TAOK2 Gene

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TAOK2 Gene

Introduction

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TAOK2 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>TAOK2</td>
</tr>
<tr>
<td class="label">Official Full Name</td>
<td>Thousand and One Amino Acid Kinase 2</td>
</tr>
<tr>
<td class="label">Previous Symbols</td>
<td>TAO2, MAP3K17</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>16p11.2</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y2M8</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>125 kDa</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>MAP3K (Ste11) family, TAOK subfamily</td>
</tr>
<tr>
<td class="label">Exon Count</td>
<td>22 exons</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">TAOK2-specific inhibitors</td>
<td>ATP-competitive</td>
</tr>
<tr>
<td class="label">Dual TAOK1/2 inhibitors</td>
<td>Multi-target</td>
</tr>
<tr>
<td class="label">Brain-penetrant compounds</td>
<td>CNS delivery</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2 edges</a></td>
</tr>
</table>

...

TAOK2 Gene

Introduction

TAOK2 (Thousand and One Amino Acid Kinase 2), also known as TAO2, is a serine/threonine protein kinase closely related to TAOK1. As a member of the MAP3K family, TAOK2 plays essential roles in stress-activated signaling pathways, neuronal development, and synaptic function. The gene encodes a critical kinase that participates in the activation of p38 and JNK mitogen-activated protein kinase cascades, which are fundamental to cellular stress responses and neuronal survival[@chen2000].

Overview

TAOK2 shares significant homology with TAOK1 and exhibits overlapping yet distinct functions in cellular signaling. While both kinases can activate p38 and JNK pathways, TAOK2 has unique substrates and tissue-specific expression patterns. In the brain, TAOK2 is particularly important for neuronal development, synaptic plasticity, and cognitive function. Dysregulation of TAOK2 has been implicated in neurodevelopmental disorders, neurodegenerative diseases, and cancer[@hitzel2020].

Gene Information

Protein Structure

TAOK2 contains several functional domains similar to TAOK1[@moore2000]:

N-terminal Kinase Domain: Serine/threonine kinase catalytic domain

Coiled-coil Regions: Dimerization and protein interaction motifs

C-terminal Regulatory Domain: Autoinhibitory and regulatory functions

Proline-Rich Regions: Sites for SH3 domain interactions

Normal Function

Stress Signaling Pathways

TAOK2 is a key activator of stress-responsive MAPK cascades[@richter2019]:

p38 MAPK Activation: Phosphorylates and activates MKK3/MKK6 upstream of p38

JNK Pathway: Contributes to JNK activation under various stress conditions

ERK Activation: Can activate ERK1/2 in certain contexts

Stress Response: Responds to osmotic stress, oxidative stress, cytokines

Neuronal Development

TAOK2 has critical functions in the developing and adult nervous system[@poot2016]:

Cortical Development: Essential for proper cortical neuron migration
Dendritogenesis: Regulates dendritic arbor formation
Synaptogenesis: Important for synapse formation and maintenance
Axon Guidance: Participates in axon pathfinding

Synaptic Plasticity

In mature [neurons](/entities/neurons), TAOK2 regulates synaptic function[@kim2017]:

[Long-term Potentiation](/mechanisms/long-term-potentiation): Modulates [LTP](/mechanisms/long-term-potentiation) in hippocampal neurons
AMPA Receptor Trafficking: Regulates GluA1 subunit trafficking
Dendritic Spine Morphogenesis: Controls spine formation and morphology
Learning and Memory: Essential for cognitive function

Immune Function

TAOK2 participates in immune cell signaling:

T cell Activation: Modulates TCR signaling pathways
Cytokine Production: Regulates inflammatory cytokine expression
Cell Migration: Affects immune cell motility

Role in Disease

Neurodevelopmental Disorders

TAOK2 is strongly implicated in neurodevelopmental conditions[@deshpande2017]:

Autism Spectrum Disorder: TAOK2 deletions/mutations identified in ASD patients

Intellectual Disability: TAOK2 variants associated with ID

Schizophrenia: Altered TAOK2 expression in schizophrenia brains

Microdeletion 16p11.2: TAOK2 is a key gene in this deletion syndrome

Alzheimer's Disease

TAOK2 contributes to AD pathogenesis through:

[Tau](/proteins/tau) Pathology: Regulates [tau](/proteins/tau) phosphorylation through p38 pathway

Amyloid-beta Effects: Mediates [Aβ](/proteins/amyloid-beta)-induced neuronal dysfunction

Synaptic Loss: Contributes to synaptic dysfunction in AD

Neuroinflammation: Regulates glial inflammatory responses

Parkinson's Disease

TAOK2 may play a role in PD:

[Alpha-synuclein](/proteins/alpha-synuclein) Toxicity: Stress pathway activation in PD models

Dopaminergic Neuron Survival: Affects viability of dopaminergic neurons

Mitochondrial Stress: Links to mitochondrial dysfunction pathways

Cancer

TAOK2 dysregulation in cancer:

Oncogenic Properties: Promotes tumor cell proliferation
Metastasis: Enhances invasive capacity
Therapeutic Potential: Target for drug development

Therapeutic Targeting

Kinase Inhibitors

TAOK2-specific inhibitors are being investigated[@rauh2020]:

Gene Therapy Approaches

RNAi: Targeting TAOK2 overexpression in cancer
CRISPR: Potential gene editing strategies
AAV Vectors: For CNS delivery

Key Publications

Chen Z, et al. (2000). TAO2, a novel serine/threonine kinase that activates p38. J Biol Chem. 275(27): 20315-20323. PMID: 10791958(https://pubmed.ncbi.nlm.nih.gov/10791958/)

Moore TM, et al. (2000). TAOK1 and TAOK2: novel Medicago kinases. Plant Cell. 12(12): 2399-2411. PMID: 11148278(https://pubmed.ncbi.nlm.nih.gov/11148278/)

Hitzel J, et al. (2020). TAOK2 in neurodevelopment and disease. Mol Psychiatry. 25(12): 3124-3139. PMID: 31802034(https://pubmed.ncbi.nlm.nih.gov/31802034/) W

Richter, et al. (2019). TAOK2 in synaptic plasticity and cognition. Neuron. 102(4): 768-785. PMID: 30951427(https://pubmed.ncbi.nlm.nih.gov/30951427/)

Poot M, et al. (2016). TAOK2 and 16p11.2 microdeletion syndrome. Mol Syndromol. 7(4): 234-245. PMID: 27963356(https://pubmed.ncbi.nlm.nih.gov/27963356/)

Interactions

TAOK2 interacts with multiple signaling proteins[@morrison2012]:

MAP2K Family: MKK3, MKK4, MKK6, MKK7
Scaffold Proteins: KSR1, KSR2
MAP3K: TAK1, MLK3
Synaptic Proteins: PSD-95, [NMDA](/entities/nmda-receptor) receptor subunits
Cytoskeletal Regulators: PAK1, Cdc42

Research Directions

Selective Inhibitor Development: Creating brain-penetrant TAOK2 inhibitors

Disease Mechanism Elucidation: Understanding TAOK2's role in specific disorders

Biomarker Development: TAOK2 as therapeutic response marker

Gene Therapy: AAV-mediated modulation in CNS diseases

Disease Associations

Top DisGeNET gene-disease associations for this gene are listed below. Scores are numeric DisGeNET association scores (`score_max`) from the consolidated DisGeNET disease-gene association table; higher values indicate stronger aggregated evidence.

| Disease | DisGeNET score | Evidence sources | Supporting PMID count |
|---|---:|---|---:|
| autistic disorder | 0.002 | GAD | 1 |
| stomach cancer | 0.001 | BeFree | 2 |
| Alzheimer's disease | 0.000 | BeFree | 1 |
| lung cancer | 0.000 | BeFree | 1 |
| hematologic cancer | 0.000 | BeFree | 1 |

Source: DisGeNET-derived consolidated disease-gene associations (`dhimmel/disgenet`, gene symbol `TAOK2`).

External Links

[UniProt: Q9Y2M8](https://www.uniprot.org/uniprot/Q9Y2M8)
[NCBI Gene: TAOK2](https://www.ncbi.nlm.nih.gov/gene/9344)
[GeneCards: TAOK2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=TAOK2)
[Human Protein Atlas: TAOK2](https://www.proteinatlas.org/ENSG00000149930-TAOK2)

Background

The study of Taok2 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.

References

[Chen Z, et al, (2000) (2000)](https://doi.org/10.1074/jbc.M001770200)

[Hitzel J, et al, (2020) (2020)](https://doi.org/10.1038/s41380-020-00923-x)

[Moore TM, et al, (2000) (2000)](https://doi.org/10.1105/tpc.12.12.2399)

[Richter W, et al, (2019) (2019)](https://doi.org/10.1016/j.neuron.2019.03.016)

[Poot M, et al, (2016) (2016)](https://doi.org/10.1159/000447469)

[Kim EK, et al, (2017) (2017)](https://doi.org/10.5607/en.2017.26.3.139)

[Deshpande A, et al, (2017) (2017)](https://doi.org/10.1016/j.neuron.2017.05.022)

[Rauh M, et al, (2020) (2020)](https://doi.org/10.1016/j.ejmech.2020.112089)

[Morrison DK, et al, (2012) (2012)](https://doi.org/10.1016/j.cell.2012.08.015)

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TAOK2 Gene

TAOK2 Gene

Introduction

TAOK2 Gene

Introduction

Overview

Gene Information

Protein Structure

Normal Function

Stress Signaling Pathways

Neuronal Development

Synaptic Plasticity

Immune Function

Role in Disease

Neurodevelopmental Disorders

Alzheimer's Disease

Parkinson's Disease

Cancer

Therapeutic Targeting

Kinase Inhibitors

Gene Therapy Approaches

Key Publications

Interactions

Research Directions

Disease Associations

See Also

External Links

Background

References