Dual specificity mitogen-activated protein kinase kinase 1

Details

Name
Dual specificity mitogen-activated protein kinase kinase 1
Synonyms
  • 2.7.12.2
  • ERK activator kinase 1
  • MAP kinase kinase 1
  • MAPK/ERK kinase 1
  • MEK 1
  • MEK1
  • PRKMK1
Gene Name
MAP2K1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001734|Dual specificity mitogen-activated protein kinase kinase 1
MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKV
GELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHE
CNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYL
REKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHY
SVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSY
GMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAF
IKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV
Number of residues
393
Molecular Weight
43438.65
Theoretical pI
6.61
GO Classification
Functions
ATP binding / MAP kinase kinase activity / protein C-terminus binding / protein kinase activity / 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
Processes
activation of MAPK activity / activation of MAPKK activity / axon guidance / cell cycle arrest / cell motility / cellular senescence / chemotaxis / epidermal growth factor receptor signaling pathway / epithelial cell proliferation involved in lung morphogenesis / ERK1 and ERK2 cascade / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / Golgi inheritance / innate immune response / insulin receptor signaling pathway / keratinocyte differentiation / labyrinthine layer development / MAPK cascade / melanosome transport / mitophagy in response to mitochondrial depolarization / mitotic nuclear division / 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 / negative regulation of homotypic cell-cell adhesion / neurotrophin TRK receptor signaling pathway / placenta blood vessel development / positive regulation of axonogenesis / positive regulation of cell migration / positive regulation of gene expression / positive regulation of GTPase activity / positive regulation of protein serine/threonine kinase activity / positive regulation of Ras protein signal transduction / positive regulation of transcription elongation from RNA polymerase II promoter / protein heterooligomerization / Ras protein signal transduction / regulation of axon regeneration / regulation of early endosome to late endosome transport / regulation of Golgi inheritance / regulation of stress-activated MAPK cascade / regulation of vascular smooth muscle contraction / response to axon injury / response to glucocorticoid / response to oxidative stress / signal transduction / small GTPase mediated signal transduction / stress-activated MAPK cascade / 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 / toll-like receptor TLR6 / trachea formation / TRIF-dependent toll-like receptor signaling pathway / vascular endothelial growth factor receptor signaling pathway / vesicle transport along microtubule
Components
axon / cell cortex / cytoplasm / cytosol / dendrite cytoplasm / early endosome / endoplasmic reticulum / extracellular exosome / focal adhesion / Golgi apparatus / late endosome / microtubule / microtubule organizing center / mitochondrion / nucleus / perikaryon / perinuclear region of cytoplasm / plasma membrane
General Function
Receptor signaling protein tyrosine phosphatase activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0016235|Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1)
ATGCCCAAGAAGAAGCCGACGCCCATCCAGCTGAACCCGGCCCCCGACGGCTCTGCAGTT
AACGGGACCAGCTCTGCGGAGACCAACTTGGAGGCCTTGCAGAAGAAGCTGGAGGAGCTA
GAGCTTGATGAGCAGCAGCGAAAGCGCCTTGAGGCCTTTCTTACCCAGAAGCAGAAGGTG
GGAGAACTGAAGGATGACGACTTTGAGAAGATCAGTGAGCTGGGGGCTGGCAATGGCGGT
GTGGTGTTCAAGGTCTCCCACAAGCCTTCTGGCCTGGTCATGGCCAGAAAGCTAATTCAT
CTGGAGATCAAACCCGCAATCCGGAACCAGATCATAAGGGAGCTGCAGGTTCTGCATGAG
TGCAACTCTCCGTACATCGTGGGCTTCTATGGTGCGTTCTACAGCGATGGCGAGATCAGT
ATCTGCATGGAGCACATGGATGGAGGTTCTCTGGATCAAGTCCTGAAGAAAGCTGGAAGA
ATTCCTGAACAAATTTTAGGAAAAGTTAGCATTGCTGTAATAAAAGGCCTGACATATCTG
AGGGAGAAGCACAAGATCATGCACAGAGATGTCAAGCCCTCCAACATCCTAGTCAACTCC
CGTGGGGAGATCAAGCTCTGTGACTTTGGGGTCAGCGGGCAGCTCATCGACTCCATGGCC
AACTCCTTCGTGGGCACAAGGTCCTACATGTCGCCAGAAAGACTCCAGGGGACTCATTAC
TCTGTGCAGTCAGACATCTGGAGCATGGGACTGTCTCTGGTAGAGATGGCGGTTGGGAGG
TATCCCATCCCTCCTCCAGATGCCAAGGAGCTGGAGCTGATGTTTGGGTGCCAGGTGGAA
GGAGATGCGGCTGAGACCCCACCCAGGCCAAGGACCCCCGGGAGGCCCCTTAGCTCATAC
GGAATGGACAGCCGACCTCCCATGGCAATTTTTGAGTTGTTGGATTACATAGTCAACGAG
CCTCCTCCAAAACTGCCCAGTGGAGTGTTCAGTCTGGAATTTCAAGATTTTGTGAATAAA
TGCTTAATAAAAAACCCCGCAGAGAGAGCAGATTTGAAGCAACTCATGGTTCATGCTTTT
ATCAAGAGATCTGATGCTGAGGAAGTGGATTTTGCAGGTTGGCTCTGCTCCACCATCGGC
CTTAACCAGCCCAGCACACCAACCCATGCTGCTGGCGTCTAA
Chromosome Location
15
Locus
15q22.1-q22.33
External Identifiers
ResourceLink
UniProtKB IDQ02750
UniProtKB Entry NameMP2K1_HUMAN
GenBank Protein ID188569
GenBank Gene IDL05624
GenAtlas IDMAP2K1
HGNC IDHGNC:6840
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB031155-Bromo-N-[(2S)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamideexperimentalunknownDetails
DB05239Cobimetinibapproved, investigationalyesinhibitorDetails
DB06892(5S)-4,5-difluoro-6-[(2-fluoro-4-iodophenyl)imino]-N-(2-hydroxyethoxy)cyclohexa-1,3-diene-1-carboxamideexperimentalunknownDetails
DB070462-[(2-chloro-4-iodophenyl)amino]-N-{[(2R)-2,3-dihydroxypropyl]oxy}-3,4-difluorobenzamideexperimentalunknownDetails
DB07101MirdametinibinvestigationalunknownDetails
DB02152K-252aexperimentalunknownDetails
DB08130N-(5-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}-1,3,4-oxadiazol-2-yl)ethane-1,2-diamineexperimentalunknownDetails
DB082082-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDEexperimentalunknownDetails
DB06616BosutinibapprovedyesinhibitorDetails
DB08911TrametinibapprovedyesinhibitorDetails
DB11689Selumetinibapproved, investigationalyesinhibitorDetails
DB11967Binimetinibapproved, investigationalyesinhibitorDetails
DB14904PimasertibinvestigationalunknowninhibitorDetails