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mitogen-activated protein kinase kinase kinase 19

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Target id: 2076

Nomenclature: mitogen-activated protein kinase kinase kinase 19

Abbreviated Name: YSK4

Family: STE20 subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1328 2q21.3 MAP3K19 mitogen-activated protein kinase kinase kinase 19
Mouse - 1311 1 E3 Map3k19 mitogen-activated protein kinase kinase kinase 19
Rat - 1306 13q12 Map3k19 mitogen-activated protein kinase kinase kinase 19
Previous and Unofficial Names Click here for help
RCK | Regulated in COPD, protein kinase | Sps1/Ste20-related protein kinase YSK4
Database Links Click here for help
Alphafold Q56UN5 (Hs), E9Q3S4 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL6191 (Hs)
Ensembl Gene ENSG00000176601 (Hs), ENSMUSG00000051590 (Mm), ENSRNOG00000003952 (Rn)
Entrez Gene 80122 (Hs), 22625 (Mm), 289001 (Rn)
Human Protein Atlas ENSG00000176601 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:80122 (Hs), mmu:22625 (Mm), rno:289001 (Rn)
Pharos Q56UN5 (Hs)
RefSeq Nucleotide NM_025052 (Hs), NM_011737 (Mm), XM_002727999 (Rn)
RefSeq Protein NP_079328 (Hs), NP_035867 (Mm), XP_002728045 (Rn)
UniProtKB Q56UN5 (Hs), E9Q3S4 (Mm)
Wikipedia MAP3K19 (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

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
BIIB068 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.9 pKd 4
⤷ pKd 6.9 (Kd 1.3x10-7 M) [4]
compound 1 [PMID: 24793884] Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - 5
⤷ [5]
Description: Measured as % inhibition using 1μM compound.
Inhibitor Comments
MAP3K19 activity is inhibited by approximately 96% in the presence of 1μM compound 1 [PMID 24793884] [5] (note that MAP3K19 is referred to by its synonym YSK4 in the article's Supplementary data table)..
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: 3,6
Key to terms and symbols Click column headers to sort
Target used in screen: YSK4
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.3 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.1 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 8.3 pKd
foretinib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 7.9 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 7.9 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.8 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 7.8 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.8 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
MAP3K19 is expressed predominantly by alveolar and interstitial macrophages and bronchial epithelial cells in the lung and is overexpressed in chronic obstructive pulmonary disease (COPD) [2], and regulates TGF-β signaling in experimental models of lung injury and pulmonary fibrosis [1].
Cell Type Associations
Immuno Cell Type:  Macrophages & monocytes
Comment:  Expressed in alveolar and interstitial macrophages.
References:  2

References

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1. Boehme SA, Franz-Bacon K, DiTirro DN, Ly TW, Bacon KB. (2016) MAP3K19 Is a Novel Regulator of TGF-β Signaling That Impacts Bleomycin-Induced Lung Injury and Pulmonary Fibrosis. PLoS ONE, 11 (5): e0154874. [PMID:27144281]

2. Boehme SA, Franz-Bacon K, Ludka J, DiTirro DN, Ly TW, Bacon KB. (2016) MAP3K19 Is Overexpressed in COPD and Is a Central Mediator of Cigarette Smoke-Induced Pulmonary Inflammation and Lower Airway Destruction. PLoS ONE, 11 (12): e0167169. [PMID:27935962]

3. 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]

4. Ma B, Bohnert T, Otipoby KL, Tien E, Arefayene M, Bai J, Bajrami B, Bame E, Chan TR, Humora M et al.. (2020) Discovery of BIIB068: A Selective, Potent, Reversible Bruton's Tyrosine Kinase Inhibitor as an Orally Efficacious Agent for Autoimmune Diseases. J Med Chem, 63 (21): 12526-12541. [PMID:32696648]

5. Reichelt A, Bailis JM, Bartberger MD, Yao G, Shu H, Kaller MR, Allen JG, Weidner MF, Keegan KS, Dao JH. (2014) Synthesis and structure-activity relationship of trisubstituted thiazoles as Cdc7 kinase inhibitors. Eur J Med Chem, 80: 364-82. [PMID:24793884]

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

STE20 subfamily: mitogen-activated protein kinase kinase kinase 19. Last modified on 12/08/2020. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2076.