Tau-Tubulin Kinase 2 (tTBK2)

TTBK2 produces a 5.6-kb transcript in which the longest open reading frame is 3,732 nucleotides, encoding a protein of 1,244 amino acids. The gene is alternatively spliced, with ubiquitous expression in human adult and fetal tissues. The N-terminus of TTBK2 encodes a serine-threonine-tyrosine kinase domain, and a C-terminal region shows homology to TTBK1. TTBK2 was expressed in all brain regions in human, rat, and mouse tissue. There was particularly high expression in Purkinje cells of the cerebellum, granular cell layer, hippocampus, midbrain, and substantia nigra. Lower expression was seen in the cortex of human, rat, and mouse brains.2 TTBK2 phosphorylation sites in tau (ser208 and ser210) are priming sites for the phosphorylation of tau by GSK-3-beta, which influences tau pathology.