Browse ITK

Summary
SymbolITK
NameIL2-inducible T-cell kinase
Aliases LYK; LPFS1; IL-2-inducible T cell kinase; IL-2-inducible T-cell kinase; T-cell-specific kinase; homolog of m ......
Chromosomal Location5q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus Note=Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation.
Domain PF00779 BTK motif
PF00169 PH domain
PF07714 Protein tyrosine kinase
PF00017 SH2 domain
PF00018 SH3 domain
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 (PubMed:12186560, PubMed:12682224, PubMed:21725281). Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3 (By similarity).

> Gene Ontology
 
Biological Process GO:0001865 NK T cell differentiation
GO:0002250 adaptive immune response
GO:0002429 immune response-activating cell surface receptor signaling pathway
GO:0002521 leukocyte differentiation
GO:0002757 immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0006968 cellular defense response
GO:0007159 leukocyte cell-cell adhesion
GO:0007202 activation of phospholipase C activity
GO:0010517 regulation of phospholipase activity
GO:0010518 positive regulation of phospholipase activity
GO:0010863 positive regulation of phospholipase C activity
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0030098 lymphocyte differentiation
GO:0030217 T cell differentiation
GO:0032609 interferon-gamma production
GO:0032633 interleukin-4 production
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0038093 Fc receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0042110 T cell activation
GO:0046631 alpha-beta T cell activation
GO:0046632 alpha-beta T cell differentiation
GO:0046777 protein autophosphorylation
GO:0050851 antigen receptor-mediated signaling pathway
GO:0050852 T cell receptor signaling pathway
GO:0060191 regulation of lipase activity
GO:0060193 positive regulation of lipase activity
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0071593 lymphocyte aggregation
GO:1900274 regulation of phospholipase C activity
Molecular Function GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
Cellular Component GO:0009898 cytoplasmic side of plasma membrane
GO:0019897 extrinsic component of plasma membrane
GO:0019898 extrinsic component of membrane
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane
GO:0098552 side of membrane
GO:0098562 cytoplasmic side of membrane
> KEGG and Reactome Pathway
 
KEGG hsa04062 Chemokine signaling pathway
hsa04660 T cell receptor signaling pathway
hsa04670 Leukocyte transendothelial migration
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-2871809: FCERI mediated Ca+2 mobilization
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-202433: Generation of second messenger molecules
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-202403: TCR signaling
Summary
SymbolITK
NameIL2-inducible T-cell kinase
Aliases LYK; LPFS1; IL-2-inducible T cell kinase; IL-2-inducible T-cell kinase; T-cell-specific kinase; homolog of m ......
Chromosomal Location5q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between ITK and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between ITK and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28714866Chronic Lymphocytic LeukemiaInhibit immunityPeripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially. Ibrutinib markedly increased CD4+ and CD8+ T cell numbers in CLL patients. This effect was more prominent in effector/effector memory subsets and was not observed with acalabrutinib. Ex vivo studies demonstrated that this may be due to diminished activation-induced cell death through ITK inhibition. Both agents reduced expression of the immunosuppressive molecules CD200 and BTLA as well as IL-10 production by CLL cells. PD-1 and CTLA-4 expression was significantly markedly reduced in T cells by both agents.
Summary
SymbolITK
NameIL2-inducible T-cell kinase
Aliases LYK; LPFS1; IL-2-inducible T cell kinase; IL-2-inducible T-cell kinase; T-cell-specific kinase; homolog of m ......
Chromosomal Location5q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of ITK in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolITK
NameIL2-inducible T-cell kinase
Aliases LYK; LPFS1; IL-2-inducible T cell kinase; IL-2-inducible T-cell kinase; T-cell-specific kinase; homolog of m ......
Chromosomal Location5q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of ITK in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0270.947
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.7430.326
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.5930.359
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1090.811
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1660.91
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.0390.983
729033130MelanomaallAnti-PD-1 (nivolumab) 26231.2530.0669
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.7260.142
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.8190.504
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.5710.0393
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.6860.148
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2220.363
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of ITK in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.42.74.70.294
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.41.75.70.231
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.67.4-4.80.565
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.57.7-3.21
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolITK
NameIL2-inducible T-cell kinase
Aliases LYK; LPFS1; IL-2-inducible T cell kinase; IL-2-inducible T-cell kinase; T-cell-specific kinase; homolog of m ......
Chromosomal Location5q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ITK. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolITK
NameIL2-inducible T-cell kinase
Aliases LYK; LPFS1; IL-2-inducible T cell kinase; IL-2-inducible T-cell kinase; T-cell-specific kinase; homolog of m ......
Chromosomal Location5q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ITK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ITK.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolITK
NameIL2-inducible T-cell kinase
Aliases LYK; LPFS1; IL-2-inducible T cell kinase; IL-2-inducible T-cell kinase; T-cell-specific kinase; homolog of m ......
Chromosomal Location5q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ITK. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolITK
NameIL2-inducible T-cell kinase
Aliases LYK; LPFS1; IL-2-inducible T cell kinase; IL-2-inducible T-cell kinase; T-cell-specific kinase; homolog of m ......
Chromosomal Location5q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ITK expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolITK
NameIL2-inducible T-cell kinase
Aliases LYK; LPFS1; IL-2-inducible T cell kinase; IL-2-inducible T-cell kinase; T-cell-specific kinase; homolog of m ......
Chromosomal Location5q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ITK and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolITK
NameIL2-inducible T-cell kinase
Aliases LYK; LPFS1; IL-2-inducible T cell kinase; IL-2-inducible T-cell kinase; T-cell-specific kinase; homolog of m ......
Chromosomal Location5q31-q32
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ITK collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting ITK.
ID Name Drug Type Targets #Targets
DB02010StaurosporineSmall MoleculeCDK2, CHRM1, CSK, GSK3B, ITK, LCK, MAPKAPK2, PDPK1, PIK3CG, PIM1, ......13
DB06589PazopanibSmall MoleculeFGF1, FGFR3, FLT1, FLT4, ITK, KDR, KIT, PDGFRA, PDGFRB, SH2B310