Details of the Target

General Information of Target

Target ID LDTP04209
Target Name Casein kinase I isoform alpha (CSNK1A1)
Gene Name CSNK1A1
Gene ID 1452
Synonyms
Casein kinase I isoform alpha; CKI-alpha; EC 2.7.11.1; CK1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MASSSGSKAEFIVGGKYKLVRKIGSGSFGDIYLAINITNGEEVAVKLESQKARHPQLLYE
SKLYKILQGGVGIPHIRWYGQEKDYNVLVMDLLGPSLEDLFNFCSRRFTMKTVLMLADQM
ISRIEYVHTKNFIHRDIKPDNFLMGIGRHCNKLFLIDFGLAKKYRDNRTRQHIPYREDKN
LTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSLPWQGLKAATKKQKYEKISEKK
MSTPVEVLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLFRILFRTLNHQYDYTFDWTM
LKQKAAQQAASSSGQGQQAQTPTGKQTDKTKSNMKGF
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
Protein kinase superfamily, CK1 Ser/Thr protein kinase family, Casein kinase I subfamily
Subcellular location
Cytoplasm
Function
Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis. May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration. Acts as a positive regulator of mTORC1 and mTORC2 signaling in response to nutrients by mediating phosphorylation of DEPTOR inhibitor. Acts as an inhibitor of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3.
TTD ID
T13075
Uniprot ID
P48729
DrugMap ID
TTFQEMX
Ensemble ID
ENST00000261798.10
HGNC ID
HGNC:2451
ChEMBL ID
CHEMBL2793

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
COLO792 SNV: p.E82Ter DBIA    Probe Info 
COLO800 SNV: p.K229N .
HEC1 SNV: p.M334V .
HEC1B SNV: p.M334V .
HUH28 SNV: p.E98K .
JHH7 SNV: p.Q56K .
KASUMI2 SNV: p.E98K .
LS180 SNV: p.A185V .
NCIH1155 SNV: p.A257V .
RKO SNV: p.K331M DBIA    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 14 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		15.00  LDD0402  [1]
STPyne
 Probe Info  		K62(10.00)  LDD0277  [2]
Probe 1
 Probe Info  		Y59(136.90); Y79(63.04); Y276(22.78)  LDD3495  [3]
DBIA
 Probe Info  		C153(2.41)  LDD3319  [4]
BTD
 Probe Info  		C249(0.79)  LDD2093  [5]
IPM
 Probe Info  		C249(1.05)  LDD1701  [5]
Acrolein
 Probe Info  		N.A.  LDD0222  [6]
ATP probe
 Probe Info  		K138(0.00); K225(0.00); K229(0.00)  LDD0199  [7]
4-Iodoacetamidophenylacetylene
 Probe Info  		C249(0.00); C263(0.00)  LDD0038  [8]
IA-alkyne
 Probe Info  		N.A.  LDD0036  [8]
Lodoacetamide azide
 Probe Info  		C263(0.00); C249(0.00)  LDD0037  [8]
Methacrolein
 Probe Info  		N.A.  LDD0218  [6]
AOyne
 Probe Info  		9.50  LDD0443  [9]
NAIA_5
 Probe Info  		C104(0.00); C263(0.00); C150(0.00); C249(0.00)  LDD2223  [10]
PAL-AfBPP Probe
Click To Hide/Show 9 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C163
 Probe Info  		6.23  LDD1843  [11]
C277
 Probe Info  		8.51  LDD1947  [11]
C363
 Probe Info  		17.27  LDD2024  [11]
FFF probe13
 Probe Info  		20.00  LDD0475  [12]
FFF probe14
 Probe Info  		14.41  LDD0477  [12]
FFF probe2
 Probe Info  		6.13  LDD0463  [12]
JN0003
 Probe Info  		20.00  LDD0469  [12]
VE-P
 Probe Info  		N.A.  LDD0396  [13]
OEA-DA
 Probe Info  		20.00  LDD0046  [14]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0524  2-Cyano-N-(2-morpholin-4-yl-ethyl)-acetamide MDA-MB-231 C249(1.07)  LDD2117  [5]
 LDCM0156  Aniline NCI-H1299 11.79  LDD0403  [1]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [6]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C249(2.32)  LDD1702  [5]
 LDCM0022  KB02 A2058 C153(2.97)  LDD2253  [4]
 LDCM0023  KB03 MDA-MB-231 C249(1.05)  LDD1701  [5]
 LDCM0024  KB05 MEWO C153(2.41)  LDD3319  [4]
 LDCM0500  Nucleophilic fragment 13a MDA-MB-231 C249(0.79)  LDD2093  [5]
 LDCM0503  Nucleophilic fragment 14b MDA-MB-231 C249(0.96)  LDD2096  [5]
 LDCM0506  Nucleophilic fragment 16a MDA-MB-231 C249(1.52)  LDD2099  [5]
 LDCM0514  Nucleophilic fragment 20a MDA-MB-231 C249(0.83)  LDD2107  [5]
 LDCM0530  Nucleophilic fragment 28a MDA-MB-231 C249(1.09)  LDD2123  [5]
 LDCM0532  Nucleophilic fragment 29a MDA-MB-231 C249(0.79)  LDD2125  [5]
 LDCM0533  Nucleophilic fragment 29b MDA-MB-231 C249(0.15)  LDD2126  [5]
 LDCM0534  Nucleophilic fragment 30a MDA-MB-231 C249(1.11)  LDD2127  [5]
 LDCM0542  Nucleophilic fragment 37 MDA-MB-231 C249(1.70)  LDD2135  [5]
 LDCM0544  Nucleophilic fragment 39 MDA-MB-231 C249(1.07)  LDD2137  [5]
 LDCM0546  Nucleophilic fragment 40 MDA-MB-231 C249(0.85)  LDD2140  [5]
 LDCM0550  Nucleophilic fragment 5a MDA-MB-231 C249(0.68)  LDD2144  [5]
 LDCM0556  Nucleophilic fragment 8a MDA-MB-231 C249(1.01)  LDD2150  [5]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
E3 ubiquitin-protein ligase Mdm2 (MDM2) MDM2/MDM4 family Q00987
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) Peptidase C14B family Q9UDY8
Leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2) TKL Ser/Thr protein kinase family Q5S007
Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) TKL Ser/Thr protein kinase family Q13546
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Protein cereblon (CRBN) CRBN family Q96SW2
Heat shock protein HSP 90-beta (HSP90AB1) Heat shock protein 90 family P08238
Other
Click To Hide/Show 9 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Protein FAM83B (FAM83B) FAM83 family Q5T0W9
Protein FAM83C (FAM83C) FAM83 family Q9BQN1
Protein FAM83D (FAM83D) FAM83 family Q9H4H8
Protein FAM83E (FAM83E) FAM83 family Q2M2I3
Protein FAM83F (FAM83F) FAM83 family Q8NEG4
Protein FAM83G (FAM83G) FAM83 family A6ND36
Protein FAM83H (FAM83H) FAM83 family Q6ZRV2
Protein Mdm4 (MDM4) MDM2/MDM4 family O15151
Caspase recruitment domain-containing protein 11 (CARD11) . Q9BXL7

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
Phase 1
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Btx-a51 Small molecular drug D5VMP4
Preclinical
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
D-4476 Small molecular drug D00JGL
Ic261 Small molecular drug D0UN8H
Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pmid24900428c14 Small molecular drug D0H4VB
Patented
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Us9096594, 3 Small molecular drug D0MN6V

References

1 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.
2 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
3 An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome. Anal Chem. 2021 Jul 27;93(29):10334-10342. doi: 10.1021/acs.analchem.1c01935. Epub 2021 Jul 12.
4 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
5 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
6 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
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 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
9 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.
10 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
11 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
12 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
13 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.
14 Mapping Protein Targets of Bioactive Small Molecules Using Lipid-Based Chemical Proteomics. ACS Chem Biol. 2017 Oct 20;12(10):2671-2681. doi: 10.1021/acschembio.7b00581. Epub 2017 Sep 20.
Mass spectrometry data entry: PXD007570