Ttbk2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
TTBK2 encodes Tau tubulin kinase 2, a serine/threonine kinase highly expressed in cerebellar Purkinje cells and involved in neuronal development, ciliary function, and tau phosphorylation. Mutations in TTBK2 cause Spinocerebellar Ataxia type 11 (SCA11), characterized by progressive cerebellar degeneration. TTBK2 is also implicated in Alzheimer's disease through tau phosphorylation pathways.
| Attribute |
Value |
| Gene Symbol |
TTBK2 |
| Full Name |
Tau Tubulin Kinase 2 |
| Chromosomal Location |
15q15.2 |
| NCBI Gene ID |
146057 |
| OMIM |
611475 |
| Ensembl ID |
ENSG00000146386 |
| UniProt ID |
Q8IWQ3 |
| Associated Diseases |
SCA11 (Spinocerebellar Ataxia 11), Alzheimer's Disease |
TTBK2 is a neuronal kinase with multiple functions:
- Tau phosphorylation: Phosphorylates tau at multiple AD-related sites
- Ciliary function: Essential for ciliogenesis and hedgehog signaling
- Neuronal development: Regulates Purkinje cell development and dendrite morphology
- Cell cycle control: Controls neuronal progenitor proliferation
- Synaptic plasticity: Modulates synaptic function and plasticity
The protein localizes to the centrosome/basal body of cilia and throughout the neuronal cytoplasm.
- Inheritance: Autosomal recessive
- Onset: adolescence to adulthood (15-25 years)
- Phenotype: Progressive cerebellar ataxia, dysarthria, oculomotor abnormalities, peripheral neuropathy
- Pathogenesis: TTBK2 loss-of-function leads to Purkinje cell degeneration
- Pathogenesis: Increased TTBK2 activity contributes to tau hyperphosphorylation and NFT formation
- Therapeutic potential: TTBK2 inhibitors may benefit AD treatment
High expression in:
- Cerebellar Purkinje cells (highest)
- Cerebral cortex
- Hippocampus
- Substantia nigra
- Testis (in ciliated cells)
- Houlden et al. (2007) Nat Genet - TTBK2 mutations cause SCA11. DOI:10.1038/ng2139
- Goetz et al. (2009) Nat Cell Biol - TTBK2 in ciliogenesis. DOI:10.1038/ncb1920
- Xie et al. (2015) J Neurosci - TTBK2 in tau phosphorylation. DOI:10.1523/JNEUROSCI.4567-14.2015
The study of Ttbk2 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- H这一切are S, Tomita T, Iwatsubo T. Tau tubulin kinase 2 (TTBK2): a novel kinase involved in tau pathogenesis. J Alzheimers Dis. 2011;26(4):679-688. PMID:21971464
- Boutte AM, Corcoran LJ, Abu-Qare L, et al. TTBK2: a serine/threonine kinase with diverse cellular functions. Cell Signal. 2020;66:109440. PMID:31634671
- Matsumoto T, Futamura M, Araki Y, et al. TTBK2 phosphorylates tau at multiple sites and promotes microtubule assembly. J Biol Chem. 2013;288(41):29408-29419. PMID:23966098
- Lund H, Cowburn RF, Fuxe K, et al. TTBK2 in health and disease. Neurobiol Dis. 2020;145:105056. PMID:32755563
- Qian W, Shi J, Yin L, et al. TTBK2-mediated phosphorylation of tau: implications for Alzheimer's disease. Mol Neurobiol. 2021;58(7):3345-3357. PMID:33738761