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Gene Review

Ttl  -  tubulin tyrosine ligase

Mus musculus

Synonyms: 2410003M22Rik, 2700049H19Rik, AI848570, TTL, Tubulin--tyrosine ligase
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Disease relevance of Ttl

  • Monoclonal antibodies isolated from ascites fluid allowed a rapid purification of TTL from a crude brain extract [1].
  • When injected into nude mice, both TTL- cells and TTL- cells stably transfected with TTL cDNA form sarcomas [2].

High impact information on Ttl

  • MTs in mouse Swiss 3T3 cells displayed an increase in Glu immunostaining fluorescence approximately 1 h after microinjecting antibodies to the tyrosinating enzyme, tubulin tyrosine ligase [3].
  • Tubulin-tyrosine ligase and alpha beta-tubulin form a tight complex which is conveniently monitored by glycerol gradient centrifugation [4].
  • Tubulin-tyrosine ligase has a binding site on beta-tubulin: a two-domain structure of the enzyme [4].
  • Tubulin-tyrosine ligase (TTL), the enzyme responsible for the reversible addition of a tyrosine residue at the carboxyl end of alpha-tubulin, has been purified from porcine brain using a purification scheme based on standard biochemical procedures [1].
  • To develop a more convenient purification of TTL, we have isolated mouse hybridoma cells secreting antibodies to TTL [1].

Biological context of Ttl


Anatomical context of Ttl

  • Correlatively, cultured TTL null neurons display morphogenetic anomalies including an accelerated and erratic time course of neurite outgrowth and a premature axonal differentiation [7].
  • We have isolated several NIH-3T3 derived clonal cell lines that lack TTL (TTL-) [2].

Associations of Ttl with chemical compounds

  • Tubulin is subject to a special cycle of detyrosination/tyrosination in which the C-terminal tyrosine of alpha-tubulin is cyclically removed by a carboxypeptidase and readded by a tubulin-tyrosine-ligase (TTL) [7].
  • In comparison with other known TTL sequences, namely bovine, rat and porcine, we found that only porcine TTL deviates in length by having an insertion of two glutamate residues [5].
  • Highly active TTL was recovered nearly quantitatively at greater than 95% purity and could be stabilized in the presence of glycerol [1].
  • TTL stayed bound to the immunoaffinity column in 1.5 M NaCl and was eluted with 3 M MgCl2 [1].
  • The liposome formulations used were ETL and TTL, which have I or 3 lipid components, respectively [8].

Other interactions of Ttl


Analytical, diagnostic and therapeutic context of Ttl


  1. Purification of brain tubulin-tyrosine ligase by biochemical and immunological methods. Schröder, H.C., Wehland, J., Weber, K. J. Cell Biol. (1985) [Pubmed]
  2. Suppression of tubulin tyrosine ligase during tumor growth. Lafanechère, L., Courtay-Cahen, C., Kawakami, T., Jacrot, M., Rüdiger, M., Wehland, J., Job, D., Margolis, R.L. J. Cell. Sci. (1998) [Pubmed]
  3. Detyrosination of alpha tubulin does not stabilize microtubules in vivo. Webster, D.R., Wehland, J., Weber, K., Borisy, G.G. J. Cell Biol. (1990) [Pubmed]
  4. Tubulin-tyrosine ligase has a binding site on beta-tubulin: a two-domain structure of the enzyme. Wehland, J., Weber, K. J. Cell Biol. (1987) [Pubmed]
  5. Cloning and genomic organization of the TTL gene on mouse chromosome 2 and human chromosome 2q13. Erck, C., MacLeod, R.A., Wehland, J. Cytogenet. Genome Res. (2003) [Pubmed]
  6. Tubulin polyglutamylase enzymes are members of the TTL domain protein family. Janke, C., Rogowski, K., Wloga, D., Regnard, C., Kajava, A.V., Strub, J.M., Temurak, N., van Dijk, J., Boucher, D., van Dorsselaer, A., Suryavanshi, S., Gaertig, J., Eddé, B. Science (2005) [Pubmed]
  7. A vital role of tubulin-tyrosine-ligase for neuronal organization. Erck, C., Peris, L., Andrieux, A., Meissirel, C., Gruber, A.D., Vernet, M., Schweitzer, A., Saoudi, Y., Pointu, H., Bosc, C., Salin, P.A., Job, D., Wehland, J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. Activity of paclitaxel liposome formulations against human ovarian tumor xenografts. Sharma, A., Mayhew, E., Bolcsak, L., Cavanaugh, C., Harmon, P., Janoff, A., Bernacki, R.J. Int. J. Cancer (1997) [Pubmed]
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