mitogen-activated protein kinase kinase 1

Nomenclature: mitogen-activated protein kinase kinase 1

Abbreviated Name: MEK1

Family: STE7 family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 393 15q22.1-q22.33 MAP2K1 mitogen-activated protein kinase kinase 1
Mouse - 393 9 C Map2k1 mitogen-activated protein kinase kinase 1
Rat - 393 8 q24 Map2k1 mitogen activated protein kinase kinase 1
Previous and Unofficial Names
ERK activator kinase 1
MAP kinase kinase 1
MAP kinase/Erk kinase 1
MAPK/ERK kinase 1
dual specificity mitogen-activated protein kinase kinase 1
Database Links
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Reference Database
KEGG BRITE Hierarchy
Orphanet Gene
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure of the human mitogen-activated protein kinase kinase 1 (MEK1) in a ternary complex with compound 1, ATP-GS AND MG2P
Resolution:  1.8Å
Species:  Human
References:  3
Enzyme Reaction
EC Number:
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
trametinib Hs Inhibition 9.15 pIC50 5
pIC50 9.15 (IC50 7x10-10 M) [5]
Description: Inhibition of unphosphorylated MEK1.
Inhibitor Comments
Trametinib inhibits both MAP2K1 (MEK1) and MAP2K2 (MEK2).
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
Reference: 2,6

Key to terms and symbols Click column headers to sort
Target used in screen: MEK1
Ligand Sp. Type Action Affinity Units
lestaurtinib Hs Inhibitor Inhibition 8.46 pKd
foretinib Hs Inhibitor Inhibition 7.92 pKd
neratinib Hs Inhibitor Inhibition 7.85 pKd
bosutinib Hs Inhibitor Inhibition 7.72 pKd
staurosporine Hs Inhibitor Inhibition 7.68 pKd
PP-242 Hs Inhibitor Inhibition 7.29 pKd
SU-14813 Hs Inhibitor Inhibition 7.11 pKd
selumetinib Hs Inhibitor Inhibition 7.0 pKd
CI-1040 Hs Inhibitor Inhibition 6.92 pKd
sunitinib Hs Inhibitor Inhibition 6.89 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

Reference: 1,4

Key to terms and symbols Click column headers to sort
Target used in screen: MEK1/MEK1
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 3.8 3.0 0.0
K-252a Hs Inhibitor Inhibition 23.6 0.0 0.0
SB 218078 Hs Inhibitor Inhibition 29.5 40.0 51.0
SU11652 Hs Inhibitor Inhibition 33.1 21.0 8.0
Syk inhibitor Hs Inhibitor Inhibition 63.6 42.0 19.0
bosutinib Hs Inhibitor Inhibition 65.3
sunitinib Hs Inhibitor Inhibition 67.8
PD98059 Hs Inhibitor Inhibition 69.1 103.0 111.0
p38 MAP kinase inhibitor Hs Inhibitor Inhibition 70.1 111.0 102.0
PD 169316 Hs Inhibitor Inhibition 74.3 109.0 127.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Cardiofaciocutaneous syndrome 3
OMIM:  615279
Orphanet:  1340
Mutations not determined


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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol.29 (11): 1039-45. [PMID:22037377]

2. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol.29 (11): 1046-51. [PMID:22037378]

3. Fischmann TO, Smith CK, Mayhood TW, Myers JE, Reichert P, Mannarino A, Carr D, Zhu H, Wong J, Yang RS et al.. (2009) Crystal structures of MEK1 binary and ternary complexes with nucleotides and inhibitors. Biochemistry48 (12): 2661-74. [PMID:19161339]

4. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem. J.451 (2): 313-28. [PMID:23398362]

5. Gilmartin AG, Bleam MR, Groy A, Moss KG, Minthorn EA, Kulkarni SG, Rominger CM, Erskine S, Fisher KE, Yang J et al.. (2011) GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin. Cancer Res.17 (5): 989-1000. [PMID:21245089]

6. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol.17 (11): 1241-9. [PMID:21095574]

How to cite this page

STE7 family: mitogen-activated protein kinase kinase 1. Last modified on 06/05/2014. Accessed on 22/10/2014. IUPHAR/BPS Guide to PHARMACOLOGY,