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FLASH GENE
Symbol TAB2 contributors: mct/npt/pgu - updated : 04-06-2014
HGNC name TGF-beta activated kinase 1/MAP3K7 binding protein 2
HGNC id 17075
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivestomach   highly
Urinarybladder   highly
Visualeye   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticneutrophil Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text expressed in the endothelial lining of the developing human heart
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one CUE domain
  • one RANBP2-type zinc finger
  • NZF domain bound to Lys63-linked di- and triubiquitin
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Map3k7ip2 (94.7pc)
    homolog to rattus Map3k7ip2 (93.7pc)
    Homologene
    FAMILY
    CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • translocating from the membrane to the cytosol upon IL1 stimulation
  • neutrophils express MAP3K7, as well as its associated partners, TAB1, TAB2, in both the cytoplasm and nucleus
  • basic FUNCTION
  • adaptor protein mediating the linking of MAP3K7 to TRAF6 and activating the former in the IL1-R signaling pathway, allowing MAP3K7 activation and subsequent IKK activation
  • involved in NF-kappaB activation and may thus be involved in type 1 diabetes through apoptosis in pancreatic beta-cells
  • activator of MAP3K7/TAK1, which is required for for the IL1 induced activation of nuclear factor kappaB and MAPK8/JNK
  • participating in the signal transduction induced by TNFSF11/RANKL through the activation of the receptor activator of NFKappaB
  • mediating MAP3K7-dependent activation of NLK and LEF1 polyubiquitylation, resulting in the inhibition of canonical Wnt signaling
  • role for TAB2 in human cardiac development
  • causes autophosphorylation and activation of mitogen-activated protein kinase kinase kinase 7 (MAP3K7, also known as TAK1)
  • activate the Jun N-terminal kinase and nuclear factor-kappaB pathways through the specific recognition of Lys 63-linked polyubiquitin chains by its Npl4 zinc-finger (NZF) domain
  • TAB2- and TAB3-mediated K63-linked polyubiquitin recognition controls B cell activation via MAPKs, but not the NR2C2/NFKB axis
  • TAB2 and TAB3 are dispensable for NR2C2 activation in B cells, indicating that TAB2 and TAB3 activate MAPKs via a pathway independent of NR2C2
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    JNK and NF-kappa B signaling pathways
    a component
  • complexed with MAP3K7 and MAP3K7IP1
  • interacting with NCOR1 and HDAC3 to form a ternary complex
  • component of a complex (MAP3K7-NLK-TAB2) that may constituttive a negative feedback mechanism for canonical Wnt signaling
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MAP3K7
  • binding partner of EDARADD
  • interacting with NUMBL
  • putative MAP3K7 interacting protein involved in the regulation of MAP3K7, that could directly interact with NLK and function as a scaffold protein to facilitate the interaction between MAP3K7 and NLK
  • binds adjacent ubiquitin moieties via two distinct binding sites
  • relationship between two central regulatory pathways in which MAP3K7-MAP3K7IP1-TAB2 selectively induces calcineurin-NFAT signalling through direct phosphorylation of RCAN1, while calcineurin activation diminishes MAP3K7 signalling by dephosphorylation of MAP3K7 and MAP3K7IP1
  • TAB2 and TAB3 bind to BECN1 and colocalize in the cytoplasm
  • TAB2 also interacts with ATG13 and is phosphorylated by ULK1
  • existence of an autophagy-stimulatory 'switch' whereby TAB2 and TAB3 abandon inhibitory interactions with Beclin 1 to engage in a stimulatory liaison with NR2C2
  • SIK1 and SIK3 negatively regulate TLR4-mediated signaling through the interruption of TAB2-TRAF6 complex and thereby the inhibition of ubiquitination of TRAF6
  • TRAF5 negatively regulated the association of TAB2 with its signaling partner TRAF6 after TLR ligation in B cells
  • TAB2 is a sensor of stress conditions in the liver and functions to protect the liver by activating the MAP3K7 pathway
  • RNF4 specifically down-regulated TAB2 through a lysosomal pathway
  • RNF4 interacts with the NR2C2-TAB2-TAB3 complex, but not TAB1
  • cell & other
    REGULATION
    Other ubiquitinated following IL1 stimulation or TRAF6 overexpression
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL6Q24
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   translocation   loss of function
    non-syndromic heart defect
    Susceptibility to type 1 diabetes
    Variant & Polymorphism
    Candidate gene heart defects
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Tab2 deficiency in mice was embryonic lethal due to liver degeneration and apoptosis, suggesting that Tab2 is essential for embryonic liver development