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ribosomal protein S6 kinase A5

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Target not currently curated in GtoImmuPdb

Target id: 1523

Nomenclature: ribosomal protein S6 kinase A5

Abbreviated Name: MSK1

Family: MSK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 802 14q32.11 RPS6KA5 ribosomal protein S6 kinase A5
Mouse - 863 12 E Rps6ka5 ribosomal protein S6 kinase, polypeptide 5
Rat - 518 6q32 Rps6ka5 ribosomal protein S6 kinase A5
Previous and Unofficial Names Click here for help
nuclear mitogen- and stress-activated protein kinase 1 | ribosomal protein S6 kinase | ribosomal protein S6 kinase, 90kDa, polypeptide 5 | ribosomal protein S6 kinase alpha-5 | RLPK | RSK-like protein kinase
Database Links Click here for help
Alphafold O75582 (Hs), Q8C050 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL4237 (Hs)
Ensembl Gene ENSG00000100784 (Hs), ENSMUSG00000021180 (Mm), ENSRNOG00000004362 (Rn)
Entrez Gene 9252 (Hs), 73086 (Mm), 314384 (Rn)
Human Protein Atlas ENSG00000100784 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:9252 (Hs), mmu:73086 (Mm), rno:314384 (Rn)
OMIM 603607 (Hs)
Pharos O75582 (Hs)
RefSeq Nucleotide NM_004755 (Hs), NM_153587 (Mm), NM_001108048 (Rn)
RefSeq Protein NP_004746 (Hs), NP_705815 (Mm), NP_001101518 (Rn)
UniProtKB O75582 (Hs), Q8C050 (Mm)
Wikipedia RPS6KA5 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the C-terminal kinase domain of MSK1
PDB Id:  3KN6
Resolution:  2.0Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the C-terminal kinase domain of msk1 in complex with AMP-PNP
PDB Id:  3KN5
Ligand:  AMP-PNP
Resolution:  2.4Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  The structure of the N-terminal kinase domain of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein
PDB Id:  1VZO
Resolution:  1.8Å
Species:  Human
References:  7
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
SB-747651A Small molecule or natural product Primary target of this compound Hs Inhibition 9.3 pIC50 2
⤷ pIC50 9.3 (IC50 5x10-10 M) [2]
compound 24 [PMID: 15955699] Small molecule or natural product Primary target of this compound Hs Inhibition 8.9 pIC50 2
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [2]
compound 23 [PMID: 35816678] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.8 pIC50 5
⤷ pIC50 6.8 (IC50 1.43x10-7 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: 3,8
Key to terms and symbols Click column headers to sort
Target used in screen: RPS6KA5(Kin.Dom.1-N-terminal)
Ligand Sp. Type Action Value Parameter
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.4 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.8 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.6 pKd
enzastaurin Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 6.2 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 5.9 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
Target used in screen: RPS6KA5(Kin.Dom.2-C-terminal)
Ligand Sp. Type Action Value Parameter
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
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
BI-2536 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.1 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.0 pKd
PHA-665752 Small molecule or natural product Hs Inhibitor Inhibition 6.0 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 5.8 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 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: 1,4
Key to terms and symbols Click column headers to sort
Target used in screen: MSK1/MSK1(RPS6KA5)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.2 0.5 -0.5
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 9.9 41.0 33.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 12.3 5.0 0.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 13.2 13.0 8.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 17.0 24.0 4.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 23.7 3.0 2.0
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 24.8
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 34.7 43.0 7.0
PKCbeta inhibitor Small molecule or natural product Hs Inhibitor Inhibition 36.9 39.0 6.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 37.5 47.0 10.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
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. Bamford MJ, Bailey N, Davies S, Dean DK, Francis L, Panchal TA, Parr CA, Sehmi S, Steadman JG, Takle AK et al.. (2005) (1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: further optimisation as highly potent and selective MSK-1-inhibitors. Bioorg Med Chem Lett, 15 (14): 3407-11. [PMID:15955699]

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. 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]

5. Ladduwahetty T, Lee MR, Maillard MC, Cachope R, Todd D, Barnes M, Beaumont V, Chauhan A, Gallati C, Haughan AF et al.. (2022) Identification of a Potent, Selective, and Brain-Penetrant Rho Kinase Inhibitor and its Activity in a Mouse Model of Huntington's Disease. J Med Chem, 65 (14): 9819-9845. [PMID:35816678]

6. Malakhova M, D'Angelo I, Kim HG, Kurinov I, Bode AM, Dong Z. (2010) The crystal structure of the active form of the C-terminal kinase domain of mitogen- and stress-activated protein kinase 1. J Mol Biol, 399 (1): 41-52. [PMID:20382163]

7. Smith KJ, Carter PS, Bridges A, Horrocks P, Lewis C, Pettman G, Clarke A, Brown M, Hughes J, Wilkinson M et al.. (2004) The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein. Structure, 12 (6): 1067-77. [PMID:15274926]

8. 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

MSK subfamily: ribosomal protein S6 kinase A5. Last modified on 13/07/2022. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1523.