TAOK2: A Key Regulator of Hippo Signaling and Neurodevelopment
Comprehensive genomic and functional analysis of TAOK2, a serine/threonine-protein kinase involved in neuronal development, cytoskeletal dynamics, and cancer.
Gene Information Card
| Symbol | TAOK2 |
|---|---|
| Full Name | TAO kinase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 9344 ncbi.nlm.nih.gov/gene/9344 |
| Ensembl ID | ENSG00000149925 |
| UniProt ID | Q9UL54 |
| OMIM ID | 616221 |
| HGNC ID | 29259 |
| Aliases | MAP3K17, PSK, TAO1, TAO2, KIAA0881 |
Description
TAOK2 (TAO kinase 2) encodes a serine/threonine-protein kinase belonging to the STE20/MAP4K family. It acts as a mitogen-activated protein kinase kinase kinase (MAP3K) that activates the p38 MAPK and JNK pathways. TAOK2 is critical for neuronal development, including dendrite morphogenesis and axon outgrowth, and regulates the Hippo signaling pathway by phosphorylating and activating MST1/2. It is also involved in cytoskeletal dynamics through interaction with microtubules and actin. Dysregulation of TAOK2 is linked to neurodevelopmental disorders such as autism spectrum disorder (ASD) and to various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autism spectrum disorder (ASD) | Copy number variations (deletions/duplications) at 16p11.2 disrupt TAOK2 expression, impairing dendritic spine development and synaptic function. | PMID: 25918371, ClinVar |
| Schizophrenia | Rare variants in TAOK2 are associated with increased risk, possibly through altered neuronal signaling. | PMID: 27816956 |
| Intellectual disability | De novo mutations in TAOK2 contribute to cognitive impairment via disrupted kinase activity. | PMID: 28191889 |
| Breast cancer | TAOK2 overexpression promotes tumor cell migration and invasion via p38 MAPK activation. | COSMIC, PMID: 23541953 |
| Colorectal cancer | TAOK2 mutations and altered expression correlate with poor prognosis and metastasis. | COSMIC, PMID: 29187737 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (cerebellum) | 10.2 | Medium |
| Testis | 8.9 | Medium |
| Lung | 6.3 | Low |
| Liver | 4.1 | Low |
| Heart | 3.8 | Low |
| Kidney | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression; used for neuronal studies |
| HeLa (cervical carcinoma) | 8.7 | Moderate expression |
| MCF7 (breast cancer) | 11.2 | High expression; linked to invasion |
| HCT116 (colorectal carcinoma) | 9.5 | Moderate expression |
| HEK293 (embryonic kidney) | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1124C>T (p.Pro375Leu) | Missense | <0.01% | Likely loss-of-function; associated with ASD |
| c.1885G>A (p.Glu629Lys) | Missense | <0.01% | Unknown significance; reported in schizophrenia |
| c.2146_2147insA (p.Thr716Asnfs*5) | Frameshift | <0.01% | Loss-of-function; truncation |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss-of-function; no protein produced |
| Amplification (16p11.2) | Copy number gain | 0.1-0.5% | Gain-of-function; overexpression in cancer |
Mutation functional classification
Loss of Function (LOF)
Missense (e.g., p.Pro375Leu) and truncating mutations (e.g., p.Thr716Asnfs*5) reduce kinase activity or protein stability, impairing neuronal development and contributing to ASD and intellectual disability.
Gain of Function (GOF)
Gene amplification at 16p11.2 leads to TAOK2 overexpression, enhancing p38 MAPK signaling and promoting cancer cell migration and invasion.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported; however, some missense variants may interfere with wild-type TAOK2 function in heterozygotes.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hippo signaling pathway (Reactome: R-HSA-2028269)
• p38 MAPK signaling pathway (Reactome: R-HSA-171007)
• JNK (c-Jun N-terminal kinase) cascade (Reactome: R-HSA-450294)
• Signaling by Rho GTPases (Reactome: R-HSA-194315)
• Developmental biology (Reactome: R-HSA-1266738)
Protein Summary
TAOK2 is a 1,235-amino-acid serine/threonine-protein kinase with an N-terminal kinase domain, a central coiled-coil region, and a C-terminal regulatory domain. It localizes to the cytoplasm, centrosome, and microtubules. TAOK2 phosphorylates and activates MST1/2 in the Hippo pathway, and also activates MAP2K3/6 to trigger p38 MAPK signaling. In neurons, it promotes dendrite arborization and spine maturation. In cancer, TAOK2 overexpression drives metastasis. The protein interacts with multiple partners including MAP2K3, MAP2K6, MST1, MST2, and tubulin.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TAOK2 Knockout HEK293 Cell Line | EDJ-KQ238 | Human | 9344 | Details Get a Quote |
| TAOK2 Knockout A-549 Cell Line | EDJ-KQ19426 | Human | 9344 | Details Get a Quote |
| TAOK2 Knockout HCT 116 Cell Line | EDJ-KQ19428 | Human | 9344 | Details Get a Quote |
| TAOK2 Knockout HeLa Cell Line | EDJ-KQ19429 | Human | 9344 | Details Get a Quote |
| TAOK2 Knockout HAP1 Cell Line | EDC07807 | Human | 9344 | Details Get a Quote |
