MAP4K1 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1)
A key regulator of the JNK and p38 MAPK signaling pathways, involved in inflammation, immune response, and cancer.
Gene Information Card
| Symbol | MAP4K1 |
|---|---|
| Full Name | Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 11184 ncbi.nlm.nih.gov/gene/11184 |
| Ensembl ID | ENSG00000104814 |
| UniProt ID | Q8NFH4 |
| OMIM ID | 601646 |
| HGNC ID | 6866 |
| Aliases | HPK1, MEKKK1, MAPKKKK1 |
Description
MAP4K1 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1), also known as HPK1 (Hematopoietic Progenitor Kinase 1), is a serine/threonine kinase that acts as an upstream activator of the JNK and p38 MAPK signaling cascades. It is predominantly expressed in hematopoietic cells and plays a critical role in T-cell receptor signaling, cytokine production, and immune regulation. MAP4K1 is involved in various cellular processes including proliferation, differentiation, apoptosis, and stress response. Dysregulation of MAP4K1 has been implicated in inflammatory diseases, autoimmune disorders, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | MAP4K1 overexpression or mutation can alter JNK/p38 signaling, promoting cell survival and proliferation in certain cancers. | COSMIC, NCBI Gene |
| Inflammatory diseases | MAP4K1 regulates cytokine production via JNK/p38 pathways; dysregulation contributes to chronic inflammation. | NCBI Gene, UniProt |
| Autoimmune disorders | Altered MAP4K1 activity in T-cells can disrupt immune tolerance and promote autoimmunity. | OMIM, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 28.5 | High |
| Lymph node | 22.1 | High |
| Bone marrow | 18.7 | High |
| Thymus | 15.3 | Medium |
| Blood | 12.8 | Medium |
| Lung | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 35.2 | High expression |
| K-562 (leukemia) | 20.1 | Medium expression |
| HeLa (cervical cancer) | 5.6 | Low expression |
| A549 (lung cancer) | 3.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | <1% | Potential loss of kinase activity |
| c.567G>A (p.Glu189Lys) | Missense | <1% | Altered substrate binding |
| c.890_891insA | Frameshift | <0.5% | Truncated protein, loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair kinase activity or protein stability, leading to reduced JNK/p38 signaling.
Gain of Function (GOF)
Mutations that enhance kinase activity, potentially driving oncogenic signaling.
Dominant Negative (DN)
Mutations that produce a truncated or inactive protein that interferes with wild-type MAP4K1 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• JNK signaling pathway (KEGG: hsa04010)
• p38 MAPK signaling pathway (KEGG: hsa04010)
• T cell receptor signaling pathway (KEGG: hsa04660)
• Fc epsilon RI signaling pathway (KEGG: hsa04664)
Protein Summary
MAP4K1 (HPK1) is a 97 kDa serine/threonine kinase composed of an N-terminal kinase domain, a proline-rich region, and a C-terminal citron homology domain. It is activated by upstream signals such as T-cell receptor engagement and functions as a MAP4K to phosphorylate and activate MAP3Ks (e.g., MEKK1, MLK3), leading to JNK and p38 activation. HPK1 also interacts with adaptor proteins like CRK and GRB2 to modulate signaling complexes. Its expression is largely restricted to hematopoietic tissues, where it regulates immune cell function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MAP4K1 Knockout HEK293 Cell Line | EDJ-KQ696 | Human | 11184 | Details Get a Quote |
| MAP4K1 Knockout HeLa Cell Line | EDJ-KQ55597 | Human | 11184 | Details Get a Quote |
| MAP4K1 Knockout A-549 Cell Line | EDJ-KQ64093 | Human | 11184 | Details Get a Quote |
| MAP4K1 Knockout HCT 116 Cell Line | EDJ-KQ72543 | Human | 11184 | Details Get a Quote |
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