MAP3K8
Mitogen-Activated Protein Kinase Kinase Kinase 8
Gene Information Card
| Symbol | MAP3K8 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 10p11.23 |
| NCBI Gene ID | 1326 ncbi.nlm.nih.gov/gene/1326 |
| Ensembl ID | ENSG00000107968 |
| UniProt ID | P41279 |
| OMIM ID | 191191 |
| HGNC ID | 6860 |
| Aliases | Tpl2, COT, EST, MEKK8, AURA2 |
Description
MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8) encodes a serine/threonine kinase that functions as a key activator of the MAPK signaling cascade. It phosphorylates and activates MAP2K1/MEK1 and MAP2K2/MEK2, leading to ERK1/2 activation. MAP3K8 also activates JNK and p38 pathways. It plays critical roles in immune responses, inflammation, and cell proliferation. Aberrant expression or mutations are implicated in various cancers and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | MAP3K8 overexpression activates ERK signaling, promoting cell proliferation and survival | COSMIC, ClinVar |
| Breast cancer | Gene amplification and increased kinase activity drive tumorigenesis | COSMIC, NCBI |
| Inflammatory bowel disease | MAP3K8 regulates TNF-alpha production via NF-kB and MAPK pathways | OMIM, NCBI |
| Rheumatoid arthritis | MAP3K8 mediates pro-inflammatory cytokine production in synovial fibroblasts | NCBI, OMIM |
| Lung cancer | MAP3K8 mutations and overexpression contribute to oncogenic signaling | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.3 | Medium |
| Lung | 6.2 | Low |
| Colon | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HeLa | 9.8 | Medium expression |
| A549 | 7.4 | Medium expression |
| MCF7 | 4.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349Trp) | Missense | 0.02% | Alters kinase domain, potential gain-of-function |
| c.1234G>A (p.Glu412Lys) | Missense | 0.01% | May affect substrate binding |
| c.789_790insA (p.Val264fs) | Frameshift | 0.005% | Loss-of-function, truncated protein |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Val264fs) lead to premature truncation and loss of kinase activity.
Gain of Function (GOF)
Missense mutations in the kinase domain (e.g., p.Arg349Trp) can enhance catalytic activity and downstream ERK signaling.
Dominant Negative (DN)
Not well characterized; some truncations may interfere with wild-type protein function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• TNF signaling pathway (KEGG: hsa04668)
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• IL-17 signaling pathway (KEGG: hsa04657)
Protein Summary
MAP3K8 (Tpl2/COT) is a 467-amino acid serine/threonine kinase with an N-terminal kinase domain and a C-terminal regulatory region. It is activated by phosphorylation and proteolytic cleavage. The protein interacts with NF-kB1/p105 and TPL2-binding proteins to regulate its stability and activity. MAP3K8 is a key mediator of inflammatory cytokine production and oncogenic signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP3K8 Knockout HEK293 Cell Line | EDJ-KQ695 | Human | 1326 | Details Get a Quote |
| MAP3K8 Knockout A-549 Cell Line | EDJ-KQ19265 | Human | 1326 | Details Get a Quote |
| MAP3K8 Knockout HCT 116 Cell Line | EDJ-KQ19266 | Human | 1326 | Details Get a Quote |
| MAP3K8 Knockout HeLa Cell Line | EDJ-KQ19267 | Human | 1326 | Details Get a Quote |
