mitogen-activated protein kinase kinase 4 | STE7 family | IUPHAR/BPS Guide to PHARMACOLOGY

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mitogen-activated protein kinase kinase 4

Target not currently curated in GtoImmuPdb

Target id: 2065

Nomenclature: mitogen-activated protein kinase kinase 4

Abbreviated Name: MKK4

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 - 399 17p12 MAP2K4 mitogen-activated protein kinase kinase 4
Mouse - 397 11 B3 Map2k4 mitogen-activated protein kinase kinase 4
Rat - 397 10 q24 Map2k4 mitogen activated protein kinase kinase 4
Previous and Unofficial Names
JNKK1 | MKK4 | PRKMK4 | Sek1 | SERK1 | dual specificity mitogen-activated protein kinase kinase 4
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of human non-phosphorylated MKK4 kinase domain complexed with AMP-PNP
PDB Id:  3ALN
Ligand:  AMP-PNP
Resolution:  2.3Å
Species:  Human
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structures of non-phosphorylated MAP2K4
PDB Id:  3VUT
Resolution:  3.5Å
Species:  Human
References:  2
Enzyme Reaction
EC Number: 2.7.12.2

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Parameter Reference
staurosporine Hs Inhibition >9.0 pIC50 4
pIC50 >9.0 (IC50 <1x10-9 M) [4]
MEK inhibitor I Hs Inhibition <6.0 pIC50 6
pIC50 <6.0 (IC50 >1x10-6 M) [6]
compound 11 [PMID: 26431428] Hs Inhibition <5.3 pIC50 5
pIC50 <5.3 (IC50 >5x10-6 M) [5]
DiscoveRx KINOMEscan® screen
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 1,7

Key to terms and symbols Click column headers to sort
Target used in screen: MEK4
Ligand Sp. Type Action Affinity Parameter
lestaurtinib Hs Inhibitor Inhibition 8.4 pKd
staurosporine Hs Inhibitor Inhibition 7.2 pKd
NVP-TAE684 Hs Inhibitor Inhibition 6.8 pKd
PLX-4720 Hs Inhibitor Inhibition 6.7 pKd
tamatinib Hs Inhibitor Inhibition 6.7 pKd
KW-2449 Hs Inhibitor Inhibition 6.6 pKd
PD-173955 Hs Inhibitor Inhibition 6.5 pKd
pazopanib Hs Inhibitor Inhibition 6.2 pKd
sunitinib Hs Inhibitor Inhibition 6.2 pKd
PP-242 Hs Inhibitor Inhibition 6.1 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »

References

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1. 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]

2. Matsumoto T, Kinoshita T, Kirii Y, Tada T, Yamano A. (2012) Crystal and solution structures disclose a putative transient state of mitogen-activated protein kinase kinase 4. Biochem. Biophys. Res. Commun., 425 (2): 195-200. [PMID:22828509]

3. Matsumoto T, Kinoshita T, Kirii Y, Yokota K, Hamada K, Tada T. (2010) Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition state. Biochem. Biophys. Res. Commun., 400 (3): 369-73. [PMID:20732303]

4. Pandey A, Volkots DL, Seroogy JM, Rose JW, Yu JC, Lambing JL, Hutchaleelaha A, Hollenbach SJ, Abe K, Giese NA et al.. (2002) Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase family. J. Med. Chem., 45 (17): 3772-93. [PMID:12166950]

5. Patel S, Freedman S, Chapman KL, Emms F, Fletcher AE, Knowles M, Marwood R, McAllister G, Myers J, Curtis N, Kulagowski JJ, Leeson PD, Ridgill M, Graham M, Matheson S, Rathbone D, Watt AP, Bristow LJ, Rupniak NM, Baskin E, Lynch JJ, Ragan CI. (1997) Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor. J Pharmacol Exp Ther, 283: 636-647. [PMID:9353380]

6. Wityak J, Hobbs FW, Gardner DS, Santella 3rd JB, Petraitis JJ, Sun JH, Favata MF, Daulerio AJ, Horiuchi KY, Copeland RA et al.. (2004) Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors. Bioorg. Med. Chem. Lett., 14 (6): 1483-6. [PMID:15006386]

7. 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 4. Last modified on 19/06/2018. Accessed on 23/04/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2065.