General Information of Target

Target ID LDTP05576
Target Name Tyrosine-protein kinase ITK/TSK (ITK)
Gene Name ITK
Gene ID 3702
Synonyms
EMT; LYK; Tyrosine-protein kinase ITK/TSK; EC 2.7.10.2; Interleukin-2-inducible T-cell kinase; IL-2-inducible T-cell kinase; Kinase EMT; T-cell-specific kinase; Tyrosine-protein kinase Lyk
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MNNFILLEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRI
KCVEIVKSDISIPCHYKYPFQVVHDNYLLYVFAPDRESRQRWVLALKEETRNNNSLVPKY
HPNFWMDGKWRCCSQLEKLATGCAQYDPTKNASKKPLPPTPEDNRRPLWEPEETVVIALY
DYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEKSPNNLETYEWY
NKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVVSENNPCIKHYHIKETND
NPKRYYVAEKYVFDSIPLLINYHQHNGGGLVTRLRYPVCFGRQKAPVTAGLRYGKWVIDP
SELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQ
LYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIH
RDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSD
VWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPE
DRPAFSRLLRQLAEIAESGL
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
Protein kinase superfamily, Tyr protein kinase family, TEC subfamily
Subcellular location
Cytoplasm
Function
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Required for TCR-mediated calcium response in gamma-delta T-cells, may also be involved in the modulation of the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells. Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3.
TTD ID
T91761
Uniprot ID
Q08881
DrugMap ID
TTNHIXL
Ensemble ID
ENST00000422843.8
HGNC ID
HGNC:6171
ChEMBL ID
CHEMBL2959

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IPM
 Probe Info 
N.A.  LDD0241  [1]
4-Iodoacetamidophenylacetylene
 Probe Info 
C289(0.00); C143(0.00); C488(0.00); C199(0.00)  LDD0038  [2]
IA-alkyne
 Probe Info 
C289(0.00); C143(0.00); C339(0.00); C488(0.00)  LDD0036  [2]
Lodoacetamide azide
 Probe Info 
C289(0.00); C594(0.00); C143(0.00); C488(0.00)  LDD0037  [2]
Compound 10
 Probe Info 
C143(0.00); C289(0.00); C488(0.00)  LDD2216  [3]
Compound 11
 Probe Info 
N.A.  LDD2213  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 T cell C74(20.00)  LDD1703  [4]

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
Receptor tyrosine-protein kinase erbB-2 (ERBB2) Tyr protein kinase family P04626
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Heat shock protein HSP 90-beta (HSP90AB1) Heat shock protein 90 family P08238
Cytokine and receptor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Tumor necrosis factor ligand superfamily member 6 (FASLG) Tumor necrosis factor family P48023
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Lymphocyte cytosolic protein 2 (LCP2) . Q13094

The Drug(s) Related To This Target

Approved
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fostamatinib Small molecular drug DB12010
Pazopanib Small molecular drug DB06589
Zanubrutinib . DB15035
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Jte-051 . D01EJJ
Phase 1
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Cpi-818 Small molecular drug D1YZ5O
Investigative
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Bms-509744 Small molecular drug D04PEI
Staurosporine Small molecular drug DB02010
Bms-488516 . D05RPN
Patented
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Pmid27774824-compound-figure3example7 Small molecular drug D02IET
Pyrazolo[4,3-c]Pyridine Derivative 2 . D09PIS

References

1 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
2 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
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 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.