MAP4K4
Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4
Gene Information Card
| Symbol | MAP4K4 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q11.2 |
| NCBI Gene ID | 9448 ncbi.nlm.nih.gov/gene/9448 |
| Ensembl ID | ENSG00000171016 |
| UniProt ID | O95819 |
| OMIM ID | 604666 |
| HGNC ID | 6866 |
| Aliases | HPK/GCK-like kinase, MEKKK4, NIK, FLH21957, FLJ10409 |
Description
MAP4K4 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4) encodes a serine/threonine kinase belonging to the Ste20 family of protein kinases. It acts upstream of the JNK and p38 MAPK signaling cascades, regulating cell migration, proliferation, and survival. MAP4K4 is implicated in cancer progression, insulin resistance, and inflammatory responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression promotes cell migration and invasion via JNK pathway activation | COSMIC, NCBI Gene |
| Type 2 diabetes | Inhibits insulin signaling through IRS-1 serine phosphorylation | NCBI Gene, UniProt |
| Rheumatoid arthritis | Regulates TNF-alpha production in synovial fibroblasts | NCBI Gene |
| Cardiovascular disease | Promotes endothelial dysfunction and inflammation | NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Lung | 9.7 | Low |
| Kidney | 11.2 | Medium |
| Testis | 15.8 | Medium |
| Spleen | 7.4 | Low |
| Pancreas | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical cancer cell line |
| A549 | 10.5 | Lung cancer cell line |
| MCF7 | 8.9 | Breast cancer cell line |
| HEK293 | 12.1 | Embryonic kidney cell line |
| HepG2 | 7.3 | Liver cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234G>A (p.Glu412Lys) | Missense | <0.1% | Unknown functional effect |
| c.567C>T (p.Arg189Trp) | Missense | <0.1% | Potential loss of kinase activity |
| c.2345_2346insA | Frameshift | <0.1% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to truncate the kinase domain, reducing or abolishing activity.
Gain of Function (GOF)
Not well documented; some missense variants may enhance kinase activity but evidence is limited.
Dominant Negative (DN)
Not reported for MAP4K4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG:04010)
• JNK cascade (Reactome:R-HSA-450294)
• TNF signaling pathway (KEGG:04668)
• Insulin signaling pathway (KEGG:04910)
Protein Summary
MAP4K4 is a 130 kDa serine/threonine kinase that contains an N-terminal kinase domain and a C-terminal citron homology domain. It phosphorylates and activates downstream MAP2K4/MKK4 and MAP2K7/MKK7, leading to JNK activation. The protein is involved in cytoskeletal reorganization, cell migration, and stress responses. Its overexpression is linked to poor prognosis in various cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP4K4 Knockout HEK293 Cell Line | EDJ-KQ100 | Human | 9448 | Details Get a Quote |
| MAP4K4 Knockout A-549 Cell Line | EDJ-KQ19272 | Human | 9448 | Details Get a Quote |
| MAP4K4 Knockout HCT 116 Cell Line | EDJ-KQ19273 | Human | 9448 | Details Get a Quote |
| MAP4K4 Knockout HeLa Cell Line | EDJ-KQ19274 | Human | 9448 | Details Get a Quote |
| MAP4K4 Knockout HAP1 Cell Line | EDC07897 | Human | 9448 | Details Get a Quote |
Displaying Records 1 To 5 Of 5 Records
