Names & Taxonomy
- Uniprot ID:
- Q02750
- Entry Name:
- MP2K1_HUMAN
- Status:
- reviewed
- Protein Names:
- Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
- Gene Names:
- MAP2K1 MEK1 PRKMK1
- Gene Names Primary:
- MAP2K1
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 393
- Sequence:
- MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKVGELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSYGMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAFIKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Function
- 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. 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.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Enzyme Regulation:
- ENZYME REGULATION: Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser-218 and Ser-222. MAP2K1/MEK1 is also the target of negative feed-back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A (By similarity). Many inhibitors have been identified including pyrrole derivatives, TAK-733 (one of a series of 8-methylpyridopyrimidine-4,7(3H,8H)-dione derivatives), CH4987655 and RDEA119/BAY 869766.
- Active Site:
- ACT_SITE 190 190 Proton acceptor.
- Cross Reference Drug Bank:
- DB06616 DB05239 DB08911
- Gene Ontology Go:
- cytoplasm
cytosol
early endosome
endoplasmic reticulum
extracellular exosome
focal adhesion
Golgi apparatus
late endosome
microtubule organizing center
mitochondrion
nucleus
plasma membrane
ATP binding
MAP kinase kinase activity
protein C-terminus binding
protein kinase activity
protein kinase binding
protein N-terminus binding
protein serine/threonine kinase activator activity
protein serine/threonine kinase activity
protein serine/threonine/tyrosine kinase activity
protein tyrosine kinase activity
receptor signaling protein tyrosine phosphatase activity
activation of MAPK activity
activation of MAPKK activity
axon guidance
Bergmann glial cell differentiation
cell cycle arrest
cell motility
cellular senescence
cerebellar cortex formation
chemotaxis
epidermal growth factor receptor signaling pathway
epithelial cell proliferation involved in lung morphogenesis
ERK1 and ERK2 cascade
face development
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
heart development
innate immune response
insulin receptor signaling pathway
keratinocyte differentiation
labyrinthine layer development
MAPK cascade
mitophagy in response to mitochondrial depolarization
movement of cell or subcellular component
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of cell proliferation
negative regulation of gene expression
neurotrophin TRK receptor signaling pathway
placenta blood vessel development
positive regulation of axonogenesis
positive regulation of gene expression
positive regulation of protein serine/threonine kinase activity
Ras protein signal transduction
regulation of apoptotic process
regulation of axon regeneration
regulation of early endosome to late endosome transport
regulation of Golgi inheritance
regulation of mitotic cell cycle
regulation of stress-activated MAPK cascade
signal transduction
small GTPase mediated signal transduction
stress-activated MAPK cascade
stress-activated protein kinase signaling cascade
thymus development
thyroid gland development
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
trachea formation
TRIF-dependent toll-like receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway - Gene Ontology Biological Process:
- activation of MAPK activity
activation of MAPKK activity
axon guidance
Bergmann glial cell differentiation
cell cycle arrest
cell motility
cellular senescence
cerebellar cortex formation
chemotaxis
epidermal growth factor receptor signaling pathway
epithelial cell proliferation involved in lung morphogenesis
ERK1 and ERK2 cascade
face development
Fc-epsilon receptor signaling pathway
fibroblast growth factor receptor signaling pathway
heart development
innate immune response
insulin receptor signaling pathway
keratinocyte differentiation
labyrinthine layer development
MAPK cascade
mitophagy in response to mitochondrial depolarization
movement of cell or subcellular component
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of cell proliferation
negative regulation of gene expression
neurotrophin TRK receptor signaling pathway
placenta blood vessel development
positive regulation of axonogenesis
positive regulation of gene expression
positive regulation of protein serine/threonine kinase activity
Ras protein signal transduction
regulation of apoptotic process
regulation of axon regeneration
regulation of early endosome to late endosome transport
regulation of Golgi inheritance
regulation of mitotic cell cycle
regulation of stress-activated MAPK cascade
signal transduction
small GTPase mediated signal transduction
stress-activated MAPK cascade
stress-activated protein kinase signaling cascade
thymus development
thyroid gland development
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
trachea formation
TRIF-dependent toll-like receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway - Gene Ontology Molecular Function:
- ATP binding
MAP kinase kinase activity
protein C-terminus binding
protein kinase activity
protein kinase binding
protein N-terminus binding
protein serine/threonine/tyrosine kinase activity
protein serine/threonine kinase activator activity
protein serine/threonine kinase activity
protein tyrosine kinase activity
receptor signaling protein tyrosine phosphatase activity - Gene Ontology Cellular Component:
- cytoplasm
cytosol
early endosome
endoplasmic reticulum
extracellular exosome
focal adhesion
Golgi apparatus
late endosome
microtubule organizing center
mitochondrion
nucleus
plasma membrane - Keywords:
- 3D-structure
ATP-binding
Acetylation
Alternative splicing
Cardiomyopathy
Complete proteome
Cytoplasm
Cytoskeleton
Direct protein sequencing
Disease mutation
Ectodermal dysplasia
Kinase
Membrane
Mental retardation
Nucleotide-binding
Nucleus
Phosphoprotein
Reference proteome
Serine/threonine-protein kinase
Transferase
Tyrosine-protein kinase - Interacts With:
- Q8N9N5; Q9NR09; P15056; Q9Y297; O15519-1; P28482; P27361; P04049; Q86Y07; Q86Y07-1; P46937