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FLASH GENE
Symbol TANK contributors: mct/npt/pgu - updated : 02-11-2015
HGNC name TRAF family member-associated NFKB activator
HGNC id 11562
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a negatively acting C terminus
  • HOMOLOGY
    interspecies homolog to murine Tank
    Homologene
    FAMILY
  • TRAF family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • mediator of NFKB activation after induction by TRAF2
  • essential for the efficient induction of IRF-dependent transcription, as are two further TBK1 adaptors, AZI2 and TBKBP1
  • TANK with AZI2 or TBKBP1 assemble TBK1 and IKKE complexes
  • required for the TBK1- and IKKepsilon-mediated IRF3/7 phosphorylations through some Toll-like receptor-dependent pathways and is part of a TRAF3-containing complex
  • dispensable role for the early phase of double-stranded RNA-mediated IRF3 phosphorylation
  • may be a critical adaptor that regulates the assembly of the TANK-binding kinase 1-inducible IkappaB kinase complex with upstream signaling molecules in multiple antiviral pathways
  • negative feedback regulator of osteoclastogenesis and osteoblastogenesis
  • TANK is critical for osteoclastogenesis by regulating NFKB1, and is also important for proper bone remodeling
  • inhibits the bone resorption activity of bone marrow-derived osteoclasts
  • negatively regulate the ubiquitination of TRAF proteins, and TANK serves as an important negative regulator of NFKB1 signaling cascades induced by genotoxic stress
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • TANK formed a complex with ZC3H12A and a deubiquitinase, USP10, which was essential for the USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NFKB1 activation upon DNA damage
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding and sequestering to the TRAF C domain of TRAF1, TRAF2, TRAF3 thereby inhibiting TRAF signaling pathway
  • associating with IKBG, with subsequent connection of IKK complexes with IKBE and IKB1 resulting
  • MARCH5 catalyzes the K63-linked poly-ubiquitination of TANK, thus impairing the ability of TANK to inhibit TRAF6
  • negatively regulates TRAF6 ubiquitination and RELA activation, and its overexpression attenuates osteoclast differentiation
  • TANK, whose expression is increased during osteoclastogenesis, inhibits osteoclast formation, activity and survival, by regulating NFKB1 activity and CFLAR expression
  • negatively regulates NFKB1 activation by DNA damage via inhibiting ubiquitination of TRAF6
  • cell & other
    REGULATION
    Other regulation of TANK expression is, at least in part, controlled by the injury-associated transcription factor SOX11
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in response to peripheral nerve injury
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularbone 
    methods for the inhibition and stimulation of TANK in osteoblasts and osteoclasts, respectively, may be a reasonable strategy to manipulate bone-destructive diseases
    ANIMAL & CELL MODELS
  • osteoblastogenesis was also increased in Tank-deficient mice
  • Tank-/- mice spontaneously develop autoimmune glomerular nephritis in an IL6-dependent manner