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mitogen-activated protein kinase kinase 6

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Target id: 2067

Nomenclature: mitogen-activated protein kinase kinase 6

Abbreviated Name: MKK6

Family: STE7 family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 334 17q24.3 MAP2K6 mitogen-activated protein kinase kinase 6
Mouse - 334 11 E1-E2 Map2k6 mitogen-activated protein kinase kinase 6
Rat - 334 10q32.1 Map2k6 mitogen-activated protein kinase kinase 6
Previous and Unofficial Names Click here for help
dual specificity mitogen-activated protein kinase kinase 6 | MAP kinase kinase 6 | MEK6 | PRKMK6 | SAPK kinase 3 | SAPKK3 | SKK3 | Stress-activated protein kinase kinase 3
Database Links Click here for help
Alphafold P52564 (Hs), P70236 (Mm), Q925D6 (Rn)
BRENDA 2.7.12.2
ChEMBL Target CHEMBL2171 (Hs)
Ensembl Gene ENSG00000108984 (Hs), ENSMUSG00000020623 (Mm), ENSRNOG00000004437 (Rn)
Entrez Gene 5608 (Hs), 26399 (Mm), 114495 (Rn)
Human Protein Atlas ENSG00000108984 (Hs)
KEGG Enzyme 2.7.12.2
KEGG Gene hsa:5608 (Hs), mmu:26399 (Mm), rno:114495 (Rn)
OMIM 601254 (Hs)
Pharos P52564 (Hs)
RefSeq Nucleotide NM_002758 (Hs), NM_011943 (Mm), NM_053703 (Rn)
RefSeq Protein NP_002749 (Hs), NP_036073 (Mm), NP_446155 (Rn)
SynPHARM 81546 (in complex with staurosporine)
UniProtKB P52564 (Hs), P70236 (Mm), Q925D6 (Rn)
Wikipedia MAP2K6 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Refined Crystal structure of non-phosphorylated MAP2K6 in a putative auto-inhibition state
PDB Id:  3VN9
Resolution:  2.6Å
Species:  Human
References:  4
Enzyme Reaction Click here for help
EC Number: 2.7.12.2

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition >9.0 pIC50 5
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [5]
DiscoveRx KINOMEscan® screen Click here for help
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: 2,6
Key to terms and symbols Click column headers to sort
Target used in screen: MEK6
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.4 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.9 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.7 pKd
tozasertib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.6 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
erlotinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
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.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 1,3
Key to terms and symbols Click column headers to sort
Target used in screen: MKK6/MKK6
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Small molecule or natural product Hs Inhibitor Inhibition 9.6 26.0 0.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 15.2 1.0 -1.5
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 19.3 27.0 10.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 21.1 0.0 1.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 56.8 -1.0 1.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 62.7 26.0 20.0
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 65.7 69.0 21.0
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 75.9
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 78.8 22.0 3.0
p38 MAP kinase inhibitor Small molecule or natural product Hs Inhibitor Inhibition 79.4 74.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling

References

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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. 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]

4. Matsumoto T, Kinoshita T, Matsuzaka H, Nakai R, Kirii Y, Yokota K, Tada T. (2012) Crystal structure of non-phosphorylated MAP2K6 in a putative auto-inhibition state. J Biochem, 151 (5): 541-9. [PMID:22383536]

5. 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]

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 6. Last modified on 12/02/2015. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2067.