MAP2K2
Summary: The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is known to play a critical role in mitogen growth factor signal transduction. It phosphorylates and thus activates MAPK1/ERK2 and MAPK2/ERK3. The activation of this kinase itself is dependent on the Ser/Thr phosphorylation by MAP kinase kinase kinases. Mutations in this gene cause cardiofaciocutaneous syndrome (CFC syndrome), a disease characterized by heart defects, cognitive disability, and distinctive facial features similar to those found in Noonan syndrome. The inhibition or degradation of this kinase is also found to be involved in the pathogenesis of Yersinia and anthrax. A pseudogene, which is located on chromosome 7, has been identified for this gene. [provided by RefSeq, Jul 2008].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| mitogen-activated protein kinase kinase 2 | MIM:601263 | Ensembl:ENSG00000126934 | HGNC:HGNC:6842 | PA30587 | 19p13.3 |
GO terms in MAP2K2
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | IBA | GO:0004674 | protein serine/threonine kinase activity |
| MF | TAS | GO:0004674 | protein serine/threonine kinase activity |
| MF | IBA | GO:0004708 | MAP kinase kinase activity |
| MF | IDA | GO:0004708 | MAP kinase kinase activity |
| MF | TAS | GO:0004712 | protein serine/threonine/tyrosine kinase activity |
| MF | IEA | GO:0004713 | protein tyrosine kinase activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IEA | GO:0005524 | ATP binding |
| MF | IDA | GO:0030165 | PDZ domain binding |
| MF | IDA | GO:0043539 | protein serine/threonine kinase activator activity |
| MF | IEA | GO:0046872 | metal ion binding |
| MF | IPI | GO:0097110 | scaffold protein binding |
| BP | TAS | GO:0000165 | MAPK cascade |
| BP | IBA | GO:0000187 | activation of MAPK activity |
| BP | TAS | GO:0000187 | activation of MAPK activity |
| BP | IBA | GO:0007346 | regulation of mitotic cell cycle |
| BP | IGI | GO:0010629 | negative regulation of gene expression |
| 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 | TAS | GO:0032872 | regulation of stress-activated MAPK cascade |
| BP | IDA | GO:0036289 | peptidyl-serine autophosphorylation |
| BP | IMP | GO:0045893 | positive regulation of transcription, DNA-templated |
| BP | IMP | GO:0070371 | ERK1 and ERK2 cascade |
| BP | TAS | GO:0070371 | ERK1 and ERK2 cascade |
| BP | IDA | GO:0071902 | positive regulation of protein serine/threonine kinase activity |
| BP | TAS | GO:0090170 | regulation of Golgi inheritance |
| BP | IMP | GO:1903800 | positive regulation of production of miRNAs involved in gene silencing by miRNA |
| BP | TAS | GO:2000641 | regulation of early endosome to late endosome transport |
| CC | NAS | GO:0005576 | extracellular region |
| CC | TAS | GO:0005634 | nucleus |
| CC | IBA | GO:0005737 | cytoplasm |
| CC | TAS | GO:0005739 | mitochondrion |
| CC | TAS | GO:0005769 | early endosome |
| CC | TAS | GO:0005770 | late endosome |
| CC | HDA | GO:0005778 | peroxisomal membrane |
| CC | IDA | GO:0005783 | endoplasmic reticulum |
| CC | IDA | GO:0005794 | Golgi apparatus |
| CC | TAS | GO:0005794 | Golgi apparatus |
| CC | TAS | GO:0005829 | cytosol |
| CC | IDA | GO:0005874 | microtubule |
| CC | IDA | GO:0005911 | cell-cell junction |
| CC | TAS | GO:0005925 | focal adhesion |
| CC | IDA | GO:0009898 | cytoplasmic side of plasma membrane |
| CC | IDA | GO:0048471 | perinuclear region of cytoplasm |
Gene expression in normal tissue: MAP2K2
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in MAP2K2
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| biocarta | anthraxpathway | anthrax toxin mechanism of action |
| biocarta | at1rpathway | angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling |
| biocarta | barrestinsrcpathway | roles of arrestin dependent recruitment of src kinases in gpcr signaling |
| biocarta | barrmapkpathway | role of -arrestins in the activation and targeting of map kinases |
| biocarta | cardiacegfpathway | role of egf receptor transactivation by gpcrs in cardiac hypertrophy |
| biocarta | cdk5pathway | phosphorylation of mek1 by cdk5/p35 down regulates the map kinase pathway |
| biocarta | cdmacpathway | cadmium induces dna synthesis and proliferation in macrophages |
| biocarta | ceramidepathway | ceramide signaling pathway |
| biocarta | edg1pathway | phospholipids as signalling intermediaries |
| biocarta | erk5pathway | role of erk5 in neuronal survival pathway |
| biocarta | erkpathway | erk1/erk2 mapk signaling pathway |
| biocarta | fcer1pathway | fc epsilon receptor i signaling in mast cells |
| biocarta | fmlppathway | fmlp induced chemokine gene expression in hmc-1 cells |
| biocarta | hcmvpathway | human cytomegalovirus and map kinase pathways |
| biocarta | her2pathway | role of erbb2 in signal transduction and oncology |
| biocarta | il2rbpathway | il-2 receptor beta chain in t cell activation |
| biocarta | keratinocytepathway | keratinocyte differentiation |
| biocarta | malpathway | role of mal in rho-mediated activation of srf |
| biocarta | mapkpathway | mapkinase signaling pathway |
| biocarta | mcalpainpathway | mcalpain and friends in cell motility |
| biocarta | melanocytepathway | melanocyte development and pigmentation pathway |
| biocarta | pyk2pathway | links between pyk2 and map kinases |
| biocarta | raccycdpathway | influence of ras and rho proteins on g1 to s transition |
| biocarta | sam68pathway | regulation of splicing through sam68 |
| biocarta | sprypathway | sprouty regulation of tyrosine kinase signals |
| biocarta | tffpathway | trefoil factors initiate mucosal healing |
| reactome | R-HSA-112409 | RAF-independent MAPK1/3 activation |
| reactome | R-HSA-112411 | MAPK1 (ERK2) activation |
| reactome | R-HSA-1266738 | Developmental Biology |
| reactome | R-HSA-162582 | Signal Transduction |
| reactome | R-HSA-1643685 | Disease |
| reactome | R-HSA-373760 | L1CAM interactions |
| reactome | R-HSA-422475 | Axon guidance |
| reactome | R-HSA-445144 | Signal transduction by L1 |
| reactome | R-HSA-5210891 | Uptake and function of anthrax toxins |
| reactome | R-HSA-5339562 | Uptake and actions of bacterial toxins |
| reactome | R-HSA-5663202 | Diseases of signal transduction |
| reactome | R-HSA-5663205 | Infectious disease |
| reactome | R-HSA-5673000 | RAF activation |
| reactome | R-HSA-5673001 | RAF/MAP kinase cascade |
| reactome | R-HSA-5674135 | MAP2K and MAPK activation |
| reactome | R-HSA-5674499 | Negative feedback regulation of MAPK pathway |
| reactome | R-HSA-5675221 | Negative regulation of MAPK pathway |
| reactome | R-HSA-5683057 | MAPK family signaling cascades |
| reactome | R-HSA-5684996 | MAPK1/MAPK3 signaling |
| reactome | R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants |
| reactome | R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants |
| reactome | R-HSA-6802949 | Signaling by RAS mutants |
| reactome | R-HSA-6802952 | Signaling by BRAF and RAF fusions |
| reactome | R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF |
| reactome | R-HSA-6802957 | Oncogenic MAPK signaling |
| humancyc | PWY66-14 | MAP kinase cascade |
| kegg | hsa04010 | MAPK signaling pathway - Homo sapiens (human) |
| kegg | hsa04012 | ErbB signaling pathway - Homo sapiens (human) |
| kegg | hsa04014 | Ras signaling pathway - Homo sapiens (human) |
| kegg | hsa04015 | Rap1 signaling pathway - Homo sapiens (human) |
| kegg | hsa04022 | cGMP-PKG signaling pathway - Homo sapiens (human) |
| kegg | hsa04024 | cAMP signaling pathway - Homo sapiens (human) |
| kegg | hsa04066 | HIF-1 signaling pathway - Homo sapiens (human) |
| kegg | hsa04068 | FoxO signaling pathway - Homo sapiens (human) |
| kegg | hsa04071 | Sphingolipid signaling pathway - Homo sapiens (human) |
| kegg | hsa04072 | Phospholipase D signaling pathway - Homo sapiens (human) |
| kegg | hsa04140 | Autophagy - animal - Homo sapiens (human) |
| kegg | hsa04150 | mTOR signaling pathway - Homo sapiens (human) |
| kegg | hsa04151 | PI3K-Akt signaling pathway - Homo sapiens (human) |
| kegg | hsa04210 | Apoptosis - Homo sapiens (human) |
| kegg | hsa04218 | Cellular senescence - Homo sapiens (human) |
| kegg | hsa04270 | Vascular smooth muscle contraction - Homo sapiens (human) |
| kegg | hsa04370 | VEGF signaling pathway - Homo sapiens (human) |
| kegg | hsa04371 | Apelin signaling pathway - Homo sapiens (human) |
| kegg | hsa04540 | Gap junction - Homo sapiens (human) |
| kegg | hsa04550 | Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human) |
| kegg | hsa04620 | Toll-like receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04650 | Natural killer cell mediated cytotoxicity - Homo sapiens (human) |
| kegg | hsa04660 | T cell receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04662 | B cell receptor signaling pathway - Homo sapiens (human) |
| kegg | hsa04664 | Fc epsilon RI signaling pathway - Homo sapiens (human) |
| kegg | hsa04720 | Long-term potentiation - Homo sapiens (human) |
| kegg | hsa04722 | Neurotrophin signaling pathway - Homo sapiens (human) |
| kegg | hsa04730 | Long-term depression - Homo sapiens (human) |
| kegg | hsa04810 | Regulation of actin cytoskeleton - Homo sapiens (human) |
| kegg | hsa04910 | Insulin signaling pathway - Homo sapiens (human) |
| kegg | hsa04912 | GnRH signaling pathway - Homo sapiens (human) |
| kegg | hsa04915 | Estrogen signaling pathway - Homo sapiens (human) |
| kegg | hsa04916 | Melanogenesis - Homo sapiens (human) |
| kegg | hsa04917 | Prolactin signaling pathway - Homo sapiens (human) |
| kegg | hsa04919 | Thyroid hormone signaling pathway - Homo sapiens (human) |
| kegg | hsa04921 | Oxytocin signaling pathway - Homo sapiens (human) |
| kegg | hsa04926 | Relaxin signaling pathway - Homo sapiens (human) |
| kegg | hsa04934 | Cushing,s syndrome - Homo sapiens (human) |
| kegg | hsa05020 | Prion diseases - Homo sapiens (human) |
| kegg | hsa05161 | Hepatitis B - Homo sapiens (human) |
| kegg | hsa05164 | Influenza A - Homo sapiens (human) |
| kegg | hsa05165 | Human papillomavirus infection - Homo sapiens (human) |
| kegg | hsa05167 | Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human) |
| kegg | hsa05200 | Pathways in cancer - Homo sapiens (human) |
| kegg | hsa05205 | Proteoglycans in cancer - Homo sapiens (human) |
| kegg | hsa05206 | MicroRNAs in cancer - Homo sapiens (human) |
| kegg | hsa05210 | Colorectal cancer - Homo sapiens (human) |
| kegg | hsa05211 | Renal cell carcinoma - Homo sapiens (human) |
| kegg | hsa05213 | Endometrial cancer - Homo sapiens (human) |
| kegg | hsa05214 | Glioma - Homo sapiens (human) |
| kegg | hsa05215 | Prostate cancer - Homo sapiens (human) |
| kegg | hsa05216 | Thyroid cancer - Homo sapiens (human) |
| kegg | hsa05218 | Melanoma - Homo sapiens (human) |
| kegg | hsa05219 | Bladder cancer - Homo sapiens (human) |
| kegg | hsa05220 | Chronic myeloid leukemia - Homo sapiens (human) |
| kegg | hsa05221 | Acute myeloid leukemia - Homo sapiens (human) |
| kegg | hsa05223 | Non-small cell lung cancer - Homo sapiens (human) |
| kegg | hsa05224 | Breast cancer - Homo sapiens (human) |
| kegg | hsa05225 | Hepatocellular carcinoma - Homo sapiens (human) |
| kegg | hsa05226 | Gastric cancer - Homo sapiens (human) |
| kegg | hsa05230 | Central carbon metabolism in cancer - Homo sapiens (human) |
| kegg | hsa05231 | Choline metabolism in cancer - Homo sapiens (human) |
| netpath | Pathway_EGFR1 | EGFR1 |
| netpath | Pathway_FSH | FSH |
| netpath | Pathway_Fibroblast__growth__factor-1 | Fibroblast growth factor-1 |
| netpath | Pathway_ID | ID |
| netpath | Pathway_IL-7 | IL-7 |
| netpath | Pathway_IL2 | IL2 |
| netpath | Pathway_IL5 | IL5 |
| netpath | Pathway_IL6 | IL6 |
| netpath | Pathway_Prolactin | Prolactin |
| netpath | Pathway_RAGE | RAGE |
| netpath | Pathway_TCR | TCR |
| wikipathways | WP127 | IL-5 Signaling Pathway |
| wikipathways | WP1449 | Regulation of toll-like receptor signaling pathway |
| wikipathways | WP1544 | MicroRNAs in cardiomyocyte hypertrophy |
| wikipathways | WP185 | Integrin-mediated Cell Adhesion |
| wikipathways | WP195 | IL-1 signaling pathway |
| wikipathways | WP2034 | Leptin signaling pathway |
| wikipathways | WP2037 | Prolactin Signaling Pathway |
| wikipathways | WP205 | IL-7 Signaling Pathway |
| wikipathways | WP22 | IL-9 Signaling Pathway |
| wikipathways | WP2203 | Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway |
| wikipathways | WP2261 | Signaling Pathways in Glioblastoma |
| wikipathways | WP2263 | Androgen Receptor Network in Prostate Cancer |
| wikipathways | WP23 | B Cell Receptor Signaling Pathway |
| wikipathways | WP2332 | Interleukin-11 Signaling Pathway |
| wikipathways | WP2374 | Oncostatin M Signaling Pathway |
| wikipathways | WP2380 | Brain-Derived Neurotrophic Factor (BDNF) signaling pathway |
| wikipathways | WP2447 | Amyotrophic lateral sclerosis (ALS) |
| wikipathways | WP2593 | JAK-STAT |
| wikipathways | WP2636 | Common Pathways Underlying Drug Addiction |
| wikipathways | WP2637 | Structural Pathway of Interleukin 1 (IL-1) |
| wikipathways | WP2795 | Cardiac Hypertrophic Response |
| wikipathways | WP2828 | Bladder Cancer |
| wikipathways | WP304 | Kit receptor signaling pathway |
| wikipathways | WP313 | Signaling of Hepatocyte Growth Factor Receptor |
| wikipathways | WP364 | IL-6 signaling pathway |
| wikipathways | WP3651 | Pathways Affected in Adenoid Cystic Carcinoma |
| wikipathways | WP366 | TGF-beta Signaling Pathway |
| wikipathways | WP382 | MAPK Signaling Pathway |
| wikipathways | WP3863 | T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection |
| wikipathways | WP3879 | 4-hydroxytamoxifen, Dexamethasone, and Retinoic Acids Regulation of p27 Expression |
| wikipathways | WP3888 | VEGFA-VEGFR2 Signaling Pathway |
| wikipathways | WP3915 | Angiopoietin Like Protein 8 Regulatory Pathway |
| wikipathways | WP3931 | ESC Pluripotency Pathways |
| wikipathways | WP3932 | Focal Adhesion-PI3K-Akt-mTOR-signaling pathway |
| wikipathways | WP3981 | miRNA regulation of prostate cancer signaling pathways |
| wikipathways | WP4155 | Endometrial cancer |
| wikipathways | WP4172 | PI3K-Akt Signaling Pathway |
| wikipathways | WP4205 | MET in type 1 papillary renal cell carcinoma |
| wikipathways | WP422 | MAPK Cascade |
| wikipathways | WP4223 | Ras Signaling |
| wikipathways | WP4239 | EMT transition in Colorectal Cancer |
| wikipathways | WP437 | EGF-EGFR Signaling Pathway |
| wikipathways | WP481 | Insulin Signaling |
| wikipathways | WP49 | IL-2 Signaling Pathway |
| wikipathways | WP51 | Regulation of Actin Cytoskeleton |
| wikipathways | WP581 | EPO Receptor Signaling |
| wikipathways | WP69 | T-Cell antigen Receptor (TCR) Signaling Pathway |
| wikipathways | WP722 | Serotonin HTR1 Group and FOS Pathway |
| wikipathways | WP732 | Serotonin Receptor 2 and ELK-SRF-GATA4 signaling |
| wikipathways | WP734 | Serotonin Receptor 4-6-7 and NR3C Signaling |
| wikipathways | WP75 | Toll-like Receptor Signaling Pathway |
| smpdb | SMP00320 | Intracellular Signalling Through Adenosine Receptor A2a and Adenosine |
| smpdb | SMP00321 | Intracellular Signalling Through Adenosine Receptor A2b and Adenosine |
| smpdb | SMP00358 | Fc Epsilon Receptor I Signaling in Mast Cells |
| smpdb | SMP00391 | Insulin Signalling |
| pid | anthraxpathway | Cellular roles of Anthrax toxin |
| pid | ar_nongenomic_pathway | Nongenotropic Androgen signaling |
| pid | cd8tcrdownstreampathway | Downstream signaling in naïve CD8+ T cells |
| pid | ceramide_pathway | Ceramide signaling pathway |
| pid | cxcr3pathway | CXCR3-mediated signaling events |
| pid | endothelinpathway | Endothelins |
| pid | erbb1_downstream_pathway | ErbB1 downstream signaling |
| pid | erbb2erbb3pathway | ErbB2/ErbB3 signaling events |
| pid | fcer1pathway | Fc-epsilon receptor I signaling in mast cells |
| pid | gmcsf_pathway | GMCSF-mediated signaling events |
| pid | il2_1pathway | IL2-mediated signaling events |
| pid | kitpathway | Signaling events mediated by Stem cell factor receptor (c-Kit) |
| pid | met_pathway | Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met) |
| pid | mtor_4pathway | mTOR signaling pathway |
| pid | netrin_pathway | Netrin-mediated signaling events |
| pid | pdgfrbpathway | PDGFR-beta signaling pathway |
| pid | shp2_pathway | SHP2 signaling |
| pid | vegfr1_2_pathway | Signaling events mediated by VEGFR1 and VEGFR2 |
| pharmgkb | PA165959425 | Pathway_PA165959425 |
| pharmgkb | PA165959584 | Sorafenib Pharmacodynamics |
| pharmgkb | PA165980050 | Vemurafenib Pathway, Pharmacodynamics |
| pharmgkb | PA165980050 | update your name in edit mode |
| pharmgkb | PA2032 | VEGF Signaling Pathway |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD579 | PF750 | 3 |
| iGMDRD126 | Tipifarnib | 3 |
| iGMDRD494 | Neopeltolide | 3 |
| iGMDRD781 | Sirolimus | 3 |
| iGMDRD75 | Lovastatin | 1 |
| iGMDRD1 | Nicotin-Amide | 1 |
| iGMDRD144 | NSC95397 | 6 |
| iGMDRD634 | SCHEMBL2608041 | 6 |
| iGMDRD401 | Afatinib | 1 |
| iGMDRD885 | Compound 110 | 3 |
| iGMDRD562 | Navitoclax | 3 |
| iGMDRD596 | Vemurafenib | 3 |
| iGMDRD268 | Cerulenin | 3 |
| iGMDRD64 | Parbendazole | 3 |
| iGMDRD148 | Pifithrin-mu | 3 |
| iGMDRD330 | BRD4132 | 3 |
| iGMDRD150 | RITA | 6 |
| iGMDRD614 | Dabrafenib | 5 |
| iGMDRD352 | PD-0325901 | 1 |
| iGMDRD49 | Mitomycin | 1 |
| iGMDRD132 | (-)-gallocatechin-3-O-gallate | 4 |
| iGMDRD154 | NSC23766 | 3 |
| iGMDRD123 | Isoevodiamine | 3 |
| iGMDRD514 | ERK inhibitor | 5 |
| iGMDRD137 | Indisulam | 3 |
| iGMDRD333 | MEK Inhibitor | 10 |
| iGMDRD396 | AS601245 | 1 |
| iGMDRD77 | Itraconazole | 3 |
| iGMDRD434 | BMS-536924 | 3 |
| iGMDRD561 | ABT-263 | 1 |
| iGMDRD839 | BRAF inhibitor | 10 |
| iGMDRD367 | Ro 28-1675 | 3 |
| iGMDRD286 | Nsc 632839 | 3 |
| iGMDRD300 | Tozasertib | 3 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in MAP2K2
CLASSFICATION
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