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Literature summary for 2.7.11.26 extracted from
- TTBK2: a tau protein kinase beyond tau phosphorylation (2015), BioMed Res. Int., 2015, 575170.
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoplasm | - |
Homo sapiens | 5737 | - |
| additional information | TTBK2 localization sites include the centriole/basal body, the midbody, and possibly the mitotic spindles | Mus musculus | - |
- |
| additional information | TTBK2 localization sites include the centriole/basal body, the midbody, and possibly the mitotic spindles. Localization at the base of primary cilia | Homo sapiens | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Mus musculus |  |
| Mg2+ | required | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + tubulin | Mus musculus | - |
ADP + phospho-tubulin | - |
? | |
| ATP + tubulin | Homo sapiens | - |
ADP + phospho-tubulin | - |
? | |
| ATP + [tau-protein] | Mus musculus | - |
ADP + O-phospho-[tau-protein] | - |
? | |
| ATP + [tau-protein] | Homo sapiens | phosphorylation at Ser208 and Ser210 | ADP + O-phospho-[tau-protein] | - |
? | |
| additional information | Homo sapiens | in addition to autophosphorylation, known phosphorylation substrates of TTBK2 include tau, tubulin, CEP164, CEP97, and TDP-43, a neurodegeneration-associated protein. The enzyme binds to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q6IQ55 | - |
- |
| Mus musculus | Q3UVR3 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| kidney adenocarcinoma cell | - |
Homo sapiens | - |
| lung adenocarcinoma cell | - |
Homo sapiens | - |
| melanoma cell | - |
Homo sapiens | - |
| additional information | upregulated TTBK2 in kidney carcinoma and melanoma cell lines | Homo sapiens | - |
| neuron | high expression level | Mus musculus | - |
| neuron | high expression level | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + CEP164 | - |
Mus musculus | ADP + phospho-CEP164 | - |
? | |
| ATP + CEP164 | - |
Homo sapiens | ADP + phospho-CEP164 | - |
? | |
| ATP + CEP97 | - |
Mus musculus | ADP + phospho-CEP97 | - |
? | |
| ATP + CEP97 | - |
Homo sapiens | ADP + phospho-CEP97 | - |
? | |
| ATP + TDP-43 | - |
Mus musculus | ADP + phospho-TDP-43 | - |
? | |
| ATP + TDP-43 | - |
Homo sapiens | ADP + phospho-TDP-43 | - |
? | |
| ATP + tubulin | - |
Mus musculus | ADP + phospho-tubulin | - |
? | |
| ATP + tubulin | - |
Homo sapiens | ADP + phospho-tubulin | - |
? | |
| ATP + [tau-protein] | - |
Mus musculus | ADP + O-phospho-[tau-protein] | - |
? | |
| ATP + [tau-protein] | phosphorylation at Ser208 and Ser210 | Homo sapiens | ADP + O-phospho-[tau-protein] | - |
? | |
| additional information | the enzyme performs autophosphorylation | Mus musculus | ? | - |
? | |
| additional information | the enzyme performs autophosphorylation | Homo sapiens | ? | - |
? | |
| additional information | in addition to autophosphorylation, known phosphorylation substrates of TTBK2 include tau, tubulin, CEP164, CEP97, and TDP-43, a neurodegeneration-associated protein. The enzyme binds to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein | Homo sapiens | ? | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| More | TTBK2 possesses a casein kinase 1 (CK1) kinase domain followed by a about 900 amino acid segment, potentially responsible for its localization and substrate recruitment | Homo sapiens |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| tau protein kinase | - |
Mus musculus |
| tau protein kinase | - |
Homo sapiens |
| tau tubulin kinase 2 | - |
Mus musculus |
| tau tubulin kinase 2 | - |
Homo sapiens |
| TTBK2 | - |
Mus musculus |
| TTBK2 | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Mus musculus | |
| ATP | - |
Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | TTBK2 is a serine/threonine protein kinase of the CK1 superfamily | Mus musculus |
| evolution | TTBK2 is a serine/threonine protein kinase of the CK1 superfamily | Homo sapiens |
| malfunction | knockout TTBK2fmly1/fmly1 mice with homozygous mutants of truncated TTBK2 at residue 450 are embryonic lethal at embryonic day 10, with indistinct brain subdivisions, distorted caudal bodies, and delayed body and brain development. Heterozygous mutant TTBK2fmly1/+ mice are completely normal and exhibit a regular lifespan | Mus musculus |
| malfunction | mutations of TTBK2 are associated with spinocerebellar ataxia type 11. Mutation of TTBK2 may potentially be more serious than mutations of other proteins involved in ciliopathies. Upregulated TTBK2 in kidney carcinoma and melanoma cell lines is correlated with resistance of the target therapeutic drug Sunitinib, while knockdown of TTBK2 in these cells increases Sunitinib sensitivity. Reduction of TTBK2 also increases Sunitinib inhibition of cancer cell migration. The enzyme phosphorylates transactive response (TAR) DNA-binding protein 43, or TDP-43, a DNA/RNA binding protein responsible for transcriptional repression, pre-mRNA splicing, and translational regulation. Hyperphosphorylation-associated aggregation of TDP-43 is a signature of two neurodegenerative diseases: amyotrophic sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP). Phosphorylation of TDP-43 by both TTBK1 and TTBK2 overexpression results in relocalization of TDP-43 from the nucleus to the cytosol. TTBK1/TTBK2 colocalize with phospho-TDP-43 in the frontal cortex of FTLD-TDP patients and in the spinal cord of ALS patients, suggesting that phosphorylation of TDP-43 by both TTBK1 and TTBK2 likely plays a role in progression of these diseases | Homo sapiens |
| additional information | structure and sequence analysis of TTBK2, potential homologues of the TTBK2 noncatalytic region, detailed overview | Homo sapiens |
| physiological function | TTBK2 is a multifunctional kinase. 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. The enzyme binds to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein. The TTBK2 pathway may be independent of the biogenesis of the ciliary transition zone. TTBK2 can also bind to EB1 through its SxIP motifs, where EB1 is a microtubule plus-end tracking protein required for ciliogenesis | Mus musculus |
| physiological function | TTBK2 is a multifunctional kinase. 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. The enzyme binds to CEP164, a centriolar protein, and EB1, a microtubule plus-end tracking protein. The TTBK2 pathway may be independent of the biogenesis of the ciliary transition zone. TTBK2 can also bind to EB1 through its SxIP motifs, where EB1 is a microtubule plus-end tracking protein required for ciliogenesis | Homo sapiens |
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