PROSITE documentation PDOC51221
TTL domain profile


Tubulin tyrosine ligase (TTL) (EC is an enzyme involved in the posttranslational modification of tubulin. Assembled microtubules are detyrosinated over time at the C-terminus of α-tubulin. After microtubular disassembly TTL restores tyrosine residues back to the detyrosinated tubulin leading to a cycle of detyrosination/tyrosination. TTL may play a role in tumor cell regulation.

The TTL domain is a ~350 amino acid module present in a family of eukaryotic proteins that could catalyze ligations of diverse amino acids to tubulins or other substrates. The domain is named after mammalian TTL. Tubulin tyrosine ligase-like (TTLL) proteins include tubulin polyglutamylases, which catalyze the posttranslational addition of multiple glutamic acids to a glutamate residue of target proteins, such as tubulin or nucleosome assembly proteins NAP1 and NAP2. Tubulin polyglutamylation may be involved in the organization of the neuronal microtubule network, in centriole stability, axoneme motility and mitosis [1]. The TTL domain contains ATP-grasp-like motifs (see <PDOC50975>) that correspond to the ATP/Mg(2+) binding site typical of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity [2].

Some proteins known to contain a TTL domain:

  • Mammalian tubulin--tyrosine ligase (TTL) (EC, which catalyzes the posttranslational addition of a tyrosine residue to the C-terminal glutamate of detyrosinated α-tubulin subunits in microtubules.
  • Mammalian tubulin--tyrosine ligase-like protein 1 (TTLL1), a tubulin polyglutamylase with preference for the α-tubulin subunit.
  • Tetrahymena TTLL6A, a tubulin polyglutamylase with preference for the β-tubulin subunit [1].

The profile we developed covers the entire TTL domain.

Last update:

June 2006 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

TTL, PS51221; TTL domain profile  (MATRIX)


1AuthorsJanke 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. Edde B.
TitleTubulin polyglutamylase enzymes are members of the TTL domain protein family.
SourceScience 308:1758-1762(2005).
PubMed ID15890843

2AuthorsGalperin M.Y. Koonin E.V.
TitleA diverse superfamily of enzymes with ATP-dependent carboxylate- amine/thiol ligase activity.
SourceProtein Sci. 6:2639-2643(1997).
PubMed ID9416615

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