Search Results
Overview
| Uniprot ID | P45985 |
|---|---|
| Protein Name | Dual specificity mitogen-activated protein kinase kinase 4 |
| Gene Name | MAP2K4 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 260 | QLVDSIAKTRDAGCR |
| 45 | QGKRKALKLNFANPP |
Function
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0005634 | nucleus |
| Molecular Function | GO:0005524 | ATP binding |
| Molecular Function | GO:0008545 | JUN kinase kinase activity |
| Molecular Function | GO:0004708 | MAP kinase kinase activity |
| Molecular Function | GO:0060090 | molecular adaptor activity |
| Molecular Function | GO:0004672 | protein kinase activity |
| Molecular Function | GO:0106310 | protein serine kinase activity |
| Molecular Function | GO:0004674 | protein serine/threonine kinase activity |
| Molecular Function | GO:0004713 | protein tyrosine kinase activity |
| Biological Process | GO:0071260 | cellular response to mechanical stimulus |
| Biological Process | GO:0090398 | cellular senescence |
| Biological Process | GO:0038127 | ERBB signaling pathway |
| Biological Process | GO:0038095 | Fc-epsilon receptor signaling pathway |
| Biological Process | GO:0036481 | intrinsic apoptotic signaling pathway in response to hydrogen peroxide |
| Biological Process | GO:0007254 | JNK cascade |
| Biological Process | GO:0000165 | MAPK cascade |
| Biological Process | GO:0007528 | neuromuscular junction development |
| Biological Process | GO:0007165 | signal transduction |
| Biological Process | GO:0034390 | smooth muscle cell apoptotic process |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[3] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.
[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.