p21 (RAC1) activated kinase 3

Target id: 2135

Nomenclature: p21 (RAC1) activated kinase 3

Abbreviated Name: PAK3

Family: PAKA subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for p21 (RAC1) activated kinase 3 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 544 Xq22.3 PAK3 p21 (RAC1) activated kinase 3
Mouse - 580 X F2 Pak3 p21 (RAC1) activated kinase 3
Rat - 544 X q14 Pak3 p21 (RAC1) activated kinase 3
Previous and Unofficial Names
beta-PAK | Oligophrenin-3 | OPHN3 | p21 (CDKN1A)-activated kinase 3 | p21-activated kinase 3 | p21 protein (Cdc42/Rac)-activated kinase 3
Database Links
BRENDA
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
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
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
FRAX597 Hs Inhibition 7.7 pIC50 7
pIC50 7.7 (IC50 1.9x10-8 M) [7]
FRAX486 Hs Inhibition 7.3 pIC50 3
pIC50 7.3 (IC50 5.53x10-8 M) [3]
PF-3758309 Hs Inhibition 7.0 pIC50 6
pIC50 7.0 (IC50 9.9x10-8 M) [6]
compound 4 [PMID: 24432870] Hs Inhibition <5.0 pIC50 6
pIC50 <5.0 (IC50 >1x10-5 M) [6]
DiscoveRx KINOMEscan® screen
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 Affinity Units
staurosporine Hs Inhibitor Inhibition 8.1 pKd
sunitinib Hs Inhibitor Inhibition 7.8 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.5 pKd
lestaurtinib Hs Inhibitor Inhibition 7.5 pKd
midostaurin Hs Inhibitor Inhibition 6.7 pKd
SU-14813 Hs Inhibitor Inhibition 6.7 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.4 pKd
KW-2449 Hs Inhibitor Inhibition 6.3 pKd
tamatinib Hs Inhibitor Inhibition 6.2 pKd
dovitinib 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
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 Hs Inhibitor Inhibition 2.4 1.5 4.0
K-252a Hs Inhibitor Inhibition 5.6 4.0 3.0
bosutinib Hs Inhibitor Inhibition 9.9
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 35.4 27.0 7.0
SB 218078 Hs Inhibitor Inhibition 41.7 79.0 124.0
midostaurin Hs Inhibitor Inhibition 54.7 33.0 107.0
indirubin derivative E804 Hs Inhibitor Inhibition 73.8 75.0 101.0
TWS119 Hs Inhibitor Inhibition 79.8 82.0 62.0
alsterpaullone Hs Inhibitor Inhibition 80.4 37.0 56.0
JAK3 inhibitor VI Hs Inhibitor Inhibition 82.9 55.0 29.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
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. U.S.A., 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 21/08/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2135.