MAP3K7: Mitogen-Activated Protein Kinase Kinase Kinase 7
A key regulator of stress-activated MAPK signaling and inflammatory responses
Gene Information Card
| Symbol | MAP3K7 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase 7 |
| Gene Type | protein-coding |
| Chromosomal Location | 6q15 |
| NCBI Gene ID | 6885 ncbi.nlm.nih.gov/gene/6885 |
| Ensembl ID | ENSG00000135341 |
| UniProt ID | O43318 |
| OMIM ID | 602614 |
| HGNC ID | 6859 |
| Aliases | TAK1, MEKK7, TAK1C, MAP3K7IP1 |
Description
MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7), also known as TAK1 (Transforming Growth Factor-β-Activated Kinase 1), is a serine/threonine kinase that plays a central role in stress-activated MAPK signaling pathways and NF-κB activation. It is activated by various stimuli including TGF-β, TNF-α, IL-1, and toll-like receptor ligands. MAP3K7 phosphorylates and activates MKK3, MKK4, MKK6, and MKK7, leading to p38 and JNK activation, and also directly activates the IKK complex to induce NF-κB signaling. It is essential for immune responses, inflammation, cell survival, and differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Frontometaphyseal dysplasia 2 (FMD2) | Loss-of-function mutations in MAP3K7 disrupt TGF-β and BMP signaling, leading to skeletal abnormalities. | ClinVar, OMIM #617137 |
| Cardiospondylocarpofacial syndrome (CSCF) | Heterozygous missense mutations impair MAP3K7 kinase activity, affecting cardiac and skeletal development. | ClinVar, OMIM #619638 |
| Various cancers (e.g., breast, lung, colorectal) | Dysregulation of MAP3K7/TAK1 signaling promotes tumor growth, metastasis, and chemoresistance via NF-κB and JNK pathways. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 12.5 | Medium |
| Brain | 8.3 | Low |
| Colon | 15.2 | Medium |
| Heart | 10.1 | Medium |
| Kidney | 14.8 | Medium |
| Liver | 11.6 | Medium |
| Lung | 13.4 | Medium |
| Spleen | 18.9 | High |
| Testis | 20.3 | High |
| Thyroid | 9.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 16.5 | Cervical adenocarcinoma |
| HEK 293 | 14.2 | Embryonic kidney |
| K562 | 12.8 | Leukemia |
| MCF7 | 11.3 | Breast cancer |
| HepG2 | 13.1 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.145C>T (p.Arg49*) | Nonsense | Rare | Loss of function; associated with FMD2 |
| c.511G>A (p.Gly171Arg) | Missense | Rare | Impaired kinase activity; CSCF phenotype |
| c.1024A>G (p.Thr342Ala) | Missense | Rare | Reduced autophosphorylation; FMD2 |
| c.1462C>T (p.Arg488Trp) | Missense | Rare | Dominant-negative effect; CSCF |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated or absent protein; associated with frontometaphyseal dysplasia 2.
Gain of Function (GOF)
Not well documented; some missense variants may enhance kinase activity in cancer contexts.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg488Trp) that impair kinase activity and interfere with wild-type MAP3K7 function; linked to cardiospondylocarpofacial syndrome.
View complete mutation data：
Gene Ontology (GO)
| • MAP kinase kinase kinase activity (GO:0004709) | • Protein serine/threonine kinase activity (GO:0004674) |
| • ATP binding (GO:0005524) | • Signal transduction (GO:0007165) |
| • Activation of NF-κB-inducing kinase activity (GO:0007250) | • Stress-activated MAPK cascade (GO:0051403) |
| • Positive regulation of I-κB kinase/NF-κB signaling (GO:0043123) | • TGF-β receptor signaling pathway (GO:0007179) |
Pathways
• TGF-β signaling pathway (KEGG hsa04350)
• MAPK signaling pathway (KEGG hsa04010)
• NF-κB signaling pathway (KEGG hsa04064)
• Toll-like receptor signaling pathway (KEGG hsa04620)
• IL-17 signaling pathway (KEGG hsa04657)
• TNF signaling pathway (KEGG hsa04668)
Protein Summary
MAP3K7 (TAK1) is a 579-amino-acid serine/threonine kinase with an N-terminal kinase domain and a C-terminal regulatory region. It forms a complex with TAB1, TAB2, or TAB3, which are essential for its activation. Upon stimulation, TAK1 autophosphorylates and subsequently activates downstream MAP2Ks and the IKK complex. The protein is ubiquitously expressed and is critical for inflammatory and stress responses. Structural studies reveal a bilobed kinase fold typical of the MAP3K family.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP3K7 Knockout HEK293 Cell Line | EDJ-KQ142 | Human | 6885 | Details Get a Quote |
| MAP3K7CL Knockout HEK293 Cell Line | EDJ-KQ14194 | Human | 56911 | Details Get a Quote |
| MAP3K7 Knockout A-549 Cell Line | EDJ-KQ18978 | Human | 6885 | Details Get a Quote |
| MAP3K7 Knockout HCT 116 Cell Line | EDJ-KQ18980 | Human | 6885 | Details Get a Quote |
| MAP3K7 Knockout HeLa Cell Line | EDJ-KQ18981 | Human | 6885 | Details Get a Quote |
| MAP3K7CL Knockout A-549 Cell Line | EDJ-KQ44138 | Human | 56911 | Details Get a Quote |
| MAP3K7CL Knockout HeLa Cell Line | EDJ-KQ44139 | Human | 56911 | Details Get a Quote |
| MAP3K7CL Knockout HCT 116 Cell Line | EDJ-KQ73710 | Human | 56911 | Details Get a Quote |
| MAP3K7 Knockout HAP1 Cell Line | EDC08167 | Human | 6885 | Details Get a Quote |
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