TTBK2

Summary

Gene Symbol: TTBK2
Description: tau tubulin kinase 2
Alias: SCA11, TTBK, tau-tubulin kinase 2
Species: human
Products:     TTBK2

Top Publications

  1. Houlden H, Johnson J, Gardner Thorpe C, Lashley T, Hernandez D, Worth P, et al. Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nat Genet. 2007;39:1434-6 pubmed
    ..We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11...
  2. Goetz S, Liem K, Anderson K. The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis. Cell. 2012;151:847-858 pubmed publisher
    ..Here, we show that Tau tubulin kinase 2 (TTBK2) is a dedicated regulator of the initiation of ciliogenesis in vivo...
  3. Chaki M, Airik R, Ghosh A, Giles R, Chen R, Slaats G, et al. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell. 2012;150:533-48 pubmed publisher
    ..Our findings link degenerative diseases of the kidney and retina, disorders of increasing prevalence, to mechanisms of DDR. ..
  4. Alesutan I, Sopjani M, Dërmaku Sopjani M, Munoz C, Voelkl J, Lang F. Upregulation of Na-coupled glucose transporter SGLT1 by Tau tubulin kinase 2. Cell Physiol Biochem. 2012;30:458-65 pubmed publisher
    The Tau-tubulin-kinase 2 (TTBK2) is a serine/threonine kinase expressed in various tissues including tumors. Up-regulation of TTBK2 increases resistance of tumor cells against antiangiogenic treatment and confers cell survival...
  5. Bender C, Ullrich A. PRKX, TTBK2 and RSK4 expression causes Sunitinib resistance in kidney carcinoma- and melanoma-cell lines. Int J Cancer. 2012;131:E45-55 pubmed publisher
    ..PRKX, TTBK2 and RSK4 expression...
  6. Bouskila M, Esoof N, Gay L, Fang E, Deak M, Begley M, et al. TTBK2 kinase substrate specificity and the impact of spinocerebellar-ataxia-causing mutations on expression, activity, localization and development. Biochem J. 2011;437:157-67 pubmed publisher
    Mutations that truncate the C-terminal non-catalytic moiety of TTBK2 (tau tubulin kinase 2) cause the inherited, autosomal dominant, SCA11 (spinocerebellar ataxia type 11) movement disorder...
  7. Bowie E, Norris R, Anderson K, Goetz S. Spinocerebellar ataxia type 11-associated alleles of Ttbk2 dominantly interfere with ciliogenesis and cilium stability. PLoS Genet. 2018;14:e1007844 pubmed publisher
    ..SCA11 is caused by mutations in the gene encoding the Serine/Threonine kinase Tau tubulin kinase 2 (TTBK2) that result in premature truncations of the protein...
  8. Kiefer S, Chang C, Kimura S, Gao M, Xie D, Zhang Y, et al. The structure of human tau-tubulin kinase 1 both in the apo form and in complex with an inhibitor. Acta Crystallogr F Struct Biol Commun. 2014;70:173-81 pubmed publisher
    ..X-ray diffraction data were collected and the structure of TTBK1 was determined by molecular replacement both as an apo structure and in complex with a kinase inhibitor. ..
  9. Huang N, Zhang D, Li F, Chai P, Wang S, Teng J, et al. M-Phase Phosphoprotein 9 regulates ciliogenesis by modulating CP110-CEP97 complex localization at the mother centriole. Nat Commun. 2018;9:4511 pubmed publisher
    ..After phosphorylation by Tau Tubulin Kinase 2 (TTBK2) at the beginning of ciliogenesis, MPP9 is targeted for degradation via the ubiquitin-proteasome ..

More Information

Publications41

  1. Jackson P. TTBK2 kinase: linking primary cilia and cerebellar ataxias. Cell. 2012;151:697-699 pubmed publisher
    ..A new mouse mutant in the TTBK2 kinase fails to make cilia, and shows neural tube and Sonic hedgehog signaling defects...
  2. Nozal V, Martinez A. Tau Tubulin Kinase 1 (TTBK1), a new player in the fight against neurodegenerative diseases. Eur J Med Chem. 2019;161:39-47 pubmed publisher
    ..Its two homologs, TTBK1 and TTBK2, show different expression patterns and different involvements in physiological mechanisms of great importance ..
  3. Zhang N, Gordon S, Fritsch M, Esoof N, Campbell D, Gourlay R, et al. Phosphorylation of synaptic vesicle protein 2A at Thr84 by casein kinase 1 family kinases controls the specific retrieval of synaptotagmin-1. J Neurosci. 2015;35:2492-507 pubmed publisher
    ..We demonstrate that Casein kinase 1 family members, including isoforms of Tau-tubulin protein kinases (TTBK1 and TTBK2), phosphorylate human SV2A at two constellations of residues, namely Cluster-1 (Ser42, Ser45, and Ser47) and ..
  4. Nahan K, Walsh K, Adeoye O, Landero Figueroa J. The metal and metalloprotein profile of human plasma as biomarkers for stroke diagnosis. J Trace Elem Med Biol. 2017;42:81-91 pubmed publisher
  5. Coutelier M, Coarelli G, Monin M, Konop J, Davoine C, Tesson C, et al. A panel study on patients with dominant cerebellar ataxia highlights the frequency of channelopathies. Brain. 2017;140:1579-1594 pubmed publisher
    ..AFG3L2 (n = 7) came next in frequency, and variants were rarely found in STBN2 (n = 2), ELOVL5, FGF14, STUB1 and TTBK2 (n = 1 each). Interestingly, possible risk factor variants were detected in SPG7 and POLG...
  6. Fernius J, Starkenberg A, Pokrzywa M, Thor S. Human TTBK1, TTBK2 and MARK1 kinase toxicity in Drosophila melanogaster is exacerbated by co-expression of human Tau. Biol Open. 2017;6:1013-1023 pubmed publisher
    ..for toxicity, we analyzed the effects of co-expressing hTau isoforms together with Tau-kinases, focusing on TTBK1, TTBK2 and MARK1. We observed toxicity when expressing each of the three kinases alone, or in combination...
  7. Lindquist S, Møller L, Dali C, Marner L, Kamsteeg E, Nielsen J, et al. A Novel TTBK2 De Novo Mutation in a Danish Family with Early-Onset Spinocerebellar Ataxia. Cerebellum. 2017;16:268-271 pubmed publisher
    Spinocerebellar ataxia type 11 (SCA11) is rare and has previously been described in four families worldwide. We report a Danish family with onset of symptoms in early childhood and affected family members in two generations...
  8. Taylor L, McMillan P, Liachko N, Strovas T, Ghetti B, Bird T, et al. Pathological phosphorylation of tau and TDP-43 by TTBK1 and TTBK2 drives neurodegeneration. Mol Neurodegener. 2018;13:7 pubmed publisher
    ..Both TTBK1 and TTBK2 were initially identified as tau kinases and TTBK1 has been shown to phosphorylate tau epitopes commonly observed ..
  9. Lee S, Lee M, Choi T, Hong H, Seo J, Kim C, et al. MCRS1 associates with cytoplasmic dynein and mediates pericentrosomal material recruitment. Sci Rep. 2016;6:27284 pubmed publisher
    ..NDE1, MCRS1 played a positive role for the initiation of ciliogenesis, possibly through its interaction with TTBK2. Zebrafish with homozygous mcrs1 mutants exhibited a reduction in the size of the brain and the eye due to ..
  10. Xu Q, Zhang Y, Wei Q, Huang Y, Hu J, Ling K. Phosphatidylinositol phosphate kinase PIPKIγ and phosphatase INPP5E coordinate initiation of ciliogenesis. Nat Commun. 2016;7:10777 pubmed publisher
    ..PIPKIγ counteracts INPP5E in regulating tau-tubulin kinase-2 (TTBK2) recruitment to the basal body, which promotes the removal of microtubule capping protein CP110 and the subsequent ..
  11. Pan Y, Viklund I, Tsai H, Pettersson S, Maruyama I. The ulcerative colitis marker protein WAFL interacts with accessory proteins in endocytosis. Int J Biol Sci. 2010;6:163-71 pubmed
    ..Therefore, these results suggest that WAFL may play an important role in endocytosis and subsequent membrane trafficking by interacting with AP2 through KIAA0196 and KIAA1033. ..
  12. Dgany O, Avidan N, Delaunay J, Krasnov T, Shalmon L, Shalev H, et al. Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1. Am J Hum Genet. 2002;71:1467-74 pubmed
    ..The specific mechanisms by which codanin-1 underlies normal erythropoiesis remain to be elucidated. ..
  13. Zheng J, Liu X, Xue Y, Gong W, Ma J, Xi Z, et al. TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway. J Hematol Oncol. 2017;10:52 pubmed publisher
    ..Herein, the expression and function of circular RNA circ-TTBK2 were investigated in human glioma cells...
  14. Liachko N, McMillan P, Strovas T, Loomis E, Greenup L, Murrell J, et al. The tau tubulin kinases TTBK1/2 promote accumulation of pathological TDP-43. PLoS Genet. 2014;10:e1004803 pubmed publisher
    ..In this kinome-wide survey, we identified homologs of the tau tubulin kinases 1 and 2 (TTBK1 and TTBK2), which were also identified in a prior screen for kinase modifiers of TDP-43 behavioral phenotypes...
  15. Agbu S, Liang Y, Liu A, Anderson K. The small GTPase RSG1 controls a final step in primary cilia initiation. J Cell Biol. 2018;217:413-427 pubmed publisher
    ..RSG1 localizes to the mother centriole in a process that depends on tau tubulin kinase 2 (TTBK2), the CPLANE complex protein Inturned (INTU), and its own GTPase activity...
  16. Edener U, Kurth I, Meiner A, Hoffmann F, Hübner C, Bernard V, et al. Missense exchanges in the TTBK2 gene mutated in SCA11. J Neurol. 2009;256:1856-9 pubmed publisher
    ..Recently, two frameshift mutations in the tau tubulin kinase 2 gene (TTBK2) were reported to cause SCA11...
  17. Liao J, Yang T, Weng R, Kuo C, Chang C. TTBK2: a tau protein kinase beyond tau phosphorylation. Biomed Res Int. 2015;2015:575170 pubmed publisher
    b>Tau tubulin kinase 2 (TTBK2) is a kinase known to phosphorylate tau and tubulin. It has recently drawn much attention due to its involvement in multiple important cellular processes...
  18. Bauer P, Stevanin G, Beetz C, Synofzik M, Schmitz Hubsch T, Wullner U, et al. Spinocerebellar ataxia type 11 (SCA11) is an uncommon cause of dominant ataxia among French and German kindreds. J Neurol Neurosurg Psychiatry. 2010;81:1229-32 pubmed publisher
    ..Recently, a large British pedigree linked to SCA11 has been reported to carry a mutation in the TTBK2 gene...
  19. Choi K, Kim J, Kim H, Jung I, Jeong S, Lee S, et al. Genetic Variants Associated with Episodic Ataxia in Korea. Sci Rep. 2017;7:13855 pubmed publisher
    ..for screening of EA genes, potential pathogenic mutations were identified in the candidate genes ATP1A2, SCN1A, TTBK2, TGM6, FGF14, and KCND3...
  20. Lee S, Joo K, Jung E, Hong H, Seo J, Kim J. Export of membrane proteins from the Golgi complex to the primary cilium requires the kinesin motor, KIFC1. FASEB J. 2018;32:957-968 pubmed publisher
    ..A decrease in the centrosomal levels of IFT20 and TTBK2 (τ-tubulin kinase 2) was associated with ciliogenesis defects in KIFC1-depleted cells...
  21. Cajanek L, Nigg E. Cep164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole. Proc Natl Acad Sci U S A. 2014;111:E2841-50 pubmed publisher
    ..leads to early defects in ciliogenesis, reminiscent of the phenotypic consequences of mutations in TTBK2 (Tau tubulin kinase 2)...
  22. Guo T, Noble W, Hanger D. Roles of tau protein in health and disease. Acta Neuropathol. 2017;133:665-704 pubmed publisher
    ..Such knowledge will enable determination of which critical molecular pathways should be targeted by potential therapeutic agents developed for the treatment of tauopathies. ..
  23. Nieding K, Matschke V, Meuth S, Lang F, Seebohm G, Strutz Seebohm N. Tau Tubulin Kinase TTBK2 Sensitivity of Glutamate Receptor GluK2. Cell Physiol Biochem. 2016;39:1444-52 pubmed publisher
    ..autosomal dominant spinocerebellar ataxia type 11 (SCA11) is caused by loss of function mutations of TTBK2 (tau tubulin kinase 2). Mutations observed in patients with SCA11 include truncated TTBK2(450)...
  24. Lei Z, Wang D, Chen N, Ma K, Lu W, Song Z, et al. Synapse Innervation and Associative Memory Cell Are Recruited for Integrative Storage of Whisker and Odor Signals in the Barrel Cortex through miRNA-Mediated Processes. Front Cell Neurosci. 2017;11:316 pubmed publisher
  25. Worth P, Giunti P, Gardner Thorpe C, Dixon P, Davis M, Wood N. Autosomal dominant cerebellar ataxia type III: linkage in a large British family to a 7.6-cM region on chromosome 15q14-21.3. Am J Hum Genet. 1999;65:420-6 pubmed
    ..We excluded linkage of the disease phenotype to this region in the second family. These results indicate the presence of two additional ADCA III loci and more clearly define the genetic heterogeneity of ADCA III. ..
  26. Kitano Takahashi M, Morita H, Kondo S, Tomizawa K, Kato R, Tanio M, et al. Expression, purification and crystallization of a human tau-tubulin kinase 2 that phosphorylates tau protein. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007;63:602-4 pubmed
    Tau-tubulin kinase 2 (TTBK2) is a Ser/Thr kinase that putatively phosphorylates residues Ser208 and Ser210 (numbered according to a 441-residue human tau isoform) in tau protein...
  27. Xu Q, Li X, Wang J, Yi J, Lei L, Shen L, et al. Spinocerebellar ataxia type 11 in the Chinese Han population. Neurol Sci. 2010;31:107-9 pubmed publisher
    ..Researchers have recently found that SCA type 11 (SCA11) is associated with mutations in the TTBK2 gene...
  28. Oda T, Chiba S, Nagai T, Mizuno K. Binding to Cep164, but not EB1, is essential for centriolar localization of TTBK2 and its function in ciliogenesis. Genes Cells. 2014;19:927-40 pubmed publisher
    ..Recruitment of Tau tubulin kinase-2 (TTBK2) to the mother centriole and subsequent removal of CP110 and its interactor Cep97 are crucial for the initiation ..
  29. Brusco A, Gellera C, Cagnoli C, Saluto A, Castucci A, Michielotto C, et al. Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families. Arch Neurol. 2004;61:727-33 pubmed
    ..In patients negative for defects in known SCA genes, repeat expansion detection data strongly suggest that, at least in our population, CAG/CTG expansions in novel genes should be considered an unlikely cause of the SCA phenotype. ..
  30. Watanabe T, Kakeno M, Matsui T, Sugiyama I, Arimura N, Matsuzawa K, et al. TTBK2 with EB1/3 regulates microtubule dynamics in migrating cells through KIF2A phosphorylation. J Cell Biol. 2015;210:737-51 pubmed publisher
    ..However, how EBs contribute to MT dynamics through +TIPs remains elusive. We focused on tau-tubulin kinase 2 (TTBK2) as an EB1/3-binding kinase and confirmed that TTBK2 acted as a +TIP...
  31. Wang C, Saar V, Leung K, Chen L, Wong G. Human amyloid ? peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans. Neurobiol Dis. 2018;109:88-101 pubmed publisher
    ..2 (TTBK2) could suppress these behaviors. Comparing the list of regulated genes from C...