Protein: Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1) (Q01986)
Organism: Rattus norvegicus (Rat)
Function: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. 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 (By similarity). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.
Subcellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:Q02750}. Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body {ECO:0000250|UniProtKB:Q02750}. Cytoplasm {ECO:0000250|UniProtKB:Q02750}. Nucleus {ECO:0000250|UniProtKB:Q02750}. Membrane {ECO:0000250|UniProtKB:Q02750}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q02750}. Note=Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis. Membrane localization is probably regulated by its interaction with KSR1. {ECO:0000250|UniProtKB:Q02750}.
Sequence: MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKVGELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELLFGCQVEGDAAETPPRPRTPGRPLSSYGMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAFIKRSDAEEVDFAGWLCSTIGLNQPSTPTHAASI
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [63-365]
- IPR050915: MAP kinase kinase (family) [9-391]
- IPR008271: Serine/threonine-protein kinase, active site (active_site) [186-198]
- IPR017441: Protein kinase, ATP binding site (binding_site) [74-97]
- IPR000719: Protein kinase domain (domain) [68-361]
Interaction partners: - Mitogen-activated protein kinase 3
- RAF proto-oncogene serine/threonine-protein kinase
- non-specific serine/threonine protein kinase
- Mitogen-activated protein kinase 1
- Dual specificity mitogen-activated protein kinase kinase 2
- Serine/threonine-protein kinase A-Raf
- GTPase NRas
- GTPase HRas
- non-specific serine/threonine protein kinase
- Ras GTPase-activating-like protein IQGAP1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0036094 (small molecule binding), GO:1901363 (heterocyclic compound binding), GO:0016740 (transferase activity), GO:0043167 (ion binding), GO:0097159 (organic cyclic compound binding), GO:0140096 (catalytic activity, acting on a protein), GO:0097367 (carbohydrate derivative binding), GO:0005515 (protein binding), GO:1901265 (nucleoside phosphate binding), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0004672 (protein kinase activity), GO:0043168 (anion binding), GO:0000166 (nucleotide binding), GO:0032553 (ribonucleotide binding), GO:0035639 (purine ribonucleoside triphosphate binding), GO:0016301 (kinase activity), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0004712 (protein serine/threonine/tyrosine kinase activity), GO:0032555 (purine ribonucleotide binding), GO:0017076 (purine nucleotide binding), GO:0005524 (ATP binding), GO:0004708 (MAP kinase kinase activity), GO:0032559 (adenyl ribonucleotide binding), GO:0030554 (adenyl nucleotide binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0044237 (cellular metabolic process), GO:0019222 (regulation of metabolic process), GO:0032879 (regulation of localization), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0023051 (regulation of signaling), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0006793 (phosphorus metabolic process), GO:0051049 (regulation of transport), GO:1901564 (organonitrogen compound metabolic process), GO:0010646 (regulation of cell communication), GO:0080134 (regulation of response to stress), GO:0060341 (regulation of cellular localization), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0019538 (protein metabolic process), GO:0080135 (regulation of cellular response to stress), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:0060627 (regulation of vesicle-mediated transport), GO:0051128 (regulation of cellular component organization), GO:0043170 (macromolecule metabolic process), GO:0036211 (protein modification process), GO:0043412 (macromolecule modification), GO:2000641 (regulation of early endosome to late endosome transport), GO:0070302 (regulation of stress-activated protein kinase signaling cascade), GO:0033043 (regulation of organelle organization), GO:0006796 (phosphate-containing compound metabolic process), GO:0010629 (negative regulation of gene expression), GO:1902531 (regulation of intracellular signal transduction), GO:0010468 (regulation of gene expression), GO:0032386 (regulation of intracellular transport), GO:0043408 (regulation of MAPK cascade), GO:1903649 (regulation of cytoplasmic transport), GO:0006468 (protein phosphorylation), GO:1903358 (regulation of Golgi organization), GO:0032872 (regulation of stress-activated MAPK cascade), GO:0016310 (phosphorylation)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0071944 (cell periphery), GO:0030054 (cell junction), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0005938 (cell cortex), GO:0005794 (Golgi apparatus), GO:0005739 (mitochondrion), GO:0070161 (anchoring junction), GO:0043227 (membrane-bounded organelle), GO:0030055 (cell-substrate junction), GO:0043231 (intracellular membrane-bounded organelle), GO:0005770 (late endosome), GO:0005769 (early endosome), GO:0031982 (vesicle), GO:0005925 (focal adhesion), GO:0097708 (intracellular vesicle), GO:0005634 (nucleus)