title: TTBK2: a tau protein kinase beyond tau phosphorylation.
abstract: 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. Here, we review the current understanding of TTBK2, including its sequence, structure, binding sites, phosphorylation substrates, and cellular processes involved. TTBK2 possesses a casein kinase 1 (CK1) kinase domain followed by a ~900 amino acid segment, potentially responsible for its localization and substrate recruitment. It is known to bind to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein. In addition to autophosphorylation, known phosphorylation substrates of TTBK2 include tau, tubulin, CEP164, CEP97, and TDP-43, a neurodegeneration-associated protein. Mutations of TTBK2 are associated with spinocerebellar ataxia type 11. In addition, TTBK2 is essential for regulating the growth of axonemal microtubules in ciliogenesis. It also plays roles in resistance of cancer target therapies and in regulating glucose and GABA transport. Reported sites of TTBK2 localization include the centriole/basal body, the midbody, and possibly the mitotic spindles. Together, TTBK2 is a multifunctional kinase involved in important cellular processes and demands augmented efforts in investigating its functions.
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, No. 1, Roosevelt Road, Section 4, Taipei 10617, Taiwan.
authors.forename: Jung-Chi
authors.initials: JC
authors.lastname: Liao
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, No. 1, Roosevelt Road, Section 4, Taipei 10617, Taiwan.
authors.forename: T Tony
authors.initials: TT
authors.lastname: Yang
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, No. 1, Roosevelt Road, Section 4, Taipei 10617, Taiwan.
authors.forename: Rueyhung Roc
authors.initials: RR
authors.lastname: Weng
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, No. 1, Roosevelt Road, Section 4, Taipei 10617, Taiwan.
authors.forename: Ching-Te
authors.initials: CT
authors.lastname: Kuo
authors.affiliation: Institute of Atomic and Molecular Sciences, Academia Sinica, No. 1, Roosevelt Road, Section 4, Taipei 10617, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Chang
mesh_terms: D001665:Binding Sites; D006801:Humans; D008868:Microtubule Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C524694:CEP164 protein, human; C500985:MAPRE1 protein, human; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D014404:Tubulin; D016875:tau Proteins; C095903:tau-tubulin kinase; D017346:Protein Serine-Threonine Kinases