MAP3K4: Mitogen-Activated Protein Kinase Kinase Kinase 4
A key regulator of stress-activated MAPK signaling and developmental processes
Gene Information Card
| Symbol | MAP3K4 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 6q26 |
| NCBI Gene ID | 4216 ncbi.nlm.nih.gov/gene/4216 |
| Ensembl ID | ENSG00000085511 |
| UniProt ID | Q9Y6R4 |
| OMIM ID | 602425 |
| HGNC ID | 6856 |
| Aliases | MEKK4, MAPK/ERK kinase kinase 4, MTK1 |
Description
MAP3K4 (Mitogen-Activated Protein Kinase Kinase Kinase 4) encodes a serine/threonine kinase that functions as a MAP3K in the stress-activated MAPK cascade. It activates downstream MAP2Ks such as MAP2K4 and MAP2K7, leading to JNK and p38 signaling. MAP3K4 is involved in embryonic development, cell migration, and response to environmental stress. Mutations and altered expression have been implicated in cancer and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered MAP3K4 expression may disrupt MAPK signaling, promoting proliferation and metastasis | COSMIC, ClinVar |
| Developmental disorders | Loss-of-function mutations impair embryonic morphogenesis | OMIM, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.2 | Low |
| Heart | 6.1 | Low |
| Liver | 4.3 | Low |
| Kidney | 5.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.1 | Cervical cancer cell line |
| HEK293 | 8.7 | Embryonic kidney cells |
| A549 | 7.3 | Lung cancer cell line |
| MCF7 | 6.5 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Loss of function |
| c.1567G>A (p.Gly523Arg) | Missense | <0.1% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the kinase domain lead to loss of signaling activity.
Gain of Function (GOF)
Not well documented; some missense variants may hyperactivate downstream pathways.
Dominant Negative (DN)
Truncated forms lacking the kinase domain can interfere with wild-type MAP3K4 function.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • MAP kinase kinase kinase activity |
| • ATP binding | • signal transduction |
| • JNK cascade | • p38 MAPK cascade |
| • positive regulation of transcription by RNA polymerase II |
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• JNK signaling cascade
• p38 signaling cascade
• TGF-beta signaling pathway
Protein Summary
MAP3K4 is a 160 kDa serine/threonine kinase containing an N-terminal regulatory domain and a C-terminal kinase domain. It phosphorylates and activates MAP2K4 and MAP2K7, which in turn activate JNK and p38 MAPKs. The protein is critical for stress responses, cell differentiation, and embryonic development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP3K4 Knockout HEK293 Cell Line | EDJ-KQ692 | Human | 4216 | Details Get a Quote |
| MAP3K4 Knockout A-549 Cell Line | EDJ-KQ19256 | Human | 4216 | Details Get a Quote |
| MAP3K4 Knockout HCT 116 Cell Line | EDJ-KQ19257 | Human | 4216 | Details Get a Quote |
| MAP3K4 Knockout HeLa Cell Line | EDJ-KQ19258 | Human | 4216 | Details Get a Quote |
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