Dual specificity mitogen-activated protein kinase kinase 1

Details

Name
Dual specificity mitogen-activated protein kinase kinase 1
Kind
protein
Synonyms
  • 2.7.12.2
  • ERK activator kinase 1
  • MAP kinase kinase 1
  • MAPK/ERK kinase 1
  • MAPKK 1
  • MEK 1
  • MEK1
  • MKK1
  • PRKMK1
Gene Name
MAP2K1
UniProtKB Entry
Q02750Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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
MAP-kinase scaffold activity / protein kinase activator activity / protein serine kinase activity / scaffold protein binding
Processes
Bergmann glial cell differentiation / cerebellar cortex formation / endodermal cell differentiation / ERBB2-ERBB3 signaling pathway / face development / heart development / insulin-like growth factor receptor signaling pathway / myelination / negative regulation of cell population proliferation / neuron differentiation / positive regulation of DNA-templated transcription / positive regulation of endodermal cell differentiation / positive regulation of ERK1 and ERK2 cascade / Schwann cell development / thymus development / thyroid gland development / type B pancreatic cell proliferation
Components
centrosome / spindle pole body
General 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 (PubMed:29433126). 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
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
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
15q22.31
External Identifiers
ResourceLink
UniProtKB IDQ02750
UniProtKB Entry NameMP2K1_HUMAN
GenBank Protein ID188569
GenBank Gene IDL05624
GeneCard IDMAP2K1
GenAtlas IDMAP2K1
HGNC IDHGNC:6840
PDB ID(s)1S9J, 2P55, 3DV3, 3DY7, 3E8N, 3EQB, 3EQC, 3EQD, 3EQF, 3EQG, 3EQH, 3EQI, 3MBL, 3ORN, 3OS3, 3PP1, 3SLS, 3V01, 3V04, 3VVH, 3W8Q, 3WIG, 3ZLS, 3ZLW, 3ZLX, 3ZLY, 3ZM4, 4AN2, 4AN3, 4AN9, 4ANB, 4ARK, 4LMN, 4MNE, 4U7Z, 4U80, 4U81, 5BX0, 5EYM, 5HZE, 5YT3, 6NYB, 6PP9, 6Q0J, 6Q0T, 6U2G, 6V2W, 6X2P, 6X2S, 6X2X, 7B3M, 7B7R, 7B94, 7B9L, 7F2X, 7M0T, 7M0U, 7M0V, 7M0W, 7M0X, 7M0Y, 7M0Z, 7MFD, 7PQV, 7UMB, 7XLP, 7XNC, 8CHF, 8DGS, 8DGT, 9AXA, 9AXC, 9AXH, 9AXM, 9AXX, 9AXY, 9AY7, 9AYA
KEGG IDhsa:5604
IUPHAR/Guide To Pharmacology ID2062
NCBI Gene ID5604
General References
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
5-Bromo-N-[(2S)-2,3-dihydroxypropoxy]-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzamideexperimentalunknowntargetDetails
Cobimetinibapproved, investigationalyestargetinhibitorDetails
(5S)-4,5-difluoro-6-[(2-fluoro-4-iodophenyl)imino]-N-(2-hydroxyethoxy)cyclohexa-1,3-diene-1-carboxamideexperimentalunknowntargetDetails
2-[(2-chloro-4-iodophenyl)amino]-N-{[(2R)-2,3-dihydroxypropyl]oxy}-3,4-difluorobenzamideexperimentalunknowntargetDetails
MirdametinibinvestigationalunknowntargetDetails
K-252aexperimentalunknowntargetDetails
N-(5-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}-1,3,4-oxadiazol-2-yl)ethane-1,2-diamineexperimentalunknowntargetDetails
2-[(4-ETHYNYL-2-FLUOROPHENYL)AMINO]-3,4-DIFLUORO-N-(2-HYDROXYETHOXY)BENZAMIDEexperimentalunknowntargetDetails
BosutinibapprovedyestargetinhibitorDetails
TrametinibapprovedyestargetinhibitorDetails
Selumetinibapproved, investigationalyestargetinhibitorDetails
Binimetinibapproved, investigationalyestargetinhibitorDetails
ReversineexperimentalyestargetinhibitorDetails
DebromohymenialdisineexperimentalyestargetinhibitorDetails
Tetrabromo-2-BenzotriazoleexperimentalyestargetinhibitorDetails
PD-98059investigationalyestargetinhibitorDetails