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FLASH GENE
Symbol TRAF3 contributors: mct/pgu - updated : 14-03-2017
HGNC name TNF receptor-associated factor 3
HGNC id 12033
Location 14q32.31      Physical location : 103.243.815 - 103.372.628
Synonym name
  • tumor necrosis factor (TNF)-receptor associated factor 3
  • latent membrane protein 1
  • CD40 associated protein 1
  • LMP1 associated protein
    • Synonym symbol(s) CRAF1, LMP1, LAP1, CAP-1, CD40bp, MIPT3, CAP-1, CAP1, IIAE5
    DNA
    TYPE functioning gene
    STRUCTURE 128.81 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure 10 exons coding
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 splicing 2567 64.5 568 - 1998 10199393
  • isoform 1
    • 11 splicing 2492 61.8 543 - 1998 10199393
  • lacking an in-frame coding segment compared to variant 1
  • isoform 2
    • 11 splicing 2428 64.5 568 - 1998 10199393
  • lacking a segment of 5' UTR
  • isoform 1
    		•
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon predominantly
     stomach   moderately
    Lymphoid/Immunelymph node   highly
     spleen   moderately
    Skin/Tegumentskin   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal RING zinc finger
  • a stretch of zinc fingers
  • a coiled coil leucine zipper domains
  • a C terminal TRAF domain, required for self association (dimerization) and receptor binding
    • conjugated ubiquitinated , sumoylated
    mono polymer homomer , heteromer , trimer
    HOMOLOGY
    interspecies homolog to rattus Traf3 (95.0pc)
    homolog to murine Traf3 (96.3pc)
    Homologene
    FAMILY
  • TNF receptor associated factor (TRAF) protein family
    • CATEGORY adaptor , regulatory , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • activating NFKB and JNK pathways
  • playing a role T-cell dependent immune responses
  • targeting NIK for degradation by the proteasome
  • serving as a critical link between TLR adaptors and downstream regulatory kinases important for IRF activation
  • being a major regulator of type I IFN production and the innate antiviral response
  • like MAVS, is required for type I interferon production in response to intracellular double-stranded RNA
  • oncoprotein encoded by the EBV and believed to play a role in transforming premalignant nasopharyngeal epithelial cells into cancer cells
  • negative regulator of LTBR signaling via NFKappaB pathways
  • can serve as a negative regulator of CD40 signaling
  • plays varied and cell type-specific, biological roles in TLR responses
  • negative regulator of IL17RA proximal signaling
  • importance of TRAF3-mediated cellular regulation via its cytoplasmic interactions with additional signaling proteins
  • potentially TRAF3 functioned as ubiquitin E3 ligase for calcineurin and promoted its degradation
  • is an important regulator of invariant natural killer T (iNKT) cell development and functions
  • enforces the requirement for T cell cross-talk in thymic medullary epithelial development (pMID: 24324158)
  • is a mediator of Treg cell function in the regulation of antibody responses, suggesting a role for TRAF3 in mediating ICOS expression in Treg cells
  • adapter protein that serves and regulates the functions of several types of receptors, located both inside the cell and at the plasma membrane
  • can serve distinct roles for different receptors in the same cell, and also has highly cell-type-dependent functions
  • regulates proliferation independent of the noncanonical NFKB pathway
  • is essential for continued PI3K/AKT and JAK/STAT signaling
  • role of TRAF3 and MAP3K14 in T cell malignancies, indicating that TRAF3 differentially governs the growth of B and T cell cancers
  • is broadly involved in different receptor-mediated signaling pathways
  • regulates signaling to T cells not only through costimulatory members of the TNFR superfamily, but also through the T cell receptor complex, and cytokine receptors
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS development , immunity/defense , inflammation
    text ectodermal diffentiation
    PATHWAY
    metabolism
    signaling signal transduction
    lymphotoxin beta R, signaling complex inducing NF-kappa B activation and cell death initiated by LT beta ligation
  • induction and regulation of apoptose
    • a component
  • heteromer with TRAF5
  • being a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex
    • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • tumor necrosis factor (TNF)-receptor 2 (TNFRSF1B)
  • the cytoplasmic tail of CD40 (TNFRSF5)
  • LMNA (lamin A/C)
  • LTBR/TNFRSF3
  • TNFRSF4
  • TNFRSF8/CD30
  • TNFRSF14/HVEM
  • TNFRSF17/BCMA
  • EDAR
  • Epstein-Barr virus BNFL1/LMP-1
  • MAP3K5
  • MAP3K14
  • TRAF-interacting protein TRIP
  • activates EIF2AK3 to induce phosphorylation of eIF2alpha, which upregulates activating transcription factor 4 (ATF4) expression
  • TNF receptor associated protein TTRAP
  • TANK/ITRAF
  • TRAF2
  • NIK
  • direct and specific interaction between the TRAF domain of TRAF3 and the TIM of MAVS is required for optimal MAVS-mediated antiviral responses
  • OTUB1 and -2 interacted with TRAF3 and TRAF6, two E3 ubiquitin ligases required for virus-triggered IRF3 and NF-kappaB activation, respectively
  • ZMYND11 directly interacted with TRAF3, a negative regulator of NF-kappaB activation
  • is a novel cellular interacting partner for Epstein-Barr virus-encoded oncoprotein, latent membrane protein 1 (TRAF3)
  • interacting with CD63 (CD63 is thus a critical mediator of TRAF3 function in- and outside-infected (tumour) cells)
  • TRAF domain of TRAF3 interacted with PPP3R1 0)
  • interaction between TRAF3 and RIPK2 (TRAF3 could inhibit RIPK2-induced NFKB1 activation)
  • in response to non-canonical NFKB stimuli, OTUD7B binds and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing aberrant non-canonical NFKB activation
  • its expression is negatively regulated by the full-length isoform of TRAF3 as formation of a MAP3K14-TRAF3-TRAF2 complex targets MAP3K14 for degradation
  • NMRAL1 interacted with TRAF3 and inhibited its ubiquitination by promoting the recruitment of OTUB1 to TRAF3
  • DOK3 was shown to bind TRAF3, and the binding of TRAF3 and TBK1 to DOK3 required the tyrosine-rich C-terminal domain of DOK3
  • NEDD4 constitutively interacts with CD40 and mediates K63-linked ubiquitination of TRAF3
  • WDR82 interacts with TRAF3, and its overexpression promotes K48-linked, but not K63-linked, polyubiquitination on TRAF3
  • TRAF3 deficiency that led to induction of two proteins important for glucose metabolism, SLC2A1 and HK2
  • TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals mediated by TNFSF13B receptor
    • cell & other
    REGULATION
    Other recruited by XEDAR in a EDA-A2 dependent fashion
    regulated by TANK/ITRAF which competes with TNFRSF5/CD40 for binding
    is post-translationally modified by the small ubiquitin-related modifier (SUMO)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    higher both in patients with Crohn disease and ulcerative colitis than in healthy controls
    constitutional       loss of function
    suffices to metabolically reprogram B cells, a finding that improves our understanding of the role of TRAF3 as a tumor suppressor
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS