MAP2K4
Mitogen-Activated Protein Kinase Kinase 4
Gene Information Card
| Symbol | MAP2K4 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 17p12 |
| NCBI Gene ID | 6416 ncbi.nlm.nih.gov/gene/6416 |
| Ensembl ID | ENSG00000065559 |
| UniProt ID | P45985 |
| OMIM ID | 601335 |
| HGNC ID | 6844 |
| Aliases | MKK4, JNKK1, MEK4, PRKMK4, SAPKK1, SEK1 |
Description
MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4) is a dual-specificity protein kinase that phosphorylates and activates MAP kinases p38 and JNK in response to cellular stress, cytokines, and growth factors. It acts as a critical mediator of signal transduction pathways involved in cell proliferation, differentiation, apoptosis, and stress response. MAP2K4 is considered a tumor suppressor in several cancer types, with loss-of-function mutations and reduced expression observed in pancreatic, breast, and lung cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pancreatic cancer | Loss of function or reduced expression of MAP2K4 impairs JNK/p38 signaling, promoting tumor progression. | PMID: 12619197, COSMIC |
| Breast cancer | Inactivating mutations and deletions of MAP2K4 are found in breast cancer cell lines and primary tumors, suggesting a tumor suppressor role. | PMID: 12058064, COSMIC |
| Lung cancer | Reduced MAP2K4 expression correlates with poor prognosis and increased metastatic potential. | PMID: 19137011 |
| Colorectal cancer | MAP2K4 mutations and loss of heterozygosity are observed, contributing to aberrant MAPK signaling. | PMID: 14559847 |
| Prostate cancer | Decreased MAP2K4 expression is associated with aggressive disease and metastasis. | PMID: 17001315 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 8.2 | Medium |
| Brain | 6.5 | Medium |
| Breast | 7.1 | Medium |
| Colon | 9.3 | Medium |
| Kidney | 10.5 | Medium |
| Liver | 7.8 | Medium |
| Lung | 8.9 | Medium |
| Pancreas | 6.0 | Medium |
| Prostate | 8.0 | Medium |
| Skin | 7.5 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.3 | Cervical cancer cell line |
| MCF7 | 9.8 | Breast cancer cell line |
| A549 | 10.1 | Lung cancer cell line |
| HCT116 | 11.5 | Colorectal cancer cell line |
| PANC-1 | 7.2 | Pancreatic cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.511G>A (p.Gly171Arg) | Missense | <1% | Loss of kinase activity; observed in pancreatic cancer |
| c.1033C>T (p.Arg345Trp) | Missense | <1% | Impaired JNK activation; reported in breast cancer |
| c.1066G>A (p.Glu356Lys) | Missense | <1% | Reduced catalytic activity; found in colorectal cancer |
| c.1210C>T (p.Arg404*) | Nonsense | <1% | Truncation leading to loss of function; rare in multiple cancers |
Mutation functional classification
Loss of Function (LOF)
Most MAP2K4 mutations in cancer are loss-of-function, reducing or abolishing kinase activity toward JNK/p38, thereby impairing stress-induced apoptosis and promoting tumorigenesis.
Gain of Function (GOF)
No confirmed gain-of-function mutations have been reported for MAP2K4 in human cancers.
Dominant Negative (DN)
Some missense mutations (e.g., p.Gly171Arg) may act in a dominant-negative manner by interfering with wild-type MAP2K4 dimerization or substrate binding.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• JNK signaling pathway (Reactome: R-HSA-450294)
• p38 MAPK signaling pathway (Reactome: R-HSA-450302)
• TNF signaling pathway (KEGG: hsa04668)
• Apoptosis (KEGG: hsa04210)
• IL-17 signaling pathway (KEGG: hsa04657)
Protein Summary
MAP2K4 (MKK4) is a 399-amino-acid dual-specificity kinase that phosphorylates threonine and tyrosine residues in the activation loop of JNK and p38 MAP kinases. It contains an N-terminal kinase domain and a C-terminal docking domain. The protein is ubiquitously expressed and localizes to the cytoplasm and nucleus. MAP2K4 is activated by upstream kinases such as MAP3K1 (MEKK1) and MAP3K4 (MEKK4) in response to environmental stress, inflammatory cytokines, and growth factors. Its tumor suppressor function is mediated through pro-apoptotic signaling via JNK and p38 pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP2K4 Knockout HEK293 Cell Line | EDJ-KQ682 | Human | 6416 | Details Get a Quote |
| MAP2K4 Knockout HeLa Cell Line | EDJ-KQ18121 | Human | 6416 | Details Get a Quote |
| MAP2K4 Knockout A-549 Cell Line | EDJ-KQ19231 | Human | 6416 | Details Get a Quote |
| MAP2K4 Knockout HCT 116 Cell Line | EDJ-KQ19232 | Human | 6416 | Details Get a Quote |
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