MAP3K4


Summary: 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].

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GO terms in MAP3K4


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Term Type
Evidence Type
GO Term ID
GO Des.
MF IBA GO:0004674 protein serine/threonine kinase activity
MF IDA GO:0004709 MAP kinase kinase kinase activity
MF IPI GO:0005515 protein binding
MF IEA GO:0005524 ATP binding
MF IEA GO:0046872 metal ion binding
BP IEA GO:0000165 MAPK cascade
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Gene expression in normal tissue: MAP3K4

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in MAP3K4


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Database
Pathway ID
Pathway Des.
biocarta mapkpathway mapkinase signaling pathway
wikipathways WP382 MAPK Signaling Pathway
wikipathways WP3915 Angiopoietin Like Protein 8 Regulatory Pathway
wikipathways WP437 EGF-EGFR Signaling Pathway
wikipathways WP481 Insulin Signaling
wikipathways WP524 G13 Signaling Pathway
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Gene-Drug: Aster Plot


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Drug ID
Drug Name
Model Num.
iGMDRD68 Paclitaxel 1
iGMDRD6 AM-580 3
iGMDRD434 BMS-536924 2
iGMDRD329 Merck60 2
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Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in MAP3K4

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Cancer
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