MKK4 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. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC; Kinase, protein; Protein kinase, STE; Protein kinase, dual-specificity (non-receptor); STE group; STE7 family
Chromosomal Location of human Ortholog: 17p12
Cellular Component:  axon; cytosol; dendrite cytoplasm; nucleus; perikaryon
Molecular Function:  ATP binding; JUN kinase kinase activity; MAP kinase kinase activity; molecular adaptor activity; protein binding; protein kinase activity; protein serine kinase activity; protein serine/threonine kinase activity; protein tyrosine kinase activity
Biological Process:  apoptotic process; cell growth involved in cardiac muscle cell development; cellular response to mechanical stimulus; cellular response to sorbitol; cellular senescence; Fc-epsilon receptor signaling pathway; JNK cascade; MAPK cascade; negative regulation of motor neuron apoptotic process; peptidyl-tyrosine phosphorylation; positive regulation of DNA replication; positive regulation of JNK cascade; positive regulation of neuron apoptotic process; positive regulation of nitric-oxide synthase biosynthetic process; positive regulation of protein phosphorylation; positive regulation of smooth muscle cell apoptotic process; response to wounding; signal transduction
Reference #:  P45985 (UniProtKB)
Alt. Names/Synonyms: c-Jun N-terminal kinase kinase 1; Dual specificity mitogen-activated protein kinase kinase 4; JNK activating kinase 1; JNK-activated kinase 1; JNK-activating kinase 1; JNKK; JNKK1; MAP kinase kinase 4; MAP2K4; MAPK/ERK kinase 4; MAPKK 4; MAPKK4; MEK 4; MEK4; mitogen-activated protein kinase kinase 4; MKK4; MP2K4; PRKMK4; SAPK kinase 1; SAPK/ERK kinase 1; SAPKK-1; SAPKK1; SEK1; SERK1; SKK1; Stress-activated protein kinase kinase 1
Gene Symbols: MAP2K4
Molecular weight: 44,288 Da
Basal Isoelectric point: 8.28  Predict pI for various phosphorylation states
CST Pathways:  Actin Dynamics  |  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  GPCR Signaling to MAPKs  |  IL6 Signaling  |  Parkinson's Disease  |  Regulation of P38 MAPKs  |  SAPK/JNK Signaling Cascades  |  T Cell Receptor Signaling  |  TGF-ß Signaling  |  Toll-Like Receptor Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  KinBase  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene