaction between TRPC4AP and TRAF2)
  • STUB1 regulates NFKB1-mediated cell invasion via the down-regulation of TRAF2
  • BIRC2, BIRC3 and the adaptor protein TRAF2 interacted with caspase-1-containing complexes
  • interacting with USP4 that is a deubiquitinase targeting TRAF2 and TRAF6 for deubiquitination
  • TRAF2-mediated ubiquitin shutoff timer that inactivates CASP8 to exert crucial control over cell-extrinsic apoptosis
  • RAD23A down-regulated TRAF2 protein level through ubiquitin–proteasome system
  • overexpression of TRAF2 augmented the cytoplasmic expression of TRAF4 which promoted cell proliferation and inhibited cell apoptosis by activating NFKB nuclear transcription)
  • TRAF2 is critical for either TNFRSF1A- or TNFRSF1B-mediated activation of NFKB and mitogen-activated protein kinase (MAPK) signaling, as well as for target gene expression
  • TNFSF12 inhibits TRAF2-mediated CD40 signaling by destabilization of CD40 signaling complexes
  • its expression is negatively regulated by the full-length isoform of TRAF3 as formation of a MAP3K14-TRAF3-TRAF2 complex targets MAP3K14 for degradation
  • HACE1 is essential for the ubiquitylation of the adaptor protein TRAF2 and formation of the apoptotic CASP8 effector complex
  • HOXA1 binds RBCK1 and TRAF2 and modulates the TNF/NFKB1 pathway in a transcription-independent manner
  • XAF1 interacts with TRAF2 and inhibits TRAF2-dependent NFKB1 activation, in part, by blocking TRAF2 polyubiquitination
  • TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals mediated by TNFSF13B receptor
  • cell & other
    REGULATION
    Phosphorylated by MAP4K4 that directly phosphorylates TRAF2, leading to its lysosomal degradation and subsequent inhibition of IL6 production
    Other degrated and ubiquitinated by BIRC2
    phosphorylation at ser 11 (involved in the regulation for the TNFalpha-induced activation of the JNK and IKK signaling pathway)
    STUB1 overexpression promoted the ubiquitination of TRAF2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in glomerulus and tubule of class III and IV lupus nephritis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerendocrinepancreas
    TRAF2/MAP3K14/NFKB2 pathway could be a valuable target for therapy of this cancer
    ANIMAL & CELL MODELS