General Information of Drug Therapeutic Target (DTT) (ID: TTAW3TO)

DTT Name HUMAN ERK activator kinase 1 (MEK1)
Synonyms PRKMK1; Mitogen-activated protein kinase kinase 1; MKK1; MEK 1; MAPKK 1; MAPK/ERKkinase 1; MAPK/ERK kinase 1; MAP kinase kinase 1; Dual specificity mitogen-activated protein kinase kinase 1
Gene Name MAP2K1
BioChemical Class
Kinase
UniProt ID
MP2K1_HUMAN
TTD ID
T99057
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.12.2
Sequence
MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKV
GELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHE
CNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYL
REKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHY
SVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSY
GMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAF
IKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV
Function
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. Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway.
KEGG Pathway
EGFR tyrosine kinase inhibitor resistance (hsa01521 )
Endocrine resistance (hsa01522 )
MAPK signaling pathway (hsa04010 )
ErbB signaling pathway (hsa04012 )
Ras signaling pathway (hsa04014 )
Rap1 signaling pathway (hsa04015 )
cGMP-PKG signaling pathway (hsa04022 )
cAMP signaling pathway (hsa04024 )
Chemokine signaling pathway (hsa04062 )
HIF-1 signaling pathway (hsa04066 )
FoxO signaling pathway (hsa04068 )
Sphingolipid signaling pathway (hsa04071 )
Phospholipase D signaling pathway (hsa04072 )
Oocyte meiosis (hsa04114 )
Autophagy - animal (hsa04140 )
mTOR signaling pathway (hsa04150 )
PI3K-Akt signaling pathway (hsa04151 )
Apoptosis (hsa04210 )
Cellular senescence (hsa04218 )
Vascular smooth muscle contraction (hsa04270 )
VEGF signaling pathway (hsa04370 )
Apelin signaling pathway (hsa04371 )
Osteoclast differentiation (hsa04380 )
Focal adhesion (hsa04510 )
Gap junction (hsa04540 )
Signaling pathways regulating pluripotency of stem cells (hsa04550 )
Neutrophil extracellular trap formation (hsa04613 )
Toll-like receptor signaling pathway (hsa04620 )
Natural killer cell mediated cytotoxicity (hsa04650 )
T cell receptor signaling pathway (hsa04660 )
B cell receptor signaling pathway (hsa04662 )
Fc epsilon RI signaling pathway (hsa04664 )
Fc gamma R-mediated phagocytosis (hsa04666 )
TNF signaling pathway (hsa04668 )
Long-term potentiation (hsa04720 )
Neurotrophin signaling pathway (hsa04722 )
Cholinergic synapse (hsa04725 )
Serotonergic synapse (hsa04726 )
Long-term depression (hsa04730 )
Regulation of actin cytoskeleton (hsa04810 )
Insulin signaling pathway (hsa04910 )
GnRH signaling pathway (hsa04912 )
Progesterone-mediated oocyte maturation (hsa04914 )
Estrogen signaling pathway (hsa04915 )
Melanogenesis (hsa04916 )
Prolactin signaling pathway (hsa04917 )
Thyroid hormone signaling pathway (hsa04919 )
Oxytocin signaling pathway (hsa04921 )
Relaxin signaling pathway (hsa04926 )
Parathyroid hormone synthesis, secretion and action (hsa04928 )
GnRH secretion (hsa04929 )
Cushing syndrome (hsa04934 )
Growth hormone synthesis, secretion and action (hsa04935 )
Alzheimer disease (hsa05010 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Alcoholism (hsa05034 )
Salmonella infection (hsa05132 )
Yersinia infection (hsa05135 )
Hepatitis C (hsa05160 )
Hepatitis B (hsa05161 )
Human cytomegalovirus infection (hsa05163 )
Influenza A (hsa05164 )
Human papillomavirus infection (hsa05165 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Human immunodeficiency virus 1 infection (hsa05170 )
Pathways in cancer (hsa05200 )
Proteoglycans in cancer (hsa05205 )
MicroRNAs in cancer (hsa05206 )
Chemical carcinogenesis - receptor activation (hsa05207 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Colorectal cancer (hsa05210 )
Renal cell carcinoma (hsa05211 )
Pancreatic cancer (hsa05212 )
Endometrial cancer (hsa05213 )
Glioma (hsa05214 )
Prostate cancer (hsa05215 )
Thyroid cancer (hsa05216 )
Melanoma (hsa05218 )
Bladder cancer (hsa05219 )
Chronic myeloid leukemia (hsa05220 )
Acute myeloid leukemia (hsa05221 )
Non-small cell lung cancer (hsa05223 )
Breast cancer (hsa05224 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Central carbon metabolism in cancer (hsa05230 )
Choline metabolism in cancer (hsa05231 )
PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235 )
Reactome Pathway
Frs2-mediated activation (R-HSA-170968 )
Signal transduction by L1 (R-HSA-445144 )
Uptake and function of anthrax toxins (R-HSA-5210891 )
RAF activation (R-HSA-5673000 )
MAP2K and MAPK activation (R-HSA-5674135 )
Negative feedback regulation of MAPK pathway (R-HSA-5674499 )
MAP3K8 (TPL2)-dependent MAPK1/3 activation (R-HSA-5684264 )
Signaling by moderate kinase activity BRAF mutants (R-HSA-6802946 )
Signaling by high-kinase activity BRAF mutants (R-HSA-6802948 )
Signaling by BRAF and RAF1 fusions (R-HSA-6802952 )
Paradoxical activation of RAF signaling by kinase inactive BRAF (R-HSA-6802955 )
Signaling downstream of RAS mutants (R-HSA-9649948 )
Signaling by MAP2K mutants (R-HSA-9652169 )
Signaling by RAF1 mutants (R-HSA-9656223 )
MAPK3 (ERK1) activation (R-HSA-110056 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Trametinib DM2JGQ3 Melanoma 2C30 Approved [1]
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1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Selumetinib DMC7W6R Neurofibromatosis type 1 LD2D.10 Phase 3 [1]
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References

1 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.