PDBsum entry 2j4o

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protein links
Protein binding PDB id
Protein chain
356 a.a. *
Waters ×83
* Residue conservation analysis
PDB id:
Name: Protein binding
Title: Structure of tab1
Structure: Mitogen-activated protein kinase kinase kinase 7-interacting protein 1. Chain: a. Fragment: n-terminal pp2c-like domain, residues 1-401. Synonym: tgf-beta-activated kinase 1-binding protein 1, tak1-binding protein 1, tab1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
2.25Å     R-factor:   0.228     R-free:   0.235
Authors: D.Van Aalten
Key ref: S.H.Conner et al. (2006). TAK1-binding protein 1 is a pseudophosphatase. Biochem J, 399, 427-434. PubMed id: 16879102 DOI: 10.1042/BJ20061077
01-Sep-06     Release date:   04-Sep-06    
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Protein chain
Pfam   ArchSchema ?
Q15750  (TAB1_HUMAN) -  TGF-beta-activated kinase 1 and MAP3K7-binding protein 1
504 a.a.
356 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     catalytic activity     1 term  


DOI no: 10.1042/BJ20061077 Biochem J 399:427-434 (2006)
PubMed id: 16879102  
TAK1-binding protein 1 is a pseudophosphatase.
S.H.Conner, G.Kular, M.Peggie, S.Shepherd, A.W.Schüttelkopf, P.Cohen, D.M.Van Aalten.
TAB1 [TAK1 (transforming growth factor-beta-activated kinase 1)-binding protein 1] is one of the regulatory subunits of TAK1, a protein kinase that lies at the head of three pro-inflammatory kinase cascades. In the current study we report the crystal structure of the N-terminal domain of TAB1. Surprisingly, TAB1 possesses a fold closely related to that of the PPM (Mg2+- or Mn2+-dependent protein phosphatase) family as demonstrated by the close structural similarity with protein phosphatase 2C alpha. However, we were unable to detect any phosphatase activity for TAB1 using a phosphopeptide or p-nitrophenyl phosphate as substrate. Although the overall protein phosphatase 2C alpha fold is conserved in TAB1, detailed structural analyses and mutagenesis studies show that several key residues required for dual metal-binding and catalysis are not present in TAB1, although binding of a single metal is supported by soaking experiments with manganese and isothermal titration calorimetry. Thus, it appears that TAB1 is a 'pseudophosphatase', possibly binding to and regulating accessibility of phosphorylated residues on substrates downstream of TAK1 or on the TAK1 complex itself.

Literature references that cite this PDB file's key reference

  PubMed id Reference
22781900 C.Adrain, and M.Freeman (2012).
New lives for old: evolution of pseudoenzyme function illustrated by iRhoms.
  Nat Rev Mol Cell Biol, 13, 489-498.  
21074407 E.Zeqiraj, and D.M.van Aalten (2010).
Pseudokinases-remnants of evolution or key allosteric regulators?
  Curr Opin Struct Biol, 20, 772-781.  
20038579 Y.Fan, Y.Yu, Y.Shi, W.Sun, M.Xie, N.Ge, R.Mao, A.Chang, G.Xu, M.D.Schneider, H.Zhang, S.Fu, J.Qin, and J.Yang (2010).
Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required for tumor necrosis factor alpha- and interleukin-1beta-induced IKK/NF-kappaB and JNK/AP-1 activation.
  J Biol Chem, 285, 5347-5360.  
19521662 D.Gao, R.Wang, B.Li, Y.Yang, Z.Zhai, and D.Y.Chen (2009).
WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway.
  Cell Mol Life Sci, 66, 2573-2584.  
19909372 H.Shinohara, and T.Kurosaki (2009).
Comprehending the complex connection between PKCbeta, TAK1, and IKK in BCR signaling.
  Immunol Rev, 232, 300-318.  
19290931 M.Karin, and E.Gallagher (2009).
TNFR signaling: ubiquitin-conjugated TRAFfic signals control stop-and-go for MAPK signaling complexes.
  Immunol Rev, 228, 225-240.  
18541005 B.M.Collins (2008).
The structure and function of the retromer protein complex.
  Traffic, 9, 1811-1822.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
18617512 Y.Yu, N.Ge, M.Xie, W.Sun, S.Burlingame, A.K.Pass, J.G.Nuchtern, D.Zhang, S.Fu, M.D.Schneider, J.Fan, and J.Yang (2008).
Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop Is Required for Interleukin (IL)-1-mediated Optimal NF{kappa}B and AP-1 Activation as Well as IL-6 Gene Expression.
  J Biol Chem, 283, 24497-24505.  
17496917 A.Adhikari, M.Xu, and Z.J.Chen (2007).
Ubiquitin-mediated activation of TAK1 and IKK.
  Oncogene, 26, 3214-3226.  
17560374 M.Lu, S.C.Lin, Y.Huang, Y.J.Kang, R.Rich, Y.C.Lo, D.Myszka, J.Han, and H.Wu (2007).
XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1 dimerization.
  Mol Cell, 26, 689-702.
PDB codes: 2poi 2pom 2pop
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