MAP4K3
Mitogen-Activated Protein Kinase Kinase Kinase Kinase 3
Gene Information Card
| Symbol | MAP4K3 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase Kinase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p22.1 |
| NCBI Gene ID | 8491 ncbi.nlm.nih.gov/gene/8491 |
| Ensembl ID | ENSG00000115966 |
| UniProt ID | Q8IVH8 |
| OMIM ID | 604923 |
| HGNC ID | 6870 |
| Aliases | GLK, MAPKKKK3, MEKKK3, RAB8IP |
Description
MAP4K3 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 3) is a serine/threonine kinase belonging to the Ste20 family. It acts upstream of the JNK and p38 MAPK signaling pathways and is involved in cellular processes such as proliferation, differentiation, apoptosis, and immune responses. MAP4K3 is also known as GLK (Germinal Center Kinase-Like Kinase) and is implicated in cancer and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | MAP4K3 overexpression or mutation activates JNK/p38 pathways promoting cell survival and proliferation | COSMIC, ClinVar |
| Inflammatory diseases | MAP4K3 regulates T-cell activation and cytokine production via JNK signaling | NCBI Gene, UniProt |
| Autoimmune disorders | Dysregulated MAP4K3 activity linked to aberrant immune responses | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Bone marrow | 8.7 | Medium |
| Testis | 6.3 | Low |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression |
| HeLa | 9.8 | Moderate expression |
| Jurkat | 12.3 | High expression (T-cell line) |
| MCF7 | 7.2 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Glu116Lys | Missense | 0.2% | Potential gain-of-function in cancer |
| p.Arg425* | Nonsense | <0.1% | Loss-of-function, rare |
| p.Ser520Phe | Missense | 0.1% | Unknown significance |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg425*) lead to truncated protein and reduced kinase activity.
Gain of Function (GOF)
Missense mutations (e.g., p.Glu116Lys) may enhance JNK pathway activation.
Dominant Negative (DN)
Not well characterized; some mutations may interfere with wild-type function.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • ATP binding |
| • JNK cascade | • signal transduction |
| • positive regulation of T cell proliferation |
Pathways
• MAPK signaling pathway
• JNK signaling
• T cell receptor signaling pathway
Protein Summary
MAP4K3 (GLK) is a 911-amino acid serine/threonine kinase with an N-terminal kinase domain and a C-terminal regulatory region. It phosphorylates and activates MAP2K7 (MKK7), leading to JNK activation. The protein is expressed in immune tissues and plays a role in T-cell activation and cytokine production. Its dysregulation is associated with cancer and inflammatory conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP4K3 Knockout HEK293 Cell Line | EDJ-KQ190 | Human | 8491 | Details Get a Quote |
| MAP4K3 Knockout A-549 Cell Line | EDJ-KQ19268 | Human | 8491 | Details Get a Quote |
| MAP4K3 Knockout HCT 116 Cell Line | EDJ-KQ19270 | Human | 8491 | Details Get a Quote |
| MAP4K3 Knockout HeLa Cell Line | EDJ-KQ19271 | Human | 8491 | Details Get a Quote |
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