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

• Human TTL has been located to chromosome 2q13 (HSA2q13) [5].
• Cloning and genomic organization of the TTL gene on mouse chromosome 2 and human chromosome 2q13 [5].
• In mouse and human TTL the genomic coding sequence is composed of seven exons with normal intron/exon boundaries [5].
• Tubulin polyglutamylase enzymes are members of the TTL domain protein family [6].

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

• These anomalies may involve a mislocalization of CLIP170, which we find lacking in neurite extensions and growth cones of TTL null neurons [7].

Analytical, diagnostic and therapeutic context of Ttl

• Using fluorescence in situ hybridization (FISH), we mapped the murine TTL gene to mouse chromosome 2 (MMU2) [5].
• A one to one complex of TTL with alpha beta-tubulin was observed by gradient centrifugation [1].
• TTLL1 is a member of a large family of proteins with a TTL homology domain, whose members could catalyze ligations of diverse amino acids to tubulins or other substrates [6].

References