Tubulin monoglycylase TTLL3 (TTLL3)

Tubulin monoglycylase TTLL3 (TTLL3) is an enzyme belonging to the tubulin tyrosine ligase-like (TTLL) family, which specializes in catalyzing the posttranslational modification of microtubule proteins, specifically by adding single glycine residues (glycylation) to the C-terminal tails of β-tubulin, and to a lesser extent α-tubulin[1][2][5]. TTLL3 plays a key role in the regulation of microtubule function, is essential for the biogenesis and maintenance of cilia and flagella, and has been shown to influence epithelial cell proliferation and colon cancer biology[2][1]. Structurally, TTLL3 exhibits a unique enzyme scaffold with two architectural elements specific to glycylases, which differentiate its activity from other TTLL family members such as glutamylases[1][5]. Disease-associated mutations in humans have been identified in colon cancer, and functional loss of TTLL3 results in cell proliferation defects associated with impaired microtubule structure and function[2][1]. TTLL3 is not currently targeted by any specific drugs or used as a biomarker, but its biochemical importance in microtubule regulation and cancer suggests it may be of interest for future therapeutic targeting.

Other names

Tubulin tyrosine ligase-like protein 3TTLL3PRO0207DKFZP434B103HOTTLtubulin monoglycylase TTLL3tubulin tyrosine ligase-like family member 3

Initiation of glycylation on β-tubulin tails via transfer of glycine residues (ATP-dependent mechanism)