ITK (IL2-inducible T-cell kinase)

2007-04-01 Berthold Streubel Affiliation

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

Identity

HGNC

ITK

LOCATION

5q33.3

LOCUSID

3702

ALIAS

EMT,LPFS1,LYK,PSCTK2

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

centromere to telomere orientation; Exons: 17

Transcription

Transcript length: 4,419 bps

Proteins

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

t(5;9)(q33;q22)

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.

Bibliography

Pubmed ID	Last Year	Title	Authors
8985255	1997	Regulatory intramolecular association in a tyrosine kinase of the Tec family.	Andreotti AH et al
11406363	2001	Tec kinases: modulators of lymphocyte signaling and development.	Lewis CM et al
8777721	1995	Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk.	Liao XC et al
9584150	1998	T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells.	Liu KQ et al
10213685	1999	Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity.	Schaeffer EM et al
16341044	2006	Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma.	Streubel B et al
10795735	2000	Tec 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 ID	Transcript ID	Uniprot
ENSG00000113263	ENST00000422843	Q08881
ENSG00000113263	ENST00000517779	E5RJY4
ENSG00000113263	ENST00000521769	E5RFR5

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
T cell receptor signaling pathway	KEGG	ko04660
Leukocyte transendothelial migration	KEGG	ko04670
T cell receptor signaling pathway	KEGG	hsa04660
Leukocyte transendothelial migration	KEGG	hsa04670
Chemokine signaling pathway	KEGG	ko04062
Chemokine signaling pathway	KEGG	hsa04062
Immune System	REACTOME	R-HSA-168256
Adaptive Immune System	REACTOME	R-HSA-1280218
TCR signaling	REACTOME	R-HSA-202403
Generation of second messenger molecules	REACTOME	R-HSA-202433
Innate Immune System	REACTOME	R-HSA-168249
Fc epsilon receptor (FCERI) signaling	REACTOME	R-HSA-2454202
FCERI mediated Ca+2 mobilization	REACTOME	R-HSA-2871809

References

Pubmed ID	Year	Title	Citations
19425169	2009	Girls homozygous for an IL-2-inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation.	77
19240061	2009	Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.	75
11830645	2002	Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A.	73
17724684	2007	Memory phenotype CD8+ T cells with innate function selectively develop in the absence of active Itk.	43
20439541	2010	The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma.	39
22289921	2012	Loss-of-function mutations within the IL-2 inducible kinase ITK in patients with EBV-associated lymphoproliferative diseases.	35
18443296	2008	Selective targeting of ITK blocks multiple steps of HIV replication.	28
25512530	2014	Genetic modifiers of EGFR dependence in non-small cell lung cancer.	27
16159638	2005	Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain-IL-2-inducible T-cell kinase gene cluster in chromosome 5 q 33.	25
21674762	2012	Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.	19

Citation

Berthold Streubel

ITK (IL2-inducible T-cell kinase)

Atlas Genet Cytogenet Oncol Haematol. 2007-04-01

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