TTBK1 » Tau-tubulin kinase 1

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Protein also known as: Brain-derived tau kinase.

Gene name: TTBK1

Family name: Protein kinase » CK1 Ser/Thr protein kinase

One or more isoforms of this protein have been shown to exist at protein level

Protein

Recommended name: Tau-tubulin kinase 1
Alternative name: Brain-derived tau kinase
Spliced into the following 2 isoforms: Iso 1; Iso 2

Gene

Recommended name: TTBK1
Alternative names: BDTK; KIAA1855

Family

Superfamily: Protein kinase
Family: CK1 Ser/Thr protein kinase

History

neXtProt: Integrated 2010-03-01; Last updated 2013-02-18
UniProtKB: Integrated 2006-05-16; Updated 2012-11-28; Entry version 76; Last sequence update 2006-05-16; Sequence version 2; Complete UniProtKB history

One or more isoforms of this protein have been shown to exist at protein level

extend overview

1 16 2

GENE REF ISO

Function

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Overview

Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU.

Evidence 2: Curated UniProtKB

Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation.

Sato S., Cerny R.L., Buescher J.L., Ikezu T.

J. Neurochem. 98, 1573-1584 (2006) [Full text:10.1111/j.1471-4159.2006.04059.x] [PubMed:16923168]

Neurofibrillary tangles, which are major pathological hallmarks of Alzheimer's disease (AD), are composed of paired helical filaments (PHFs) containing hyperphosphorylated tau. Specific kinases regulate tau phosphorylation and are closely linked to the pathogenesis of AD. We have characterized a human tau-tubulin kinase 1 (TTBK1) gene located on chromosome 6p21.1. TTBK1 is a serine/threonine/tyrosine kinase that is conserved among species and belongs to the casein kinase 1 superfamily. It is specifically expressed in the brain, especially in the cytoplasm of cortical and hippocampal neurons. TTBK1 phosphorylates tau proteins in both a Mg2+- and a Mn2+-dependent manner. Phosphopeptide mapping and immunoblotting analysis confirmed a direct tau phosphorylation by TTBK1 at Ser198, Ser199, Ser202 and Ser422, which are also phosphorylated in PHFs. TTBK1 also induces tau aggregation in human neuronal cells in a dose-dependent manner. We conclude that TTBK1 is a neuron-specific dual kinase involved in tau phosphorylation at AD-related sites and is also associated with tau aggregation.

ref

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CuratedUniProtKB

GO molecular function

ATP bindingdefinition[GO:0005524]

Interacting selectively and non-covalently with ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.

IEAUniProtKB KW

Protein serine/threonine kinase activitydefinition[GO:0004674]

Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.

IEAUniProtKB KW

Enzymatic activity

This protein acts as an enzyme. It is known to catalyze the following reaction

EC 2.7.11.1: ATP + a protein ⇄ ADP + a phosphoprotein.

Evidence 2: Curated UniProtKB

Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation.

Sato S., Cerny R.L., Buescher J.L., Ikezu T.

J. Neurochem. 98, 1573-1584 (2006) [Full text:10.1111/j.1471-4159.2006.04059.x] [PubMed:16923168]

Neurofibrillary tangles, which are major pathological hallmarks of Alzheimer's disease (AD), are composed of paired helical filaments (PHFs) containing hyperphosphorylated tau. Specific kinases regulate tau phosphorylation and are closely linked to the pathogenesis of AD. We have characterized a human tau-tubulin kinase 1 (TTBK1) gene located on chromosome 6p21.1. TTBK1 is a serine/threonine/tyrosine kinase that is conserved among species and belongs to the casein kinase 1 superfamily. It is specifically expressed in the brain, especially in the cytoplasm of cortical and hippocampal neurons. TTBK1 phosphorylates tau proteins in both a Mg2+- and a Mn2+-dependent manner. Phosphopeptide mapping and immunoblotting analysis confirmed a direct tau phosphorylation by TTBK1 at Ser198, Ser199, Ser202 and Ser422, which are also phosphorylated in PHFs. TTBK1 also induces tau aggregation in human neuronal cells in a dose-dependent manner. We conclude that TTBK1 is a neuron-specific dual kinase involved in tau phosphorylation at AD-related sites and is also associated with tau aggregation.

ref

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CuratedUniProtKB

It requires the following cofactor

Divalent cations. Magnesium or, to a lesser extent, manganese, but not calcium or zinc.

Evidence 2: Curated UniProtKB

Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation.

Sato S., Cerny R.L., Buescher J.L., Ikezu T.

J. Neurochem. 98, 1573-1584 (2006) [Full text:10.1111/j.1471-4159.2006.04059.x] [PubMed:16923168]

Neurofibrillary tangles, which are major pathological hallmarks of Alzheimer's disease (AD), are composed of paired helical filaments (PHFs) containing hyperphosphorylated tau. Specific kinases regulate tau phosphorylation and are closely linked to the pathogenesis of AD. We have characterized a human tau-tubulin kinase 1 (TTBK1) gene located on chromosome 6p21.1. TTBK1 is a serine/threonine/tyrosine kinase that is conserved among species and belongs to the casein kinase 1 superfamily. It is specifically expressed in the brain, especially in the cytoplasm of cortical and hippocampal neurons. TTBK1 phosphorylates tau proteins in both a Mg2+- and a Mn2+-dependent manner. Phosphopeptide mapping and immunoblotting analysis confirmed a direct tau phosphorylation by TTBK1 at Ser198, Ser199, Ser202 and Ser422, which are also phosphorylated in PHFs. TTBK1 also induces tau aggregation in human neuronal cells in a dose-dependent manner. We conclude that TTBK1 is a neuron-specific dual kinase involved in tau phosphorylation at AD-related sites and is also associated with tau aggregation.

ref

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CuratedUniProtKB

Keywords

Molecular function

Kinase definition [KW-0418]

Enzyme that catalyzes the transfer of phosphate (phosphoryl or pyrophosphoryl transfer) usually from ATP to a second substrate.

Serine/threonine-protein kinase definition [KW-0723]

Protein which catalyzes the phosphorylation of serine or threonine residues on target proteins by using ATP as phosphate donor. Such phosphorylation may cause changes in the function of the target protein. Protein kinases share a conserved catalytic core common to both serine/ threonine and tyrosine protein kinases.

Transferase definition [KW-0808]

Enzyme that transfers a chemical group, e.g. a methyl group or a glycosyl group from one compound (donor) to another compound (acceptor).

Technical term

Reference proteome definition [KW-1185]

A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.

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Function

Keywords

neXtProt