MAP3K1
Mitogen-Activated Protein Kinase Kinase Kinase 1: A Key Regulator of Cell Signaling and Development
Gene Information Card
| Symbol | MAP3K1 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q11.2 |
| NCBI Gene ID | 4214 ncbi.nlm.nih.gov/gene/4214 |
| Ensembl ID | ENSG00000095015 |
| UniProt ID | Q13233 |
| OMIM ID | 600982 |
| HGNC ID | 6848 |
| Aliases | MEKK1, MEKK, MAPKKK1, MAP3K1 |
Description
MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) encodes a serine/threonine kinase that functions as a key upstream activator of the JNK and ERK signaling pathways. It is involved in a wide range of cellular processes including proliferation, differentiation, apoptosis, and stress response. The protein contains a kinase domain, a regulatory domain, and a caspase cleavage site. Mutations in MAP3K1 are associated with developmental disorders (e.g., 46,XY sex reversal) and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 46,XY sex reversal 6 | Loss-of-function mutations impair testis-determining pathway, leading to gonadal dysgenesis | OMIM #613762 |
| Breast cancer | Somatic mutations and altered expression contribute to tumorigenesis and metastasis | COSMIC, ClinVar |
| Prostate cancer | Amplifications and overexpression linked to aggressive disease | COSMIC |
| Lung cancer | Somatic mutations and copy number alterations reported | COSMIC |
| Colorectal cancer | Mutations in MAP3K1 may affect MAPK signaling | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Lymph node | 10.2 | Medium |
| Adrenal gland | 9.8 | Medium |
| Thyroid | 8.5 | Medium |
| Breast | 7.1 | Medium |
| Lung | 6.3 | Low |
| Colon | 5.4 | Low |
| Prostate | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression |
| HeLa | 12.8 | High expression |
| MCF7 | 9.5 | Medium expression |
| A549 | 7.3 | Medium expression |
| HepG2 | 6.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.190G>A (p.Glu64Lys) | Missense | <0.1% | Unknown; reported in developmental disorders |
| c.1045C>T (p.Arg349*) | Nonsense | <0.1% | Loss of function; associated with 46,XY sex reversal |
| c.1567G>A (p.Glu523Lys) | Missense | <0.1% | Unknown; reported in cancer |
| c.2051_2052del (p.Glu684Glyfs*2) | Frameshift | <0.1% | Loss of function; associated with 46,XY sex reversal |
| c.2635C>T (p.Arg879Trp) | Missense | <0.1% | Unknown; reported in cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and some missense mutations that disrupt kinase activity or protein stability, leading to impaired JNK/ERK signaling and associated with 46,XY sex reversal.
Gain of Function (GOF)
Not well characterized; some missense mutations in cancer may lead to constitutive activation of downstream pathways.
Dominant Negative (DN)
Truncating mutations that retain the regulatory domain but lack the kinase domain can interfere with wild-type function, observed in some developmental cases.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • MAP kinase kinase kinase activity |
| • ATP binding | • signal transduction |
| • JNK cascade | • ERK1 and ERK2 cascade |
| • apoptotic process | • cell differentiation |
| • male gonad development |
Pathways
• MAPK signaling pathway (KEGG: hsa04010)
• JNK signaling pathway
• ERK signaling pathway
• Apoptosis
• TGF-beta signaling pathway
Protein Summary
MAP3K1 (MEKK1) is a 196 kDa serine/threonine kinase that phosphorylates and activates MAP2K4 and MAP2K7, leading to JNK activation, and also activates MAP2K1/2 to drive ERK signaling. It contains an N-terminal regulatory domain, a central kinase domain, and a C-terminal region. The protein is ubiquitously expressed with highest levels in testis and lymphoid tissues. It plays critical roles in embryonic development, immune response, and stress signaling. Caspase-mediated cleavage generates a constitutively active fragment that promotes apoptosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP3K14 Knockout HEK293 Cell Line | EDJ-KQ577 | Human | 9020 | Details Get a Quote |
| MAP3K1 Knockout HEK293 Cell Line | EDJ-KQ685 | Human | 4214 | Details Get a Quote |
| MAP3K11 Knockout HEK293 Cell Line | EDJ-KQ686 | Human | 4296 | Details Get a Quote |
| MAP3K12 Knockout HEK293 Cell Line | EDJ-KQ687 | Human | 7786 | Details Get a Quote |
| MAP3K13 Knockout HEK293 Cell Line | EDJ-KQ688 | Human | 9175 | Details Get a Quote |
| MAP3K10 Knockout HEK293 Cell Line | EDJ-KQ2672 | Human | 4294 | Details Get a Quote |
| MAP3K19 Knockout HEK293 Cell Line | EDJ-KQ9448 | Human | 80122 | Details Get a Quote |
| MAP3K15 Knockout HEK293 Cell Line | EDJ-KQ14195 | Human | 389840 | Details Get a Quote |
| MAP3K11 Knockout HCT 116 Cell Line | EDJ-KQ18126 | Human | 4296 | Details Get a Quote |
| MAP3K1 Knockout HeLa Cell Line | EDJ-KQ18156 | Human | 4214 | Details Get a Quote |
| MAP3K14 Knockout A-549 Cell Line | EDJ-KQ18975 | Human | 9020 | Details Get a Quote |
| MAP3K14 Knockout HCT 116 Cell Line | EDJ-KQ18976 | Human | 9020 | Details Get a Quote |
| MAP3K14 Knockout HeLa Cell Line | EDJ-KQ18977 | Human | 9020 | Details Get a Quote |
| MAP3K10 Knockout HCT 116 Cell Line | EDJ-KQ22096 | Human | 4294 | Details Get a Quote |
| MAP3K15 Knockout A-549 Cell Line | EDJ-KQ42924 | Human | 389840 | Details Get a Quote |
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