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ribosomal protein S6 kinase A3

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Target not currently curated in GtoImmuPdb

Target id: 1528

Nomenclature: ribosomal protein S6 kinase A3

Abbreviated Name: RSK2

Family: RSK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 740 Xp22.12 RPS6KA3 ribosomal protein S6 kinase A3
Mouse - 740 X 73.27 cM Rps6ka3 ribosomal protein S6 kinase polypeptide 3
Rat - 740 Xq21 Rps6ka3 ribosomal protein S6 kinase A3
Previous and Unofficial Names Click here for help
ISPK1  | MAPKAPK1B | RSKα3 | Coffin-Lowry syndrome | mental retardation, X-linked 19 | ribosomal protein S6 kinase, 90kD, polypeptide 3 | ribosomal protein S6 kinase alpha-3 | CLS | HU-3 | MRX19 | ribosomal protein S6 kinase, 90kDa, polypeptide 3
Database Links Click here for help
Alphafold P51812 (Hs), P18654 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL2345 (Hs), CHEMBL3297641 (Mm)
Ensembl Gene ENSG00000177189 (Hs), ENSMUSG00000031309 (Mm), ENSRNOG00000006632 (Rn)
Entrez Gene 6197 (Hs), 110651 (Mm), 501560 (Rn)
Human Protein Atlas ENSG00000177189 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:6197 (Hs), mmu:110651 (Mm), rno:501560 (Rn)
OMIM 300075 (Hs)
Orphanet ORPHA118405 (Hs)
Pharos P51812 (Hs)
RefSeq Nucleotide NM_004586 (Hs), NM_148945 (Mm), NM_001192004 (Rn)
RefSeq Protein NP_004577 (Hs), NP_683747 (Mm), NP_001178933 (Rn)
SynPHARM 81041 (in complex with BI-D1870)
UniProtKB P51812 (Hs), P18654 (Mm)
Wikipedia RPS6KA3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Rsk2 C-terminal Kinase Domain with inhibitor (E)-methyl 3-(4-amino-7-(3-hydroxypropyl)-5-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-2-cyanoacrylate
PDB Id:  4D9T
Resolution:  2.4Å
Species:  Human
References:  9
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
BIX 02565 Small molecule or natural product Primary target of this compound Hs Inhibition 9.0 pIC50 7
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [7]
compound 8h [PMID: 22765894] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 6
⤷ pIC50 8.5 (IC50 3x10-9 M) [6]
compound 25b [PMID: 22564207] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.9 pIC50 5
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [5]
FMK Small molecule or natural product Hs Inhibition 7.8 pIC50 2
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [2]
BI-D1870 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.6 pIC50 8
⤷ pIC50 7.6 (IC50 2.4x10-8 M) [8]
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: 3,10
Key to terms and symbols Click column headers to sort
Target used in screen: RSK2(Kin.Dom.1-N-terminal)
Ligand Sp. Type Action Value Parameter
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
enzastaurin Small molecule or natural product Hs Inhibitor Inhibition 7.1 pKd
GSK-1838705A Small molecule or natural product Hs Inhibitor Inhibition 6.8 pKd
GSK-461364A Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.6 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 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: Rsk2/RSK2
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 -1.3 0.0 0.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition -0.7 0.0 -1.0
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 1.8
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 2.3 11.0 3.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.5 1.0 1.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 2.6 1.0 1.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 3.2 1.0 0.0
PKCbeta inhibitor Small molecule or natural product Hs Inhibitor Inhibition 3.8 3.0 1.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 1.0 1.0
Gö 6983 Small molecule or natural product Hs Inhibitor Inhibition 6.6 2.0 -1.0
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
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Coffin-Lowry syndrome
Disease Ontology: DOID:3783
OMIM: 303600
Orphanet: ORPHA192
Disease:  Mental retardation, X-linked 19; MRX19
Synonyms: Non-specific X-linked mental retardation [Disease Ontology: DOID:0050776]
X-linked non-syndromic intellectual disability [Orphanet: ORPHA777]
Disease Ontology: DOID:0050776
OMIM: 300844
Orphanet: ORPHA777

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. Cohen MS, Hadjivassiliou H, Taunton J. (2007) A clickable inhibitor reveals context-dependent autoactivation of p90 RSK. Nat Chem Biol, 3 (3): 156-60. [PMID:17259979]

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. Gingrich DE, Lisko JG, Curry MA, Cheng M, Quail M, Lu L, Wan W, Albom MS, Angeles TS, Aimone LD et al.. (2012) Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase. J Med Chem, 55 (10): 4580-93. [PMID:22564207]

6. Kim MH, Tsuhako AL, Co EW, Aftab DT, Bentzien F, Chen J, Cheng W, Engst S, Goon L, Klein RR et al.. (2012) The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett, 22 (15): 4979-85. [PMID:22765894]

7. Kirrane TM, Boyer SJ, Burke J, Guo X, Snow RJ, Soleymanzadeh L, Swinamer A, Zhang Y, Madwed JB, Kashem M et al.. (2012) Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity. Bioorg Med Chem Lett, 22 (1): 738-42. [PMID:22056746]

8. Sapkota GP, Cummings L, Newell FS, Armstrong C, Bain J, Frodin M, Grauert M, Hoffmann M, Schnapp G, Steegmaier M et al.. (2007) BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem J, 401 (1): 29-38. [PMID:17040210]

9. Serafimova IM, Pufall MA, Krishnan S, Duda K, Cohen MS, Maglathlin RL, McFarland JM, Miller RM, Frödin M, Taunton J. (2012) Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles. Nat Chem Biol, 8 (5): 471-6. [PMID:22466421]

10. 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

RSK subfamily: ribosomal protein S6 kinase A3. Last modified on 04/11/2016. Accessed on 14/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1528.