Tchem MAP2K4 Dual specificity mitogen-activated protein kinase kinase 4

Protein Summary

Description

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. This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Uniprot Accession IDs

• P45985
• B2R7N7
• B3KYB2
• D3DTS5
• Q5U0B8
• Q6FHX4
• Q6P9H2
• Q6PIE6
• MAP kinase kinase 4

Gene Name

• MAP2K4

Ensembl ID

• ENST00000353533
• ENSP00000262445
• ENSG00000065559
• ENST00000415385
• ENSP00000410402

Symbol

• JNKK1
• MEK4
• MKK4
• PRKMK4
• SEK1
• SERK1
• SKK1
• JNKK
• MEK4
• MKK4
• SEK1
• SKK1
• JNKK1
• SERK1
• MAPKK4
• PRKMK4
• SAPKK1
• SAPKK-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	1
interacting protein	0.99
biological process	0.98
molecular function	0.98
pathway	0.97

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Ste Group / Ste7 Family / Dual Specificity Mitogen-activated Protein Kinase Kinase 4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 414.91   (req: < 5)

Gene RIFs: 104   (req: <= 3)

Antibodies: 1275   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 414.91   (req: >= 5)

Gene RIFs: 104   (req: > 3)

Antibodies: 1275   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 24

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 7

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0