TTLL6

tubulin tyrosine ligase like 6

Ensembl:
ENSG00000170703
UniProt:
Q8N841
OMIM:
610849
Synonyms:
FLJ35808

Cilia effects upon perturbation of TTLL6

Cilia number / % ciliated:
No effect
Loss-of-function effect:
Decrease

Ciliogenesis screen results (2 screens)

  • Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.59) PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680

Phenotypes

Mouse phenotype:
increased circulating potassium level, decreased circulating glucose level

Subcellular localization

basal body, cilia, flagella

Functional category

  • Ciliary assembly/disassembly
  • Actin & cytoskeleton regulation
  • T cell biology
  • Cell migration & adhesion

Function

Main axonemal tubulin glutamylase of ciliated cells. Knockdown caused loss of axonemal glutamylation but not basal body glutamylation (21262966). Ciliary entry and distribution of TTLL6 is regulated by CEP41 (22246503). Critical in the regulation of axonemal motility and ciliary beating in ependymal cells, as it cannot be replaced by any of the other glutamylases (23897886). TTLL6 glutamylase preferentially modifies α-tubulin tails in microtubules via quadrivalent recognition spanning two tubulin dimers. Implicated in ciliopathies via defective axoneme polyglutamylation.

Model organism evidence

Mus musculus (2 references)

By systematically screening enzymes of the TTLL family for specific functions in ependymal cilia, we demonstrate that the glycylating enzymes TTLL3 and TTLL8 were required for stability and maintenance of ependymal cilia, whereas the polyglutamylase TTLL6 was necessary for coordinated beating be

We show that CEP41 is localized to the basal body and primary cilia, and regulates ciliary entry of TTLL6, an evolutionarily conserved polyglutamylase enzyme.

PMIDs: 23897886, 22246503

Danio rerio (3 references)

We show that CEP41 is localized to the basal body and primary cilia, and regulates ciliary entry of TTLL6, an evolutionarily conserved polyglutamylase enzyme.

Similarly, knockdown of ttll6 strongly reduced cilia tubulin glutamylation but only partially affected cilia structure and motility.

PMIDs: 22246503, 21262966, 17761526

C. elegans (1 reference)

Cilia and basal bodies are essential organelles for a broad spectrum of functions, including the development of left-right asymmetry, kidney function, cerebrospinal fluid transport, generation of photoreceptor outer segments, and hedgehog signaling.

PMIDs: 17761526