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].

NameOMIM IDEnsembl IDHGNC IDPHARMGKB IDMap Location
mitogen-activated protein kinase kinase kinase 4MIM:602425Ensembl:ENSG00000085511HGNC:HGNC:6856PA306006q26

GO terms in MAP3K4


Term TypeEvidence TypeGO Term IDGO Des.
MFIBAGO:0004674protein serine/threonine kinase activity
MFIDAGO:0004709MAP kinase kinase kinase activity
MFIPIGO:0005515protein binding
MFIEAGO:0005524ATP binding
MFIEAGO:0046872metal ion binding
BPIEAGO:0000165MAPK cascade
BPIDAGO:0000186activation of MAPKK activity
BPIEAGO:0001890placenta development
BPIBAGO:0007346regulation of mitotic cell cycle
BPIMPGO:0010225response to UV-C
BPIEAGO:0010468regulation of gene expression
BPIEAGO:0019100male germ-line sex determination
BPIBAGO:0023014signal transduction by protein phosphorylation
BPIBAGO:0032147activation of protein kinase activity
BPIMPGO:0032212positive regulation of telomere maintenance via telomerase
BPISSGO:0035556intracellular signal transduction
BPIDAGO:0043507positive regulation of JUN kinase activity
BPIMPGO:0051973positive regulation of telomerase activity
BPIEAGO:0060718chorionic trophoblast cell differentiation
BPIDAGO:1900745positive regulation of p38MAPK cascade
BPIMPGO:1904355positive regulation of telomere capping
CCIBAGO:0005737cytoplasm
CCIDAGO:0005737cytoplasm
CCIEAGO:0048471perinuclear region of cytoplasm

Gene expression in normal tissue: MAP3K4

Gene-model tissue-cancer distribution: Bubble Plot

Gene-drug pathway distribution

Pathways in MAP3K4


DatabasePathway IDPathway Des.
biocartamapkpathwaymapkinase signaling pathway
wikipathwaysWP382MAPK Signaling Pathway
wikipathwaysWP3915Angiopoietin Like Protein 8 Regulatory Pathway
wikipathwaysWP437EGF-EGFR Signaling Pathway
wikipathwaysWP481Insulin Signaling
wikipathwaysWP524G13 Signaling Pathway
wikipathwaysWP710DNA Damage Response (only ATM dependent)
smpdbSMP00320Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
smpdbSMP00321Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
netpathPathway_EGFR1EGFR1
netpathPathway_IL6IL6
pidp38_mkk3_6pathwayp38 MAPK signaling pathway
kegghsa04010MAPK signaling pathway - Homo sapiens (human)
kegghsa04912GnRH signaling pathway - Homo sapiens (human)

Gene-Drug: Aster Plot


Drug IDDrug NameModel Num.
iGMDRD68Paclitaxel1
iGMDRD6AM-5803
iGMDRD434BMS-5369242
iGMDRD329Merck602
iGMDRD871BRD63686
iGMDRD286Nsc 6328391
iGMDRD300Tozasertib1
iGMDRD505Pevonedistat6
iGMDRD150RITA5
iGMDRD57Chloropentafluorobenzene3
iGMDRD237ABT-7513
iGMDRD775NCGC00346967-011
iGMDRD292NSC878772
iGMDRD945ML2143
iGMDRD154NSC237663
iGMDRD123Isoevodiamine5
iGMDRD255SB2250025
iGMDRD8024-methylfasudil3
iGMDRD474Avrainvillamide1
iGMDRD441TW 371
iGMDRD318PAC-13
iGMDRD506Fedratinib5
iGMDRD577BIX012942
iGMDRD562Navitoclax4
iGMDRD188Piperlongumine3
iGMDRD64Parbendazole6
iGMDRD126Tipifarnib5
iGMDRD151CHM-13
iGMDRD483SCH-5290743
iGMDRD781Sirolimus2
iGMDRD639YK 4-2793
iGMDRD193Fqi16
iGMDRD446LY 21832403
iGMDRD466Chaetocin3

Gene in drug-gene network: Network Plot

Gene-drug targets distribution

Gene Structure: PDB

Models in MAP3K4

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