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.

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 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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