Enabling Protein Degradation Drug Discovery

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  • Name
    Catalogue Number
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  • Name:
    TAK1_TAB1 complex [6His-tagged]
    Catalogue Number:
    50 µg
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  • Species
  • Source
    Sf21 insect cell-baculovirus ex­pression
  • Quantity
    50 µg
  • Storage
  • Concentration
    1 mg/ml
  • Formulation
    50 mM Tris/HCl pH 7.5, 0.1 mM EGTA, 150 mM NaCl, 270 mM sucrose, 0.03% Brij, 0.1% b-Mercapto-ethanol, 1 mM Benzamidine, 0.2 mM PMSF
  • Molecular Weight
    ~44.5 kDa
  • Stability
    12 months at -70°C; aliquot as required
  • Protein Sequence
    Accession number: TAK1: NP_003179.1; TAB1: NP_006107.1. For full protein sequence information download the Certificate of Analysis pdf.
  • QA; Protein Identification
    Confirmed by mass spectrometry.
  • QA; Activity
    Activity Assay: The specific activity of His-TAK1-TAB1 was determined using the method described by Hastie et al. (2006) with the enzyme being assayed at several concentrations.  His-TAK1-TAB1 was incubated for 10 minutes at 30°C in kinase reaction buffer in the presence of EP3151 peptide substrate (300 µM) and [γ-32P]ATP (100 µM). Duplicate reactions were stopped by spotting the assay mixture onto Whatman P81 paper - capturing the phosphorylated substrate.  The radioactivity incorporated was measured on a scintillation counter and the enzyme's mean specific activity was calculated. 

    His-TAK1-TAB1 specific activity: 92.5 Units/mg (92.5 Units/ml)

    1 Unit = 1 nmole of phosphate incorporated into the substrate in 1 minute

    Substrate: EP3151 (RLGRDKYKTLRQIRQ)

Protein ubiquitylation and protein phosphorylation are the two major mechanisms that regulate the functions of proteins in eukaryotic cells.  However, these different posttranslational modifications do not operate independently of one another, but are frequently interlinked to enable biological processes to be controlled in a more complex and sophisticated manner. Studying how protein phosphorylation events control the ubiquitin system and how ubiquitylation regulates protein phosphorylation has become a focal point of the study of cell regulation and human disease. Cloning of human TAK1 (TGFβ-activated protein kinase 1) was first described by Kondo et al. (1998). In vivo, TAK1 activation requires its association with TAK1 binding protein 1 (TAB1), which triggers TAK1 autophosphorylation at Thr184 and Thr187 (Sakurai et al., 2000; Shibuya et al., 1996). TAK1 plays a central role in the innate immune system by activating the canonical IKK complex and hence the transcription factor NFκB, as well as several MAP kinase cascades.  Its activation in the MyD88 signaling pathway of the innate immune system depends on TRAF6.  This E3 ubiquitin ligase generates Lys63-linked polyubiquitin chains that interact with the TAB2 and TAB3 regulatory components of the TAK1 complex.  This induces a conformational change that allows TAK1 to activate itself (Wang et al., 2001; Xia et al., 2009). 


Hastie CJ, McLauchlan HJ, Cohen P (2006) Assay of protein kinases using radiolabeled ATP: a protocol. Nat Protoc 1, 968-71.

Kondo M, Osada H, Uchida K, Yanagisawa K, Masuda A, Takagi K, Takahashi T (1998) Molecular cloning of human TAK1 and its mutational analysis in human lung cancer. Int J Cancer 75, 559-63.

Sakurai H, Miyoshi H, Mizukami J, Sugita T (2000) Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1. FEBS Lett 474, 141-5.

Shibuya H, Yamaguchi K, Shirakabe K, Tonegawa A, Gotoh Y, Ueno N, Irie K, Nishida E, Matsumoto K (1996) TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction. Science 272, 1179-82.

Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-51.

Xia ZP, Sun L, Chen X, Pineda G, Jiang X, Adhikari A, Zeng W, Chen ZJ (2009) Direct activation of protein kinases by unanchored polyubiquitin chains. Nature 461, 114-9.

Background kindly written by:

Sir Philip Cohen FRS, FRSE

University of Dundee

Director of the Medical Research Council Protein Phosphorylation Unit (1990-2012)


Director of the Scottish Institute for Cell Signalling incorporating the Protein Ubiquitylation Unit (2008-2012)


Co-Director of the Division of Signal Transduction Therapy (1998-2012)


Deputy Director of the Division of Signal Transduction Therapy (from July 2012)

Professor Cohen’s research group is studying the interplay between protein phosphorylation and protein ubiquitylation
in the regulation of innate immunity.