Tubulin tyrosine ligase like 4 (TTLL4)

Tubulin tyrosine ligase like 4 (TTLL4) is an enzyme belonging to the tubulin tyrosine ligase-like (TTLL) family, primarily functioning as a monoglutamylase. It initiates polyglutamylation—a posttranslational modification that adds a single glutamate residue to the γ-carboxyl group of specific glutamate residues on tubulin and various non-tubulin targets, such as nucleosome assembly proteins (NAP1L1, NAP1L4), the nucleotidyltransferase CGAS, and the transcription factor KLF4. TTLL4 is classified as an initiator, not an elongator of polyglutamate side chains, acting preferentially but not exclusively on the β-tail of tubulin substrates. The enzyme plays crucial roles in microtubule cytoskeleton organization, maintenance of ciliary function, neurodevelopment, and regulation of innate immune responses by modifying key proteins. Loss of regulation in polyglutamylation by TTLL4 and related enzymes is implicated in neurodegenerative processes and certain developmental disorders. TTLL4 acts in the cytosol and is expressed in various brain regions, with tissue-specific functions highlighted by distinct substrate isoform preferences.

Other names

Tubulin monoglutamylase TTLL4Protein monoglutamylase TTLL4Tubulin--tyrosine ligase-like protein 4KIAA0173Tubulin polyglutamylase TTLL4TTLL4_HUMAN