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].
Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
---|---|---|---|---|---|
mitogen-activated protein kinase kinase kinase 4 | MIM:602425 | Ensembl:ENSG00000085511 | HGNC:HGNC:6856 | PA30600 | 6q26 |
GO terms in MAP3K4
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 |
BP | IDA | GO:0000186 | activation of MAPKK activity |
BP | IEA | GO:0001890 | placenta development |
BP | IBA | GO:0007346 | regulation of mitotic cell cycle |
BP | IMP | GO:0010225 | response to UV-C |
BP | IEA | GO:0010468 | regulation of gene expression |
BP | IEA | GO:0019100 | male germ-line sex determination |
BP | IBA | GO:0023014 | signal transduction by protein phosphorylation |
BP | IBA | GO:0032147 | activation of protein kinase activity |
BP | IMP | GO:0032212 | positive regulation of telomere maintenance via telomerase |
BP | ISS | GO:0035556 | intracellular signal transduction |
BP | IDA | GO:0043507 | positive regulation of JUN kinase activity |
BP | IMP | GO:0051973 | positive regulation of telomerase activity |
BP | IEA | GO:0060718 | chorionic trophoblast cell differentiation |
BP | IDA | GO:1900745 | positive regulation of p38MAPK cascade |
BP | IMP | GO:1904355 | positive regulation of telomere capping |
CC | IBA | GO:0005737 | cytoplasm |
CC | IDA | GO:0005737 | cytoplasm |
CC | IEA | GO:0048471 | perinuclear region of cytoplasm |
Gene expression in normal tissue: MAP3K4
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in MAP3K4
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 |
wikipathways | WP710 | DNA Damage Response (only ATM dependent) |
smpdb | SMP00320 | Intracellular Signalling Through Adenosine Receptor A2a and Adenosine |
smpdb | SMP00321 | Intracellular Signalling Through Adenosine Receptor A2b and Adenosine |
netpath | Pathway_EGFR1 | EGFR1 |
netpath | Pathway_IL6 | IL6 |
pid | p38_mkk3_6pathway | p38 MAPK signaling pathway |
kegg | hsa04010 | MAPK signaling pathway - Homo sapiens (human) |
kegg | hsa04912 | GnRH signaling pathway - Homo sapiens (human) |
Gene-Drug: Aster Plot
Drug ID | Drug Name | Model Num. |
---|---|---|
iGMDRD68 | Paclitaxel | 1 |
iGMDRD6 | AM-580 | 3 |
iGMDRD434 | BMS-536924 | 2 |
iGMDRD329 | Merck60 | 2 |
iGMDRD871 | BRD6368 | 6 |
iGMDRD286 | Nsc 632839 | 1 |
iGMDRD300 | Tozasertib | 1 |
iGMDRD505 | Pevonedistat | 6 |
iGMDRD150 | RITA | 5 |
iGMDRD57 | Chloropentafluorobenzene | 3 |
iGMDRD237 | ABT-751 | 3 |
iGMDRD775 | NCGC00346967-01 | 1 |
iGMDRD292 | NSC87877 | 2 |
iGMDRD945 | ML214 | 3 |
iGMDRD154 | NSC23766 | 3 |
iGMDRD123 | Isoevodiamine | 5 |
iGMDRD255 | SB225002 | 5 |
iGMDRD802 | 4-methylfasudil | 3 |
iGMDRD474 | Avrainvillamide | 1 |
iGMDRD441 | TW 37 | 1 |
iGMDRD318 | PAC-1 | 3 |
iGMDRD506 | Fedratinib | 5 |
iGMDRD577 | BIX01294 | 2 |
iGMDRD562 | Navitoclax | 4 |
iGMDRD188 | Piperlongumine | 3 |
iGMDRD64 | Parbendazole | 6 |
iGMDRD126 | Tipifarnib | 5 |
iGMDRD151 | CHM-1 | 3 |
iGMDRD483 | SCH-529074 | 3 |
iGMDRD781 | Sirolimus | 2 |
iGMDRD639 | YK 4-279 | 3 |
iGMDRD193 | Fqi1 | 6 |
iGMDRD446 | LY 2183240 | 3 |
iGMDRD466 | Chaetocin | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in MAP3K4