Recombinant Human Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)

Code CSB-EP013413HU
Size $306
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Product Details

Greater than 85% as determined by SDS-PAGE.
Target Names
Uniprot No.
Research Area
Signal Transduction
Homo sapiens (Human)
Expression Region
Target Protein Sequence
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
51.6 kDa
Protein Length
Full Length of Mature Protein
Tag Info
N-terminal 10xHis-tagged and C-terminal Myc-tagged
Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA
Please contact us to get it.

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Target Background

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 proinflammatory 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.
Gene References into Functions
  1. These results provide valuable insights into the role of acetylation in MKK4-JNK signaling in T cells. PMID: 29248490
  2. This study demonstrates that MKK4 employs a subtle combination of interaction modes in order to bind to p38 alpha, leading to a complex displaying significantly different dynamics across the bound regions. PMID: 29276882
  3. MKK4 overexpression enhanced TNF-alpha-mediated signaling activation and transcription of downstream catabolic genes, and consequently worsened cartilage degradation. PMID: 29072705
  4. Study provides evidence that phosphorylated MKK4 (pMKK4) might function as a tumor suppressor in colorectal cancer (CRC). Downregulation of pMKK4 was associated with a more aggressive phenotype and with increases in local invasion and metastasis. pMKK4 was also strongly associated with disease-free survival. PMID: 28423721
  5. Androgen-induced miR-27A acted as a tumor suppressor by targeting MAP2K4 and mediated prostate cancer progression PMID: 27594411
  6. the expression level of MAP2K4 was inversely associated with the expression of miR-802 in tongue squamous cell carcinoma (TSCC) tissues; demonstration that the MAP2K4 expression was upregulated in TSCC cell lines; elevated expression of miR-802 inhibited TSCC cell viability and invasion through inhibiting MAP2K4 expression PMID: 28319306
  7. MKK4 activates non-canonical NFkappaB signaling by promoting NFkappaB2-p100 processing. PMID: 28733031
  8. Manipulating the expression of both miR-222 and miR-25 influenced diverse gene expression changes in thyroid cells. Increased expression of miR-25 reduced MEK4 and TRAIL protein expression, and cell adhesion and apoptosis are important aspects of miR-25 functioning in thyroid cells. PMID: 27353001
  9. Association between MKK4 promoter polymorphism and breast cancer risk in Kashmiri population PMID: 27509166
  10. In Chinese Han ischemic stroke patients rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels. PMID: 26856463
  11. the presence of the -1304T > G polymorphism is likely to decrease risk of cancer (Meta-Analysis) PMID: 26554761
  12. The plasma level of protein MAP2K4 was found to suggestively associate negatively with the volume of the left entorhinal cortex in asymptomatic older twins. PMID: 26080319
  13. MAP2K4 increases human prostate cancer metastasis, and prolonged over expression induces long term changes in cell signaling pathways leading to independence from p38 MAPK and JNK. PMID: 25019290
  14. MKK4 is activated in vitro by reduced Trx but not oxidized Trx in the absence of an upstream kinase, suggesting that autophosphorylation of this protein occurs due to reduction of Cys-246 and Cys-266 by Trx. PMID: 26028649
  15. Data suggest a genetic interaction between MAP2K4 and HLA-DRB1, and the importance of rs10468473 and MAP2K4 splice variants in the development of autoantibody-positive RA. PMID: 25732927
  16. knockdown of Sec8 enhances the binding of JIP4 to MAPK kinase 4, thereby decreasing the phosphorylation of MAPK kinase 4, JNK, and p38. PMID: 25244576
  17. Demonstrate that Mkk4 is a negative regulator of the TGF-beta1 signaling associated with atrial remodeling and arrhythmogenesis with age. PMID: 24721794
  18. MicroRNA-27a promotes proliferation, migration and invasion by targeting MAP2K4 in human osteosarcoma cells. PMID: 24556602
  19. Single nucleotide polymorphisms in MAP2K4 gene is associated with gastric cancer. PMID: 23921907
  20. Arrestin-3 directly interacts with MKK7 and promotes JNK3alpha2 phosphorylation by both MKK4 and MKK7 in vitro as well as in intact cells. PMID: 23960075
  21. If both p53 and the SAPKK MKK4 are simultaneously inactivated, persistent polo-like kinase 4 activity combined with the lack of SAPK-mediated inhibition of centrosome duplication conspire to induce supernumerary centrosomes under stress. PMID: 23653187
  22. Rs12939944 located in the MAP2K4 intron was associated with decreased risk. PMID: 23299404
  23. MicroRNA-92a negatively regulates Toll-like receptor (TLR)-triggered inflammatory response in macrophages by targeting MKK4 kinase PMID: 23355465
  24. Crystal structures combined with small-angle X-ray scattering experiments revealed that the apo form of non-phosphorylated MAP2K4 (npMAP2K4) exists in a transient state which has a longer conformation compared with the typical kinase folding. PMID: 22828509
  25. Results suggest that the functional -1304G variant in the MKK4 promoter decreases the risk of PCa by increasing the promoter activity. PMID: 22526163
  26. the functional -1304G variant in the MKK4 promoter contributes to a decreased risk of cervical cancer PMID: 22335172
  27. Overexpression of MAP2K4 in osteosarcoma was correlated with poor treatment response, disease progression and poor overall survival. PMID: 22154052
  28. Suggest that in pancreatic ductal adenocarcinomas, the MKK4 protein was directly related to high cell proliferation. PMID: 22158075
  29. protective role of genetic variant MKK4 -1304T>G is restrained in nasopharyngeal carcinoma (NPC) with Epstein-Barr Virus (EBV) infection. These findings implicate the role of EBV and MKK4 -1304 T>G interaction as a causative factor for the NPC. PMID: 21702039
  30. MKK4 was identified as playing a key role in Tau-S422 phosphorylation in human neuroblastoma cells. PMID: 21638028
  31. The purpose of the study was to investigate the potential contribution of HPK1, MEKK1, TAK1, p-MKK4 to the development of extramammary Paget disease PMID: 21915030
  32. Building on the foundation of daring hypotheses: using the MKK4 metastasis suppressor to develop models of dormancy and metastatic colonization. PMID: 21925502
  33. 8 out of 11 cancer-associated MAP2K4 mutations reduce MKK4 protein stability or impair its kinase activity PMID: 21896780
  34. MAP2K4 is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort. PMID: 21575258
  35. These results indicated that MKK4 acts as a tumor suppressor and may represent an important therapeutic target for the treatment of ovarian cancer PMID: 21487811
  36. Compared with the -1304TT genotype, patients with the -1304TG genotype had a significantly decreased risk of acute myeloid leukemia PMID: 21518142
  37. Loss of MKK4 expression is associated with endometrial cancer. PMID: 21372598
  38. These results suggest that JNK affects the association of alpha-catenin with the adherens junction complex and regulates adherens junctions. PMID: 21030692
  39. Data indicate that MKK4 gene knockdown in MDAH2774 cells over-expressing MKK4 increased invasion activity. PMID: 20309881
  40. the crystal structures of human non-phosphorylated MKK4 kinase domain (npMKK4) complexed with AMP-PNP (npMKK4/AMP) and a ternary complex of npMKK4, AMP-PNP and p38alpha peptide (npMKK4/AMP/p38) were determined. PMID: 20732303
  41. Functional -1304G variant in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity. PMID: 20554746
  42. Elevated MKK4 abundance inhibited cell proliferation and increased the phosphorylation and activity of p38 and PRAK. Thus, multiple microRNAs acting on a single target, the MKK4 mRNA, collectively influence MKK4 abundance during replicative senescence PMID: 19861690
  43. There appears to be consistent rate of genetic inactivation of MAP2K4 among most tumor types, including breast cancer. PMID: 11754110
  44. JNK-dependent phosphorylation and thus inactivation of Mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage PMID: 12223490
  45. Jun N-terminal kinase has a role in IL-4 induction PMID: 12368275
  46. in the setting of wild-type PTEN, PI3K- and MKK4/JNK-dependent pathways cooperate to maintain cell survival. PMID: 12714585
  47. regulation of fibroblast functions important for wound healing by basal JNK activity PMID: 12730213
  48. docking site in MKK4 mediates high affinity binding to JNK MAPKs and competes with similar docking sites in JNK substrates PMID: 12788955
  49. JNK, MKK-4, and MKK-7 form an active signaling complex in rheumatoid arthritis and this novel JNK signalsome is activated in response to IL-1 and migrates to the nucleus PMID: 13130464
  50. JNK and p38 MAPK activities in UVA-induced signaling pathways leading to AP-1 activation and c-Fos expression PMID: 14511403

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Subcellular Location
Cytoplasm. Nucleus.
Protein Families
Protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase subfamily
Tissue Specificity
Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.
Database Links

HGNC: 6844

OMIM: 601335

KEGG: hsa:6416

STRING: 9606.ENSP00000262445

UniGene: Hs.514681

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