MAP2K4
Summary: 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].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| mitogen-activated protein kinase kinase 4 | MIM:601335 | Ensembl:ENSG00000065559 | HGNC:HGNC:6844 | PA30589 | 17p12 |
GO terms in MAP2K4
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | TAS | GO:0004672 | protein kinase activity |
| MF | IBA | GO:0004674 | protein serine/threonine kinase activity |
| MF | IBA | GO:0004708 | MAP kinase kinase activity |
| MF | IEA | GO:0004713 | protein tyrosine kinase activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IEA | GO:0005524 | ATP binding |
| MF | IBA | GO:0008545 | JUN kinase kinase activity |
| MF | IEA | GO:0008545 | JUN kinase kinase activity |
| MF | IEA | GO:0031435 | mitogen-activated protein kinase kinase kinase binding |
| BP | IBA | GO:0000187 | activation of MAPK activity |
| BP | IEA | GO:0006915 | apoptotic process |
| BP | TAS | GO:0007165 | signal transduction |
| BP | TAS | GO:0007254 | JNK cascade |
| BP | IBA | GO:0007257 | activation of JUN kinase activity |
| BP | IEA | GO:0007257 | activation of JUN kinase activity |
| BP | IBA | GO:0007346 | regulation of mitotic cell cycle |
| BP | IEA | GO:0009611 | response to wounding |
| BP | IEA | GO:0018108 | peptidyl-tyrosine phosphorylation |
| BP | IBA | GO:0023014 | signal transduction by protein phosphorylation |
| BP | IBA | GO:0032147 | activation of protein kinase activity |
| BP | IEA | GO:0034393 | positive regulation of smooth muscle cell apoptotic process |
| BP | IEA | GO:0043525 | positive regulation of neuron apoptotic process |
| BP | IEA | GO:0045740 | positive regulation of DNA replication |
| BP | IEA | GO:0051770 | positive regulation of nitric-oxide synthase biosynthetic process |
| BP | IEA | GO:0061049 | cell growth involved in cardiac muscle cell development |
| BP | IEP | GO:0071260 | cellular response to mechanical stimulus |
| BP | IEA | GO:0072709 | cellular response to sorbitol |
| BP | IEA | GO:2000672 | negative regulation of motor neuron apoptotic process |
| CC | IEA | GO:0005634 | nucleus |
| CC | IBA | GO:0005737 | cytoplasm |
| CC | TAS | GO:0005829 | cytosol |
| CC | IEA | GO:0030424 | axon |
| CC | IEA | GO:0032839 | dendrite cytoplasm |
| CC | IEA | GO:0043204 | perikaryon |
Gene expression in normal tissue: MAP2K4
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in MAP2K4
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| kegg | hsa04010 | MAPK signaling pathway - Homo sapiens (human) |
| kegg | hsa04012 | ErbB signaling pathway - Homo sapiens (human) |
| kegg | hsa04620 | Toll-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04664 | Fc epsilon RI signaling pathway - Homo sapiens (human) |
| kegg | hsa04668 | TNF signaling pathway - Homo sapiens (human) |
| kegg | hsa04912 | GnRH signaling pathway - Homo sapiens (human) |
| kegg | hsa04926 | Relaxin signaling pathway - Homo sapiens (human) |
| kegg | hsa05120 | Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human) |
| kegg | hsa05142 | Chagas disease (American trypanosomiasis) - Homo sapiens (human) |
| kegg | hsa05161 | Hepatitis B - Homo sapiens (human) |
| kegg | hsa05164 | Influenza A - Homo sapiens (human) |
| kegg | hsa05166 | HTLV-I infection - Homo sapiens (human) |
| kegg | hsa05167 | Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human) |
| kegg | hsa05169 | Epstein-Barr virus infection - Homo sapiens (human) |
| kegg | hsa05418 | Fluid shear stress and atherosclerosis - Homo sapiens (human) |
| netpath | Pathway_IL1 | IL1 |
| netpath | Pathway_IL6 | IL6 |
| biocarta | at1rpathway | angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling |
| biocarta | ceramidepathway | ceramide signaling pathway |
| biocarta | egfpathway | egf signaling pathway |
| biocarta | faspathway | fas signaling pathway (cd95) |
| biocarta | fcer1pathway | fc epsilon receptor i signaling in mast cells |
| biocarta | gleevecpathway | inhibition of cellular proliferation by gleevec |
| biocarta | keratinocytepathway | keratinocyte differentiation |
| biocarta | mapkpathway | mapkinase signaling pathway |
| biocarta | p38mapkpathway | p38 mapk signaling pathway |
| biocarta | pdgfpathway | pdgf signaling pathway |
| biocarta | pyk2pathway | links between pyk2 and map kinases |
| biocarta | smrtepathway | map kinase inactivation of smrt corepressor |
| biocarta | stresspathway | tnf/stress related signaling |
| biocarta | tcrpathway | t cell receptor signaling pathway |
| biocarta | tnfr1pathway | tnfr1 signaling pathway |
| biocarta | tollpathway | toll-like receptor pathway |
| reactome | R-HSA-1280215 | Cytokine Signaling in Immune system |
| reactome | R-HSA-1280215 | Cytokine Signaling in Immune system |
| reactome | R-HSA-1643685 | Disease |
| reactome | R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade |
| reactome | R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade |
| reactome | R-HSA-166058 | MyD88:Mal cascade initiated on plasma membrane |
| reactome | R-HSA-166058 | MyD88:Mal cascade initiated on plasma membrane |
| reactome | R-HSA-166166 | MyD88-independent TLR4 cascade |
| reactome | R-HSA-166166 | MyD88-independent TLR4 cascade |
| reactome | R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade |
| reactome | R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade |
| reactome | R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade |
| reactome | R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade |
| reactome | R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade |
| reactome | R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade |
| reactome | R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade |
| reactome | R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade |
| reactome | R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade |
| reactome | R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade |
| reactome | R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade |
| reactome | R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade |
| reactome | R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade |
| reactome | R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade |
| reactome | R-HSA-168249 | Innate Immune System |
| reactome | R-HSA-168249 | Innate Immune System |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-168256 | Immune System |
| reactome | R-HSA-168898 | Toll-Like Receptors Cascades |
| reactome | R-HSA-168898 | Toll-Like Receptors Cascades |
| reactome | R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade |
| reactome | R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade |
| reactome | R-HSA-2262752 | Cellular responses to stress |
| reactome | R-HSA-2262752 | Cellular responses to stress |
| reactome | R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling |
| reactome | R-HSA-2559580 | Oxidative Stress Induced Senescence |
| reactome | R-HSA-2559580 | Oxidative Stress Induced Senescence |
| reactome | R-HSA-2559583 | Cellular Senescence |
| reactome | R-HSA-2559583 | Cellular Senescence |
| reactome | R-HSA-2871796 | FCERI mediated MAPK activation |
| reactome | R-HSA-446652 | Interleukin-1 family signaling |
| reactome | R-HSA-448424 | Interleukin-17 signaling |
| reactome | R-HSA-448424 | Interleukin-17 signaling |
| reactome | R-HSA-449147 | Signaling by Interleukins |
| reactome | R-HSA-449147 | Signaling by Interleukins |
| reactome | R-HSA-450294 | MAP kinase activation |
| reactome | R-HSA-450294 | MAP kinase activation |
| reactome | R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 |
| reactome | R-HSA-5210891 | Uptake and function of anthrax toxins |
| reactome | R-HSA-5339562 | Uptake and actions of bacterial toxins |
| reactome | R-HSA-5663205 | Infectious disease |
| reactome | R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation |
| reactome | R-HSA-8953897 | Cellular responses to external stimuli |
| reactome | R-HSA-8953897 | Cellular responses to external stimuli |
| reactome | R-HSA-9020702 | Interleukin-1 signaling |
| reactome | R-HSA-937061 | TRIF(TICAM1)-mediated TLR4 signaling |
| reactome | R-HSA-937061 | TRIF(TICAM1)-mediated TLR4 signaling |
| reactome | R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation |
| reactome | R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation |
| reactome | R-HSA-975155 | MyD88 dependent cascade initiated on endosome |
| reactome | R-HSA-975155 | MyD88 dependent cascade initiated on endosome |
| reactome | R-HSA-975871 | MyD88 cascade initiated on plasma membrane |
| reactome | R-HSA-975871 | MyD88 cascade initiated on plasma membrane |
| smpdb | SMP00358 | Fc Epsilon Receptor I Signaling in Mast Cells |
| wikipathways | WP1449 | Regulation of toll-like receptor signaling pathway |
| wikipathways | WP1544 | MicroRNAs in cardiomyocyte hypertrophy |
| wikipathways | WP195 | IL-1 signaling pathway |
| wikipathways | WP1993 | Angiogenesis overview |
| wikipathways | WP2261 | Signaling Pathways in Glioblastoma |
| wikipathways | WP231 | TNF alpha Signaling Pathway |
| wikipathways | WP2526 | PDGF Pathway |
| wikipathways | WP254 | Apoptosis |
| wikipathways | WP2637 | Structural Pathway of Interleukin 1 (IL-1) |
| wikipathways | WP2795 | Cardiac Hypertrophic Response |
| wikipathways | WP314 | Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation |
| wikipathways | WP3611 | Photodynamic therapy-induced AP-1 survival signaling. |
| wikipathways | WP3639 | Apoptotic Signaling Pathway |
| wikipathways | WP364 | IL-6 signaling pathway |
| wikipathways | WP366 | TGF-beta Signaling Pathway |
| wikipathways | WP3680 | Association Between Physico-Chemical Features and Toxicity Associated Pathways |
| wikipathways | WP382 | MAPK Signaling Pathway |
| wikipathways | WP3888 | VEGFA-VEGFR2 Signaling Pathway |
| wikipathways | WP3915 | Angiopoietin Like Protein 8 Regulatory Pathway |
| wikipathways | WP3941 | Oxidative Damage |
| wikipathways | WP3972 | PDGFR-beta pathway |
| wikipathways | WP399 | Wnt Signaling Pathway and Pluripotency |
| wikipathways | WP400 | p38 MAPK Signaling Pathway |
| wikipathways | WP422 | MAPK Cascade |
| wikipathways | WP4239 | EMT transition in Colorectal Cancer |
| wikipathways | WP481 | Insulin Signaling |
| wikipathways | WP75 | Toll-like Receptor Signaling Pathway |
| pid | anthraxpathway | Cellular roles of Anthrax toxin |
| pid | ar_tf_pathway | Regulation of Androgen receptor activity |
| pid | cd40_pathway | CD40/CD40L signaling |
| pid | cdc42_pathway | CDC42 signaling events |
| pid | ceramide_pathway | Ceramide signaling pathway |
| pid | ephrinbrevpathway | Ephrin B reverse signaling |
| pid | erbb1_downstream_pathway | ErbB1 downstream signaling |
| pid | fak_pathway | Signaling events mediated by focal adhesion kinase |
| pid | fcer1pathway | Fc-epsilon receptor I signaling in mast cells |
| pid | il6_7pathway | IL6-mediated signaling events |
| pid | lymphangiogenesis_pathway | VEGFR3 signaling in lymphatic endothelium |
| pid | met_pathway | Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met) |
| pid | nephrin_neph1_pathway | Nephrin/Neph1 signaling in the kidney podocyte |
| pid | p38alphabetapathway | Regulation of p38-alpha and p38-beta |
| pid | pdgfrbpathway | PDGFR-beta signaling pathway |
| pid | rac1_pathway | RAC1 signaling pathway |
| pid | rhoa_pathway | RhoA signaling pathway |
| pid | tcrjnkpathway | JNK signaling in the CD4+ TCR pathway |
| pid | trail_pathway | TRAIL signaling pathway |
| pharmgkb | PA165985892 | Tacrolimus/Cyclosporine Pathway, Pharmacodynamics |
| pharmgkb | PA2032 | VEGF Signaling Pathway |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD507 | GSK690693 | 1 |
| iGMDRD736 | UNC1215 | 1 |
| iGMDRD309 | 17AAG | 1 |
| iGMDRD52 | Rotenone | 4 |
| iGMDRD440 | Nutlin-3A | 1 |
| iGMDRD441 | TW 37 | 6 |
| iGMDRD284 | Palbociclib | 1 |
| iGMDRD562 | Navitoclax | 2 |
| iGMDRD577 | BIX01294 | 5 |
| iGMDRD888 | Compound 44 | 6 |
| iGMDRD399 | Selumetinib | 2 |
| iGMDRD127 | Seliciclib | 1 |
| iGMDRD451 | Serdemetan | 1 |
| iGMDRD524 | ISX-9 | 7 |
| iGMDRD371 | THR1 Inhibitor | 1 |
| iGMDRD23 | Gossypol | 5 |
| iGMDRD190 | Nilotinib | 1 |
| iGMDRD420 | Leucascandrolide A | 5 |
| iGMDRD889 | Compound 7d-cis | 2 |
| iGMDRD599 | Salermide | 7 |
| iGMDRD136 | Nutlin-3 | 1 |
| iGMDRD494 | Neopeltolide | 6 |
| iGMDRD144 | NSC95397 | 3 |
| iGMDRD427 | ABT737 | 6 |
| iGMDRD61 | Kinetin riboside | 2 |
| iGMDRD152 | 179324-69-7 | 3 |
| iGMDRD718 | Pyrvinium pamoate | 5 |
| iGMDRD608 | Refametinib | 1 |
| iGMDRD634 | SCHEMBL2608041 | 9 |
| iGMDRD280 | CYTOCHALASIN B | 3 |
| iGMDRD202 | Curcumin | 1 |
| iGMDRD271 | Brefeldin A | 5 |
| iGMDRD103 | SN-38 | 6 |
| iGMDRD231 | Importazole | 1 |
| iGMDRD267 | Oligomycin A | 1 |
| iGMDRD660 | GSK-1070916 | 1 |
| iGMDRD6 | AM-580 | 1 |
| iGMDRD329 | Merck60 | 4 |
| iGMDRD993 | QL-XII-61 | 1 |
| iGMDRD871 | BRD6368 | 6 |
| iGMDRD82 | Quiflapon | 3 |
| iGMDRD246 | NPC26 | 3 |
| iGMDRD886 | Compound 1541A | 1 |
| iGMDRD300 | Tozasertib | 2 |
| iGMDRD248 | BRD4354 | 2 |
| iGMDRD584 | VER 155008 | 2 |
| iGMDRD330 | BRD4132 | 4 |
| iGMDRD84 | Lovastatin acid | 2 |
| iGMDRD79 | Gemcitabine | 3 |
| iGMDRD701 | NVP-AUY922 | 2 |
| iGMDRD424 | Tamatinib | 1 |
| iGMDRD150 | RITA | 10 |
| iGMDRD560 | MK-2206 | 7 |
| iGMDRD536 | PLX-4720 | 1 |
| iGMDRD351 | GW843682X | 1 |
| iGMDRD352 | PD-0325901 | 1 |
| iGMDRD85 | Ursolic acid | 1 |
| iGMDRD49 | Mitomycin | 1 |
| iGMDRD945 | ML214 | 1 |
| iGMDRD123 | Isoevodiamine | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in MAP2K4
CLASSFICATION
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