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Gene Review

T  -  T, brachyury homolog (mouse)

Homo sapiens

Synonyms: Brachyury protein, Protein T, SAVA, TFT
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Disease relevance of T


Psychiatry related information on T

  • CONCLUSION: Although the stereo viewing system promises improved depth perception and the TFT and image projection displays are supposed to improve hand-eye coordination, none of these systems provided better task performance than the standard viewing system in this pelvi-trainer experiment [5].

High impact information on T

  • To test this hypothesis, we have analysed the expression of brachyury, otx and goosecoid homologues in the polychaete Platynereis dumerilii, which develops by means of a trochophora larva-the primary, ciliary larva prototypic for Protostomia [6].
  • Mutations in Brachyury and other T-box genes result in drastic embryonic phenotypes, indicating that T-box gene products are essential in tissue specification, morphogenesis and organogenesis [7].
  • Among those, homologs to forkhead, emx, aristaless, goosecoid, brachyury, wnt and nanos genes are regulated during apical patterning in cnidarians, suggesting that key components of early organizer activity were conserved across evolution and recruited for either anterior, axial, or dorso-ventral patterning in bilaterians [8].
  • The C-terminal region binds tetrahydrofolate, comprises three domains arranged in a ring-like structure and is related to the T-protein of the glycine cleavage system [9].
  • Brachyury is the founder member of the T-box family of transcription factors, which is characterized by a DNA-binding domain of approximately 200 amino acids [10].

Chemical compound and disease context of T


Biological context of T

  • We find that Tbx3 binds the canonical Brachyury binding site as a monomer and represses transcription [15].
  • The defining feature of the family is a conserved sequence coding for a DNA-binding motif known as the T-box, named after the first-discovered T-box gene, T or Brachyury [16].
  • While all were expressed during embryogenesis, only four of them (CpTbx2, CpTbx3, CpUbiqT and brachyury) were detected in developing limbs and/or tails [17].
  • Except for brachyury, they were continuously expressed in normal adult appendages and showed elevated expression levels in regenerating limbs, whereas only CpTbx2 showed significant up-regulation in regenerating tails [17].
  • The 5' flanking region of both HrBra and HrTbx6 contains T-protein binding motifs near their minimal promoters that are associated with the autoregulative activation of these genes [18].

Anatomical context of T

  • We investigated the hypothesis, that the entocodon could be homologous to the third germ layer of bilaterians by analyzing the structures and expression patterns of the homologues of Brachyury, Mef2, and Snail in the jellyfish Podocoryne carnea [19].
  • The epiblast shows a stage-dependent and topographically restricted susceptibility to express Brachyury, a T-box gene pivotal for mesoderm formation, and to transform into (histologically proven) mesoderm [20].
  • To model these developmental stages in vitro, an ES cell line was established that expresses CD4 from the foxa2 locus in addition to GFP from the brachyury locus [21].
  • Brachyury, the blastopore and the evolution of the mesoderm [22].
  • The role of Brachyury and other T-box genes in the differentiation of mesoderm and endoderm of vertebrates is well established [22].

Associations of T with chemical compounds

  • T-protein, one of the components of the glycine cleavage system, catalyzes the synthesis of the H-protein-bound intermediate from methylenetetrahydrofolate, ammonia, and H-protein having a reduced lipoyl prosthetic group (Okamura-Ikeda, K., Fujiwara, K., and Motokawa, Y. (1982) J. Biol. Chem. 257, 135-139) [23].
  • Tetrahydrofolate (or folinic acid) is bound near the center of the tripartite T-protein [2].
  • Thiophene-based n-type semiconductors exhibiting similar film morphologies and microstructures on various bilayer gate dielectrics therefore provide an incisive means to probe TFT performance parameters versus semiconductor-dielectric interface relationships [24].
  • T-protein, a component of the glycine cleavage system, catalyzes the formation of ammonia and 5,10-methylenetetrahydrofolate from the aminomethyl moiety of glycine attached to the lipoate cofactor of H-protein [25].
  • These hydrogen bonding networks are employed in holding not only the folate-binding space but also the positions and the orientations of alpha-helix G and the following loop in the middle region, which seems to play a pivotal role in the T-protein catalysis [25].

Physical interactions of T

  • The JCV T protein binds cellular p53 (a tumor suppressor gene product), which as a result loses its normal down regulating influence on the cell cycle [26].
  • E2F-6 is found in a multimeric protein complex that contains Mga and Max, and thus the complex can bind not only to the E2F-binding site but also to Myc- and Brachyury-binding sites [27].

Enzymatic interactions of T

  • Therefore, it was concluded that the loss of glycine decarboxylase activity was due to an inhibition of the reaction catalyzed by T-protein, which required ATP for its activation [28].

Other interactions of T

  • Here, we describe the first Brachyury and a Tbx2/3 homologue from a ctenophore [29].
  • However, the T-box gene Brachyury could be isolated from sponges, placozoans and cnidarians [29].
  • The most proximal of these Brachyury elements is most significant quantitatively in mediating T-bet-dependent promoter augmentation [30].
  • We identified several additional monomeric Brachyury consensus elements within the proximal IFN-gamma promoter that operate cooperatively to increase both constitutive and stimulated promoter activity [30].
  • The N terminus of Arix contains an amino acid motif similar to a region in Brachyury and Pax9 transcription factors [31].

Analytical, diagnostic and therapeutic context of T


  1. Expression of SV40 tumour antigens enables human endothelial cells to grow independently from foetal calf serum and exogenous growth factors. Hohenwarter, O., Jakoubek, A., Schmatz, C., Katinger, H. J. Biotechnol. (1994) [Pubmed]
  2. Crystal structure of T-protein of the glycine cleavage system. Cofactor binding, insights into H-protein recognition, and molecular basis for understanding nonketotic hyperglycinemia. Lee, H.H., Kim, d.o. .J., Ahn, H.J., Ha, J.Y., Suh, S.W. J. Biol. Chem. (2004) [Pubmed]
  3. Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. Vujovic, S., Henderson, S., Presneau, N., Odell, E., Jacques, T.S., Tirabosco, R., Boshoff, C., Flanagan, A.M. J. Pathol. (2006) [Pubmed]
  4. Derivation and characterization of POJ cells, transformed human fetal glial cells that retain their permissivity for JC virus. Mandl, C., Walker, D.L., Frisque, R.J. J. Virol. (1987) [Pubmed]
  5. Quantitative evaluation of three advanced laparoscopic viewing technologies: a stereo endoscope, an image projection display, and a TFT display. Wentink, M., Jakimowicz, J.J., Vos, L.M., Meijer, D.W., Wieringa, P.A. Surgical endoscopy. (2002) [Pubmed]
  6. Evolution of the bilaterian larval foregut. Arendt, D., Technau, U., Wittbrodt, J. Nature (2001) [Pubmed]
  7. Crystallographic structure of the T domain-DNA complex of the Brachyury transcription factor. Müller, C.W., Herrmann, B.G. Nature (1997) [Pubmed]
  8. Conserved and divergent genes in apex and axis development of cnidarians. Galliot, B. Curr. Opin. Genet. Dev. (2000) [Pubmed]
  9. Channelling and formation of 'active' formaldehyde in dimethylglycine oxidase. Leys, D., Basran, J., Scrutton, N.S. EMBO J. (2003) [Pubmed]
  10. T-box genes: what they do and how they do it. Smith, J. Trends Genet. (1999) [Pubmed]
  11. The phylogenetic origin of the bifunctional tyrosine-pathway protein in the enteric lineage of bacteria. Ahmad, S., Jensen, R.A. Mol. Biol. Evol. (1988) [Pubmed]
  12. Brachyury is expressed by human teratocarcinoma cells in the absence of mesodermal differentiation. Gokhale, P.J., Giesberts, A.M., Andrews, P.W. Cell Growth Differ. (2000) [Pubmed]
  13. Streptococcus pyogenes pharyngitis: characterization of strains by multilocus enzyme genotype, M and T protein serotype, and pyrogenic exotoxin gene probing. Musser, J.M., Gray, B.M., Schlievert, P.M., Pichichero, M.E. J. Clin. Microbiol. (1992) [Pubmed]
  14. 5-(Trifluoromethyl)-beta-l-2'-deoxyuridine, the L-enantiomer of trifluorothymidine: stereospecific synthesis and antiherpetic evaluations. Salvetti, R., Marchand, A., Pregnolato, M., Verri, A., Spadari, S., Focher, F., Briant, M., Sommadossi, J.P., Mathé, C., Gosselin, G. Bioorg. Med. Chem. (2001) [Pubmed]
  15. A dominant repression domain in Tbx3 mediates transcriptional repression and cell immortalization: relevance to mutations in Tbx3 that cause ulnar-mammary syndrome. Carlson, H., Ota, S., Campbell, C.E., Hurlin, P.J. Hum. Mol. Genet. (2001) [Pubmed]
  16. T-box genes in development: from hydra to humans. Papaioannou, V.E. Int. Rev. Cytol. (2001) [Pubmed]
  17. Expression of five novel T-box genes and brachyury during embryogenesis, and in developing and regenerating limbs and tails of newts. Sone, K., Takahashi, T.C., Takabatake, Y., Takeshima, K., Takabatake, T. Dev. Growth Differ. (1999) [Pubmed]
  18. Both the functional specificity and autoregulative activity of two ascidian T-box genes HrBra and HrTbx6 are likely to be mediated by the DNA-binding domain. Takahashi, H., Mitani, Y., Satoh, N. Dev. Growth Differ. (2005) [Pubmed]
  19. Conservation of Brachyury, Mef2, and Snail in the myogenic lineage of jellyfish: a connection to the mesoderm of bilateria. Spring, J., Yanze, N., Jösch, C., Middel, A.M., Winninger, B., Schmid, V. Dev. Biol. (2002) [Pubmed]
  20. Hypoblast controls mesoderm generation and axial patterning in the gastrulating rabbit embryo. Idkowiak, J., Weisheit, G., Plitzner, J., Viebahn, C. Dev. Genes Evol. (2004) [Pubmed]
  21. Wnt and TGF-beta signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells. Gadue, P., Huber, T.L., Paddison, P.J., Keller, G.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  22. Brachyury, the blastopore and the evolution of the mesoderm. Technau, U. Bioessays (2001) [Pubmed]
  23. Mechanism of the glycine cleavage reaction. Properties of the reverse reaction catalyzed by T-protein. Okamura-Ikeda, K., Fujiwara, K., Motokawa, Y. J. Biol. Chem. (1987) [Pubmed]
  24. Gate dielectric chemical structure-organic field-effect transistor performance correlations for electron, hole, and ambipolar organic semiconductors. Yoon, M.H., Kim, C., Facchetti, A., Marks, T.J. J. Am. Chem. Soc. (2006) [Pubmed]
  25. Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia. Okamura-Ikeda, K., Hosaka, H., Yoshimura, M., Yamashita, E., Toma, S., Nakagawa, A., Fujiwara, K., Motokawa, Y., Taniguchi, H. J. Mol. Biol. (2005) [Pubmed]
  26. p53 and proliferating cell nuclear antigen expression in JC virus-infected cells of progressive multifocal leukoencephalopathy. Ariza, A., Mate, J.L., Fernández-Vasalo, A., Gómez-Plaza, C., Pérez-Piteira, J., Pujol, M., Navas-Palacios, J.J. Hum. Pathol. (1994) [Pubmed]
  27. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Ogawa, H., Ishiguro, K., Gaubatz, S., Livingston, D.M., Nakatani, Y. Science (2002) [Pubmed]
  28. Activation of glycine decarboxylase in pea leaf mitochondria by ATP. Zhang, Q., Wiskich, J.T. Arch. Biochem. Biophys. (1995) [Pubmed]
  29. T-box and homeobox genes from the ctenophore Pleurobrachia pileus: comparison of Brachyury, Tbx2/3 and Tlx in basal metazoans and bilaterians. Martinelli, C., Spring, J. FEBS Lett. (2005) [Pubmed]
  30. Identification of cooperative monomeric Brachyury sites conferring T-bet responsiveness to the proximal IFN-gamma promoter. Cho, J.Y., Grigura, V., Murphy, T.L., Murphy, K. Int. Immunol. (2003) [Pubmed]
  31. The homeodomain protein Arix promotes protein kinase A-dependent activation of the dopamine beta-hydroxylase promoter through multiple elements and interaction with the coactivator cAMP-response element-binding protein-binding protein. Swanson, D.J., Adachi, M., Lewis, E.J. J. Biol. Chem. (2000) [Pubmed]
  32. The T-box transcription factor Brachyury mediates cartilage development in mesenchymal stem cell line C3H10T1/2. Hoffmann, A., Czichos, S., Kaps, C., Bächner, D., Mayer, H., Kurkalli, B.G., Zilberman, Y., Turgeman, G., Pelled, G., Gross, G., Gazit, D. J. Cell. Sci. (2002) [Pubmed]
  33. Brachyury expression in tailless Molgulid ascidian embryos. Takada, N., York, J., Davis, J.M., Schumpert, B., Yasuo, H., Satoh, N., Swalla, B.J. Evol. Dev. (2002) [Pubmed]
  34. JC virus T protein during productive infection in human fetal brain and kidney cells. Major, E.O., Traub, R.G. Virology (1986) [Pubmed]
  35. Structure and chromosomal localization of the aminomethyltransferase gene (AMT). Nanao, K., Takada, G., Takahashi, E., Seki, N., Komatsu, Y., Okamura-Ikeda, K., Motokawa, Y., Hayasaka, K. Genomics (1994) [Pubmed]
  36. Oligonucleotide-arrayed TFT photosensor applicable for DNA chip technology. Tanaka, T., Hatakeyama, K., Sawaguchi, M., Iwadate, A., Mizutani, Y., Sasaki, K., Tateishi, N., Takeyama, H., Matsunaga, T. Biotechnol. Bioeng. (2006) [Pubmed]
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