ITK (IL2-inducible T-cell kinase)

2007-04-01   Berthold Streubel  

Department of Pathology, Medical University of Vienna, Waehringer, Guertel 18-20, A-1090 Vienna, Austria

Identity

HGNC
LOCATION
5q33.3
LOCUSID
ALIAS
EMT,LPFS1,LYK,PSCTK2
FUSION GENES

DNA/RNA

Description

centromere to telomere orientation; Exons: 17

Transcription

Transcript length: 4,419 bps

Proteins

Atlas Image
ITK protein

Description

Number of residues: 620 residues; Molecular weight: 71 kDa; Conserved domains: PH-Tec, Tec pleckstrin homology (PH) domain; BTK, Brutons tyrosine kinase Cys-rich motif; SH3, Src homology 3 domains; SH2, Src homology 2 domains; TyrKc, Tyrosine kinase, catalytic domain.

Function

Although originally described as an important component of proximal TCR signaling pathways, the Tec family tyrosine kinase Itk has become increasingly recognized for its important role in regulating T-helper-cell differentiation. Itk has a crucial role in Th2 responses, both the protective responses to pathogenic infections in addition to the pathological responses resulting in allergic asthma. Itk is not required for Th2 differentiation per se, but effector Th2 cytokine production during recall responses is severely impaired in the absence of Itk.

Implicated in

Entity name
Disease
peripheral T-cell lymphomas, unspecified (PTCL-u). ITK-SYK transcripts were detected in 5 of 30 (17%) unspecified peripheral T-cell lymphomas, but not in cases of angioimmunoblastic T-cell lymphoma (n=9) and ALK-negative anaplastic large cell lymphoma (n=7)
Hybrid gene
N-terminal pleckstrin homology domain and proline-rich region of ITK fused to the tyrosine kinase domain of SYK.

Article Bibliography

Pubmed IDLast YearTitleAuthors
89852551997Regulatory intramolecular association in a tyrosine kinase of the Tec family.Andreotti AH et al
114063632001Tec kinases: modulators of lymphocyte signaling and development.Lewis CM et al
87777211995Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk.Liao XC et al
95841501998T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells.Liu KQ et al
102136851999Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity.Schaeffer EM et al
163410442006Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma.Streubel B et al
107957352000Tec kinases: a family with multiple roles in immunity.Yang WC et al

Other Information

Locus ID:

NCBI: 3702
MIM: 186973
HGNC: 6171
Ensembl: ENSG00000113263

Variants:

dbSNP: 3702
ClinVar: 3702
TCGA: ENSG00000113263
COSMIC: ITK

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000113263ENST00000422843Q08881
ENSG00000113263ENST00000517779E5RJY4
ENSG00000113263ENST00000521769E5RFR5

Expression (GTEx)

0
5
10
15
20

Pathways

PathwaySourceExternal ID
T cell receptor signaling pathwayKEGGko04660
Leukocyte transendothelial migrationKEGGko04670
T cell receptor signaling pathwayKEGGhsa04660
Leukocyte transendothelial migrationKEGGhsa04670
Chemokine signaling pathwayKEGGko04062
Chemokine signaling pathwayKEGGhsa04062
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
TCR signalingREACTOMER-HSA-202403
Generation of second messenger moleculesREACTOMER-HSA-202433
Innate Immune SystemREACTOMER-HSA-168249
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated Ca+2 mobilizationREACTOMER-HSA-2871809

References

Pubmed IDYearTitleCitations
363266972023Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis.5
379925722023Targeting kinase ITK treats autoimmune arthritis via orchestrating T cell differentiation and function.2
363266972023Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis.5
379925722023Targeting kinase ITK treats autoimmune arthritis via orchestrating T cell differentiation and function.2
352105492022ITK independent development of Th17 responses during hypersensitivity pneumonitis driven lung inflammation.1
352105492022ITK independent development of Th17 responses during hypersensitivity pneumonitis driven lung inflammation.1
326289642021ITK deficiency presenting as autoimmune lymphoproliferative syndrome.5
326404872021BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy.19
339314842021Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads.7
342820552021Interleukin-2 inducible T-cell kinase: a potential prognostic biomarker and tumor microenvironment remodeling indicator for hepatocellular carcinoma.1
347023002021Cytotoxic lymphocytes-related gene ITK from a systematic CRISPR screen could predict prognosis of ovarian cancer patients with distant metastasis.2
326289642021ITK deficiency presenting as autoimmune lymphoproliferative syndrome.5
326404872021BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy.19
339314842021Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads.7
342820552021Interleukin-2 inducible T-cell kinase: a potential prognostic biomarker and tumor microenvironment remodeling indicator for hepatocellular carcinoma.1

Citation

Berthold Streubel

ITK (IL2-inducible T-cell kinase)

Atlas Genet Cytogenet Oncol Haematol. 2007-04-01

Online version: http://atlasgeneticsoncology.org/gene/43329/itkid43329ch5q33