Gene Symbol: Tab1
Description: TGF-beta activated kinase 1/MAP3K7 binding protein 1
Alias: 2310012M03Rik, Map3k7ip1, b2b449Clo, TGF-beta-activated kinase 1 and MAP3K7-binding protein 1, TGF-beta-activated kinase 1-binding protein 1, Tak1-binding protein 1, beta activated kinase-1 binding protein-1, mitogen-activated protein kinase kinase kinase 7-interacting protein 1
Species: mouse
Products:     Tab1

Top Publications

  1. Takaesu G, Inagaki M, Takubo K, Mishina Y, Hess P, Dean G, et al. TAK1 (MAP3K7) signaling regulates hematopoietic stem cells through TNF-dependent and -independent mechanisms. PLoS ONE. 2012;7:e51073 pubmed publisher
    ..hematopoietic stem cells (HSCs) harboring deletion of Tak1 and its activators, Tak1 binding proteins 1 and 2 (Tab1 and Tab2) using a competitive transplantation assay in a mouse model...
  2. Komatsu Y, Shibuya H, Takeda N, Ninomiya Tsuji J, Yasui T, Miyado K, et al. Targeted disruption of the Tab1 gene causes embryonic lethality and defects in cardiovascular and lung morphogenesis. Mech Dev. 2002;119:239-49 pubmed
    ..TGF-beta activated kinase-1 binding protein-1 (TAB1) was identified as a molecule that activates TGF-beta activated kinase-1 (TAK1)...
  3. Nikopoulos G, Martins J, Adams T, Karaczyn A, Adams D, Vary C, et al. NRAGE: a potential rheostat during branching morphogenesis. Mech Dev. 2009;126:337-49 pubmed publisher
    ..Our results suggested that in early kidney development NRAGE might have multiple roles during renal branching morphogenesis through association with both the BMP and GDNF signaling pathways. ..
  4. Omori E, Inagaki M, Mishina Y, Matsumoto K, Ninomiya Tsuji J. Epithelial transforming growth factor ?-activated kinase 1 (TAK1) is activated through two independent mechanisms and regulates reactive oxygen species. Proc Natl Acad Sci U S A. 2012;109:3365-70 pubmed publisher
    ..Here we determine the mechanism by which TAK1 kinase is activated in epithelial tissues. TAB1 and TAB2 are structurally unrelated TAK1 binding protein partners...
  5. Scholz R, Sidler C, Thali R, Winssinger N, Cheung P, Neumann D. Autoactivation of transforming growth factor beta-activated kinase 1 is a sequential bimolecular process. J Biol Chem. 2010;285:25753-66 pubmed publisher
    ..TAK1 autoactivation involves the interplay with TAK1-binding proteins (TAB), e.g. TAB1 and TAB2, and phosphorylation of several activation segment residues...
  6. Shim J, Xiao C, Paschal A, Bailey S, Rao P, Hayden M, et al. TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev. 2005;19:2668-81 pubmed
    ..biochemical studies have revealed the existence of a TAK1 complex, which includes TAK1 and the adapter proteins TAB1 and TAB2, it remains unclear which members of this complex are essential for signaling...
  7. Mendoza H, Campbell D, Burness K, Hastie J, Ronkina N, Shim J, et al. Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the TAB3 regulatory subunit and activity of the TAK1 complex. Biochem J. 2008;409:711-22 pubmed mechanism by which p38alpha MAPK down-regulates TAK1 and showed that p38alpha MAPK phosphorylates TAB1 at Ser(423) and Thr(431)...
  8. Inagaki M, Komatsu Y, Scott G, Yamada G, Ray M, Ninomiya Tsuji J, et al. Generation of a conditional mutant allele for Tab1 in mouse. Genesis. 2008;46:431-9 pubmed publisher
    b>TAK1 binding protein 1 (TAB1) binds and induces autophosphorylation of TGF-beta activating kinase (TAK1)...
  9. Morioka S, Inagaki M, Komatsu Y, Mishina Y, Matsumoto K, Ninomiya Tsuji J. TAK1 kinase signaling regulates embryonic angiogenesis by modulating endothelial cell survival and migration. Blood. 2012;120:3846-57 pubmed publisher
    ..TAK1 binding proteins 1 and 2 (TAB1 and TAB2) are activators of TAK1, but their roles in embryonic TAK1 signaling have not been determined...

More Information


  1. Inagaki M, Omori E, Kim J, Komatsu Y, Scott G, Ray M, et al. TAK1-binding protein 1, TAB1, mediates osmotic stress-induced TAK1 activation but is dispensable for TAK1-mediated cytokine signaling. J Biol Chem. 2008;283:33080-6 pubmed publisher
    ..TAK1-binding protein 1 (TAB1) is constitutively associated with TAK1 through its C-terminal region...
  2. Xing J, Weng L, Yuan B, Wang Z, Jia L, Jin R, et al. Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract. Nat Immunol. 2016;17:1373-1380 pubmed publisher
    ..These data identify TRIM29 as a key negative regulator of alveolar macrophages and might have important clinical implications for local immunity and immunopathology. ..
  3. Yu J, Zhang F, Wang S, Zhang Y, Fan M, Xu Z. TAK1 is activated by TGF-? signaling and controls axonal growth during brain development. J Mol Cell Biol. 2014;6:349-51 pubmed publisher
  4. Akiyama S, Yonezawa T, Kudo T, Li M, Wang H, Ito M, et al. Activation mechanism of c-Jun amino-terminal kinase in the course of neural differentiation of P19 embryonic carcinoma cells. J Biol Chem. 2004;279:36616-20 pubmed
    ..In contrast, two TAK1-binding proteins, TAB1 and TAB2, which are involved in the activation of TAK1, were localized in the neurites and the nuclei of the ..
  5. Xu W, Wang C, Liang M, Chen L, Fu Q, Zhang F, et al. A20 prevents obesity-induced development of cardiac dysfunction. J Mol Med (Berl). 2018;96:159-172 pubmed publisher
    ..A20 represses TAK1 activation and the downstream inhibition of P38, JNK1/2, and the NF-?B pathway. TAK1 overexpression retards the beneficial effects of A20. ..
  6. Yang C, Li J, Chiu L, Lan J, Chen D, Chuang H, et al. Dual-specificity phosphatase 14 (DUSP14/MKP6) negatively regulates TCR signaling by inhibiting TAB1 activation. J Immunol. 2014;192:1547-57 pubmed publisher
    ..DUSP14 directly interacted with TGF-?-activated kinase 1 (TAK1)-binding protein 1 (TAB1) and dephosphorylated TAB1 at Ser(438), leading to TAB1-TAK1 complex inactivation in T cells...
  7. Shi M, Deng W, Bi E, Mao K, Ji Y, Lin G, et al. TRIM30 alpha negatively regulates TLR-mediated NF-kappa B activation by targeting TAB2 and TAB3 for degradation. Nat Immunol. 2008;9:369-77 pubmed publisher
    ..Our results collectively indicate that TRIM30alpha negatively regulates TLR-mediated NF-kappaB activation by targeting degradation of TAB2 and TAB3 by a 'feedback' mechanism. ..
  8. Liu Q, Busby J, Molkentin J. Interaction between TAK1-TAB1-TAB2 and RCAN1-calcineurin defines a signalling nodal control point. Nat Cell Biol. 2009;11:154-61 pubmed publisher
    ..TAB2 interacted directly with RCAN1 in vitro and in vivo, recruiting TAK1, TAB1 and calcineurin, forming a macromolecular signalling complex...
  9. Liu X, Seh C, Cheung P. HSP90 is required for TAK1 stability but not for its activation in the pro-inflammatory signaling pathway. FEBS Lett. 2008;582:4023-31 pubmed publisher
    ..Our results suggest that Hsp90 is required for the folding and stability of TAK1 but is displaced and no longer required when TAK1 is complexed to TAK1-binding protein-1 (TAB1).
  10. DeNicola G, Martin E, Chaikuad A, Bassi R, Clark J, Martino L, et al. Mechanism and consequence of the autoactivation of p38α mitogen-activated protein kinase promoted by TAB1. Nat Struct Mol Biol. 2013;20:1182-90 pubmed publisher
    ..a variety of mechanisms, including autophosphorylation initiated by TGFβ-activated kinase 1 binding protein 1 (TAB1) during myocardial ischemia and other stresses...
  11. Blanco S, Santos C, Lazo P. Vaccinia-related kinase 2 modulates the stress response to hypoxia mediated by TAK1. Mol Cell Biol. 2007;27:7273-83 pubmed
    ..Furthermore, reduction of the endogenous VRK2 level with short hairpin RNA can increase the response induced by hypoxia, suggesting that the intracellular levels of VRK2 can determine the magnitude of this stress response. ..
  12. Theivanthiran B, Kathania M, Zeng M, Anguiano E, Basrur V, Vandergriff T, et al. The E3 ubiquitin ligase Itch inhibits p38α signaling and skin inflammation through the ubiquitylation of Tab1. Sci Signal. 2015;8:ra22 pubmed publisher
    ..Itch bound directly to the TGF-β-activated kinase 1-binding protein 1 (Tab1) through a conserved PPXY motif and inhibited the activation of p38α...
  13. Pathak S, Borodkin V, Albarbarawi O, Campbell D, Ibrahim A, van Aalten D. O-GlcNAcylation of TAB1 modulates TAK1-mediated cytokine release. EMBO J. 2012;31:1394-404 pubmed publisher
    ..TAK1 is found in complex with binding partners TAB1-3, phosphorylation and ubiquitination of which has been found to regulate TAK1 activity...
  14. Yang Y, Zhou C, Wang Y, Liu W, Liu C, Wang L, et al. The E3 ubiquitin ligase RNF114 and TAB1 degradation are required for maternal-to-zygotic transition. EMBO Rep. 2017;18:205-216 pubmed publisher
    ..We show that five substrates could be degraded by RNF114-mediated ubiquitination, including TAB1. Furthermore, the degradation of TAB1 in mouse early embryos is required for MZT, most likely because it activates ..
  15. Lilley B, Pan Y, Sanes J. SAD kinases sculpt axonal arbors of sensory neurons through long- and short-term responses to neurotrophin signals. Neuron. 2013;79:39-53 pubmed publisher
    ..We propose that SAD kinases integrate long- and short-duration signals from extrinsic cues to sculpt axon arbors within the CNS. ..
  16. Mihaly S, Morioka S, Ninomiya Tsuji J, Takaesu G. Activated macrophage survival is coordinated by TAK1 binding proteins. PLoS ONE. 2014;9:e94982 pubmed publisher
    ..Here we report that TGF?- activated kinase (TAK1) activators, TAK1-binding protein 1 (TAB1) and TAK1-binding protein 2 (TAB2), are critical molecules in the regulation of activated macrophage survival...
  17. Oh D, Talukdar S, Bae E, Imamura T, Morinaga H, Fan W, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 2010;142:687-98 pubmed publisher
    ..In conclusion, GPR120 is a functional omega-3 FA receptor/sensor and mediates potent insulin sensitizing and antidiabetic effects in vivo by repressing macrophage-induced tissue inflammation. ..
  18. Kim S, Kwak J, Na H, Kim J, Ding Y, Choi M. Transforming growth factor-beta (TGF-beta1) activates TAK1 via TAB1-mediated autophosphorylation, independent of TGF-beta receptor kinase activity in mesangial cells. J Biol Chem. 2009;284:22285-96 pubmed publisher
    ..b>TAB1 does not interact with TGF-beta receptors, but TAB1 is indispensable for TGF-beta1-induced TAK1 activation...
  19. Ko R, Park J, Ha H, Choi Y, Lee S. Glycogen synthase kinase 3β ubiquitination by TRAF6 regulates TLR3-mediated pro-inflammatory cytokine production. Nat Commun. 2015;6:6765 pubmed publisher
    ..TRAF6 is determined to be a direct E3 ligase for GSK3β, and TRAF6-mediated GSK3β ubiquitination is essential for poly I:C-dependent cytokine production by promoting the TLR3 adaptor protein TRIF-assembled signalling complex. ..
  20. Makeeva N, Roomans G, Welsh N. Role of TAB1 in nitric oxide-induced p38 activation in insulin-producing cells. Int J Biol Sci. 2006;3:71-6 pubmed
    The aim of present study was to elucidate the role of TAB1 in nitric oxide-induced activation of p38 MAPK. For this purpose we over-expressed TAB1 in insulin-producing beta-TC6 cells...
  21. Chen H, Liu Y, Li D, Song J, Xia M. PGC-1β suppresses saturated fatty acid-induced macrophage inflammation by inhibiting TAK1 activation. IUBMB Life. 2016;68:145-55 pubmed publisher
    ..Mechanistically, we revealed that TGF-β-activated kinase 1 (TAK1) and its adaptor protein TAK1 binding protein 1 (TAB1) played a dominant role in the regulatory effects of PGC-1β...
  22. Morioka S, Broglie P, Omori E, Ikeda Y, Takaesu G, Matsumoto K, et al. TAK1 kinase switches cell fate from apoptosis to necrosis following TNF stimulation. J Cell Biol. 2014;204:607-23 pubmed publisher
    ..Our results reveal that TAK1 activation drives RIPK3-dependent necrosis and inhibits apoptosis. TAK1 acts as a switch between apoptosis and necrosis. ..
  23. Rochira J, Matluk N, Adams T, Karaczyn A, Oxburgh L, Hess S, et al. A small peptide modeled after the NRAGE repeat domain inhibits XIAP-TAB1-TAK1 signaling for NF-?B activation and apoptosis in P19 cells. PLoS ONE. 2011;6:e20659 pubmed publisher
    ..from BMP ligands, neurotrophin receptor-mediated MAGE homolog (NRAGE) binds and functions with the XIAP-TAK1-TAB1 complex to activate p38(MAPK) and induces apoptosis in cortical neural progenitors...
  24. Makeeva N, Roomans G, Myers J, Welsh N. Transforming growth factor-beta-activated protein kinase 1-binding protein (TAB)-1alpha, but not TAB1beta, mediates cytokine-induced p38 mitogen-activated protein kinase phosphorylation and cell death in insulin-producing cells. Endocrinology. 2008;149:302-9 pubmed
    ..aim of the present study was to elucidate the role of the TGF-beta-activated protein kinase 1-binding protein 1 (TAB1) in the cytokine-induced activation of p38...
  25. Ikeda Y, Morioka S, Matsumoto K, Ninomiya Tsuji J. TAK1 binding protein 2 is essential for liver protection from stressors. PLoS ONE. 2014;9:e88037 pubmed publisher
    ..These results demonstrate that TAB2 is a sensor of stress conditions in the liver and functions to protect the liver by activating the TAK1 pathway. ..
  26. Neil J, Schiemann W. Altered TAB1:I kappaB kinase interaction promotes transforming growth factor beta-mediated nuclear factor-kappaB activation during breast cancer progression. Cancer Res. 2008;68:1462-70 pubmed publisher
    ..malignant counterparts, 4T1 cells, by inducing assembly of TGF-beta-activated kinase 1 (TAK1)-binding protein 1 (TAB1):I kappaB kinase beta (IKK beta) complexes, which led to the stimulation of a TAK1:IKK beta:p65 pathway...
  27. Halle M, Gomez M, Stuible M, Shimizu H, McMaster W, Olivier M, et al. The Leishmania surface protease GP63 cleaves multiple intracellular proteins and actively participates in p38 mitogen-activated protein kinase inactivation. J Biol Chem. 2009;284:6893-908 pubmed publisher a GP63- and protein degradation-dependent manner, which likely involves cleavage of the upstream adaptor TAB1. Our results establish that GP63 plays a central role in a number of hostcell molecular events that likely ..