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FLASH GENE
Symbol TRAF5 contributors: mct/npt - updated : 08-09-2017
HGNC name TNF receptor-associated factor 5
HGNC id 12035
Location 1q32.3      Physical location : 211.499.956 - 211.548.284
Synonym name
  • tumor necrosis factor (TNF)-receptor-associated factor 5
  • RING finger protein 84
  • Synonym symbol(s) RNF84, MGC:39780
    DNA
    TYPE functioning gene
    STRUCTURE 48.36 kb     11 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 3988 - 557 - 1997 9126477
    11 - 3988 - 557 - 1997 9126477
    11 - 4013 - 557 - 1997 9126477
    11 - 4046 - 568 - 1997 9126477
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines follicular dendritic 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
  • HOMOLOGY
    Homologene
    FAMILY
  • TRAF family
  • CATEGORY adaptor , signaling cytokine
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    basic FUNCTION
  • activating NFKB through the cytoplasmic domain of CD40 (TNFRSF5), modulating its activity
  • regulate diverse physiological roles, ranging from T and B cell signaling and inflammatory responses to organogenesis and cell survival (Au 2007)
  • important positive signaling element that enhances T cell expansion and pathogen containment by providing a survival advantage to responding Ag-specific CD8(+) T cells during infection (Kraus 2008)
  • implicated in several biological roles in T-lymphocyte responses (Kraus 2009)
  • major requirement for TRAF5 in signaling by a specific receptor, as well as playing an important role in biological function in B lymphocytes (Kraus 2009)
  • possible function for TRAF5 in mediating the activation of IRF3 and NF-kappaB downstream of MAVS through the recruitment of IKBKG
  • is a negative regulator of TLR signaling
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text B cell proliferation
    PATHWAY
    metabolism
    signaling signal transduction
    CD40/TNFRSF5 pathways leading to NF-kappa B activation and protecting against cell DEAT
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CD30 in NF-kappa B activation interaction
  • TRAF5 plays a crucial role in TNFRSF18-induced signaling pathways that augment T cell activation
  • related ubiquitin ligase TRAF5 is a downstream target of MAVS that mediates both IRF3 and NF-kappaB activation
  • NUMBL interacted directly with TRAF5, which signals upstream and is required for the activation of NFKB, and committed it to proteasomal degradation by promoting K48-linked polyubiquitination of TRAF5
  • TRAF5 negatively regulated the association of TAB2 with its signaling partner TRAF6 after TLR ligation in B cells
  • is a negative regulator of the IL6R signaling pathway that limits the induction of proinflammatory CD4(+) T cells that require IL6 for their development
  • TRAF5, known as an E3 ubiquitin protein ligase and signal transducer, interacts with and ubiquitinates RORC via Lys-63-linked polyubiquitination, and stabilizes the RORC protein level depending on its RING finger domain
  • increasing TRAF5 ameliorates nonalcoholic fatty liver by blocking MAPK8 activity
  • TRAF5 binds to the signal-transducing receptor IL6ST through the C-terminal TRAF domain and inhibits Th17 development mediated by IL6
  • cell & other
  • interacting with the lymphotoxin beta receptor (LTBR) to IL18 interaction, NF-kappa B dependent
  • REGULATION
    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
    Susceptibility
  • to Behçet disease and Vogt-Koyanagi-Harada syndrome (VKH)
  • Variant & Polymorphism SNP
  • rs6540679, rs12569232, rs10863888 of TRAF5 significantly associated with Behçet disease and VKH syndrome
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetemetabolic syndrom 
    represents a potential therapeutic target for obesity-related metabolic disorders
    ANIMAL & CELL MODELS
    defect in CD40 (TNFRSF5) and CD27 (TNFRSF7) in murine Tra5(-/-)