Tbio MAP3K4 Mitogen-activated protein kinase kinase kinase 4

Protein Summary

Description

Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014]

Uniprot Accession IDs

• Q9Y6R4
• A6H8W0
• B7ZLD3
• B9EG75
• Q5VTT8
• Q5VTT9
• Q92612
• Q9H408

Gene Name

• MAP3K4

Ensembl ID

• ENST00000366919
• ENSP00000355886
• ENSG00000085511
• ENST00000392142
• ENSP00000375986

Symbol

• KIAA0213
• MAPKKK4
• MEKK4
• MTK1
• MTK1
• MEKK4
• MEKK 4
• MAPKKK4
• PRO0412

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.99
transcription factor perturbation	0.99
disease perturbation	0.93
histone modification site profile	0.83
biological process	0.8

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Ste Group / Ste11 Family / Mitogen-activated Protein Kinase 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: 49.76   (req: < 5)

Gene RIFs: 21   (req: <= 3)

Antibodies: 293   (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: 49.76   (req: >= 5)

Gene RIFs: 21   (req: > 3)

Antibodies: 293   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 19

Tchem

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

Active Ligand: 0

Tclin

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

Active Drug: 0