MAP3K5
Mitogen-Activated Protein Kinase Kinase Kinase 5 (ASK1)
Gene Information Card
| Symbol | MAP3K5 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q23.3 |
| NCBI Gene ID | 4217 ncbi.nlm.nih.gov/gene/4217 |
| Ensembl ID | ENSG00000197442 |
| UniProt ID | Q99683 |
| OMIM ID | 602448 |
| HGNC ID | 6857 |
| Aliases | ASK1, MAPKKK5, MEKK5 |
Description
MAP3K5 (Mitogen-Activated Protein Kinase Kinase Kinase 5), also known as ASK1 (Apoptosis Signal-regulating Kinase 1), encodes a serine/threonine kinase that activates the JNK and p38 MAP kinase pathways in response to various stress stimuli, including reactive oxygen species, tumor necrosis factor-alpha, and endoplasmic reticulum stress. It plays a critical role in apoptosis, differentiation, and inflammation. Dysregulation of MAP3K5 is implicated in cancer, neurodegenerative diseases, and cardiovascular disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | MAP3K5 can act as a tumor suppressor or oncogene depending on context; altered expression and mutations affect apoptosis and cell survival pathways. | ClinVar, COSMIC |
| Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's) | Oxidative stress-induced activation of ASK1 contributes to neuronal cell death via JNK/p38 signaling. | NCBI Gene, OMIM |
| Cardiovascular diseases | ASK1 mediates cardiomyocyte apoptosis under ischemia/reperfusion injury and pressure overload. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Liver | 6.1 | Low |
| Kidney | 7.9 | Medium |
| Lung | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.2 | Cervical cancer cell line |
| HEK293 | 8.7 | Embryonic kidney cell line |
| MCF7 | 6.5 | Breast cancer cell line |
| A549 | 7.1 | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | <0.1% | Altered kinase activity; potential loss of function |
| c.567G>A (p.Trp189*) | Nonsense | <0.01% | Truncation; loss of function |
| c.890A>G (p.Asn297Ser) | Missense | <0.05% | Unknown effect; reported in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt the kinase domain lead to loss of ASK1 activity, impairing stress-induced apoptosis.
Gain of Function (GOF)
Missense mutations that enhance kinase activity or prevent inhibitory interactions (e.g., with thioredoxin) may increase JNK/p38 signaling, promoting cell death or inflammation.
Dominant Negative (DN)
Mutations that produce a truncated or inactive kinase domain can interfere with wild-type ASK1 signaling, reducing apoptosis.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine kinase activity | • MAP kinase kinase kinase activity |
| • apoptotic process | • signal transduction |
| • response to oxidative stress | • JNK cascade |
| • p38MAPK cascade |
Pathways
• MAPK signaling pathway
• Apoptosis
• TNF signaling pathway
• p53 signaling pathway
• FoxO signaling pathway
Protein Summary
MAP3K5 (ASK1) is a 1,374-amino-acid serine/threonine kinase with an N-terminal thioredoxin-binding domain, a central kinase domain, and a C-terminal regulatory region. It is activated by dissociation from thioredoxin under oxidative stress, leading to autophosphorylation and subsequent activation of MKK3/6 and MKK4/7, which in turn activate p38 and JNK. ASK1 is a key mediator of stress-induced apoptosis and is regulated by multiple binding partners, including 14-3-3 proteins and TRAF2.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP3K5 Knockout HEK293 Cell Line | EDJ-KQ693 | Human | 4217 | Details Get a Quote |
| MAP3K5 Knockout A-549 Cell Line | EDJ-KQ19259 | Human | 4217 | Details Get a Quote |
| MAP3K5 Knockout HCT 116 Cell Line | EDJ-KQ19260 | Human | 4217 | Details Get a Quote |
| MAP3K5 Knockout HeLa Cell Line | EDJ-KQ19261 | Human | 4217 | Details Get a Quote |
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