General Information of Target

Target ID LDTP01351
Target Name Serine/threonine-protein kinase PAK 3 (PAK3)
Gene Name PAK3
Gene ID 5063
Synonyms
OPHN3; Serine/threonine-protein kinase PAK 3; EC 2.7.11.1; Beta-PAK; Oligophrenin-3; p21-activated kinase 3; PAK-3
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSDGLDNEEKPPAPPLRMNSNNRDSSALNHSSKPLPMAPEEKNKKARLRSIFPGGGDKTN
KKKEKERPEISLPSDFEHTIHVGFDAVTGEFTPDLYGSQMCPGKLPEGIPEQWARLLQTS
NITKLEQKKNPQAVLDVLKFYDSKETVNNQKYMSFTSGDKSAHGYIAAHPSSTKTASEPP
LAPPVSEEEDEEEEEEEDENEPPPVIAPRPEHTKSIYTRSVVESIASPAVPNKEVTPPSA
ENANSSTLYRNTDRQRKKSKMTDEEILEKLRSIVSVGDPKKKYTRFEKIGQGASGTVYTA
LDIATGQEVAIKQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYL
AGGSLTDVVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTD
FGFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNE
NPLRALYLIATNGTPELQNPERLSAVFRDFLNRCLEMDVDRRGSAKELLQHPFLKLAKPL
SSLTPLIIAAKEAIKNSSR
Target Bioclass
Enzyme
Family
Protein kinase superfamily, STE Ser/Thr protein kinase family, STE20 subfamily
Subcellular location
Cytoplasm
Function
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as a downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC).
Uniprot ID
O75914
Ensemble ID
ENST00000262836.6
HGNC ID
HGNC:8592
ChEMBL ID
CHEMBL2999

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
BTD
 Probe Info 
C424(0.66)  LDD2100  [1]
IPM
 Probe Info 
N.A.  LDD0025  [2]
JW-RF-010
 Probe Info 
N.A.  LDD0026  [2]
Compound 10
 Probe Info 
N.A.  LDD2216  [3]
NAIA_5
 Probe Info 
N.A.  LDD2223  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0539  3-(4-Isopropylpiperazin-1-yl)-3-oxopropanenitrile MDA-MB-231 C424(0.43)  LDD2132  [1]
 LDCM0538  4-(Cyanoacetyl)morpholine MDA-MB-231 C424(0.88)  LDD2131  [1]
 LDCM0507  Nucleophilic fragment 16b MDA-MB-231 C424(0.66)  LDD2100  [1]
 LDCM0527  Nucleophilic fragment 26b MDA-MB-231 C424(1.02)  LDD2120  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Rho-related GTP-binding protein RhoJ (RHOJ) Rho family Q9H4E5

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fostamatinib Small molecular drug DB12010

References

1 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
2 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
3 Multiplexed CuAAC Suzuki-Miyaura Labeling for Tandem Activity-Based Chemoproteomic Profiling. Anal Chem. 2021 Feb 2;93(4):2610-2618. doi: 10.1021/acs.analchem.0c04726. Epub 2021 Jan 20.
Mass spectrometry data entry: PXD022279
4 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264