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FLASH GENE
Symbol TRAF4 contributors: mct/npt/pgu - updated : 21-11-2014
HGNC name TNF receptor-associated factor 4
HGNC id 12034
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon  
 intestinesmall intestine  highly
 stomach   highly
Nervousbrain     Mus musculus
Reproductivefemale systembreastmammary gland   Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
Epithelialsecretoryglandularendocrine  Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousneuron Mus musculus
Nervousoligodendrocyte Mus musculus
Reproductiveepithelial cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text trachea, axial skeleton, neurulation
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal RING zinc finger followed by a stretch of zinc fingers
  • a (coiled coil)leucine zipper domains
  • a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs
  • a C terminal TRAF domain, required for self association (dimerization) and receptor binding, which mediates interaction with target receptors and effectors
  • secondary structure additional flexible loop (residues 421-426), which contains a previously identified phosphorylated site S426 exposing on the surface
    HOMOLOGY
    interspecies ortholog to murine Traf
    Homologene
    FAMILY
  • TRAF family
  • CATEGORY adaptor , signaling cytokine
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
        intracellular
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus
    text
  • remaining in the cytoplasm following DNA damage
  • consistently found at TJs in normal mammary epithelia as well as in well-differentiated in situ carcinomas
  • highly mobile and shuttles between TJs and the cytoplasm
  • predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), but it accumulates in the cytoplasm of malignant MECs
  • basic FUNCTION
  • involved in embryonic development
  • may be involved in the oxidative activation of MAPK8/JNK
  • may play a role in TP53-mediated proapoptotic signaling in the response to cellular stress
  • participates in the molecular mechanism underlying silencing of TLR-mediated signaling through the interaction with molecules harboring phagosome/endosome membrane
  • playing an oncogenic role
  • implicated in one of the emerging TJ-dependent signaling pathways that responds to cell polarity by regulating the cell proliferation/differentiation balance, and subsequently epithelium homeostasis
  • new functions for TRAF4 as a SMURF1-regulated mediator of BMP and Nodal signaling that are essential for neural crest development and neural plate morphogenesis
  • inhibits NOD2-induced NFKB activation and directly binds to NOD2 to inhibit NOD2-induced bacterial killing
  • acts in a TNF receptor- and Jun N-terminal protein kinase (JNK)-independent manner to fine-tune the assembly of adherens junctions in the invaginating mesodermal cells
  • pivotal contribution of TRAF4 to myelination and to cerebellar homeostasis, and the loss of TRAF4 function is linked to demyelinating or neurodegenerative diseases
  • may play an important role in the activation of NFKB1 via TRAF2
  • is required for efficient TGFB-induced migration, epithelial-to-mesenchymal transition, and breast cancer metastasis
  • acts as a negative regulator of TJ and increases cell migration
  • participates in several signaling pathways, such as NFKB and JNK signaling pathways
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • as a silencer in TLR-mediated signaling through the association with TRAF6 and TICAM1
  • common target of TP53 family members and localization of TRAF4 is associated with differentiation of squamous cell carcinoma of the head and neck cells
  • interacts with the kinase domain of MAP3K4 (MAP3K4 is the MAPK kinase kinase for TRAF4 regulation of the JNK pathway)
  • is a new target of SMURF1, which polyubiquitylates TRAF4 to trigger its proteasomal destruction
  • is a novel binding partner of GP6 and GP1BB in human platelets
  • key negative regulator of NOD2 signaling
  • binding to NOD2, is required for TRAF4 phosphorylation and subsequent inhibition of NOD2 signaling
  • interacting with TRAF2 (overexpression of TRAF2 augmented the cytoplasmic expression of TRAF4 which promoted cell proliferation and inhibited cell apoptosis by activating NFKB nuclear transcription)
  • can regulate the TGFB pathway and is a key determinant in breast cancer pathogenesis
  • TRAF4 mediated the translocation of CTNNB1 from the cytoplasm to the nucleus, thereby facilitating activation of the Wnt signaling pathway in breast cancer
  • cell & other
    REGULATION
    activated by NFKB in T cells
    Other regulated by p53 in response to temperature sensitive p53, overexpression of p53 by use of an adenovirus, and stabilization of p53 in response to DNA damage
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in metastatic axillary lymph nodes primary breast cancer
    tumoral     --over  
    in lung adenocarcinomas
    tumoral     --over  
    might contribute to breast cancer progression by destabilizing TJs and favoring cell migration
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    TRAF4 offers a candidate molecular target for lung cancer prevention and therapy
    ANIMAL & CELL MODELS
  • TRAF4 deficient mice to display impaired neural tube closure,axial skeleton malformations and tracheal ring disruption
  • TRAF4-deficient mice (TRAF4-KO) exhibit altered locomotion coordination typical of ataxia