Journal of Molecular Evolution

, Volume 66, Issue 5, pp 472–483

Phylogenetic and Structural Analysis of Translationally Controlled Tumor Proteins

  • Jesús Hinojosa-Moya
  • Beatriz Xoconostle-Cázares
  • Elías Piedra-Ibarra
  • Alfonso Méndez-Tenorio
  • William J. Lucas
  • Roberto Ruiz-Medrano


The translationally controlled tumor protein (TCTP) is conserved in all eukaryotes studied thus far. Recent evidence points to an important role for TCTP in the induction of cell proliferation in animals through an interaction with G proteins. TCTP may also constitute an intercellular secreted signal that modulates the immune response in the vertebrates. Because of its sequence conservation and ubiquity, the analysis of its amino acid sequence divergence between different taxa may provide insight into the structural constraints on the evolution of this protein. In the present study, we analyzed the phylogeny of TCTP sequences from a wide range of organisms and found that, with some exceptions, the groupings formed were consistent with the evolutionary history. Indeed, at the level of lower-order taxa, the groupings are in agreement with their established phylogeny, thus indicating that the substitution rates of the TCTP residues varied evenly between members of the same clade. Predicted three-dimensional structures of representative TCTPs, based on the reported 3D structure of Schizosaccharomyces pombe, indicated that these proteins are highly conserved among diverse taxonomic groups. However, analysis of the primary structure indicated subtle differences in the domain-forming pocket that potentially interacts with G proteins, particularly among Diplomonadidae, Apicomplexa, and other parasites of vertebrates. These differences support the notion that these specific TCTPs could block the normal immune response by acting as dominant negative mutants. Structural differences were also observed in a reported sequence of TCTP from Plasmodium knowlesi, in which the presence of an extra α-helix could also interfere in the interaction with G proteins.


Translationally controlled tumor protein Apicomplexa Diplomonadidae G proteins Parasite evolution Protein structure 

Supplementary material

Ramachandran Analysis (from Procheck Analysis) (TIFF 1139 kb)
239_2008_9099_MOESM2_ESM.tif (777 kb)
Phylogeny of the TCTP family reconstructed with genetic distances (Dayhoff, et al., 1978) model and neighbor-joining method. In the consensus tree the clades supported with bootstrap values lower than 50% (1000 trials) have been collapsed. The tree was rooted with the G. lamblia (diplomonadidae) TCTP sequence (upper part of the tree). The accession number and the species are indicated in each terminal branch (TIF 777 kb)
239_2008_9099_MOESM3_ESM.tif (35 kb)
Phylogenetic tree of TCTP using the maximum likelihood model (Quartet puzzling procedure, 50000 puzzling steps and Dayhoff substitution model). The multiple alignment was bootstrapped (13 trials) and subjected to phylogenetic reconstruction. In the consensus tree the significance of each branch is indicated by a bootstrap value. The branches with support lower than 50% were collapsed. The tree was rooted with the G. lamblia (diplomonadidae) TCTP sequence (upper part of the tree). Accession numbers are given in brackets along with the species name (TIF 34 kb)
239_2008_9099_MOESM4_ESM.tif (416 kb)
Sequence alignment of TCTPs from diverse taxa using the ClulstalX program Aligments were manually corrected with the Seqvu program. Asterisks indicate the position of the three conserved residues, Glu 12, Leu 74 and Glu 134, which interact with G proteins in the S. pombe and D. melanogaster TCTPs. Conserved residues are enclosed in yellow boxes (TIF 415 kb)


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Jesús Hinojosa-Moya
    • 1
  • Beatriz Xoconostle-Cázares
    • 1
  • Elías Piedra-Ibarra
    • 1
    • 2
  • Alfonso Méndez-Tenorio
    • 3
  • William J. Lucas
    • 4
  • Roberto Ruiz-Medrano
    • 1
  1. 1.Departamento de Biotecnología y BioingenieríaCINVESTAV-IPNMexicoMexico
  2. 2.Facultad de Estudios Superiores IztacalaUNAMTlalnepantlaMexico
  3. 3.Escuela Nacional de Ciencias Biológicas del Instituto Politécnico NacionalMexicoMexico
  4. 4.Section of Plant Biology, College of Biological SciencesUniversity of CaliforniaDavisUSA

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