Dual specificity mitogen-activated protein kinase kinase 2
Also known as: MAP2K2, MEK2, MKK2, PRKMK2
Function
Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation.
Classification
- Family (Pfam)
- PF00069 Pkinase
- InterPro
- Kinase-like_dom_sf, MAP_kinase_kinase, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
- Functional cluster
- Protein Serine/Threonine Kinases
Experimental structures · PDB · 2
A predicted model is available from AlphaFold.
Gene Ontology · 39
- GO:0005911 cell-cell junction
- GO:0009898 cytoplasmic side of plasma membrane
- GO:0005829 cytosol
- GO:0005769 early endosome
- GO:0005783 endoplasmic reticulum
- GO:0005576 extracellular region
- GO:0005925 focal adhesion
- GO:0005794 Golgi apparatus
- GO:0005770 late endosome
- GO:0005874 microtubule
- GO:0005739 mitochondrion
- GO:0005634 nucleus
- GO:0048471 perinuclear region of cytoplasm
- GO:0005778 peroxisomal membrane
- GO:0005524 ATP binding
- GO:0004708 MAP kinase kinase activity
- GO:0005078 MAP-kinase scaffold activity
- GO:0046872 metal ion binding
- GO:0030165 PDZ domain binding
- GO:0106310 protein serine kinase activity
- GO:0043539 protein serine/threonine kinase activator activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0004712 protein serine/threonine/tyrosine kinase activity
- GO:0004713 protein tyrosine kinase activity
- GO:0097110 scaffold protein binding
- GO:0038133 ERBB2-ERBB3 signaling pathway
- GO:0070371 ERK1 and ERK2 cascade
- GO:0048009 insulin-like growth factor receptor signaling pathway
- GO:0000165 MAPK cascade
- GO:0042552 myelination
- GO:0036289 peptidyl-serine autophosphorylation
- GO:2000147 positive regulation of cell motility
- GO:0045893 positive regulation of DNA-templated transcription
- GO:0010628 positive regulation of gene expression
- GO:0071902 positive regulation of protein serine/threonine kinase activity
- GO:2000641 regulation of early endosome to late endosome transport
- GO:0090170 regulation of Golgi inheritance
- GO:0032872 regulation of stress-activated MAPK cascade
- GO:0014044 Schwann cell development
Disease associations
- cardiofaciocutaneous syndrome 4 MONDO:0014114
Drugs targeting this protein · 15
- CI-1040 inhibitor
- REFAMETINIB inhibitor
- RO-4987655 inhibitor
- TAK-733 inhibitor
- TRAMETINIB inhibitor
- BALAMAPIMOD inhibitor
- SELUMETINIB SULFATE inhibitor
- TRAMETINIB DIMETHYL SULFOXIDE inhibitor
- PIMASERTIB inhibitor
- COBIMETINIB inhibitor
- COBIMETINIB FUMARATE inhibitor
- AZD-8330 inhibitor
- BINIMETINIB inhibitor
- AVUTOMETINIB inhibitor
- MIRDAMETINIB inhibitor
Related proteins · sequence + function similarity
- Dual specificity mitogen-activated protein kinase kinase 2 0.99
- Dual specificity mitogen-activated protein kinase kinase 2 0.99
- Dual specificity mitogen-activated protein kinase kinase 2 0.99
- Dual specificity mitogen-activated protein kinase kinase 2 0.98
- Dual specificity mitogen-activated protein kinase kinase 1 0.98
- Dual specificity mitogen-activated protein kinase kinase 1 0.98
- Dual specificity mitogen-activated protein kinase kinase 1 0.98
- Dual specificity mitogen-activated protein kinase kinase 1 0.98
- Dual specificity mitogen-activated protein kinase kinase 1 0.97
- Dual specificity mitogen-activated protein kinase kinase 2 0.97
- Dual specificity mitogen-activated protein kinase kinase 1 0.97
- Dual specificity mitogen-activated protein kinase kinase 1 0.97
Co-cited proteins · studied together in the literature
- Dual specificity mitogen-activated protein kinase kinase 1 8 shared papers
- Serine/threonine-protein kinase B-raf 3 shared papers
- Glutaminase kidney isoform, mitochondrial 1 shared papers
- Lethal factor 2 shared papers
- Dual specificity mitogen-activated protein kinase kinase 1 2 shared papers
- Dual specificity mitogen-activated protein kinase kinase dSOR1 1 shared papers
- Kinase suppressor of Ras 2 1 shared papers
- Kinase suppressor of Ras 1 2 shared papers
- Inhibitor of nuclear factor kappa-B kinase subunit alpha 1 shared papers
- RAF proto-oncogene serine/threonine-protein kinase 1 shared papers
- Raf homolog serine/threonine-protein kinase Raf 1 shared papers
- Serine/threonine-protein kinase Sgk1 1 shared papers
Literature · 24 cited papers
- MEK drives BRAF activation through allosteric control of KSR proteins. Nature · 2018
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by Raf-Mek-Erk signaling in cancer cell metabolism. Proc. Natl. Acad. Sci. U.S.A. · 2012
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Molecular and functional analysis of a novel MEK2 mutation in cardio-facio-cutaneous syndrome: transmission through four generations. Am. J. Med. Genet. A · 2010
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
- Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration. J. Hepatol. · 2009
- Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
- Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
- … and 12 more in the literature graph
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