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mitogen-activated protein kinase kinase kinase 3

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Target id: 2078

Nomenclature: mitogen-activated protein kinase kinase kinase 3

Abbreviated Name: MEKK3

Family: STE11 family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 626 17q23.3 MAP3K3 mitogen-activated protein kinase kinase kinase 3
Mouse - 626 11 E1 Map3k3 mitogen-activated protein kinase kinase kinase 3
Rat - 626 10 q32.1 Map3k3 mitogen activated protein kinase kinase kinase 3
Previous and Unofficial Names Click here for help
MAP/ERK kinase kinase 3 | MAPKKK3
Database Links Click here for help
Alphafold Q99759 (Hs), Q61084 (Mm)
BRENDA 2.7.11.25
ChEMBL Target CHEMBL5970 (Hs)
Ensembl Gene ENSG00000198909 (Hs), ENSMUSG00000020700 (Mm), ENSRNOG00000061424 (Rn)
Entrez Gene 4215 (Hs), 26406 (Mm), 303604 (Rn)
Human Protein Atlas ENSG00000198909 (Hs)
KEGG Enzyme 2.7.11.25
KEGG Gene hsa:4215 (Hs), mmu:26406 (Mm), rno:303604 (Rn)
OMIM 602539 (Hs)
Pharos Q99759 (Hs)
RefSeq Nucleotide NM_002401 (Hs), NM_011947 (Mm), NM_001107058 (Rn)
RefSeq Protein NP_002392 (Hs), NP_036077 (Mm), NP_001100528 (Rn)
UniProtKB Q99759 (Hs), Q61084 (Mm)
Wikipedia MAP3K3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of the Complex of Human Mitogen Activated Protein Kinase Kinase 5 Phox Domain (MAP2K5-phox) with Human Mitogen Activated Protein Kinase Kinase Kinase 3 (MAP3K3B-phox)
PDB Id:  2O2V
Resolution:  1.83Å
Species:  Human
References: 
Enzyme Reaction Click here for help
EC Number: 2.7.11.25

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
compound 5n [PMID: 20483621] Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - 3
⤷ [3]
Description: Measured as % inhibition using 1μM compound.
Inhibitor Comments
1μM compound 5n [PMID 20483621] inhibits MAP3K3 activity by 88% [3].
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: 2,4
Key to terms and symbols Click column headers to sort
Target used in screen: MAP3K3
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.2 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.3 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.9 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.9 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.8 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.7 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
Key to terms and symbols Click column headers to sort
Target used in screen: nd/MEKK3
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.4
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.4
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.9
K-252a Small molecule or natural product Hs Inhibitor Inhibition 6.9
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 11.8
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 18.4
JNJ-7706621 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 27.5
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 30.6
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 31.0
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 42.0
Displaying the top 10 most potent ligands  View all ligands in screen »

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. Milkiewicz KL, Weinberg LR, Albom MS, Angeles TS, Cheng M, Ghose AK, Roemmele RC, Theroff JP, Underiner TL, Zificsak CA et al.. (2010) Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase. Bioorg Med Chem, 18 (12): 4351-62. [PMID:20483621]

4. 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

STE11 family: mitogen-activated protein kinase kinase kinase 3. Last modified on 24/02/2015. Accessed on 25/10/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2078.