Recombinant Human Tau-tubulin kinase 2 (TTBK2), partial

Function

Serine/threonine kinase that acts as a key regulator of ciliogenesis: controls the initiation of ciliogenesis by binding to the distal end of the basal body and promoting the removal of CCP110, which caps the mother centriole, leading to the recruitment of IFT proteins, which build the ciliary axoneme. Has some substrate preference for proteins that are already phosphorylated on a Tyr residue at the +2 position relative to the phosphorylation site. Able to phosphorylate tau on serines in vitro (PubMed:23141541). Phosphorylates MPHOSPH9 which promotes its ubiquitination and proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative regulator of ciliogenesis) from the mother centrioles, promoting the initiation of ciliogenesis (PubMed:30375385). Required for recruitment of CPLANE2 and INTU to the mother centriole (By similarity)

Subcellular Location

Cell projection, cilium; Cytoplasm, cytoskeleton, cilium basal body; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole; Cytoplasm, cytosol; Nucleus

Disease Association

Spinocerebellar ataxia 11 (SCA11) : Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA11 is an autosomal dominant cerebellar ataxia (ADCA). It is a relatively benign, late-onset, slowly progressive neurologic disorder. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Interacts with CEP164 (PubMed:22863007). Interacts with MCRS1; the interaction is required for recruitment of TTBK2 to the mother centriole (PubMed:27263857)

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• Houlden H. et al. Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. — Nat. Genet. (2007)
• Bouskila M. et al. TTBK2 kinase substrate specificity and the impact of spinocerebellar-ataxia-causing mutations on expression, activity, localization and development. — Biochem. J. (2011)
• Rigbolt K.T. et al. System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. — Sci. Signal. (2011)
• Chaki M. et al. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. — Cell (2012)