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p21 (RAC1) activated kinase 3

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Target not currently curated in GtoImmuPdb

Target id: 2135

Nomenclature: p21 (RAC1) activated kinase 3

Abbreviated Name: PAK3

Family: PAKA subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 559 Xq23 PAK3 p21 (RAC1) activated kinase 3
Mouse - 559 X F2 Pak3 p21 (RAC1) activated kinase 3
Rat - 544 Xq33 Pak3 p21 (RAC1) activated kinase 3
Previous and Unofficial Names Click here for help
Oligophrenin-3 | OPHN3 | beta-PAK | p21 (CDKN1A)-activated kinase 3 | p21-activated kinase 3 | p21 protein (Cdc42/Rac)-activated kinase 3
Database Links Click here for help
Alphafold O75914 (Hs), Q61036 (Mm), Q62829 (Rn)
BRENDA 2.7.11.1
CATH/Gene3D 3.90.810.10
ChEMBL Target CHEMBL2999 (Hs)
Ensembl Gene ENSG00000077264 (Hs), ENSMUSG00000031284 (Mm), ENSRNOG00000004676 (Rn)
Entrez Gene 5063 (Hs), 18481 (Mm), 29433 (Rn)
Human Protein Atlas ENSG00000077264 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:5063 (Hs), mmu:18481 (Mm), rno:29433 (Rn)
OMIM 300142 (Hs)
Orphanet ORPHA159942 (Hs)
Pharos O75914 (Hs)
RefSeq Nucleotide NM_002578 (Hs), NM_001195046 (Mm), NM_019210 (Rn)
RefSeq Protein NP_001121638 (Hs), NP_001181975 (Mm), NP_062083 (Rn)
UniProtKB O75914 (Hs), Q61036 (Mm), Q62829 (Rn)
Wikipedia PAK3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  SOLUTION STRUCTURE OF CDC42HS COMPLEXED WITH A PEPTIDE DERIVED FROM P-21 ACTIVATED KINASE, NMR, 20 STRUCTURES
PDB Id:  1EES
Resolution:  0.0Å
Species:  Mouse
References:  5
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
FRAX597 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pIC50 7
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [7]
FRAX486 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pIC50 3
⤷ pIC50 7.3 (IC50 5.53x10-8 M) [3]
PF-3758309 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 6
⤷ pIC50 7.0 (IC50 9.9x10-8 M) [6]
compound 4 [PMID: 24432870] Small molecule or natural product Click here for species-specific activity table Hs Inhibition <5.0 pIC50 6
⤷ pIC50 <5.0 (IC50 >1x10-5 M) [6]
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: 2,8
Key to terms and symbols Click column headers to sort
Target used in screen: PAK3
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.1 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.7 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.7 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 6.3 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.2 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 6.1 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: PAK3/PAK3
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 2.4 1.5 4.0
K-252a Small molecule or natural product Hs Inhibitor Inhibition 5.6 4.0 3.0
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.9
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 35.4 27.0 7.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 41.7 79.0 124.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 54.7 33.0 107.0
indirubin derivative E804 Small molecule or natural product Hs Inhibitor Inhibition 73.8 75.0 101.0
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 79.8 82.0 62.0
alsterpaullone Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 80.4 37.0 56.0
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 82.9 55.0 29.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Mental retardation, X-linked 30; MRX30
Synonyms: Non-specific X-linked mental retardation [Disease Ontology: DOID:0050776]
X-linked non-syndromic intellectual disability [Orphanet: ORPHA777]
Disease Ontology: DOID:0050776
OMIM: 300558
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. 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. Dolan BM, Duron SG, Campbell DA, Vollrath B, Shankaranarayana Rao BS, Ko HY, Lin GG, Govindarajan A, Choi SY, Tonegawa S. (2013) Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc Natl Acad Sci USA, 110 (14): 5671-6. [PMID:23509247]

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. Gizachew D, Guo W, Chohan KK, Sutcliffe MJ, Oswald RE. (2000) Structure of the complex of Cdc42Hs with a peptide derived from P-21 activated kinase. Biochemistry, 39 (14): 3963-71. [PMID:10747784]

6. Karpov AS, Amiri P, Bellamacina C, Bellance MH, Breitenstein W, Daniel D, Denay R, Fabbro D, Fernandez C, Galuba I et al.. (2015) Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor. ACS Med Chem Lett, 6 (7): 776-81. [PMID:26191365]

7. Licciulli S, Maksimoska J, Zhou C, Troutman S, Kota S, Liu Q, Duron S, Campbell D, Chernoff J, Field J et al.. (2013) FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. J Biol Chem, 288 (40): 29105-14. [PMID:23960073]

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

PAKA subfamily: p21 (RAC1) activated kinase 3. Last modified on 03/12/2015. Accessed on 23/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2135.