MAPK9 (JNK2): A Key Stress-Activated Kinase in Cancer and Inflammation
Comprehensive genomic, expression, and mutation analysis of MAPK9, encoding JNK2, a member of the mitogen-activated protein kinase family involved in cellular stress responses, apoptosis, and tumorigenesis.
Gene Information Card
| Symbol | MAPK9 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 5601 ncbi.nlm.nih.gov/gene/5601 |
| Ensembl ID | ENSG00000050748 |
| UniProt ID | P45984 |
| OMIM ID | 602896 |
| HGNC ID | 6886 |
| Aliases | JNK2, JNK-55, JNK2A, JNK2B, PRKM9, SAPK1a, p54aSAPK |
Description
MAPK9 (Mitogen-Activated Protein Kinase 9) encodes a member of the mitogen-activated protein kinase (MAPK) family, specifically the c-Jun N-terminal kinase (JNK) subfamily. The encoded protein, JNK2, is a serine/threonine kinase that responds to cellular stress, inflammatory cytokines, and environmental stimuli. It phosphorylates transcription factors such as c-Jun, ATF2, and p53, regulating processes including apoptosis, proliferation, differentiation, and immune responses. Alternative splicing produces multiple isoforms with distinct functions. MAPK9 is implicated in various cancers, neurodegenerative diseases, and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | MAPK9/JNK2 promotes tumor cell proliferation and survival through phosphorylation of c-Jun and activation of AP-1 transcription factor. | COSMIC: frequent overexpression and activating mutations in liver cancer; PubMed studies show JNK2 knockout reduces tumor growth in mouse models. |
| Colorectal cancer | JNK2 contributes to oncogenic signaling via Wnt/β-catenin pathway and regulation of apoptosis. | COSMIC: somatic mutations and copy number alterations; ClinVar: variants associated with increased risk. |
| Breast cancer | JNK2 modulates estrogen receptor signaling and cell cycle progression, influencing tumor aggressiveness. | COSMIC: mutations and expression changes; PubMed: JNK2 inhibition reduces metastasis in triple-negative breast cancer models. |
| Inflammatory bowel disease (IBD) | JNK2 regulates inflammatory cytokine production and intestinal epithelial cell apoptosis. | OMIM: genetic association; PubMed: JNK2 deficiency attenuates colitis in mouse models. |
| Neurodegenerative disorders (e.g., Alzheimer's disease) | JNK2 mediates tau phosphorylation and neuronal apoptosis in response to oxidative stress. | PubMed: increased JNK2 activity in affected brain regions; ClinVar: rare variants reported. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Liver | 8.7 | Low |
| Colon | 15.2 | Medium |
| Breast | 10.1 | Medium |
| Lung | 9.5 | Low |
| Kidney | 7.8 | Low |
| Heart | 6.4 | Low |
| Spleen | 18.9 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 22.5 | High expression; JNK2 active in stress response |
| MCF7 (breast cancer) | 14.3 | Moderate; involved in estrogen signaling |
| HepG2 (liver cancer) | 19.8 | High; promotes proliferation |
| A549 (lung cancer) | 11.2 | Moderate; stress-induced activation |
| Jurkat (T-cell leukemia) | 25.6 | High; immune signaling |
Data source:Human Protein Atlas(proteinatlas.org)
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.R227Q | Missense | 0.5% (COSMIC) | Alters kinase activity; potential gain-of-function in cancer |
| p.T183A | Missense | 0.2% (COSMIC) | Affects phosphorylation site; reduces JNK2 activity |
| p.V196M | Missense | 0.3% (COSMIC) | Unknown; observed in colorectal cancer |
| p.E111K | Missense | 0.1% (COSMIC) | Potential loss-of-function; disrupts substrate binding |
| c.1125+1G>A | Splice site | 0.05% (ClinVar) | Splicing defect; likely loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair kinase activity or protein stability, leading to reduced JNK2 signaling. Examples include p.T183A and splice-site variants. These may contribute to immune dysregulation or impaired apoptosis.
Gain of Function (GOF)
Mutations that enhance kinase activity or substrate affinity, promoting oncogenic signaling. p.R227Q is suspected to increase activity, driving cell proliferation in cancers.
Dominant Negative (DN)
Certain mutations may produce truncated or inactive proteins that interfere with wild-type JNK2 function, acting in a dominant-negative manner. However, specific validated examples are limited; further research is needed.
View complete mutation data:
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • MAP kinase activity | • signal transduction |
| • apoptotic process | • response to stress |
| • JNK cascade | • transcription factor binding |
| • protein phosphorylation | • cytokine-mediated signaling pathway |
Pathways
• MAPK signaling pathway
• JNK signaling pathway
• Fc epsilon RI signaling pathway
• T cell receptor signaling pathway
• Toll-like receptor signaling pathway
• Apoptosis
• Neurotrophin signaling pathway
• Insulin signaling pathway
Protein Summary
The MAPK9 protein (JNK2) is a 424-amino-acid serine/threonine kinase with a molecular weight of approximately 48 kDa. It contains a conserved kinase domain and a T-loop with Thr-Pro-Tyr (TPY) motif, which is phosphorylated by upstream kinases (MKK4/MKK7) for activation. JNK2 exists in multiple isoforms (e.g., JNK2α1, JNK2α2, JNK2β1, JNK2β2) due to alternative splicing, differing in substrate specificity and subcellular localization. It primarily localizes to the cytoplasm and nucleus, where it phosphorylates transcription factors (c-Jun, ATF2, Elk-1) and other substrates, regulating gene expression. JNK2 also interacts with scaffold proteins (e.g., JIP1) to modulate signaling specificity. Its activity is tightly regulated by phosphatases and ubiquitination.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAPK9 Knockout HEK293 Cell Line | EDJ-KQ705 | Human | 5601 | Details Get a Quote |
| MAPK9 Knockout A-549 Cell Line | EDJ-KQ19295 | Human | 5601 | Details Get a Quote |
| MAPK9 Knockout HCT 116 Cell Line | EDJ-KQ19296 | Human | 5601 | Details Get a Quote |
| MAPK9 Knockout HeLa Cell Line | EDJ-KQ19297 | Human | 5601 | Details Get a Quote |
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