General Information of Target

Target ID LDTP03503
Target Name Myristoylated alanine-rich C-kinase substrate (MARCKS)
Gene Name MARCKS
Gene ID 4082
Synonyms
MACS; PRKCSL; Myristoylated alanine-rich C-kinase substrate; MARCKS; Protein kinase C substrate, 80 kDa protein, light chain; 80K-L protein; PKCSL
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGAQFSKTAAKGEAAAERPGEAAVASSPSKANGQENGHVKVNGDASPAAAESGAKEELQA
NGSAPAADKEEPAAAGSGAASPSAAEKGEPAAAAAPEAGASPVEKEAPAEGEAAEPGSPT
AAEGEAASAASSTSSPKAEDGATPSPSNETPKKKKKRFSFKKSFKLSGFSFKKNKKEAGE
GGEAEAPAAEGGKDEAAGGAAAAAAEAGAASGEQAAAPGEEAAAGEEGAAGGDPQEAKPQ
EAAVAPEKPPASDETKAAEEPSKVEEKKAEEAGASAAACEAPSAAGPGAPPEQEAAPAEE
PAAAAASSACAAPSQEAQPECSPEAPPAEAAE
Target Type
Clinical trial
Target Bioclass
Other
Family
MARCKS family
Subcellular location
Cytoplasm, cytoskeleton
Function
Membrane-associated protein that plays a role in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis through lipid sequestering and/or protein docking to membranes. Thus, exerts an influence on a plethora of physiological processes, such as embryonic development, tissue regeneration, neuronal plasticity, and inflammation. Sequesters phosphatidylinositol 4,5-bisphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells, an action reversed by protein kinase C, ultimately inhibiting exocytosis. During inflammation, promotes the migration and adhesion of inflammatory cells and the secretion of cytokines such as tumor necrosis factor (TNF), particularly in macrophages. Plays an essential role in bacteria-induced intracellular reactive oxygen species (ROS) formation in the monocytic cell type. Participates in the regulation of neurite initiation and outgrowth by interacting with components of cellular machinery including CDC42 that regulates cell shape and process extension through modulation of the cytoskeleton. Plays also a role in axon development by mediating docking and fusion of RAB10-positive vesicles with the plasma membrane.
TTD ID
T05351
Uniprot ID
P29966
DrugMap ID
TTHRM39
Ensemble ID
ENST00000612661.2
HGNC ID
HGNC:6759
ChEMBL ID
CHEMBL4804244

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 18 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
AZ-9
 Probe Info 
3.29  LDD0393  [1]
FBPP2
 Probe Info 
3.48  LDD0318  [2]
CHEMBL5175495
 Probe Info 
7.48  LDD0196  [3]
TG42
 Probe Info 
7.24  LDD0326  [4]
FBP2
 Probe Info 
2.45  LDD0317  [2]
m-APA
 Probe Info 
15.00  LDD0403  [5]
Jackson_14
 Probe Info 
2.04  LDD0123  [6]
AMP probe
 Probe Info 
K152(0.00); K153(0.00)  LDD0200  [7]
ATP probe
 Probe Info 
K152(0.00); K153(0.00); K165(0.00); K11(0.00)  LDD0199  [7]
ATP probe
 Probe Info 
K152(0.00); K153(0.00)  LDD0035  [8]
IPM
 Probe Info 
N.A.  LDD0025  [9]
NHS
 Probe Info 
K152(0.00); K11(0.00); K165(0.00); K153(0.00)  LDD0010  [10]
SF
 Probe Info 
N.A.  LDD0028  [11]
STPyne
 Probe Info 
K30(0.00); K11(0.00)  LDD0009  [10]
VSF
 Probe Info 
C321(0.00); C279(0.00)  LDD0007  [10]
Phosphinate-6
 Probe Info 
N.A.  LDD0018  [12]
1c-yne
 Probe Info 
K175(0.00); K40(0.00); K11(0.00); K69(0.00)  LDD0228  [13]
AOyne
 Probe Info 
15.00  LDD0443  [14]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STS-1
 Probe Info 
N.A.  LDD0068  [15]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0156  Aniline NCI-H1299 15.00  LDD0403  [5]
 LDCM0016  Ranjitkar_cp1 MDA-MB-231 2.04  LDD0123  [6]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Phase 2
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Bio-11006 Small molecular drug DQM0X1
Bio-11006 . D0C3XD

References

1 2H-Azirine-Based Reagents for Chemoselective Bioconjugation at Carboxyl Residues Inside Live Cells. J Am Chem Soc. 2020 Apr 1;142(13):6051-6059. doi: 10.1021/jacs.9b12116. Epub 2020 Mar 23.
2 Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping. RSC Chem Biol. 2020 Aug 12;1(4):209-213. doi: 10.1039/d0cb00048e. eCollection 2020 Oct 1.
Mass spectrometry data entry: PXD018580
3 Charting the Chemical Space of Acrylamide-Based Inhibitors of zDHHC20. ACS Med Chem Lett. 2022 Sep 26;13(10):1648-1654. doi: 10.1021/acsmedchemlett.2c00336. eCollection 2022 Oct 13.
4 Design and synthesis of tailored human caseinolytic protease P inhibitors. Chem Commun (Camb). 2018 Aug 28;54(70):9833-9836. doi: 10.1039/c8cc05265d.
Mass spectrometry data entry: PXD010277
5 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
6 Appendage and Scaffold Diverse Fully Functionalized Small-Molecule Probes via a Minimalist Terminal Alkyne-Aliphatic Diazirine Isocyanide. J Org Chem. 2018 Sep 21;83(18):11245-11253. doi: 10.1021/acs.joc.8b01831. Epub 2018 Aug 31.
7 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
8 Comparison of Quantitative Mass Spectrometry Platforms for Monitoring Kinase ATP Probe Uptake in Lung Cancer. J Proteome Res. 2018 Jan 5;17(1):63-75. doi: 10.1021/acs.jproteome.7b00329. Epub 2017 Nov 22.
Mass spectrometry data entry: PXD006095 , PXD006096
9 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
10 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
11 Solid Phase Synthesis of Fluorosulfate Containing Macrocycles for Chemoproteomic Workflows. bioRxiv [Preprint]. 2023 Feb 18:2023.02.17.529022. doi: 10.1101/2023.02.17.529022.
Mass spectrometry data entry: PXD039931
12 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
13 Tunable Amine-Reactive Electrophiles for Selective Profiling of Lysine. Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202112107. doi: 10.1002/anie.202112107. Epub 2021 Dec 16.
14 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
15 Proteome profiling reveals potential cellular targets of staurosporine using a clickable cell-permeable probe. Chem Commun (Camb). 2011 Oct 28;47(40):11306-8. doi: 10.1039/c1cc14824a. Epub 2011 Sep 16.