Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

ITK (Q08881) - Overview - Molecular Target Synopsis

Protein


ITK, Tyrosine-protein kinase ITK/TSK
Enzyme Classification 2.7.10.2
UniProt Q08881

Also Known as ITK_HUMAN, ITK, EMT, LYK

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 (PubMed:12186560, PubMed:12682224, PubMed:21725281). Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3. Homooligomerizes; this association negatively regulates kinase activity (By similarity). Interacts with PPIA/CYPA; this interaction regulates TCR signal strength via a proline-directed conformational switch in ITK. Interacts with THEMIS (By similarity). Interacts with FASLG. Interacts with VAV1; this interaction is important for VAV1 localization and TCR-induced actin polarization. Interacts with TBX21.

4RFM
ITK KINASE DOMAIN IN COMPLEX WITH COMPOUND 1 N-{1-[(1,1-DIOXO-1-THIAN- 2-YL)(PHENYL)METHYL]-1H- PYRAZOL-4-YL}-5,5-DIFLUORO-5A-METHYL-1H,4H, 4AH,5H,5AH,6H-CYCLOPROPA[F]INDAZOLE-3-CARBOXAMIDE
RCSB/PDB
Inspect Structure
See all 3D Structures for ITK

Isoforms / Transcripts (Protein Coding)


Drugs


ITK is targeted by Approved Drug Pazopanib. (see details)
Pazopanib

Sub-cellular localization


UniProt: ITK is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: ITK is active in the following subcellular-locations: cell-cell junction, cytosol, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project ITK has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MOLT_4, CCRF_CEM, SR

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Jurkat, Clone E6-1, SU-DHL-1, SR

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

RNA Interference


ITK was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SKGT4, SMOV2. (see details)

3D Structures


For ITK there are:
36 structures (59 chains) solved
32 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

ITK is solved in complex with the approved drug(s):

B49/SUNITINIB (3MIY_A, 3MIY_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


ITK has been screened with 1516 compounds (2578 bioactivities), 547 compounds have bioactivities that show binding affinity of <= 500nM (821 bioactivities). (see details)