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mitogen-activated protein kinase kinase 3

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Target not currently curated in GtoImmuPdb

Target id: 2064

Nomenclature: mitogen-activated protein kinase kinase 3

Abbreviated Name: MKK3

Family: STE7 family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 347 17p11.2 MAP2K3 mitogen-activated protein kinase kinase 3
Mouse - 347 11 B2 Map2k3 mitogen-activated protein kinase kinase 3
Rat - 347 10 q22 Map2k3 mitogen activated protein kinase kinase 3
Previous and Unofficial Names Click here for help
dual specificity mitogen activated protein kinase kinase 3 | MAP kinase kinase 3 | MKK3 | PRKMK3
Database Links Click here for help
Alphafold P46734 (Hs), O09110 (Mm)
BRENDA 2.7.12.2
ChEMBL Target CHEMBL2109 (Hs), CHEMBL3721303 (Mm)
Ensembl Gene ENSG00000034152 (Hs), ENSMUSG00000018932 (Mm), ENSRNOG00000065992 (Rn)
Entrez Gene 5606 (Hs), 26397 (Mm), 303200 (Rn)
Human Protein Atlas ENSG00000034152 (Hs)
KEGG Enzyme 2.7.12.2
KEGG Gene hsa:5606 (Hs), mmu:26397 (Mm), rno:303200 (Rn)
OMIM 602315 (Hs)
Pharos P46734 (Hs)
RefSeq Nucleotide NM_145109 (Hs), NM_008928 (Mm), NM_001100674 (Rn)
RefSeq Protein NP_659731 (Hs), NP_032954 (Mm), NP_001094144 (Rn)
UniProtKB P46734 (Hs), O09110 (Mm)
Wikipedia MAP2K3 (Hs)
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
MEK inhibitor I Small molecule or natural product Click here for species-specific activity table Hs Inhibition <6.0 pIC50 4
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [4]
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
(R)-STU104 Small molecule or natural product Immunopharmacology Ligand Hs Binding 7.2 pKi 3
⤷ pKi 7.2 (Ki 7.1x10-8 M) [3]
Description: Binding affinity to immobilised human MKK3 determined by SPR
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: 2,5
Key to terms and symbols Click column headers to sort
Target used in screen: MEK3
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.3 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.8 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
GSK-1838705A Small molecule or natural product Hs Inhibitor Inhibition 6.0 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling
General Comments
SARS-CoV-2: p38 MAP kinase activity is reported to be upregulated by SARS-CoV-2 infection in vitro [1]. siRNA-mediated knockdown of MAP2K3 in A549-ACE2 cells significantly reduces SARS-CoV-2 replication, without reducing cell viability.

References

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1. Bouhaddou M, Memon D, Meyer B, White KM, Rezelj VV, Marrero MC, Polacco BJ, Melnyk JE, Ulferts S, Kaake RM. (2020) The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell, Article Online Now. DOI: 10.1016/j.cell.2020.06.034

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. Tang ML, Li H, Ning JF, Shen X, Sun X. (2022) Discovery of First-in-Class TAK1-MKK3 Protein-Protein Interaction (PPI) Inhibitor (R)-STU104 for the Treatment of Ulcerative Colitis through Modulating TNF-α Production. J Med Chem, 65 (9): 6690-6709. [PMID:35442672]

4. 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]

5. 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 3. Last modified on 24/05/2022. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2064.