MAPK10 (JNK3): A Key Stress-Activated Kinase in Neuronal and Cancer Biology
Comprehensive genomic, functional, and clinical insights into MAPK10, a member of the c-Jun N-terminal kinase family, with implications in neurodegeneration, cancer, and inflammatory disorders.
Gene Information Card
| Symbol | MAPK10 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase 10 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q21.3 |
| NCBI Gene ID | 5602 ncbi.nlm.nih.gov/gene/5602 |
| Ensembl ID | ENSG00000109339 |
| UniProt ID | P53779 |
| OMIM ID | 602897 |
| HGNC ID | 6872 |
| Aliases | JNK3, JNK3A, JNK3B, p493F12, PRKM10, SAPK1b |
Description
MAPK10 encodes the c-Jun N-terminal kinase 3 (JNK3), a serine/threonine protein kinase that belongs to the mitogen-activated protein kinase (MAPK) family. JNK3 is predominantly expressed in the brain, but also in other tissues. It is activated by various stress stimuli, including inflammatory cytokines, UV radiation, and oxidative stress, and plays critical roles in neuronal apoptosis, synaptic plasticity, and neurodegeneration. MAPK10 is also implicated in cancer, where its expression and mutations can influence tumor progression and drug resistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegenerative disorders (e.g., Alzheimer's, Parkinson's, Huntington's) | JNK3 activation promotes neuronal apoptosis via phosphorylation of c-Jun and other substrates, contributing to disease pathology. | PMID: 12873373; PMID: 15608628 |
| Epilepsy | JNK3 is activated in seizure-induced neuronal injury and modulates excitotoxicity. | PMID: 10433269 |
| Ischemic stroke | JNK3 mediates neuronal death following cerebral ischemia. | PMID: 12604775 |
| Cancer (e.g., glioblastoma, breast, lung) | MAPK10 mutations and altered expression affect cell proliferation, apoptosis, and chemosensitivity. | COSMIC; PMID: 21746835 |
| Inflammatory diseases | JNK3 regulates inflammatory cytokine production and immune responses. | PMID: 15917231 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | Brain-specific expression, especially in neurons |
| Testis | Moderate | Detected in testis |
| Heart | Low | Low expression |
| Kidney | Low | Low expression |
| Liver | Not detected | No significant expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal cell line, used for JNK3 studies |
| U87MG (glioblastoma) | Moderate | Expression associated with tumor aggressiveness |
| HeLa (cervical carcinoma) | Low | Low expression |
| MCF7 (breast cancer) | Moderate | Expression linked to apoptosis regulation |
| A549 (lung carcinoma) | Low | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg191Cys | Missense | Rare (0.01%) | Potential loss of kinase activity; observed in cancer |
| p.Pro252Leu | Missense | Rare | Functional impact unknown; found in COSMIC |
| p.Gly364Arg | Missense | Rare | May affect ATP binding; reported in cancer |
| c.1125+1G>A | Splice site | Rare | Predicted to disrupt splicing; clinical significance unknown |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair kinase activity or protein stability, leading to reduced JNK3 signaling, may contribute to neurodevelopmental defects or altered stress responses.
Gain of Function (GOF)
Some mutations may enhance JNK3 activity, promoting excessive apoptosis or oncogenic signaling, though evidence is limited.
Dominant Negative (DN)
Certain mutations could produce a dominant-negative effect, interfering with wild-type JNK3 function, but no confirmed clinical examples are documented.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein kinase activity |
| • MAP kinase activity | • signal transduction |
| • apoptotic process | • response to stress |
| • JNK cascade | • protein phosphorylation |
| • nucleus | • cytoplasm |
Pathways
• MAPK signaling pathway
• JNK cascade
• Fc epsilon RI signaling pathway
• Toll-like receptor signaling pathway
• Neurotrophin signaling pathway
• Apoptosis
• IL-17 signaling pathway
Protein Summary
MAPK10 (JNK3) is a 464-amino acid protein kinase with a conserved kinase domain. It is activated by upstream kinases (MKK4/MKK7) via dual phosphorylation on Thr-221 and Tyr-223. JNK3 phosphorylates transcription factors such as c-Jun, ATF2, and ELK1, regulating gene expression involved in apoptosis, inflammation, and differentiation. JNK3 also interacts with scaffold proteins (e.g., JIP) and mitochondrial proteins, influencing cell survival. Its brain-enriched expression makes it a potential therapeutic target for neurodegenerative diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAPK10 Knockout HEK293 Cell Line | EDJ-KQ697 | Human | 5602 | Details Get a Quote |
| MAPK10 Knockout HeLa Cell Line | EDJ-KQ54216 | Human | 5602 | Details Get a Quote |
| MAPK10 Knockout A-549 Cell Line | EDJ-KQ62710 | Human | 5602 | Details Get a Quote |
| MAPK10 Knockout HCT 116 Cell Line | EDJ-KQ71182 | Human | 5602 | Details Get a Quote |
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