MAP3K3
Mitogen-Activated Protein Kinase Kinase Kinase 3
Gene Information Card
| Symbol | MAP3K3 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q23.3 |
| NCBI Gene ID | 4215 ncbi.nlm.nih.gov/gene/4215 |
| Ensembl ID | ENSG00000108469 |
| UniProt ID | Q99759 |
| OMIM ID | 602539 |
| HGNC ID | 6855 |
| Aliases | MEKK3, MAPKKK3, MEKK 3 |
Description
MAP3K3 (MEKK3) encodes a serine/threonine kinase that functions as a mitogen-activated protein kinase kinase kinase (MAP3K). It activates the JNK and ERK pathways by phosphorylating and activating MAP2Ks. MEKK3 is involved in cell proliferation, differentiation, and stress response. Mutations and altered expression are linked to various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Aortic aneurysm, familial thoracic 8 | Gain-of-function mutations in MAP3K3 lead to increased MEKK3 activity, disrupting vascular smooth muscle cell homeostasis. | OMIM #617349 |
| Capillary malformation-arteriovenous malformation 2 | Activating mutations (e.g., p.Arg441Cys) in MAP3K3 cause abnormal endothelial cell signaling. | OMIM #618196 |
| Breast cancer | Overexpression and amplification of MAP3K3 promote tumor growth via MAPK pathway activation. | COSMIC, NCBI |
| Lung cancer | MAP3K3 mutations and copy number alterations contribute to oncogenic signaling. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Lung | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 7.8 | Medium |
| Testis | 15.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.5 | Embryonic kidney cells |
| HeLa | 8.9 | Cervical cancer cells |
| A549 | 7.2 | Lung cancer cells |
| MCF7 | 6.8 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1321C>T (p.Arg441Cys) | Missense | Rare | Gain-of-function; associated with capillary malformation-arteriovenous malformation |
| c.1322G>A (p.Arg441His) | Missense | Rare | Gain-of-function; linked to vascular anomalies |
| Amplification | Copy number gain | Frequent in breast cancer | Increased MEKK3 expression and pathway activation |
Mutation functional classification
Loss of Function (LOF)
Not well characterized; likely leads to reduced MAPK signaling.
Gain of Function (GOF)
Common; p.Arg441Cys/His mutations increase kinase activity and downstream signaling.
Dominant Negative (DN)
Not reported for MAP3K3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• TNF signaling pathway (KEGG: hsa04668)
• VEGF signaling pathway (KEGG: hsa04370)
Protein Summary
MEKK3 is a 626-amino acid serine/threonine kinase with an N-terminal regulatory domain and a C-terminal kinase domain. It phosphorylates and activates MAP2K1/MEK1 and MAP2K4/SEK1, leading to ERK and JNK activation. MEKK3 also interacts with TRAF2 and RIPK1 to modulate NF-κB signaling. The protein is widely expressed and plays critical roles in development, immunity, and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP3K3 Knockout HEK293 Cell Line | EDJ-KQ691 | Human | 4215 | Details Get a Quote |
| MAP3K3 Knockout HCT 116 Cell Line | EDJ-KQ18134 | Human | 4215 | Details Get a Quote |
| MAP3K3 Knockout A-549 Cell Line | EDJ-KQ19253 | Human | 4215 | Details Get a Quote |
| MAP3K3 Knockout HeLa Cell Line | EDJ-KQ19255 | Human | 4215 | Details Get a Quote |
